28595099	Circadian rhythm dysfunction is thought to play a key role in the pathogenesis of bipolar disorder (BD). We focused on circadian rhythm sleep-wake disorders (CRSWD) as possible predictors for bipolar disorder in patients with remitted mood disorders.One hundred four BD (41 type I and 63 type II) outpatients and 73 age- and sex-matched major depressive disorder (MDD) outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of the disorder, and family history of psychiatric disorders. Severity of mood status was evaluated by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview and sleep logs based on the International Classification of Sleep Disorders, third edition.	The rate of CRSWD in BD subjects was significantly higher than that in MDD subjects (33.7% vs 9.6%; P < 0.001). A multiple logistic regression analysis revealed that comorbid CRSWD (OR = 3.35, 95% CI = 1.24 - 9.07; P = 0.018), two or more previous mood episodes within the past year (OR = 3.57, 95% CI = 1.10 - 11.63; P = 0.035), and antidepressant-related switch to mania/hypomania (OR = 10.01, 95% CI = 1.20 - 83.52; P = 0.033) were significantly associated with BD in patients with remitted mood disorders.	CRSWD, as well as other factors, could be diagnostic predictors for BD in patients with remitted mood disorders. Combinations of these factors might be useful for predicting a BD diagnosis among the mood disorders in a clinical setting.	
28590702	The hypothalamus controls many homeostatic and instinctive physiological processes, including the sleep-wake cycle, food intake, and sexually dimorphic behaviors. These behaviors are regulated by environmental and physiological cues, although the molecular and cellular mechanisms that underlie these effects are still poorly understood. Recently, it has become clear that both the juvenile and adult hypothalamus exhibit neurogenesis, which modifies homeostatic neural circuitry. In this manuscript, we report data addressing the role of sex-specific and dietary factors in controlling neurogenesis in the mediobasal hypothalamus. We report that a high fat diet (HFD) activates neurogenesis in the median eminence (ME) of young adult female, but not male mice, and that focal irradiation of the ME in HFD-fed mice reduces weight gain in females, but not males. These results suggest that some physiological effects of HFD are mediated by sexually dimorphic neurogenesis in the ME. We present these findings in the context of other studies on the cellular and molecular mechanisms that regulate neurogenesis in postnatal and adult hypothalamus.
28589638	Amplitude-integrated electroencephalogram (aEEG) is widely used in neonates to detect electrical seizure and predict outcome following hypoxic ischaemic encephalopathy and other encephalopathy. Because accurate interpretation is important for clinical decision-making and family counselling, inter-observer reliability is a major concern. We aimed to evaluate inter-observer reliability in the interpretation of aEEG tracings in a neonatal intensive care unit.Three neonatal intensive care unit clinicians with different levels of experience in reading aEEG independently reviewed and scored aEEG traces using standardised criteria, categories and interpretation rules. Inter-observer reliability was evaluated using weighted Cohen's κ and intra-class correlation coefficients.	All 131 tracings from 120 neonates were reviewed by the neontalogist, 128 (97.7%) by the clinical nurse specialist, 73 (55.7%) by the nurse educator and 70 (53.4%) by all three clinicians. The majority (88 of 120, 73.3%) were term infants (mean gestational age 38 weeks, standard deviation 3.2). Average duration of recording was 27 h (standard deviation 19.1, range 1-105 h). Inter-observer reliability varied across categories and observers - from very good to excellent for the main background activity (intra-class correlation coefficients 0.93-0.98); good to very good for seizures; and moderate to very good for sleep-wake cycle and quality of recording (weighted κs' 0.71-0.85, 0.50-0.75, 0.46-0.81, respectively).	While certain aEEG features appear challenging to inter-observer reliability, our findings suggest that with training and consensus guidelines, levels of reliability needed to enhance clinical and prognostic usefulness of aEEG are achievable across clinicians with different levels of experience in reading aEEG.	
28587149	In vertebrates, melatonin is primarily secreted from the pineal gland but it affects various biological processes including the sleep-wake cycle, vasomotor control, immune system and bone homeostasis. Melatonin has been known to promote osteoblast differentiation and bone maturation, but a direct role of melatonin on osteoclast differentiation is still elusive. The present study investigated the effect of melatonin on the differentiation of macrophages to osteoclasts. The presence of melatonin significantly reduced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and the siRNA-mediated knockdown of the melatonin receptor failed to overcome the anti-osteoclastogenic effect of melatonin. Although melatonin treatment did not affect the phosphorylation of extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), it markedly inhibited the activation of NF-κB and subsequent induction of nuclear factor of activated T cell cytoplasmic 1(NFATc1). Thus, our results suggest that melatonin could suppress osteoclast differentiation through downregulation of NF-κB pathway with concomitant decrease in the NFATc1 transcription factor induction. Furthermore, melatonin seems to have an anti-osteoclastogenic effect independent of plasma membrane melatonin receptors. In addition to previously reported properties of melatonin, our study proposes another aspect of melatonin and bone homeostasis.
28582324	Review of the literature pertaining to clinical presentation, classification, epidemiology, pathophysiology, diagnosis, and treatment of sleep-related movement disorders and disturbances of motor control.Sleep-related movement disorders and disturbances of motor control are typically characterized by positive motor symptoms and are often associated with sleep disturbances and consequent daytime symptoms (e.g. fatigue, sleepiness). They often represent the first or main manifestation of underlying disorders of the central nervous system, which require specific work-up and treatment. Diverse and often combined cause factors have been identified. Although recent data provide some evidence regarding abnormal activation and/or disinhibition of motor circuits during sleep, for the majority of these disorders the pathogenetic mechanisms remain speculative. The differential diagnosis is sometimes difficult and misdiagnoses are not infrequent. The diagnosis is based on clinical and video-polysomnographic findings. Treatment of sleep-related motor disturbances with few exceptions (e.g. restless legs/limbs syndrome) are based mainly on anecdotal reports or small series.	More state-of-the-art studies on the cause, pathophysiology, and treatment of sleep-related movement disorders and disturbances of motor control are needed.	
28579782	Patients with non-24-hour sleep-wake rhythm disorder (N24SWD) exhibit a sleep pattern that is asynchronous with the external light-dark cycle, typically involving a cycling, relapsing-remitting pattern of sleep disturbances, including nighttime insomnia and daytime sleepiness. Here, we report the case of a patient with N24SWD comorbid with major depressive disorder, who was successfully treated with a low dose of aripiprazole.A 47-year-old female presented with an 8-year complaint of difficulty falling asleep and waking up in the morning. The patient was diagnosed with major depressive disorder at the age of 35 years and was treated with various antidepressants since that time. At the age of 40 years, the patient's sleep-wake cycle began to extend without exacerbation of depressive symptoms. The patient was diagnosed with N24SWD at the age of 43 years. Ramelteon 8 mg/d and then melatonin 1 mg/d were administered, but these did not provide effective treatment. In January 2016, after treatment with aripiprazole 3 mg/d in the morning for 4 weeks, the patient's sleep-wake cycle became markedly synchronized to the environmental light-dark cycle. Her sleep-wake cycle remained synchronized when the same dose of aripiprazole was administered for at least 6 months.	Treatment-refractory asynchrony of the sleep-wake cycle in an N24SWD patient with depression was successfully treated with aripiprazole. Although the detailed mechanism of action is unclear, aripiprazole may be an appropriate treatment for patients with circadian rhythm sleep-wake disorders.	
28577340	Pediatric obstructive sleep-disordered breathing is associated with growth retardation, but also with obesity that has a tendency to persist following treatment. We investigated the effect of upper airways obstruction (AO) and of obstruction removal (OR) in juvenile rats on gut-derived ghrelin and related hypothalamic factors, feeding, and growth hormone (GH) homeostasis. Here, we show that after seven weeks of AO, animals gained less weight compared to controls, despite an increase in food intake due to elevated ghrelin and hypothalamic feeding factors. OR rats who had complete restoration of tracheal diameter, consumed more food due to increased ghrelin and exhibited growth retardation due to deregulation of GH homeostasis. This study is the first to show dysregulation of the hormonal axes controlling feeding behavior and growth that are not fully restored following OR. Thus, surgical treatment by itself may not be sufficient to prevent post-surgical increased food intake and growth retardation.
28575719	Several lines of evidence indicate that the sleep-wake state of cortical neurons is regulated not only through neuronal projections from the lower brain, but also through the cortical neurons' intrinsic ability to initiate a slow firing pattern related to the slow-wave oscillation observed in electroencephalography of the sleeping brain. Theoretical modeling and experiments with genetic and pharmacological perturbation suggest that ion channels and kinases acting downstream of calcium signaling regulate the cortical-membrane potential and sleep duration. In this review, we introduce possible Ca2+-dependent hyperpolarization mechanisms in cortical neurons, in which Ca2+ signaling associated with neuronal excitation evokes kinase cascades, and the activated kinases modify ion channels or pumps to regulate the cortical sleep/wake firing mode.
28574585	The purpose of this study was to explore whether associations between self-reported sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness differed in older community-dwelling men and women.Cross-sectional.	A community-dwelling sample of 675 older men and women (mean age 77.7 years, SD 3.8 years) was used. All participants underwent a clinical examination by a cardiologist. Validated questionnaires were used to investigate sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness. Subjects were divided into short sleepers (≤6 hours), n = 231; normal sleepers (7-8 hours), n = 338; and long sleepers (≥9 hours), n = 61. ancovas were used to explore sex-specific effects.	Depressive symptoms were associated with short sleep in men, but not in women. Fatigue was associated with both short and long sleep duration in men. No sex-specific associations of sleep duration with daytime sleepiness or anxiety were found.	Nurses investigating sleep duration and its correlates, or effects, in clinical practice need to take sex into account, as some associations may be sex specific. Depressive symptoms and fatigue can be used as indicators to identify older men with sleep complaints.	
28572056	Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise.
28571798	Viruses have long been implicated in the pathogenesis of classical encephalitis lethargica, which was first described by Constantin von Economo in 1917. In this article, I propose the hypothesis that an airborne virus travels along the olfactory conduit to infect the olfactory bulb; this local infection or induced neuroinflammation, in turn, retrogradely targets certain neuronal populations with sleep-wake regulatory functions in the hypothalamus and midbrain, leading to the development of wakeful inactivity, a hallmark clinical feature of the disease. Furthermore, the olfactory vector hypothesis may also explain the pathomechanism of the debilitating complication of the disease, i.e., postencephalitic parkinsonism, in terms of a recently discovered nigro-olfactory projection.
28567500	Impaired sleep and alertness affect the majority of Parkinson's disease (PD) patients, negatively impacting safety and quality of life. The etiology of impaired sleep-wake cycle in PD is multifactorial and encompasses medication side effects, nocturnal PD motor symptoms, and presence of co-existent sleep and neuropsychiatric disorders. The primary neurodegenerative process of PD involves brain regions that regulate the sleep-wake cycle, such as brainstem and hypothalamic nuclei. Sleep disorders in PD include insomnia, REM sleep behavior disorder (RBD), sleep disordered breathing (SDB), restless legs syndrome (RLS), and circadian disruption. Despite its high prevalence in the PD population, there is a paucity of clinical studies that have investigated treatment of sleep dysfunction associated with PD. Therefore, we aim to review available evidence and outline treatment strategies for improvement of disorders of sleep and wakefulness in PD patients. Evidence supporting the efficacy of pharmacological and non-pharmacological treatment strategies in PD is limited. There is thus a great need but also opportunity for development of well-designed clinical trials for impaired sleep and alertness in PD. Providing education about sleep hygiene and strategies for its implementation represents the initial step in management. Prompt diagnosis and treatment of co-existent primary sleep and psychiatric disorders are critical, as this may significantly improve sleep and alertness. While the optimal treatment for insomnia in PD has not been established, available strategies include cognitive-behavioral therapy, medications with soporific properties, and light therapy. Safety measures, clonazepam, and melatonin are the mainstay of treatment for RBD. Continuous positive airway pressure is an effective treatment for SDB in PD. The treatment algorithm for RLS associated with PD mirrors that used for idiopathic RLS. Circadian disruption has emerged as an important etiology of impaired sleep-wake cycles in PD, and circadian-based interventions hold promise for novel treatment approaches.
28560797	Sleep deprivation during pregnancy is an emerging concern, as it can adversely affect the development of the offspring brain. This study was conducted to evaluate the effects of deprivation of rapid eye movement (REM) sleep during the third term of pregnancy on the sleep-wake profiles of neonates in the Wistar rat model. Sleep-wake patterns were assessed through electrophysiological measures and behavioural observations during postnatal days 1-21 on pups born to REM sleep-deprived dams and control rats. Pups of REM sleep-deprived dams had active sleep that was not only markedly higher in percentage during all the days studied, but also had reduced latency during later postnatal days 15-21. Quiet sleep and wake periods were lower. These factors, along with less frequent but longer sleep-wake cycles, indicated maturational delay in the sleep-wake neural networks. The disruption of time-bound growth of sleep-wake neural networks was substantiated further by the decreased slope of survival plots in the sleep bouts. Examination of altered sleep-wake patterns during early development may provide crucial information concerning deranged neural development in the offspring. This is the first report, to our knowledge, to show that maternal sleep deprivation during pregnancy can delay and impair the development of sleep-wake profile in the offspring.
28553739	Many biochemical, physiological, and behavioral processes such as glucose metabolism, body temperature, and sleep-wake cycles show regular daily rhythms. These circadian rhythms are adjusted to the environmental light-dark cycle by a central pacemaker located in the suprachiasmatic nucleus (SCN) in order for the processes to occur at appropriate times of day. Here, we investigated the expression and function of a synaptic organizing protein, C1QL3, in the SCN. We found that C1ql3 is robustly expressed in the SCN. C1ql3 knockout mice have a reduced density of excitatory synapses in the SCN. In addition, these mice exhibited less consolidated activity to the active portions of the day and period lengthening following a 15-minute phase-delaying light pulse. These data identify C1QL3 as a signaling molecule that is highly expressed in SCN neurons, where it contributes to the formation and/or maintenance of glutamatergic synapses and plays a role in circadian behaviors, which may include circadian aftereffects.
28552556	Infant rats randomly cycle between the sleeping and waking states, which are tightly correlated with the activity of mutually inhibitory brainstem sleep and wake populations. Bouts of sleep and wakefulness are random; from P2-P10, sleep and wake bout lengths are exponentially distributed with increasing means, while during P10-P21, the sleep bout distribution remains exponential while the distribution of wake bouts gradually transforms to power law. The locus coeruleus (LC), via an undeciphered interaction with sleep and wake populations, has been shown experimentally to be responsible for the exponential to power law transition. Concurrently during P10-P21, the LC undergoes striking physiological changes - the LC exhibits strong global 0.3 Hz oscillations up to P10, but the oscillation frequency gradually rises and synchrony diminishes from P10-P21, with oscillations and synchrony vanishing at P21 and beyond. In this work, we construct a biologically plausible Wilson Cowan-style model consisting of the LC along with sleep and wake populations. We show that external noise and strong reciprocal inhibition can lead to switching between sleep and wake populations and exponentially distributed sleep and wake bout durations as during P2-P10, with the parameters of inhibition between the sleep and wake populations controlling mean bout lengths. Furthermore, we show that the changing physiology of the LC from P10-P21, coupled with reciprocal excitation between the LC and wake population, can explain the shift from exponential to power law of the wake bout distribution. To our knowledge, this is the first study that proposes a plausible biological mechanism, which incorporates the known changing physiology of the LC, for tying the developing sleep-wake circuit and its interaction with the LC to the transformation of sleep and wake bout dynamics from P2-P21.
28552056	Chronic pain is a multifaceted and complex condition that is divided into somatic, visceral, and neuropathic pain. Although opioids and nonsteroidal anti-inflammatory drugs cause analgesia and are effective in the treatment of chronic pain, their utility is hampered by side effects, abuse potential, and development of tolerance to their pain-relieving effects. So, finding alternative analgesics with good efficacy and low side effects is of great interest and the orexinergic system is a potential candidate. Orexin-A and -B are exclusively expressed in the lateral hypothalamus and are involved in the feeding, sleep/wake cycle, cardiovascular function, hormone secretion, seizure, and pain modulation. Orexin peptides and their receptors have been proposed as an opportunity for developing analgesic drugs. In experimental studies, orexin peptides induce analgesia that is comparable to morphine. Furthermore, there is evidence that orexin receptors 1 and 2 participate in responsiveness to both stressful stimuli and pain. Thus, direct and indirect activation of the orexinergic system is a new therapeutic approach to pain control. This article will review the most recent and important studies describing the role of the orexins in pain modulation.
28550253	Sleep disturbances are routinely encountered in Alzheimer's disease (AD) and affect about 25-40% of patients in the mild-to-moderate stages of the disease. In many, sleep pathology may represent a symptom of the underlying neurodegeneration. However, a history of sleep disruption occurring years prior to onset of cognitive symptoms could represent a potential risk factor for AD. The aim of the present narrative review was to evaluate current evidence linking sleep disturbances with AD development and to understand the mechanisms that may contribute to this. Although the mechanisms by which poor sleep may contribute to AD genesis is not fully understood, emerging evidence linking disturbances in the sleep wake cycle with Aβ deposition is shedding light on the relationship between sleep pathology and the subsequent development of AD. Aβ burden appears to be enhanced by sleep-wake cycle disruptions and is suspected as being an important mechanism by which sleep disruptions contribute in AD development. Other mechanisms triggered by sleep disruption may also be involved in AD development, such as brain hypoxia, oxidative stress, circadian activity rhythms disturbances, overexpression of orexins, and blood-brain barrier impairment. Further understanding of the link between sleep disturbances and future development of AD is still needed before sleep disturbances are clearly marked as a preventable risk factor for AD. In these circumstances, early lifestyle interventions to help increase the quantity and quality of sleep may have a favorable outcome on decreasing the incidence of AD and this needs to be investigated further.
28548869	Wakefulness and sleep are fundamental characteristics of the brain. We, therefore, hypothesized that transmitter systems contribute to their regulation and will exhibit circadian alterations. We assessed the concentration of various neurotransmitter receptors and transporters including adenosinergic (A1AR, A2AAR, and ENT1), dopaminergic (D1R, D2R, and DAT), and serotonergic (5-HT2AR) target proteins. Adult male Sprague Dawley rats were used and maintained in a 12 h light: 12 h dark cycle (lights on from 07:00 h to 19:00 h). We measured receptor and transporter concentrations in different brain regions, including caudate putamen, basal forebrain, and cortex in 4 hour-intervals over a 24 hour-period using quantitative in vitro autoradiography. Investigated receptors and transporters showed no fluctuations in any of the analyzed regions using one-way ANOVA. Only in the horizontal diagonal band of Broca, the difference of A1AR concentration between light and dark phases (t-test) as well as the cosinor analysis of the 24 hour-course were significant, suggesting that this region underlies receptor fluctuations. Our findings suggest that the availability of the investigated neurotransmitter receptors and transporters does not undergo changes in a 24 hour-period. While there are reports on changes in adenosine and dopamine receptors during sleep deprivation, we found no changes in the investigated adenosine, dopamine, and serotonin receptors during regular and undisturbed day-night cycles.
28548639	Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka 'masking') mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output.
28547821	Substance use (SU) and sleep problems appear interrelated, but few studies have examined the influence of adolescent sleep patterns on development of SU disorders. This study prospectively examined the influence of sleep habits on subsequent SU in youth who later transitioned into heavy drinking. At time 1 (T1), participants (n = 95) were substance-naive 12- to 14-year-olds. Path-analytic models examined whether the effects of T1 risk factors (familial SU disorder, inhibition control, and externalizing and internalizing traits) on time 3 (M = 19.8 years old) tobacco, alcohol, and cannabis were mediated by time 2 (M = 15.1 years old) sleep chronotype, daytime sleepiness, and erratic sleep/wake behaviors. Significant direct path effects of T1 risk factors and time 2 sleep behaviors on time 3 SU were found, Ps < 0.05. In models that examined the effect of each individual sleep behavior separately on SU, more erratic sleep/wake and greater daytime sleepiness predicted higher lifetime use events for all substances (Ps < 0.01). Higher evening chronotype tendencies predicted lower tobacco and higher alcohol and cannabis lifetime use events (Ps < 0.01). Erratic sleep/wake behaviors mediated the effect of inhibitory control on subsequent SU; less erratic sleep/wake behaviors predicted better inhibition control (β̂= -0.20, P < 0.05). Early-mid adolescent psychiatric health and sleep behaviors prior to drinking onset predicted greater SU 5 years later. Participants were substance-naïve at baseline, allowing for the examination of temporal order in the relationship between sleep problems and alcohol use. Early adolescent sleep problems may be an important risk factor for SU in later life.
28545363	Age-related cognitive impairment and the prevalence of neurodegenerative disease contribute to decreasing quality of life in affected individuals and their families as well as demand considerable societal responsibility. Sleep supports overall brain activity and contributes to both physical and mental health. As a result sleep is an attractive target for exploring ways to promote health in accelerated cognitive aging. The aims of this study were to characterise cognitive performance and sleep-wake behaviour in older adults with different degrees of cognitive impairment. Cognitive ability in a variety of domains of amnestic mild cognitive impairment (aMCI) individuals, moderate AD patients and cognitively healthy adults was assessed with the Mini-Mental-State-Examination and five computerised tests (CANTABeclipse™). It was imperative to exclude mixed diagnosis, comorbidities (psychiatric, neurological, sleep disorders), anti-dementia medication, institutionalised subjects, and to study participants within their home to minimise confounders. Sleep profiles were assessed with the Jupiter Sleep Questionnaire and Pittsburgh Sleep Quality Index completed by participants and carers. Participants' sleep-wake activity was monitored for three weeks using a wrist-worn actigraph and a semi-standardised diary. Groups were compared according to their diagnostic category and then pooled to correlate sleep data with cognitive performance. Mild cognitive impairment in aMCI individuals was reflected in domains of verbal and visuospatial memory but not attentional capacity or episodic memory. All self-reported and objective measures of sleep quality and sleep quantity of the aMCIs were within the normal range and comparable to those of cognitively healthy controls. Moderate AD patients scored significantly lower on all cognitive tests and had lower rest-activity amplitudes and distinctively longer nightly sleep periods that were not associated with sleep disorders, sleep medication or poor sleep efficiency. Self-rated and actigraphic quality of sleep was equally good (i.e. 90% sleep efficiency) in all groups. This investigation is of clinical importance, because major confounding variables were excluded. The lack of comorbidities might be responsible for the absence of sundown syndrome and sleep disturbances commonly reported in AD patients. Whether there is interdependence between progressive decline in cognition and long sleep duration remains elusive. Future studies should address whether prolonged sleep at night and decreased day-time activity can be altered to delay the progression of cognitive decline.
28542191	Brain activity displays a large repertoire of dynamics across the sleep-wake cycle and even during anesthesia. It was suggested that criticality could serve as a unifying principle underlying the diversity of dynamics. This view has been supported by the observation of spontaneous bursts of cortical activity with scale-invariant sizes and durations, known as neuronal avalanches, in recordings of mesoscopic cortical signals. However, the existence of neuronal avalanches in spiking activity has been equivocal with studies reporting both its presence and absence. Here, we show that signs of criticality in spiking activity can change between synchronized and desynchronized cortical states. We analyzed the spontaneous activity in the primary visual cortex of the anesthetized cat and the awake monkey, and found that neuronal avalanches and thermodynamic indicators of criticality strongly depend on collective synchrony among neurons, LFP fluctuations, and behavioral state. We found that synchronized states are associated to criticality, large dynamical repertoire and prolonged epochs of eye closure, while desynchronized states are associated to sub-criticality, reduced dynamical repertoire, and eyes open conditions. Our results show that criticality in cortical dynamics is not stationary, but fluctuates during anesthesia and between different vigilance states.
28541527	Dysregulation of sleep is associated with metabolic diseases, and metabolic rate is acutely regulated by sleep-wake behavior. In humans and rodent models, sleep loss is associated with obesity, reduced metabolic rate, and negative energy balance, yet little is known about the neural mechanisms governing interactions between sleep and metabolism. We have developed a system to simultaneously measure sleep and metabolic rate in individual Drosophila, allowing for interrogation of neural systems governing interactions between sleep and metabolic rate. Like mammals, metabolic rate in flies is reduced during sleep and increased during sleep deprivation suggesting sleep-dependent regulation of metabolic rate is conserved across phyla. The reduction of metabolic rate during sleep is not simply a consequence of inactivity because metabolic rate is reduced ~30 minutes following the onset of sleep, raising the possibility that CO2 production provides a metric to distinguish different sleep states in the fruit fly. To examine the relationship between sleep and metabolism, we determined basal and sleep-dependent changes in metabolic rate is reduced in starved flies, suggesting that starvation inhibits normal sleep-associated effects on metabolic rate. Further, translin mutant flies that fail to suppress sleep during starvation demonstrate a lower basal metabolic rate, but this rate was further reduced in response to starvation, revealing that regulation of starvation-induced changes in metabolic rate and sleep duration are genetically distinct. Therefore, this system provides the unique ability to simultaneously measure sleep and oxidative metabolism, providing novel insight into the physiological changes associated with sleep and wakefulness in the fruit fly.
28539902	The term "sleep experiences," coined by Watson (2001), denotes an array of unusual nocturnal consciousness phenomena; for example, nightmares, vivid or recurrent dreams, hypnagogic hallucinations, dreams of falling or flying, confusional arousals, and lucid dreams. Excluding the latter, these experiences reflect a single factor of atypical oneiric cognitions ("general sleep experiences"). The current study is an opinionated mini-review on the associations of this factor-measured with the Iowa sleep experiences survey (ISES, Watson, 2001)-with psychopathological symptoms and stress. Findings support a strong relation between psychological distress and general sleep experiences. It is suggested that that they should be viewed as a sleep disturbance; they seem to represent involuntary intrusions of wakefulness into sleep, resulting in aroused sleep. These intrusions may stem from excessively thin boundaries between consciousness states (e.g., "transliminality"), or, conversely, they may follow an attempt at disconnecting mental elements (e.g., dissociation), which paradoxically results in a "rebound effect." The extent to which unusual dreaming is experienced as intrusive, rather than controlled, may explain why general sleep experiences are related to psychopathology, whereas lucid dreams are related to psychological resilience. In conclusion, the exploration of the interplay between psychopathology and sleep should be expanded from focusing almost exclusively on quantitative aspects (e.g., sleep efficiency, latency) to including qualitative conscious experiences which may reflect poor sleep quality. Taking into account nocturnal consciousness-including unusual dreaming and permeable sleep-wake boundaries-may unveil rich information on night-time emotional states and broaden our definition of poor sleep quality.
28538168	The diverse cell-types of the basal forebrain control sleep-wake states, cortical activity and reward processing. Large, slow-firing, cholinergic neurons suppress cortical delta activity and promote cortical plasticity in response to reinforcers. Large, fast-firing, cortically-projecting GABAergic neurons promote wakefulness and fast cortical activity. In particular, parvalbumin/GABAergic neurons promote neocortical gamma band activity. Conversely, excitation of slower-firing somatostatin/GABAergic neurons promotes sleep through inhibition of cortically-projecting neurons. Activation of glutamatergic neurons promotes wakefulness, likely by exciting other cortically-projecting neurons. Similarly, cholinergic neurons indirectly promote wakefulness by excitation of wake-promoting, cortically-projecting GABAergic neurons and/or inhibition of sleep-promoting somatostatin/GABAergic neurons. Both glia and neurons increase the levels of adenosine during prolonged wakefulness. Adenosine presynaptically inhibits glutamatergic inputs to wake-promoting cholinergic and GABAergic/parvalbumin neurons, promoting sleep.
28537447	The hypothalamic peptide hypocretin 1 (orexin A) may be assayed in cerebrospinal fluid to diagnose narcolepsy type 1. This testing is not commercially available, and factors contributing to assay variability have not previously been comprehensively explored. In the present study, cerebrospinal fluid hypocretin concentrations were determined in duplicate in 155 patient samples, across a range of sleep disorders. Intra-assay variability of these measures was analyzed. Inter-assay correlation between samples tested at Emory and at Stanford was high (r = 0.79, p < 0.0001). Intra-assay correlation between samples tested in duplicate in our center was also high (r = 0.88, p < 0.0001); intra-assay variability, expressed as the difference between values as a percentage of the higher value, was low at 9.4% (SD = 7.9%). Although both time the sample spent in the freezer (r = 0.16, p = 0.04) and age of the kit used for assay (t = 3.64, p = 0.0004) were significant predictors of intra-kit variability in univariate analyses, only age of kit was significant in multivariate linear regression (F = 4.93, p = 0.03). Age of radioimmunoassay kit affects intra-kit variability of measured hypocretin values, such that kits closer to expiration exhibit significantly more variability.
28536294	The role of vitamin D in osteomineral metabolism is well known. Several studies have suggested its action on different biological mechanisms, such as nociceptive sensitivity and sleep-wake cycle modulation. Sleep is an important biological process regulated by different regions of the central nervous system, mainly the hypothalamus, in combination with several neurotransmitters. Pain, which can be classified as nociceptive, neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that contributes to hyperalgesia. Sleep deprivation is an important condition related to hyperalgesia, and recently it has also been associated with vitamin D. Poor sleep efficiency and sleep disorders have been shown to have an important role in hyperalgesia, and be associated with different vitamin D values. Vitamin D has been inversely correlated with painful manifestations, such as fibromyalgia and rheumatic diseases. Studies have demonstrated a possible action of vitamin D in the regulatory mechanisms of both sleep and pain. The supplementation of vitamin D associated with good sleep hygiene may have a therapeutic role, not only in sleep disorders but also in the prevention and treatment of chronic pain conditions.
28526554	Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). A deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Multiple approaches, including molecular genetic, electrophysiological, pharmacological, and neuroanatomical studies have suggested that orexins play critical roles in the maintenance of wakefulness by regulating the function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness. Here, I review recent advances in the understanding of how orexins regulate sleep/wakefulness and prevent narcolepsy.
28526553	Sleep is one of the most important physiological functions in mammals. It is regulated by not only homeostatic regulation but also circadian clock. Several neuropeptide-producing neurons located in the hypothalamus are implicated in the regulation of sleep/wakefulness. Among them, orexin/hypocretin-producing neurons (orexin neurons) are a crucial component for maintenance of wakefulness, because lack of orexin function results in narcolepsy, which is a sleep disorder. Recent findings have identified substances that excite or inhibit neural activity of orexin neurons. Furthermore neural projections of the neurons which release these substances have been revealed. In addition to orexin, melanin concentrating hormone (MCH)-producing neurons in the lateral hypothalamic area (LHA) are also implicated in the regulation of sleep/wakefulness. MCH neurons are active during sleep but become silent during wakefulness. Recently developed innovative methods including optogenetics and pharmacogenetics have provided substantial insights into the regulation of sleep/wakefulness. In vivo optical recordings and retrograde and anterograde tracing methods will allow us to understand additional details regarding important interactions between these two types of neurons in the LHA and other neurons in the brain. Finally we discuss the circadian clock and sleep/wake cycle. Understanding of the neural networks and its circadian modulation of sleep/wake cycles remain to be investigated.
28526411	Brain histamine acts as a neurotransmitter and regulates various physiological functions, such as learning and memory, sleep-wake cycles, and appetite regulation. We have recently shown that histamine H3 receptor (H3R) is expressed in primary mouse microglia and has a strong influence on critical functions in microglia, including chemotaxis, phagocytosis, and cytokine secretion in vitro. However, the importance of H3R in microglial activity in vivo remains unknown. Here, we examined the effects of JNJ10181457 (JNJ), a selective and potent H3R inverse agonist, on microglial functions ex vivo and in vivo. First, we injected ATP, which is a typical chemoattractant, into hippocampal slices to investigate the effect of JNJ on chemotaxis. ATP-induced microglial migration toward the injected site was significantly suppressed by JNJ treatment. Next, we examined whether JNJ affected microglial phagocytosis in hippocampal slices and in the prefrontal cortex. Microglial engulfment of dead neurons induced by N-methyl-d-aspartate was inhibited in the presence of JNJ. The increase in zymosan particle uptake by activated microglia in the prefrontal cortex was prevented by JNJ administration. Finally, we determined the importance of JNJ in a lipopolysaccharide (LPS)-induced depression model. JNJ reduced the LPS-induced upregulation of microglial pro-inflammatory cytokines and improved depression-like behaviour in the tail-suspension test. These results demonstrate the inhibitory effects of JNJ on chemotaxis, phagocytosis, and cytokine production in microglia inside the brain, and highlight the importance of microglial H3R for brain homeostasis.
28526259	By affecting the internal timing mechanisms of the brain, light regulates human physiology and behavior, perhaps most notably the sleep-wake cycle. Humans spend over 90% of their waking hours indoors, yet light in the built environment is not designed to affect circadian rhythms.Using a device calibrated to measure light that is effective for the circadian system (circadian-effective light), collect personal light exposures in office workers and relate them to their sleep and mood.	The research was conducted in 5 buildings managed by the US General Services Administration.	This study recruited 109 participants (69 females), of whom 81 (54 females) participated in both winter and summer.	Self-reported measures of mood and sleep, and objective measures of circadian-effective light and activity rhythms were collected for 7 consecutive days.	Compared to office workers receiving low levels of circadian-effective light in the morning, receiving high levels in the morning is associated with reduced sleep onset latency (especially in winter), increased phasor magnitudes (a measure of circadian entrainment), and increased sleep quality. High levels of circadian-effective light during the entire day are also associated with increased phasor magnitudes, reduced depression, and increased sleep quality.	The present study is the first to measure personal light exposures in office workers using a calibrated device that measures circadian-effective light and relate those light measures to mood, stress, and sleep. The study's results underscore the importance of daytime light exposures for sleep health.	
28522096	To compare sleep and circadian variability in adults with delayed sleep-wake phase disorder (DSWPD) to healthy controls.Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break.	Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD.	
28522076	To compare diurnal and nocturnal electrophysiological data from narcolepsy patients with undetectable (<20 pg/mL), low (20-110 pg/mL) and normal (>110 pg/mL) cerebrospinal fluid (CSF) hypocretin-1 levels.A total of 109 narcolepsy patients and 37 controls were studied; all had available CSF hypocretin-1 measurements. The sleep laboratory studies were conducted between 2008 and 2014. The study retrospectively examined measurements of sleep stage transitions in diurnal and nocturnal continuous polysomnography. The percentage distribution of time awake and rapid eye movement (REM) sleep, and the occurrence of sleep onset REM (SOREM) in the nocturnal polysomnography were also measured.	Participants with undetectable hypocretin-1 levels had significantly higher frequencies of transitions than controls and those with normal hypocretin-1 levels. Participants with low hypocretin-1 levels showed more transitions than controls and, in some cases, also more than those with normal hypocretin-1. Participants with normal hypocretin-1 failed to show any significant difference from the controls, except in the overall diurnal transitions.	Undetectable hypocretin-1 levels in particular, but also low hypocretin-1 levels, were associated with a less stable phenotype featuring more sleep state transitions and SOREM episodes. In addition, there was a distinction between nocturnal and diurnal REM sleep in hypocretin-deficient participants, expressed as increased diurnal REM sleep, which was not reflected in nocturnal sleep.	
28521121	Acetylcholine is a major modulator of learning and memory, and its availability varies across the sleep-wake cycle. In this issue of Neuron, Papouin et al. (2017) describe a D-serine-dependent pathway involving astroglia by which the transmitter tunes the hippocampus toward memory encoding during wakefulness.
28511597	Although not discernible at first glance, sleep is a highly active and regulated brain state. Although we spend practically one third of our lifetimes in this stage, its importance is often taken for granted. Sleep loss can lead to disease, error and economic loss. Our understanding of how sleep is achieved has greatly advanced in recent years, and with that, the management of sleep disorders has improved. There is still room for improvement and recently many new compounds have reached clinical trials with a few being approved for commercial use. Areas covered: In this review, the authors make the case of sleep disorders as a matter of public health. The mechanisms of sleep transition are discussed emphasizing the wake and sleep promoting interaction of different brain regions. Finally, advances in pharmacotherapy are examined in the context of chronic insomnia and narcolepsy. Expert opinion: The orexinergic system is an example of a breakthrough in sleep medicine that has catalyzed drug development. Nevertheless, sleep is a topic still with many unanswered questions. That being said, the melanin-concentrating hormone system is becoming increasingly relevant and we speculate it will be the next target of sleep medication.
28506629	According to a two-stage memory consolidation model, during waking theta states, afferent activity from the neocortex to the hippocampus induces transient synaptic modification in the hippocampus, where the information is deposited as a labile form of memory trace. During subsequent sharp-wave ripples (SPW-Rs), the newly acquired hippocampal information is transferred to the neocortex and stored as a long-lasting memory trace. Consistent with this hypothesis, waking theta states and SPW-Rs distinctly control information flow in the hippocampal-entorhinal loop. Although both waking theta states and rapid eye movement (REM) sleep are characterized by prominent hippocampal theta oscillations, the two brain states involve distinct temporal coordination and oscillatory coupling in the hippocampal-entorhinal circuit. While distinct brain states have distinct network dynamics, firing rates of individual neurons in the hippocampal-entorhinal circuitry follow lognormal-like distributions in all states. Firing rates of the same neurons are positively correlated across brain states and testing environments, suggesting that memory is allocated in preconfigured, rather than tabula rasa-type, skewed neuronal networks. The fast-firing minority and slow-firing majority neurons, which can support network stability and flexibility, are under distinct homeostatic regulations that are initiated by spindles and SPW-Rs during slow wave sleep and implemented during subsequent REM sleep.
28503116	Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms (24-hour cycles) in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing based on an internal 24-hour clock.First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, research related to the physiological effects of melatonin is reviewed.	The physiological effects of melatonin are various and include detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Also, protective and therapeutic effects of melatonin are reported, especially with regard to brain or gastrointestinal protection, psychiatric disorders, cardiovascular diseases and oncostatic effects.	This review highlights the high number and diversity of major melatonin effects and opens important perspectives for measuring melatonin as a biomarker (biomarker of early identification of certain disorders and also biomarker of their follow-up) and using melatonin with clinical preventive and therapeutic applications in newborns, children and adults based on its physiological regulatory effects.	
28500869	Daily, animals need to decide when to stop engaging in cognitive processes and behavioral responses to the environment, and go to sleep. The main processes regulating the daily organization of sleep and wakefulness are circadian rhythms and homeostatic sleep pressure. In addition, motivational processes such as food seeking and predator evasion can modulate sleep/wake behaviors. Here, we discuss the principal processes regulating the propensity to stay awake or go to sleep-focusing on neuronal and behavioral aspects. We first introduce the neuronal populations involved in sleep/wake regulation. Next, we describe the circadian and homeostatic drives for sleep. Then, we highlight studies demonstrating various effects of motivational processes on sleep/wake behaviors, and discuss possible neuronal mechanisms underlying their control.
28496429	An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep-wake cycle, feeding-fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.
28491049	Sleep problems have not been directly reported in phenylketonuria (PKU). In PKU, the metabolic pathway of phenylalanine is disrupted, which, among others, causes deficits in the neurotransmitters and sleep modulators dopamine, norepinephrine, and serotonin. Understanding sleep problems in PKU patients may help explain the pathophysiology of brain dysfunction in PKU patients. In this explorative study, we investigated possible sleep problems in adult treated PKU patients and untreated PKU mice. In the PKU patients, sleep characteristics were compared to healthy first degree relatives by assessment of sleep disturbances, sleep-wake patterns, and sleepiness with the help of four questionnaires: Holland sleep disorder questionnaire, Pittsburgh sleep quality index, Epworth sleepiness scale, and Munich Chronotype Questionnaire. The results obtained with the questionnaires show that PKU individuals suffer more from sleep disorders, a reduced sleep quality, and an increased latency to fall asleep and experience more sleepiness during the day. In the PKU mice, activity patterns were recorded with passive infrared recorders. PKU mice switched more often between active and non-active behavior and shifted a part of their resting behavior into the active period, confirming that sleep quality is affected as a consequence of PKU. Together, these results give the first indication that sleep problems are present in PKU. More detailed future research will give a better understanding of these problems, which could ultimately result in the improvement of treatment strategies by including sleep quality as an additional treatment target.
28488270	Depression is associated with disturbances to sleep and the 24-h sleep-wake pattern (known as the rest-activity rhythm: RAR). However, there remains a need to identify the specific sleep/RAR correlates of depression symptom severity in population subgroups, such as strained dementia caregivers, who are at elevated risk for major depressive disorder. We assessed the cross-sectional associations of sleep/RARs with non-sleep depression symptom severity among 57 (mean age: 74 years, standard deviation: 7.4) strained dementia caregivers who were currently without clinical depression. We derived sleep measures from polysomnography and actigraphy, modelled RARs using a sigmoidally transformed cosine curve and measured non-sleep depression symptom severity using the Hamilton Depression Rating Scale (HRDS) with sleep items removed. The following sleep-wake measures were associated with greater depression symptom severity (absolute Spearman's correlations ranged from 0.23 to 0.32): more time awake after sleep onset (WASO), higher RAR middle level (mesor), relatively shorter active periods (alpha), earlier evening settling time (down-mesor) and less steep RARs (beta). In multivariable analysis, high WASO and low RAR beta were associated independently with depression symptom severity. Predicted non-sleep HDRS means (95% confidence intervals) in caregivers with and without these characteristics were: normal WASO/beta = 3.7 (2.3-5.0), high WASO/normal beta = 5.5 (3.5-7.6), normal WASO/low beta = 6.3 (3.6-8.9) and high WASO/low beta = 8.1 (5.3-10.9). Thus, in our sample of strained caregivers, greater sleep fragmentation (WASO) and less sustained/sharply segregated resting and active periods (low RAR beta) correlate uniquely with depression symptom severity. Longitudinal studies are needed to establish whether these independent sleep-wake correlates of depression symptoms explain heightened depression risk in dementia caregivers.
28486925	Sleep and epilepsy are mutually related in a complex, bidirectional manner. However, our understanding of this relationship remains unclear. In this paper, we address the issues involved in these phenomena and also discuss the various therapies used to modify them. The literatures of the neurobiological basis of the interactions between sleep and epilepsy indicate that non-rapid eye movement sleep and idiopathic generalized epilepsy share the same thalamocortical networks. Neuromodulators-such as adenosine, melatonin, prostaglandin D2, serotonin, and histamine-promote wakefulness and are considered to have antiepilepsy effects; antiepileptic drugs, in turn, also have effects on sleep. Furthermore, many drugs that regulate the sleep-wake cycle can also serve as potential antiseizure agents. The nonpharmacological management of epilepsy-including ketogenic diet, epilepsy surgery, neurostimulation, vagus nerve stimulation, deep brain stimulation, responsive cortical neurostimulation, and transcranial magnetic stimulation-can also have therapeutic effects on sleep.
28479786	The objective of this study is to assess the prevalence of sleep disorders among children aging between 4 and 9 years using Hindi version of Pediatric Sleep Questionnaire (PSQ).This study had two parts first, translation and validation of PSQ into Hindi language, and second, assessment of the prevalence of sleep disorders using PSQ Hindi version. Hindi PSQ was distributed in randomly chosen primary schools in a semi-urban area. The children were requested to get them filled by their parents. When the questionnaires were returned, responses were analyzed.	Most of the items of the Hindi version had perfect agreement with original questionnaire in a bilingual population (κ =1). Totally, 435 children were included in the field study having average age of 6.3 years. Obstructive sleep apnea was reported in 7.5% children; symptoms suggestive of restless legs syndrome were reported by 2%-3%; teeth grinding by 13.9% and sleep talking by 22.6% children.	PSQ Hindi version is a validated tool to screen for sleep disorders among children. Sleep disorders are fairly prevalent among young children in India.	
28478762	To assess stages of Alzheimer's disease (AD) pathogenesis and the efficacy of drugs during clinical trials, there has been immense interest in the field to establish baseline cerebrospinal fluid (CSF) concentrations for potential AD biomarkers such as amyloid-β (Aβ) and tau. Significant within-person variations in CSF Aβ concentrations over time found that this variation followed the sleep-wake cycle. A recent paper in Molecular Neurodegeneration reported the absence of diurnal variations in multiple classical and candidate AD biomarkers, such as soluble APP, Aβ, tau, p-tau, YKL-40, VILIP-1, or apolipoprotein E. This commentary addresses these apparently discordant results regarding the diurnal variability of APP and Aβ compared with the literature. Despite our concerns, we appreciate the authors' interest in this important topic and contribution to improve our knowledge about the factors influencing Aβ diurnal variation.
28470767	Chronic fatigue syndrome (CFS) is characterized by long-lasting, disabling and unexplained fatigue that is often accompanied by unrefreshing sleep. The aim of this cross-sectional study was to investigate sleep-wake rhythm and perceived sleep in adolescent CFS patients compared to healthy individuals. We analysed baseline data on 120 adolescent CFS patients and 39 healthy individuals included in the NorCAPITAL project. Activity measures from a uniaxial accelerometer (activPAL) were used to estimate mid-sleep time (mid-point of a period with sleep) and time in bed. Scores from the Karolinska Sleep Questionnaire (KSQ) were also assessed. The activity measures showed that the CFS patients stayed significantly longer in bed, had a significantly delayed mid-sleep time and a more varied sleep-wake rhythm during weekdays compared with healthy individuals. On the KSQ, the CFS patients reported significantly more insomnia symptoms, sleepiness, awakening problems and a longer sleep onset latency than healthy individuals. These results might indicate that disrupted sleep-wake phase could contribute to adolescent CFS; however, further investigations are warranted.
28468274	In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause-effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep-wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.
28460563	Sleep disorders are a group of conditions that affect the ability to sleep well on a regular basis and cause significant impairments in social and occupational functions. Although currently approved medications are efficacious, they are far from satisfactory. Benzodiazepines, antidepressants, antihistamines and anxiolytics have the potential for dependence and addiction. Moreover, some of these medications can gradually impair cognition. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous hormone produced by the pineal gland and released exclusively at night. Exogenous melatonin supplementation is well tolerated and has no obvious short- or long-term adverse effects. Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep. It is centrally involved in anti-oxidation, circadian rhythmicity maintenance, sleep regulation and neuronal survival. This narrative review aims to provide a comprehensive overview of various therapeutic functions of melatonin in insomnia, sleep-related breathing disorders, hypersomnolence, circadian rhythm sleep-wake disorders and parasomnias. Melatonin offers an alternative treatment to the currently available pharmaceutical therapies for sleep disorders with significantly less side effects.
28457485	The rapid clinical antidepressant effects of the glutamatergic modulator ketamine may be due to its ability to restore synaptic plasticity and related effects on sleep-wake and circadian systems. Preclinical studies indicate that ketamine alters expression of circadian clock-associated molecules, and clinical studies of ketamine on plasticity-related biomarkers further suggest an association with sleep slow waves and sleep homeostasis.Wrist-activity monitors were used to examine the pharmacologic and rapid antidepressant effects of ketamine on markers of circadian timekeeping (amplitude and timing) in mood disorders. Circadian amplitude and timing of activity at baseline, postinfusion day 1 (D1), and day 3 (D3) were measured in 51 patients with major depressive disorder or bipolar disorder.	Compared with either placebo or baseline, a mood-independent decrease of the central circadian value (mesor) was present on D1 after ketamine treatment. Mood-associated circadian effects between rapid (D1) responders and nonresponders were found at baseline, D1, and D3. At baseline, a phase-advanced activity pattern and lower mesor distinguished subsequent responders from nonresponders. On D1, ketamine nonresponders had a lower mesor and a blunted 24-hour amplitude relative to baseline. On D3, patients with a persisting clinical response exhibited a higher amplitude and mesor compared with nonresponders.	The findings are the first to demonstrate an association between ketamine's clinical antidepressant effects and circadian timekeeping. The results suggest that traitlike circadian activity patterns indicate rapid mood response to ketamine, and that mediators of continuing ketamine-induced mood changes include altered timing and amplitude of the circadian system.	
28456884	Power naps are extensively practiced worldwide and there exists ample documentation of their efficacy in reversing daytime sleepiness. The source of their efficacy, however, as well as the cause and manifestation of many other common sleep-wake phenomena, cannot be entirely explained by the most commonly accepted model of sleep-wake regulation, the two-process model of Borbély, which considers the drives of the circadian and homeostatic sleep processes only. When considering the causes and manifestations of these unexplained phenomena, there appears to be evidence of a wake-promoting drive that is independent of the circadian oscillator indicated in the two-process model of sleep-wake regulation. Although this posited secondary wake drive, herein referred to as the psycho-sensory wake drive, is always active during the awake state, its strength unpredictably varies during a normal day and, therefore, cannot be incorporated into the prevalent two-process model by any current mathematical formula. However, a supplemental graphic model superimposing it on the drives of Process S and Process C can provides plausible and parsimonious explanations for many otherwise unexplainable sleep-wake phenomena and enables rational guidelines for their effective practical management.
28455701	Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of β1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1A. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.
28449911	The Sleep Condition Indicator (SCI) and Insomnia Severity Index (ISI) are commonly used instruments to assess insomnia. We evaluated their psychometric properties, particularly their discriminant validity against structured clinical interview (according to DSM-5 and ICSD-3), and their concurrent validity with measures of sleep and daytime functioning.A total of 158 young adults, 16% of whom were diagnosed with DSM-5 insomnia disorder and 13% with ICSD-3 Chronic Insomnia by structured interview, completed the ISI and SCI twice in 7-14 days, in addition to measures of sleep and daytime function.	The Chinese version of the SCI was validated with good psychometric properties (ICC = 0.882). A cutoff of ≥8 on the ISI, ≤5 on the SCI short form, and ≤21 on the SCI achieved high discriminant validity (AUC > 0.85) in identifying individuals with insomnia based on both DSM-5 and ICSD-3 criteria. The SCI and ISI had comparable associations with subjective (0.18 < r < 0.51) and actigraphic sleep (0.31 < r < 0.43) and daytime functioning (0.34 < r < 0.53).	The SCI, SCI short form, and ISI were found to correctly identify individuals with DSM-5- and ICSD-3-defined insomnia disorder. Moreover, they showed good concordance with measures of daytime dysfunction, as well as subjective and objective sleep. The SCI and ISI are recommended for use in clinical and research settings.	
28449905	To further characterize sleep disorders associated with narcolepsy, we assessed the sleep-wake patterns, rapid eye movement (REM), and non-REM (NREM) sleep cycles in Chinese teenagers with narcolepsy.A total of 14 Chinese type 1 narcoleptic patients (13.4 ± 2.6 years of age) and 14 healthy age- and sex-matched control subjects (13.6 ± 1.8 years of age) were recruited. Ambulatory 24-h polysomnography was recorded for two days, with test subjects adapting to the instruments on day one and the study data collection performed on day two.	Compared with the controls, the narcoleptic patients showed a 1.5-fold increase in total sleep time over 24 h, characterized by enhanced slow-wave sleep and REM sleep. Frequent sleep-wake transitions were identified in nocturnal sleep with all sleep stages switching to wakefulness, with more awakenings and time spent in wakefulness after sleep onset. Despite eight cases of narcolepsy with sleep onset REM periods at night, the mean duration of NREM-REM sleep cycle episode and the ratio of REM/NREM sleep between patients and controls were not significantly different.	Our study identified hypersomnia in teenage narcolepsy despite excessive daytime sleepiness. Sleep fragmentation extended to all sleep stages, indicating impaired sleep-wake cycles and instability of sleep stages. The limited effects on NREM-REM sleep cycles suggest the relative conservation of ultradian regulation of sleep.	
28449903	Hypersomnia is frequently reported after mild traumatic brain injury (mTBI), but its cause(s) remain elusive. This study examined sleep/wake activity after mTBI and its association with pain, a comorbidity often associated with insomnia.Actigraphy recording was performed for 7 ± 2 consecutive days in 56 individuals at one month post-mTBI (64% male; 38 ± 12 years), 24 individuals at one year post-mTBI (58% male; 44 ± 11years), and in 20 controls (50% male; 37 ± 12 years). Pain intensity and its effect on quality of life was assessed with a visual analogue scale and the Short Form Health Survey (SF-36) bodily pain subscale.	Overall, few differences in sleep/wake patterns were found between mTBI patients and controls. However, higher percentages of mTBI individuals with moderate-to-severe pain were found to require more than eight hours of sleep per day (37% vs11%; p = 0.04) and to be frequent nappers (defined as those who took three or more naps per week) (42% vs 22%; p = 0.04) compared to those with mild or no pain at one month postinjury. Correcting for age and depression, The SF-36 score was found to be a significant predictor of sleep duration exceeding eight hours per day at one month (odds ratio = 0.95; 95% confidence interval = 0.92-0.99; p = 0.01), but not at one year post-mTBI. Pain and increased sleep need (in terms of hours per day or napping frequency) were found to co-exist in as much as 29% of mTBI patients at one month postinjury.	Pain could be associated with more pronounced sleep need in about one-third of mTBI patients during early recovery. Unalleviated pain, found in more than 60% of mTBI patients, should therefore be looked for in all mTBI patients reporting new onset of sleep disorder, not only in those with insomnia.	
28448375	The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) has self-reported health measures available for both pediatric and adult populations, but no pediatric measures are available currently in the sleep domains.The purpose of this observational study was to perform preliminary validation studies on age-appropriate, self-reported sleep measures in healthy adolescents.	This study examined 25 healthy adolescents' self-reported daytime sleepiness, sleep disturbance, sleep-related impairment, and sleep patterns. Healthy adolescents completed a physical exam at the National Institutes of Health Clinical Center (Bethesda, MD), had no chronic medical conditions, and were not taking any chronic medications. The Cleveland Adolescent Sleepiness Questionnaire (CASQ), PROMIS Sleep Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b) questionnaires were completed, and sleep patterns were assessed using actigraphy.	Total scores on the three sleep questionnaires were correlated (all Spearman's r > .70, p < .001). Total sleep time determined by actigraphy was negatively correlated with the CASQ (p = .01), PROMIS Sleep Disturbance (p = .02), and PROMIS Sleep-Related Impairment (p = .02).	The field of pediatric sleep is rapidly expanding, and researchers and clinicians will benefit from well-designed, psychometrically sound sleep questionnaires. Findings suggest the potential research and clinical utility of adult versions of PROMIS sleep measures in adolescents. Future studies should include larger, more diverse samples and explore additional psychometric properties of PROMIS sleep measures to provide age-appropriate, validated, and reliable measures of sleep in adolescents.	
28448332	To describe and explore patterns of postpartum sleep, fatigue, and depressive symptoms in low-income urban women.In this descriptive, exploratory, nonexperimental study, participants were recruited from an inpatient postpartum unit. Subjective measures were completed by 132 participants across five time points. Objective sleep/wake patterns were measured by 72-hour wrist actigraphy at 4 and 8 weeks. Mean sample age was 25 years, high school educated with 3.1 children. Over half the sample reported an annual income less than 50% of the federal poverty level.	Objectively, total nighttime sleep was 5.5 hours (week 4) and 5.4 hours (week 8). Subjectively, 85% met criteria for "poor sleep quality" at week 4, and nearly half were persistently and severely fatigued through 8 weeks postpartum.	The majority (65%) of women in this study met the definition of "short sleep duration," defined as sleeping ≤ 6 hours per night. Adverse effects of this short sleep on physical and mental health as well as safety and functioning, especially within the context of poverty, may be profound. There is an urgent need for further research on sleep in low-income underrepresented women to identify interventions that can improve sleep and fatigue as well as discern the implications of sleep deprivation on the safety and physical and mental health of this population.	
28446040	Poor social interactions have been recognized as a symptom since the beginnings of psychiatry. As far as socially withdrawn youth (SWY) are concerned, studies were mostly conducted on patients seeking care. Our psychiatric outreach team called Psymobile was able to reach SWY patients who were not seeking mental health care.To identify the clinical and socio-demographic characteristics of SWY patients referred to our Psymobile unit.	We carried out a retrospective study on the records of patients aged 18-34 years, who were referred to Psymobile for 'withdrawal', between April 2012 and December 2015.	In total, 66 patients were included in the study. SWY are predominantly male (80%) from large families or single-parent ones. About 42% had no prior contact with a mental health professional before being referred to Psymobile. The mean duration of withdrawal is 29 months. In all, 42% of SWY use cannabis and 73% present disorders of the sleep-wake schedule. About 71% maintain relations with their families and 73% go out occasionally. They are mostly diagnosed with schizophrenia (37%) or mood disorders (23%).	Over one-third of Psymobile patients aged 18-34 years were referred on grounds of social withdrawal. Our data may illustrate more accurately the situation of youth social withdrawal amid the general population than data from help-seeking patients or online questionnaires.	
28443381	Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.
28442402	During dusk and dawn, the ambient illumination undergoes drastic changes in irradiance (or intensity) and spectrum (or color). While the former is a well-studied factor in synchronizing behavior and physiology to the earth's 24-h rotation, color sensitivity in the regulation of circadian rhythms has not been systematically studied. Drawing on the concept of color opponency, a well-known property of image-forming vision in many vertebrates (including humans), we consider how the spectral shifts during twilight are encoded by a color-opponent sensory system for non-image-forming (NIF) visual functions, including phase shifting and melatonin suppression. We review electrophysiological evidence for color sensitivity in the pineal/parietal organs of fish, amphibians and reptiles, color coding in neurons in the circadian pacemaker in mice as well as sporadic evidence for color sensitivity in NIF visual functions in birds and mammals. Together, these studies suggest that color opponency may be an important modulator of light-driven physiological and behavioral responses.
28440811	We evaluated the circadian phenotypes of patients with delayed sleep-wake phase disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22.80±0.47 (mean±s.d.) h in control-derived fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived fibroblasts were 22.67±0.67 h and 23.18±0.70 h, respectively. The N24SWD group showed a significantly longer in vitro period than did the control or DSWPD group. Furthermore, in vitro period was associated with response to chronotherapy in the N24SWD group. Longer in vitro periods were observed in the non-responders (mean±s.d.: 23.59±0.89 h) compared with the responders (mean±s.d.: 22.97±0.47 h) in the N24SWD group. Our results indicate that prolonged circadian periods contribute to the onset and poor treatment outcome of N24SWD. In vitro rhythm assays could be useful for predicting circadian phenotypes and clinical prognosis in patients with CRSDs.
28439383	Quality of sleep (QoS) in individuals is affected by their occupation and is one of the factors affecting the quality of life (QoL). Few studies have evaluated the relationship between QoS and QoL in military women personnel. The aim of this study was to assess QoL and QoS, and compare their relationship among military and non-military women in Tehran.This cross-sectional study was carried out on 90 women working in Tehran during 2014, 30 were military forces, 30 were military staff, and 30 were civilian organizations staff. The female subjects were selected from Amin Police University and Tehran Health Insurance Organization using simple random sampling. The 36-Item Short Form Health Survey (SF-36) and Pittsburgh Sleep Quality Index (PSQI) were used to measure QoL and QoS, respectively. The relationship between QoL and QoS was assessed using Pearson's correlation coefficient.	The mean scores of QoL in the military forces, military staff, and civilian organizations staff were 58.94±17.71, 67.18±13.52, and 69.10±12.51, respectively. Among the study participants, 62.9% of military forces, 20.0% of military staff, and 17.1% of the civilian organizations staff had poor QoS. Mental health as one of the dimensions of QoL was significantly different between military forces and civilian organizations staff. The association between QoL and QoS was statistically significant in military forces and military staff women.	Low QoS and QoL in the army necessitates that the authorities offer programs and appropriate strategies to improve mental health of QoL and promotion of QoS.	
28435883	Sleep is found widely in the animal kingdom. Despite this, few conserved molecular pathways that govern sleep across phyla have been described. The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. However, the role of FABP7 in regulating sleep remains poorly understood. We found that the missense mutation FABP7.T61M is associated with fragmented sleep in humans. This phenotype was recapitulated in mice and fruitflies bearing similar mutations: Fabp7-deficient mice and transgenic flies that express the FABP7.T61M missense mutation in astrocytes also show fragmented sleep. These results provide novel evidence for a distinct molecular pathway linking lipid-signaling cascades within astrocytes in sleep regulation among phylogenetically disparate species.
28435104	Parkinson's disease (PD) is more commonly associated with its motor symptoms and the related degeneration of dopamine (DA) neurons. However, it is becoming increasingly clear that PD patients also display a wide range of non-motor symptoms, including memory deficits and disruptions of their sleep-wake cycles. These have a large impact on their quality of life, and often precede the onset of motor symptoms, but their etiology is poorly understood. The fruit fly Drosophila has already been successfully used to model PD, and has been used extensively to study relevant non-motor behaviours in other contexts, but little attention has yet been paid to modelling non-motor symptoms of PD in this genetically tractable organism. We examined memory performance and circadian rhythms in flies with loss-of-function mutations in two PD genes: PINK1 and parkin. We found learning and memory abnormalities in both mutant genotypes, as well as a weakening of circadian rhythms that is underpinned by electrophysiological changes in clock neurons. Our study paves the way for further work that may help us understand the mechanisms underlying these neglected aspects of PD, thus identifying new targets for treatments to address these non-motor problems specifically and perhaps even to halt disease progression in its prodromal phase.
28434992	Sleep, a common event in daily life, has clear benefits for brain function, but what goes on in the brain when we sleep remains unclear. Sleep was long regarded as a silent state of the brain because the brain seemingly lacks interaction with the surroundings during sleep. Since the discovery of electrical activities in the brain at rest, electrophysiological methods have revealed novel concepts in sleep research. During sleep, the brain generates oscillatory activities that represent characteristic states of sleep. In addition to electrophysiology, opto/chemogenetics and two-photon Ca2+ imaging methods have clarified that the sleep/wake states organized by neuronal and glial ensembles in the cerebral cortex are transitioned by neuromodulators. Even with these methods, however, it is extremely difficult to elucidate how and when neuromodulators spread, accumulate, and disappear in the extracellular space of the cortex. Thus, real-time monitoring of neuromodulator dynamics at high spatiotemporal resolution is required for further understanding of sleep. Toward direct detection of neuromodulator behavior during sleep and wakefulness, in this review, we discuss developing imaging techniques based on the activation of G-protein-coupled receptors that allow for visualization of neuromodulator dynamics.
28434991	The mesolimbic dopamine pathway between the ventral tegmental area (VTA) and the nucleus accumbens (NAc) plays a central role in motivational behaviors. Recent findings indicate that the VTA and NAc are also involved in sleep/wake regulation - the topic of this review. First, we present an overview of the growing evidence from rodent studies revealing a wake-regulatory role of VTA dopamine neurons. We also discuss brain areas and their neurotransmitters or neuromodulators that may regulate the activity of wake-promoting VTA dopamine neurons. This is followed by a summary of current knowledge of the role of the NAc in regulating slow-wave sleep and a discussion of where and how this control of sleep physiology might be regulated by upstream neurotransmitters and neuromodulators, including dopamine and the classic somnogen adenosine.
28433628	The detailed molecular mechanisms underlying the regulation of sleep/wake cycles in mammals are elusive. In this regulation, at least two mechanisms with fast and slow time scales are involved. In the faster time scale, a state of non-rapid-eye-movement (NREM) sleep can be microscopically characterized by the millisecond-to-second-order electrical behavior of neurons, namely slow-wave oscillations described by electrophysiology. In the slower time scale, the total duration of NREM sleep is homeostatically regulated by sleep pressure (the need for sleep), which is usually sustained for hours or even days and can be macroscopically described by electroencephalogram (EEG). The longer dynamics of sleep regulation are often explained by the accumulation of sleep-inducing substances (SISs). However, we still do not have a concrete model to connect fast, microscopic dynamics and slow, macroscopic dynamics. In this review, we introduce a recent Ca2+-dependent hyperpolarization hypothesis, in which the Ca2+-dependent hyperpolarization of cortical-membrane potential induces slow-wave oscillation. Slow dynamics of the Ca2+-dependent hyperpolarization pathway might be regulated by recently identified sleep-promoting kinases as well as classical SISs. Therefore, cortical Ca2+-dependent hyperpolarization may be a fundamental mechanism connecting fast neural activity to the slow dynamics of sleep pressure.
28433001	Electrophysiological recordings indicate that neurons which discharge maximally in association with distinct sleep-wake states are distributed through the brain, albeit in differing proportions. As studied using juxtacellular recording and labeling within the basal forebrain, four functional principal cell types are distinguished as: wake/paradoxical sleep (W/PS)-, slow wave sleep (SWS)-, W- and PS-max active. They are each comprised by both GABA and glutamate neurons, in addition to acetylcholine neurons belonging to the W/PS group. By their discharge profiles and interactions, the GABA and glutamate neurons of different groups are proposed to have the capacity to generate sleep-wake states with associated EEG and EMG activities, though to also be importantly regulated by neuromodulatory systems, each of which belong to one functional cell group.
28431742	We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology, cerebro-cerebellar interactions during sleep, or the contributions of sleep to cerebellum-dependent memory consolidation. Likewise, we do not understand why cerebellar malfunction can lead to changes in the sleep-wake cycle and sleep disorders. In this review, we evaluate how sleep and cerebellar processing may influence one another and highlight which scientific routes and technical approaches could be taken to uncover the mechanisms underlying these interactions.
28431626	Recent publications focusing on sleep-wake alternation, using actigraphic recordings in hunter-gatherers, stressed the existence of a potential effect of electricity availability on sleep habits. These reports prompted us to achieve a new analysis of the polysomnographic data already obtained in healthy African volunteers in equatorial Africa during two different investigations. Comparison of the 24-h polysomnographic sleep patterns were done between 9 volunteers sleeping in a laboratory in Abidjan (Abidjan cohort) and 11 villagers living in electricity-free bush villages (Sinfra cohort). Sleep was lighter in the villagers, with more stage 1 and less slow wave sleep (SWS). Latency to SWS was also shorter. Total sleep time, however, was not different between the two groups. There were no indications as to whether the observed differences were attributable to the availability of electrical power. Reactivity of human sleep structure to the environment was discussed in terms of multifactorial influences such as daylight length, temperature, humidity, electromagnetic field, time of sleep onset, thermoregulatory mechanisms, stress or anxiety.
28427008	The lateral hypothalamic area (LHA) of the diencephalon is crucially involved in controlling instinctive behavior such as sleep-wake cycle and feeding behavior. LHA is a heterogeneous structure that contains spatially intermingled, genetically distinct cell populations. Among LHA neurons, orexin/hypocretin (OX) neuron is the key cell type that promotes waking, and specific loss of OX neurons results in narcolepsy. Melanin-concentrating hormone (MCH) containing neurons are known to be active during rapid eye movement (REM) sleep and stimulation of these neurons promotes REM sleep. Here we review the classical and more recent findings in this field and discuss the molecular and cellular network organization of LHA neurons that could ultimately regulate the switch between wakefulness and general states of sleep.
28426386	Exposure to workplace hazards, such as dust, solvents, and fumes, has the potential to adversely affect the health of people. However, the effects of workplace hazards on health may differ when exposure occurs at different times in the circadian cycle, and among people who work longer hours or who do not obtain adequate sleep. The aim of the present study was to document exposures to workplace hazards across a national sample of New Zealanders, comparing people who work a standard 08:00 -17:00 h Monday-to-Friday working week (Std hours) and those who do not (N-Std hours). New Zealanders (n = 10 000) aged 20-64 yrs were randomly selected from the Electoral Roll to take part in a nationwide survey of workplace exposures. Telephone interviews were conducted between 2004 and 2006, using a six-part questionnaire addressing demographics, detailed information on the current or most recent job (including exposures to a range of workplace hazards), sleep, sleepiness, and health status. N-Std hours were categorised on the basis of: being required to start work prior to 07:00 h or finish work after 21:00 h and/or; having a regular on-call commitment (at least once per week) and/or; working rotating shifts and/or; working night shift(s) in the last month. The response rate was 37% (n = 3003), with 22.2% of participants (n = 656) categorised as working N-Std hours. Industry sectors with the highest numbers of participants working N-Std hours were manufacturing, health and community services, and agriculture, fishing, and forestry. Response rate was 37% (n = 3003) with 22.2% (n = 656) categorised as working N-Std hours. Participants working N-Std hours were more likely to be exposed to all identified hazards, including multiple hazards (OR = 2.45, 95% CI = 2.01-3.0) compared to those working Std hours. Participants working N-Std hours were also more likely to report 'never/rarely' getting enough sleep (OR = 1.38, 95% CI = 1.15-1.65), 'never/rarely' waking refreshed (OR = 1.23, 95% CI = 1.04-1.47), and excessive sleepiness (OR = 1.77, 95% CI = 1.29-2.42). New Zealanders working N-Std hours are more likely to be exposed to hazards in the workplace, to be exposed to multiple hazards, and to report inadequate sleep and excessive sleepiness than their colleagues working a standard 08:00-17:00 h Monday-to-Friday working week. More research is needed on the effects of exposure to hazardous substances outside the usual waking day, on the effects of exposure to multiple hazards, and on the combination of hazard exposure and sleep restriction as a result of shift work.
28424614	Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.
28422354	We present one of the first quantitative studies on auditory verbal experiences ("hearing voices") and auditory verbal agency (inner speech, and specifically "talking to (imaginary) voices or characters") in healthy participants across states of consciousness. Tools of quantitative linguistic analysis were used to measure participants' implicit knowledge of auditory verbal experiences (VE) and auditory verbal agencies (VA), displayed in mentation reports from four different states. Analysis was conducted on a total of 569 mentation reports from rapid eye movement (REM) sleep, non-REM sleep, sleep onset, and waking. Physiology was controlled with the nightcap sleep-wake mentation monitoring system. Sleep-onset hallucinations, traditionally at the focus of scientific attention on auditory verbal hallucinations, showed the lowest degree of VE and VA, whereas REM sleep showed the highest degrees. Degrees of different linguistic-pragmatic aspects of VE and VA likewise depend on the physiological states. The quantity and pragmatics of VE and VA are a function of the physiologically distinct state of consciousness in which they are conceived.
28421896	We investigated differences in the prevalence of anosognosia and neuropsychiatric symptoms (NPSs) characteristics according to disease severity in patients with early-onset Alzheimer disease (EOAD).We recruited 616 patients with EOAD. We subdivided participants into 2 groups based on the presence or absence of anosognosia and then again by Clinical Dementia Rating (CDR) scale. We compared the differences in the Neuropsychiatric Inventory (NPI) scores according to anosognosia and disease severity.	The percentage of patients with anosognosia in each CDR group steadily increased as the CDR rating increased (CDR 0.5 8.6% vs CDR 1 13.6% vs CDR 2 26.2%). The NPI total score was significantly higher in patients with anosognosia in the CDR 0.5 and 1 groups; by contrast, it had no association in the CDR 2 group. Frontal lobe functions were associated with anosognosia only in the CDR 0.5 and 1 groups. After stratification by CDR, in the CDR 0.5 group, the prevalence of agitation ( P = .040) and appetite ( P = .013) was significantly higher in patients with anosognosia. In the CDR 1 group, patients with anosognosia had a significantly higher prevalence of delusions ( P = .032), hallucinations ( P = .048), and sleep disturbances ( P = .047). In the CDR 2 group, we found no statistical difference in the frequency of symptoms between patients with and without anosognosia.	These results confirm that the prevalence of anosognosia as well as the individual NPS and cognitive functions associated with it differ according to EOAD severity.	
28421617	Abundant cross-sectional evidence links eveningness (a preference for later sleep-wake timing) and increased alcohol and drug use among adolescents and young adults. However, longitudinal studies are needed to examine whether eveningness is a risk factor for subsequent alcohol and drug use, particularly during adolescence, which is marked by parallel peaks in eveningness and risk for the onset of alcohol use disorders. This study examined whether eveningness and other sleep characteristics were associated with concurrent or subsequent substance involvement in a longitudinal study of adolescents.Participants were 729 adolescents (368 females; age 12 to 21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence study. Associations between the sleep variables (circadian preference, sleep quality, daytime sleepiness, sleep timing, and sleep duration) and 3 categorical substance variables (at-risk alcohol use, alcohol bingeing, and past-year marijuana use [y/n]) were examined using ordinal and logistic regression with baseline age, sex, race, ethnicity, socioeconomic status, and psychiatric problems as covariates.	At baseline, greater eveningness was associated with greater at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed similar associations across the 3 substance outcomes at baseline. Greater baseline eveningness was also prospectively associated with greater bingeing and past-year use of marijuana at the 1-year follow-up, after covarying for baseline bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and shorter baseline weekday sleep duration, were similarly associated with greater bingeing and past-year use of marijuana at the 1-year follow-up after covarying for baseline values.	Findings suggest that eveningness and sleep timing may be under recognized risk factors and future areas of intervention for adolescent involvement in alcohol and marijuana that should be considered along with other previously identified sleep factors such as insomnia and insufficient sleep.	

28416429	Though benign in the majority of cases, sleepwalking sometimes causes injuries due, among other causes, to falls. Such accidents can be life-threatening - a situation that has been termed Elpenor syndrome (in reference to an accident experienced by a character in Homer's epic The Odyssey) - in particular when entailing defenestration. This syndrome has been described in adults and adolescents; we report here a case in a child.This 10-year-old girl was admitted at night to our hospital after a 3-m fall at home. She was alert (Glasgow score, 15) at admission; a frontal wound and a deformation of the right wrist were noted. Brain CT scans showed a frontal skull fracture and frontal lobe contusion, wrist x-rays showed a displaced right fracture. The patient underwent urgent neurosurgery (wound excision and suture after reduction of skull fracture) and closed reduction and immobilization of the wrist fracture, both under general anesthesia. She underwent a psychiatric assessment in the intensive care unit 3 days after her fall. She was alert, well-oriented in time and space, and spoke fluently. She had no memory of her fall, only remembering going to bed in the evening before the accident and waking up in the ambulance on the way to the hospital. She displayed no sign of a concurrent mental illness and no suicidal ideas. Her parents reported that the evening of the accident she and her two brothers had all fallen asleep about 11:00 pm while watching TV, in the double bed of the guest room, placed just beside its window. At approximately 1:00 am, her father, who was going to bed and had just made noise in the hall, heard a cry from the guest room. He entered the room immediately and saw the opened window and his daughter lying on the outside ground; the brothers only awakened after the fall. The family had returned 2 days before from a 6-month stay in the United States, with jet-lag, sleep deprivation, and a disorganized sleep/wake rhythm in the patient. There was no medication before the accident, no substance use (including caffeine), and no concurrent medical problem. Over the 2 preceding years, the patient had undergone two witnessed episodes of early-nighttime arousal with altered consciousness and calm wandering (including going downstairs on one occasion), both strongly suggesting sleepwalking. There was a history of sleepwalking in her father and her older brother. Life-threatening sleepwalking (Elpenor syndrome) was diagnosed. The child and her parents were educated about sleepwalking; regularization of sleep schedules and sleep extension (avoidance of sleep deprivation, short napping when possible) were prescribed. We also recommended securing the home (bed, windows, and stairways). No pharmacological treatment was instituted. During the following 18 months, the child manifested only one noted sleepwalking episode, without risk-taking. She had no neurological or psychopathological sequela from her accident, of which she never had a memory.	Elpenor syndrome can occur in a child; consequently, it is important to inform parents of children with sleepwalking about the necessity of always securing the night-time environment.	
28414966	What are the molecular and cellular mechanisms that link neurological disorders and sleep disturbances? The transparent zebrafish model could bridge this gap in knowledge due to its unique genetic and imaging toolbox, and amenability to high-throughput screening. Sleep is well-characterized in zebrafish and key regulators of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin (Hcrt), whereas novel sleep regulating proteins are continually being identified, such as Kcnh4a, Neuromedin U, and QRFP. Sleep deficiencies have been observed in various zebrafish models for genetic neuropsychiatric disorders, ranging from psychomotor retardation and autism to anxiety disorders. Understanding the link between neuropsychiatric disorders and sleep phenotypes in zebrafish may ultimately provide a platform for identifying therapeutic targets for clinical trials in humans.
28413931	Glucose variations are common throughout sleep and wakefulness in people with type 1 diabetes mellitus (T1DM). The objective of this investigation was to characterize the time-varying coupling between glucose and unstructured physical activity over a 60-hr period in young adults with T1DM. The hypothesis was that coupling would differ during sleep versus wakefulness and would exhibit circadian variations.Young adults with T1DM treated with an insulin pump participated in the study. Glucose variations were monitored with a continuous glucose monitoring system, and activity was assessed using an activity-monitoring band worn on the nondominant wrist. Simultaneous glucose and physical activity data across a continuous 60-hr period were used for analysis. Wavelet coherence analysis was employed to quantify the coupling between physical activity and glucose. Cosinor analysis was used to assess whether glucose/activity coherence exhibited significant circadian variations.	Participants comprised 23 adults, aged 18-30 years, with T1DM. Coherence analysis demonstrated substantial coupling between physical activity and glucose variations during both wakefulness and sleep. For rapid (10-30 min) fluctuations, mean coherence was higher during sleep than wakefulness ( F = 10.86, p = .003). Rapid glucose variations consistently led to changes in activity ( p = .001) during sleep but not during wake. Cosinor analysis revealed significant circadian modulation of glucose/activity coupling, especially for fluctuation periods 2-4 hr.	Unstructured physical activity and glucose variations demonstrated strong time- and frequency-dependent coupling over a 60-hr period in young adults with T1DM, with sleep/wake differences and circadian modulation evident in this relationship.	
28412838	The aim was to investigate the prevalence of self-reported sleep complaints in New Zealand adults and determine the independent association of sleep complaints with adverse health outcomes.We used 2002/03 New Zealand Health Survey data (n = 12,500 adults, ≥15 years). The prevalence of self-reported sleep complaints was estimated by ethnicity. The relationship between sleep complaints and mental health, physical health and health risk behaviors were investigated using multivariable logistic regression models.	The prevalence of each sleep complaint measure was highest for the indigenous Māori population (23.6% reported 'any' sleep complaint; 10.3% reported multiple sleep complaints). Reporting 'any' sleep complaint was associated with higher odds of poorer mental health, diagnosed high blood pressure, diagnosed diabetes, diagnosed heart disease, poor/fair self-rated health, obesity, current smoking, and hazardous drinking.	The higher prevalence of sleep complaints among Māori and the consistent association with poor health suggests a potential role for suboptimal sleep in ethnic health inequities.	
28412140	It is increasingly recognized that sleep disturbances and Alzheimer's disease (AD) share a bidirectional relationship. AD patients exhibit sleep problems and alterations in the regulation of circadian rhythms; conversely, poor quality of sleep increases the risk of development of AD. The aim of the current study was to determine whether chronic sleep restriction potentiates the brain impact of amyloid-β oligomers (AβOs), toxins that build up in AD brains and are thought to underlie synapse damage and memory impairment. We further investigated whether alterations in levels of pro-inflammatory mediators could play a role in memory impairment in sleep-restricted mice. We found that a single intracerebroventricular (i.c.v.) infusion of AβOs disturbed sleep pattern in mice. Conversely, chronically sleep-restricted mice exhibited higher brain expression of pro-inflammatory mediators, reductions in levels of pre- and post-synaptic marker proteins, and exhibited increased susceptibility to the impact of i.c.v. infusion of a sub-toxic dose of AβOs (1pmol) on performance in the novel object recognition memory task. Sleep-restricted mice further exhibited an increase in brain TNF-α levels in response to AβOs. Interestingly, memory impairment in sleep-restricted AβO-infused mice was prevented by treatment with the TNF-α neutralizing monoclonal antibody, infliximab. Results substantiate the notion of a dual relationship between sleep and AD, whereby AβOs disrupt sleep/wake patterns and chronic sleep restriction increases brain vulnerability to AβOs, and point to a key role of brain inflammation in increased susceptibility to AβOs in sleep-restricted mice.
28411771	Psychocutaneous disease, defined in this review as primary psychiatric disease with skin manifestations, is commonly encountered in dermatology. Dermatologists can play an important role in the management of psychocutaneous disease because patients visit dermatology for treatment of their skin problems but often refuse psychiatric intervention. This review describes common psychocutaneous syndromes, including delusional, factitious, obsessive-compulsive and related, and eating disorders, as well as psychogenic pruritus, cutaneous sensory (pain) syndromes, posttraumatic stress disorder, and sleep-wake disorders. The updated classification of these disorders in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition is included. Strategies for management are reviewed.
28411158	The basal forebrain (BF) controls sleep-wake cycles, attention and reward processing. Compared to cholinergic and GABAergic neurons, BF glutamatergic neurons are less well understood, due to difficulties in identification. Here, we use vesicular glutamate transporter 2 (vGluT2)-tdTomato mice, expressing a red fluorescent protein (tdTomato) in the major group of BF glutamatergic neurons (vGluT2+) to characterize their intrinsic electrical properties and cholinergic modulation. Whole-cell, patch-clamp recordings were made from vGluT2+ neurons in coronal BF slices. Most BF vGluT2+ neurons were small/medium sized (<20µm), exhibited moderately sized H-currents and had a maximal firing frequency of ∼50Hz. However, vGluT2+ neurons in dorsal BF (ventral pallidum) had larger H-currents and a higher maximal firing rate (83Hz). A subset of BF vGluT2+ neurons exhibited burst/cluster firing. Most vGluT2+ neurons had low-threshold calcium spikes/currents. vGluT2+ neurons located in ventromedial regions of BF (in or adjacent to the horizontal limb of the diagonal band) were strongly hyperpolarized by the cholinergic agonist, carbachol, a finding apparently in conflict with their increased discharge during wakefulness/REM sleep and hypothesized role in wake-promotion. In contrast, most vGluT2+ neurons located in lateral BF (magnocellular preoptic area) or dorsal BF did not respond to carbachol. Our results suggest that BF glutamatergic neurons are heterogeneous and have morphological, electrical and pharmacological properties which distinguish them from BF cholinergic and GABAergic neurons. A subset of vGluT2+ neurons, possibly those neurons which project to reward-related areas such as the habenula, are hyperpolarized by cholinergic inputs, which may cause phasic inhibition during reward-related events.
28408870	Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation following enforced waking with associated cortical activation during the day when mice normally sleep the majority of the time. Sleep deprived mice were prevented from falling asleep by unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep freely following deprivation. In parallel with changes in c-Fos reflecting changes in activity, (β2-3 subunits of) GABAA Rs were increased on the membrane of CaMKIIα+ neurons with enforced waking and returned to baseline levels with SR in barrel cortex on sides both contra- and ipsilateral to the whisker stimulation. The GABAAR increase was correlated with increased gamma electroencephalographic (EEG) activity across conditions. On the other hand, (GluA1 subunits of) AMPA Rs were progressively removed from the membrane of CaMKIIα+ neurons by (Rab5+) early endosomes during enforced waking and returned to the membrane by (Rab11+) recycling endosomes during SR. The internalization of the GluA1Rs paralleled the expression of Arc, which mediates homeostatic regulation of AMPA receptors through an endocytic pathway. The reciprocal changes in GluA1Rs relative to GABAARs suggest homeostatic down-scaling during enforced waking and sensory stimulation and restorative up-scaling during recovery sleep. Such homeostatic changes with sleep-wake states and their associated cortical activities could stabilize excitability and activity in excitatory cortical neurons.
28408639	Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Postmortem studies showed increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Lithium (Li+) has been shown to effectively treat the mood disturbances in bipolar disorder patients. We previously showed that NCS-1 at low levels increased, and at high levels decreased, gamma oscillations in RAS pedunculopontine neurons (PPN), and that Li+ decreased these oscillations. We previously described the effects of each agent on oscillations, G-protein mechanisms, and Ca2+ currents. However, we designed the present experiments to determine the nature of the interaction of NCS-1 and Li+ at physiological concentrations that would have an effect within minutes of application. As expected, Li+ decreased gamma oscillation amplitude, while NCS-1 increased the amplitude of gamma oscillations. We identified NCS-1 at 2 μmol/L as a concentration that increased gamma oscillations within 5-10 min, and Li+ at 10 μmol/L as a concentration that decreased gamma oscillations within 5 min. The combined application of NCS-1 and Li+ at these concentrations showed that Li+ reduced the effects of NCS-1 on oscillation amplitude within 5-10 min. These results demonstrate that at physiological levels, Li+ acts to reduce the effects of NCS-1 so that, given over expression of NCS-1, Li+ would have salutary effects.
28402850	The circadian clock generates biological rhythms of metabolic and physiological processes, including the sleep-wake cycle. We previously identified a missense mutation in the flavin adenine dinucleotide (FAD) binding pocket of CRYPTOCHROME2 (CRY2), a clock protein that causes human advanced sleep phase. This prompted us to examine the role of FAD as a mediator of the clock and metabolism. FAD stabilized CRY proteins, leading to increased protein levels. In contrast, knockdown of Riboflavin kinase (Rfk), an FAD biosynthetic enzyme, enhanced CRY degradation. RFK protein levels and FAD concentrations oscillate in the nucleus, suggesting that they are subject to circadian control. Knockdown of Rfk combined with a riboflavin-deficient diet altered the CRY levels in mouse liver and the expression profiles of clock and clock-controlled genes (especially those related to metabolism including glucose homeostasis). We conclude that light-independent mechanisms of FAD regulate CRY and contribute to proper circadian oscillation of metabolic genes in mammals.
28399462	The synaptic homeostasis hypothesis (SHY) states that wake brings about a net overall increase in synaptic strength in many brain circuits that needs to be renormalized by sleep. I will review recent studies that were either specifically designed to test SHY or were interpreted accordingly, including several experiments that focused on changes in neuronal firing rates. I will emphasize that central to SHY is the idea that what is being regulated across the sleep/wake cycle is synaptic strength, not firing rate, and firing rate taken in isolation is not necessarily an adequate proxy for synaptic strength.
28397310	Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders.
28391130	All animals have a fundamental and unavoidable requirement for rest, yet we still do not fully understand the processes that initiate, maintain, and regulate sleep. The larval zebrafish is an optically translucent, genetically tractable model organism that exhibits sleep states regulated by conserved sleep circuits, thereby offering a unique system for investigating the genetic and neural control of sleep. Recent studies using high throughput monitoring of larval sleep/wake behaviour have unearthed novel modulators involved in regulating arousal and have provided new mechanistic insights into the role of established sleep/wake modulators. In addition, the application of computational tools to large behavioural datasets has allowed for the identification of neuroactive compounds that alleviate sleep symptoms associated with genetic neurological disorders.
28390292	A possible mechanism of disrupted circadian rhythms in delirium was identified using resting-state functional connectivity. Thirty-four delirious patients and 38 non-delirious controls were scanned for resting-state functional MRI. Seed-based connectivity of the suprachiasmatic nucleus was compared between the groups. In delirious patients functional connectivity from the circadian clock was increased to the dorsal anterior cingulate cortex and decreased to the posterior cingulate cortex, parahippocampal gyrus, cerebellum, and thalamus. A dysregulation of the default mode network and mental coordination processing areas by the circadian clock may be the underlying pathophysiology of sleep-wake cycle disturbance and symptom fluctuation in delirium.
28387679	Intracranial accumulation of amyloid-β (Aβ) is a characteristic finding of Alzheimer's disease (AD). It is thought to be the result of Aβ overproduction by neurons and impaired clearance by several systems, including degradation by microglia. Sleep disturbance is now considered a risk factor for AD, but studies focusing on how sleep modulates microglial handling of Aβ have been scarce.To determine whether phagocytosis and degradation of extracellular Aβ fibrils by BV2 microglial cells were impaired by treatment with orexin-A/B, a major modulator of the sleep-wake cycle, which may mimic sleep deprivation conditions.	BV2 cells were treated with orexin and Aβ for various durations and phagocytic and autophagic processes for degradation of extracellular Aβ were examined.	After treatment with orexin, the formation of actin filaments around Aβ fibrils, which is needed for phagocytosis, was impaired, and phagocytosis regulating molecules such as PI3K, Akt, and p38-MAPK were downregulated in BV2 cells. Orexin also suppressed autophagic flux, through disruption of the autophagosome-lysosome fusion process, resulting in impaired Aβ degradation in BV2 cells.	Our results demonstrate that orexin can hinder clearance of Aβ through the suppression of phagocytosis and autophagic flux in microglia. This is a novel mechanism linking AD and sleep, and suggests that attenuated microglial function, due to sleep deprivation, may increase Aβ accumulation in the brain.	
28386207	The ventral tegmental area (VTA) is crucial for brain functions, such as voluntary movement and cognition; however, the role of VTA in sleep-wake regulation when directly activated or inhibited remains unknown. In this study, we investigated the effects of activation or inhibition of VTA neurons on sleep-wake behavior using the pharmacogenetic "designer receptors exclusively activated by designer drugs (DREADD)" approach. Immunohistochemistry staining was performed to confirm the microinjection sites, and combined with electrophysiological experiments, to determine whether the VTA neurons were activated or inhibited. The hM3Dq-expressing VTA neurons were excited confirmed by clozapine-N-oxide (CNO)-driven c-Fos expression and firing in patch-clamp recordings; whereas the hM4Di-expressing VTA neurons inhibited by reduction of firing. Compared with controls, the activation of VTA neurons at 9:00 (inactive period) produced a 120.1% increase in the total wakefulness amount for 5 h, whereas NREM and REM sleep were decreased by 62.5 and 92.2%, respectively. Similarly, when VTA neurons were excited at 21:00 (active period), the total wakefulness amount increased 81.5%, while NREM and REM sleep decreased 64.6 and 93.8%, respectively, for 8 h. No difference of the amount and EEG power density of the NREM sleep was observed following the arousal effects of CNO. The inhibition of VTA neurons during active or inactive periods gave rise to no change in the time spent in the wakefulness, REM, and NREM sleep compared with control. The results indicated that VTA neurons activated pharmacogentically played important roles in promoting wakefulness.
28386121	Living systems exhibit non-randomly organized biochemical, physiological, and behavioral processes that follow distinctive patterns. In particular, animal behavior displays both fractal dynamics and periodic rhythms yet the relationship between these two dynamic regimens remain unexplored. Herein we studied locomotor time series of visually isolated Japanese quails sampled every 0.5 s during 6.5 days (>106 data points). These high-resolution, week-long, time series enabled simultaneous evaluation of ultradian rhythms as well as fractal organization according to six different analytical methods that included Power Spectrum, Enright, Empirical Mode Decomposition, Wavelet, and Detrended Fluctuation analyses. Time series analyses showed that all birds exhibit circadian rhythms. Although interindividual differences were detected, animals presented ultradian behavioral rhythms of 12, 8, 6, 4.8, 4 h and/or lower and, irrespective of visual isolation, synchronization between these ultradian rhythms was observed. Moreover, all birds presented similar overall fractal dynamics (for scales ∼30 s to >4.4 h). This is the first demonstration that avian behavior presents fractal organization that predominates at shorter time scales and coexists with synchronized ultradian rhythms. This chronobiological pattern is advantageous for keeping the organism's endogenous rhythms in phase with internal and environmental periodicities, notably the feeding, light-dark and sleep-wake cycles.
28385601	Depression and substance use disorder (SUD) often co-exist and are typically associated with an inaccurate diagnosis, worsened clinical course and poor medication adherence compared to either disorder alone. To date, the biological mechanisms contributing to their strong association remain largely unknown. In this review, we critically analyze preclinical literature on psychostimulant drugs and reconsider the common view that depression is a risk factor for drug use and the development of SUD. Unexpectedly, this investigation led us to conclude that depressive-like states in rodents are associated with a low predisposition to drug intake, at least when considering initial, voluntary and regulated psychostimulant intake. We identified several conceptual gaps and methodological challenges potentially misleading when modeling depression and SUD comorbidity. On the basis of these observations, we propose new innovative perspectives to guide future experiments and advance our knowledge in this field, including the use of newly refined rodent models that better capture hallmarks of depression and SUD.
28385173	Hypothesis The hypotheses of all the four included studies share the common idea that it is possible to augment the effect of antidepressant drug treatment by applying different interventions and with each intervention attain a clinically meaningful better effect compared to a control condition, and with minor side effects, thus improving the short- and medium-term outcome in major depression. Procedures Study design The basic study design has been the double blind randomised controlled trial (RCT). In the light therapy study, all patients were treated with sertraline for the whole of the study duration. In the first five weeks of the study, patients were randomised to treatment with either 60 minutes of bright white or 30 minutes of dim red light (sham condition). In the four weeks follow-up period, patients were treated with sertraline alone. In the Pindolol study, all patients were treated with venlafaxine and randomised to augmentation with either active or placebo matching pindolol tablets. In the PEMF study patients were continued on ongoing medication and randomised to augmentation with active or inactive (sham) 30 minutes daily PEMF treatment on weekdays. In the Chronos study all patients were treated with duloxetine and randomized to either a combination of three wake therapies with daily bright light treatment and sleep time stabilisation (wake group) or to daily exercise of minimum 30 minutes as an active control intervention (exercise group). The Chronos study was divided into: (1) a one-week run-in phase where duloxetine were started (and continued for the whole 29 week study period), (2) a one-week inpatient intervention phase where patient in the wake group did three wake therapies (sleep abstinence for the whole night and the following day until evening) in combination with daily light therapy and guidance on sleep time stabilisation and patients in the exercise group started a daily exercise program, (3) a seven week continuation phase where patient in the wake group continued light therapy and sleep time stabilisation and patients in the exercise group continued an individual exercise program, and (4) a 20 week follow-up phase with the same treatment elements but where duloxetine dosage could be adjusted or changed to other antidepressants. Recruitment Patients recruited for these studies were allocated from general practitioners, psychiatric specialist practices and for the lesser part from open psychiatric wards. Only a few patients were re-cruited through advertisements (in the PEMF and Chronos studies).   Inclusion criteria Inclusion criteria were major depression according to the DSM-IV, including a depressive episode as part of a bipolar disorder. For the PEMF study, treatment resistance was a specific inclusion criterion. Duration of studies Study duration was nine weeks for the light therapy study, 19 days for the Pindolol study, five weeks for the PEMF study, and 29 weeks for the Chronos study. Assessments In all studies, assessments were done with clinician rated scales, patient self-assessment scales, including quality of life scales and a side effect scale. As clinician rated scales we used the Hamilton depression rating scale: the HAM-D17 and its 6 item subscale: the HAM-D6, the Bech Rafaelsen Melancholia scale (MES), and the Bech Rafaelsen Mania scale (MAS). As self-assessment scales we used the Major Depression Inventory (MDI), the Symptom Check-list (SCL-92), and the Preskorn scale. For side effects we used the UKU scale. Further scales used are mentioned in the specific study sections. Assessments in the light therapy study were done weekly for the first six weeks and finally after nine weeks; at four time points in the Pindolol study (baseline, days 6, 11 and 19), weekly for five weeks in the PEMF study and weekly for the first nine weeks of the Chronos study and thereafter every four weeks. The clinical setting for evaluation has been the Psychiatric Research Unit at Mental Health Centre North Zealand. For the Bright Light study, Pindolol and PEMF study patients were also seen at a psychiatric specialist practice in Copenhagen. Biochemical measures In the Light therapy study saliva cortisol was collected at baseline before start of light therapy and sertraline and blood was drawn for thyroid analysis. In the Chronos study saliva and 24 hour urine cortisol was collected in the patients randomised to the exercise group. Main results The main results from the Bright Light study covering the first five weeks of the study are given in the PhD thesis "Adjunctive bright light in nonseasonal major depression" defended and awarded on the 18 November 2004 at the University of Copenhagen. Results from the cortisol measurement and for the four weeks extension period were published in separate papers after the PhD thesis and are included in this thesis. Results from the Bright Light study Analysis of the saliva cortisol measurements taken at baseline of the study as cortisol awakening profiles (CAR) showed that patients responded differentially to light treatment according to their CAR levels (dichotomized to high or low about the mean). Thus, in the bright light group HAM-D17 scores were reduced by 15.7 (4.2) points for patients with a low CAR (below mean), and 11.4 (4.8) points for patients with a high CAR (above mean). In the dim light group the corresponding values were 11.1 (5.2) for patients with a low CAR and 11.3 (5.3) for patients with a high CAR. This interaction between CAR and treatment group was statistically significant (p = 0.006). Survival analysis, for the first five weeks of the study period, showed a statistically significant higher response rate (χ2= 9.6, p =0.002) and higher remission rate (χ2 = 12.5, p = 0.0004) for the bright light treated group versus the dim light treated group. At end of the five weeks of light treatment response rates were 66.7% versus 40.7 % and remission rates were 41.7 % versus 14.8 % for the bright versus dim light treated group. In the subsequent publication that covered the four weeks extension period where light treatment was discontinued, data showed that the attained differences in response and remission rates between groups were not sustained. The offset of effect was nearly complete after four weeks of continued treatment on sertraline only. Thus, at end-point, response rates were 79.2 % versus 75.9 % and remission rates were 60 .4 % versus 55.6% in the bright versus dim light groups. The conclusion reached was that bright light in non-seasonal depression should be used to achieve an earlier antidepressant response and that light therapy probably should be of longer duration. Results from the Pindolol study The results from the Pindolol study showed that pindolol did not augment the effect of venlafaxine for the whole sample. However, for those patients classified as slow metabolizers, based on their O-desmethylvenlafaxine/venlafaxine ratio (ODV/V), pindolol did augment the antidepressant effect. For patients classified as fast metabolizers, pindolol worsened the outcome. This interaction between ODV/V ratio and treatment group was statistically significant (p = 0.01). Results from the PEMF study The results from the PEMF Study showed that treatment with active versus sham PEMF augmented the effect of the ongoing anti-depressant medication treatment. Thus, patients in the active PEMF group attained a statistically significant greater score reduction from week one and at all subsequent assessments compared to the sham treated group (p < 0.01). Response and remission rates in the active PEMF group were also larger than in the sham treated group with response rates at endpoint of 61.0 % versus 12.9 % (p < 0.01) and remission rates of 33.9 % versus 4.1 % (p < 0.05). Results from the Chronos study The Chronos study, published in three papers, covers a one-week intervention phase, a seven weeks continuation phase, and a 20 weeks follow-up phase. Results from the intervention week showed that patient treated in the wake group, from the day after the first wake therapy, had en clinically and statistically significant better antidepressant effect compared to the exercise group. On the HAM-D6 scale (which does not contains sleep items), patients in the wake group had a response rate after the first wake therapy of 58.7% versus 13.7% i the exercise group (p <0.0001) and a remission rate of 38.6% versus 2.9% (p <0.0001). After the second recovery sleep (the night after the second wake therapy = dag 5) patients in the wake group had a response rate of 75.0% versus 25.1% in the exercise group (p <0.0001) and remission rates of 58.6% versus 6.0% (p <0.0001). Results from the continuation phase showed, on the HAM-D17 scale which was used at all the following assessments, at week two response rates of 41.4% in the wake group and 12.8% in the exercise group (p = 0.003) and remission rates of 23.9% versus 5.4% (p = 0,004). This clinically relevant and statistically significant difference between the wake and exercise groups was maintained at all the subsequent assessments with response rates of 71.4% versus 47.3% (p = 0.04) and remission rates of 45.6% versus 23.1% (p = 0.04), at week nine. Results from the 20 weeks follow-up phase showed a continued better effect in the wake group at all visits with HAM-D17 depression scored at week 29 of 7.5 (SE = 0.9) in the wake group versus 10.1 (SE = 0.9), (p = 0.02) in the exercise group. Remission rates were higher in the wake group with endpoint rates of 61.9% versus 37.9% (p = 0.01) in the exercise group. Response rates was only numerically, but not statistically, higher in the wake group with 74.6% versus 64.4% in the exercise group (p = 0.22). The sleep diary data showed a statistically smaller day-to-day variation in sleep onset, sleep midpoint, sleep offset and sleep duration in the wake group compared to the exercise group as a sign of better day-to-day sleep-wake cycle control in the wake group (p < 0.01). In the first nine weeks of the study patients in the wake group had a moderate sleep phase advance that diminished during the follow-up period. The hypothesised predictors for response to wake therapy were confirmed. Thus, in the wake group, a positive diurnal variation (morning worst, evening best) was associated with a better out-come, after the wake therapies, compared to a negative diurnal variation (morning best, evening worst). In the exercise group, the reverse was found, as a positive diurnal variation was associated with worse outcome, compared to a negative diurnal variation. This interaction between group and diurnal variation was statistically significant (p = 0.0004). The positive predictive value of response to the first wake therapy (i.e. maintaining response also at week two) was 56.3 % and the negative predictive value of non-response to the first wake therapy (i.e. maintaining no response also at week two) was 75.0 %. The impact of naps on depression severity was examined. In the wake group, patients who napped on the days after wake therapy compared to those patients not napping, had a more severe deterioration at the following assessment at week two (p = 0.02). Patients in the exercise group were able to perform exercise with a mean of 63.0 minutes/day (55.3) for the first eight weeks.
28385162	Human studies demonstrate that sleep impairment is a concurrent comorbidity of autism spectrum disorders (ASD), but its etiology remains largely uncertain. One of the prominent theories of ASD suggests that an imbalance in synaptic excitation/inhibition may contribute to various aspects of ASD, including sleep impairments. Following the identification of Nlgn3R451C mutation in patients with ASD, its effects on synaptic transmission and social behaviours have been examined extensively in the mouse model. However, the contributory role of this mutation to sleep impairments in ASD remains unknown. In this study, we showed that Nlgn3R451C knock-in mice, an established genetic model for ASD, exhibited normal duration and distribution of sleep/wake states but significantly altered electroencephalography (EEG) power spectral profiles for wake and sleep.
28385085	Background Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions. Though relatively common, little is known about its characteristic symptoms or associated features. Methods A cross-sectional study of 49 undergraduates with EHS was performed. A clinical interview established diagnosis. Results The most common accompanying symptoms were tachycardia, fear, and muscle jerks/twitches with the most severe associated with respiration difficulties. Visual phenomena were more common than expected (27%). EHS episodes were perceived as having a random course, but were most likely to occur during wake-sleep transitions and when sleeping in a supine position. Only 11% reported EHS to a professional, and 8% of those with recurrent EHS attempted to prevent episodes. Conclusions EHS episodes are complex (Mean (M) = 4.5 additional symptoms), often multisensorial, and usually associated with clinically-significant fear. They are rarely reported to professionals and treatment approaches are limited.
28383527	Reduced tongue muscle tone precipitates obstructive sleep apnea (OSA), and activation of the tongue musculature can lessen OSA. The hypoglossal motor nucleus (HMN) innervates the tongue muscles but there is no pharmacological agent currently able to selectively manipulate a channel (e.g., Kir2.4) that is highly restricted in its expression to cranial motor pools such as the HMN. To model the effect of manipulating such a restricted target, we introduced a "designer" receptor into the HMN and selectively modulated it with a "designer" drug. We used cre-dependent viral vectors (AAV8-hSyn-DIO-hM3Dq-mCherry) to transduce hypoglossal motoneurons of ChAT-Cre+ mice with hM3Dq (activating) receptors. We measured sleep and breathing in three conditions: (i) sham, (ii) after systemic administration of clozapine-N-oxide (CNO; 1 mg/kg) or (iii) vehicle. CNO activates hM3Dq receptors but is otherwise biologically inert. Systemic administration of CNO caused significant and sustained increases in tongue muscle activity in non-REM (261 ± 33% for 10 hrs) and REM sleep (217 ± 21% for 8 hrs), both P < 0.01 versus controls. Responses were specific and selective for the tongue with no effects on diaphragm or postural muscle activities, or sleep-wake states. These results support targeting a selective and restricted "druggable" target at the HMN (e.g., Kir2.4) to activate tongue motor activity during sleep.
28382959	Obstructive sleep apnoea (OSA) is known to commonly co-exist with primary aldosteronism (PA), but it is unknown if treatment of PA improves sleep apnoea parameters in these patients. We therefore aimed to determine whether specific medical or surgical treatment of PA improves OSA, as measured by the apnoea-hypopnoea index (AHI). We recruited patients undergoing diagnostic workup for PA if they had symptoms suggestive of OSA. Patients with confirmed PA underwent polysomnography (PSG) at baseline and again at least 3 months after specific treatment for PA. Of 34 patients with PA, 7 (21%) had no evidence of OSA (AHI <5), 9 (26%) had mild (AHI ⩾5 and <15), 8 (24%) moderate (AHI ⩾15 and <30) and 10 (29%) severe OSA (AHI ⩾30). Body mass index tertile, neck circumference and 24 h urinary sodium correlated with the AHI. Twenty patients had repeat PSG performed after treatment for PA (mineralocorticoid receptor antagonists in 13 with bilateral PA and adrenalectomy in 7 with unilateral PA). In this group the median (s.d.) AHI reduced from 22.5 (14.7) to 12.3 (12.1) (P=0.02). Neck circumference reduced with PA treatment (41.6 vs 41.2 cm, P=0.012). OSA is common in patients with primary aldosteronism and may improve with specific therapy for this disease. Aldosterone and sodium-mediated fluid retention in the upper airways and neck region may be a potential mechanism for this relationship.
28381508	To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies.This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques.	Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16.	Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.	
28380364	The small ventral lateral neurons (sLNvs) constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF), coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters. Adult-specific RNAi-mediated downregulation of the glycine transporter or impairment of glycine synthesis in LNv neurons increased period length by nearly an hour without affecting rhythmicity of locomotor activity. Electrophysiological recordings showed that glycine reduces spiking frequency in circadian neurons. Interestingly, downregulation of glycine receptor subunits in specific sLNv targets impaired rhythmicity, revealing involvement of glycine in information processing within the network. These data identify glycinergic inhibition of specific targets as a cue that contributes to the synchronization of the circadian network.
28377393	Up to 70% of children with attention-deficit/hyperactivity disorder (ADHD) experience sleep problems. We have demonstrated the efficacy of a brief behavioural intervention for children with ADHD in a large randomised controlled trial (RCT) and now aim to examine whether this intervention is effective in real-life clinical settings when delivered by paediatricians or psychologists. We will also assess the cost-effectiveness of the intervention.Children aged 5-12 years with ADHD (n=320) are being recruited for this translational cluster RCT through paediatrician practices in Victoria and Queensland, Australia. Children are eligible if they meet criteria for ADHD, have a moderate/severe sleep problem and meet American Academy of Sleep Medicine criteria for either chronic insomnia disorder or delayed sleep-wake phase disorder; or are experiencing sleep-related anxiety. Clinicians are randomly allocated at the level of the paediatrician to either receive the sleep training or not. The behavioural intervention comprises 2 consultations covering sleep hygiene and standardised behavioural strategies. The primary outcome is change in the proportion of children with moderate/severe sleep problems from moderate/severe to no/mild by parent report at 3 months postintervention. Secondary outcomes include a range of child (eg, sleep severity, ADHD symptoms, quality of life, behaviour, working memory, executive functioning, learning, academic achievement) and primary caregiver (mental health, parenting, work attendance) measures. Analyses will address clustering at the level of the paediatrician using linear mixed effect models adjusting for potential a priori confounding variables.	Ethics approval has been granted. Findings will determine whether the benefits of an efficacy trial can be realised more broadly at the population level and will inform the development of clinical guidelines for managing sleep problems in this population. We will seek to publish in leading international paediatric journals, present at major conferences and through established clinician networks.	ISRCTN50834814, Pre-results.	
28373571	Adenosine and functional A1 adenosine receptor (A1AR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral A1AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [18F]CPFPX positron emission tomography was used to quantify A1AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A1AR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in A1AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A1AR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in A1AR availability. Sleep deprivation resulted in a higher A1AR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in A1AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A1AR availability might be causal for individual responses to sleep loss.
28370506	Food intake during the rest phase promotes circadian desynchrony, which has been associated with metabolic diseases. However, the link between circadian rhythm and metabolic alterations is not well understood. To investigate this issue, we explored the circadian rhythm of c-Fos immunoreactivity (IR) in rats fed during the day, during the night or with free access to food for 3 weeks. The analysis was focused on the hypothalamic nuclei, which are interconnected and involved in the control of energy homeostasis and/or arousal: lateral hypothalamus (LH), perifornical area, arcuate, ventrolateral pre-optic (VLPO) and tuberomammillary nuclei. The results show that food intake during the rest phase flattened the circadian c-Fos expression in the LH and perifornical area, and induced a phase shift in the VLPO area. In addition, c-Fos expression was analyzed in the orexin and melanin-concentrating hormone (MCH) neurons of the LH, which are involved in the control of food intake and arousal, and in α-melanin-stimulating hormone and neuropeptide Y (NPY) cells in the arcuate nucleus, all of which are involved in feeding-fasting cycles, energy homeostasis and sending projections to the LH. The results indicate that feeding during the rest phase decreased orexin neuron activation in the light in comparison with the other groups. Feeding during this phase also flattened the activity rhythm of MCH and α-melanin-stimulating hormone neurons and increased NPY IR when the light was turned on. This evidence indicates that mealtime differentially affected the hypothalamic nuclei under investigation leading to a circadian conflict that might account for metabolic impairment.
28369624	This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients.In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery.	Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p < .001). Actigraphy recordings revealed longer bedtimes (+1:06 ± 0:51 hours, p < .001) without shifting of circadian timing. Upon polysomnography, we observed an increase in sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus.	Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes.	
28367676	Within the human population, there is large interindividual variability in the timing of sleep and circadian rhythms. This variability has been attributed to individual differences in sleep physiology, circadian physiology, and/or light exposure. Recent experimental evidence suggests that the latter is necessary to evoke large interindividual differences in sleep and circadian timing. We used a validated model of human sleep and circadian physiology to test the hypothesis that intrinsic differences in sleep and circadian timing are amplified by self-selected use of artificial light sources. We tested the model under 2 conditions motivated by an experimental study (Wright et al., 2013): (1) a "natural" light cycle, and (2) a "realistic" light cycle that included attenuation of light due to living indoors when natural light levels are high and use of electric light when natural light levels are low. Within these conditions, we determined the relationship between intrinsic circadian period (within the range of 23.7-24.6 h) and timing of sleep onset, sleep offset, and circadian rhythms. In addition, we simulated a work week, with fixed wake time for 5 days and free sleep times on weekends. Under both conditions, a longer intrinsic period resulted in later sleep and circadian timing. Compared to the natural condition, the realistic condition evoked more than double the variation in sleep timing across the physiological range of intrinsic circadian periods. Model predictions closely matched data from the experimental study. We found that if the intrinsic circadian period was long (>24.2 h) under the realistic condition, there was significant mismatch in sleep timing between weekdays and weekends, which is known as social jetlag. These findings indicate that individual tendencies to have very delayed schedules can be greatly amplified by self-selected modifications to the natural light/dark cycle. This has important implications for therapeutic treatment of advanced or delayed sleep phase disorders.
28366532	Sleep is a deeply conserved, yet fundamentally mysterious behavioral state. Knowledge of the circuitry of sleep-wake regulation is an essential step in understanding the physiology of the sleeping brain. Recent efforts in Drosophila have revealed new populations which impact sleep, as well as provided unprecedented mechanistic and electrophysiological detail of established sleep-regulating neurons. Multiple, distributed centers of sleep-wake circuitry exist in the fly, including the mushroom bodies, central complex and the circadian clock cells. Intriguingly, certain populations have been implicated in specific roles in homeostatic rebound sleep, occurring after sleep loss. In short, our knowledge of fly sleep circuitry advances towards a greater view of brain-wide connectivity and integration of the signals and correlates of the state of sleep.
28366332	Napping is a widely used countermeasure to sleepiness and impaired performance caused by sleep loss and circadian pressure. Sleep inertia, the period of grogginess and impaired performance experienced after waking, is a potential side effect of napping. Many industry publications recommend naps of 30 min or less to avoid this side effect. However, the evidence to support this advice is yet to be thoroughly reviewed.Electronic databases were searched, and defined criteria were applied to select articles for review. The review covers literature on naps of 30 min or less regarding (a) sleep inertia, (b) slow-wave sleep (SWS) and (c) the relationship between sleep inertia and SWS.	The review found that although the literature on short afternoon naps is relatively comprehensive, there are very few studies on naps of 30 min or less at night. Studies have mixed results regarding the onset of SWS and the duration and severity of sleep inertia following short naps, making guidelines regarding their use unclear. The varying results are likely due to differing sleep/wake profiles before the nap of interest and the time of the day at waking.	The review highlights the need to have more detailed guidelines about the implementation of short naps according to the time of the day and prior sleep/wake history. Without this context, such a recommendation is potentially misleading. Further research is required to better understand the interactions between these factors, especially at night, and to provide more specific recommendations.	
28365867	A prominent hypothesis, the "flip-flop switch" model, predicts that histaminergic (HAergic) neurons in the tuberomammillary nucleus (TMN), an important component of the ascending arousal system, are inactivated by GABA mainly from the ventrolateral preoptic nucleus to allow the appearance and maintenance of sleep. However, which sleep state and the band of EEG activity induced by GABAergic inactivation of the TMN are unclear. In this study, alterations of sleep-wake states and cortical EEG power spectral density were investigated following muscimol, a GABAA-receptor agonist, microinjected bilaterally into the TMN in freely moving rats and HA pretreated rats, respectively. Muscimol dosed at 0.25 and 0.50 μg/side into the TMN during dark period dose-dependently increased slow wave sleep (SWS) accompanied by an increase in cortical EEG delta (0.5-4 Hz) and spindle (8.2-12 Hz) activities. In the meanwhile, wakefulness and EEG beta (12.2-30 Hz) activity were decreased significantly, while paradoxical sleep and EEG theta (4.2-8 Hz) activity were not changed. The increase of muscimol-induced SWS was because of prolonged SWS bout duration and not to an increased bout number. Muscimol (0.50 μg/side) administration 2 h after HA (0.125 μg/side) treatment during light period reversed the HA-induced wakefulness and EEG beta 2 (20.2-30 Hz) activity into SWS and EEG delta activity. These results demonstrate that the GABAergic inactivation of the TMN in freely moving rats and HA-treated rats promotes SWS and slow activity of cortical EEG, suggesting that the potential function of the GABAA receptor in the TMN is to dampen vigilant arousal.
28364862	We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (eβ:1.53;95%CI:1.04-2.26).
28364512	We investigate how characteristics of sleep-wake dynamics in humans are modified by narcolepsy, a clinical condition that is supposed to destabilize sleep-wake regulation. Subjects with and without cataplexy are considered separately. Differences in sleep scoring habits as a possible confounder have been examined.Four groups of subjects are considered: narcolepsy patients from China with (n = 88) and without (n = 15) cataplexy, healthy controls from China (n = 110) and from Europe (n = 187, 2 nights each). After sleep-stage scoring and calculation of sleep characteristic parameters, the distributions of wake-episode durations and sleep-episode durations are determined for each group and fitted by power laws (exponent α) and by exponentials (decay time τ).	We find that wake duration distributions are consistent with power laws for healthy subjects (China: α = 0.88, Europe: α = 1.02). Wake durations in all groups of narcolepsy patients, however, follow the exponential law (τ = 6.2-8.1 min). All sleep duration distributions are best fitted by exponentials on long time scales (τ = 34-82 min).	We conclude that narcolepsy mainly alters the control of wake-episode durations but not sleep-episode durations, irrespective of cataplexy. Observed distributions of shortest wake and sleep durations suggest that differences in scoring habits regarding the scoring of short-term sleep stages may notably influence the fitting parameters but do not affect the main conclusion.	
28364494	To determine the relationship between an ecologically-relevant change in sleep behavior and its subsequent effects on daytime alertness and feeding behavior.Fifty healthy, young participants (10 male, 40 female) completed two 3-hour study sessions that were at least five days apart. The first session was a baseline evaluation. On the night prior to Session 2, the amount of time in bed was manipulated to be 60%-130% of the individual's habitual sleep time. Within both sessions, subjective (Stanford Sleepiness Scale) and objective (Psychomotor Vigilance Test) alertness were measured. During the middle of each session, a 40-minute ad libitum meal opportunity allowed participants to eat from eight different food items. Food healthfulness, caloric density, distribution, and number of calories were measured and compared to alertness levels.	The induced variation in time in bed resulted in induced variation in both subjective and objective (p < .05) measures of alertness. Decreased subjective alertness was associated with increased total caloric consumption (p < .05), and a greater number of calories consumed from less healthy food (p < .05), as rated by both the investigators and by the participant. Decreased objective alertness was associated with less healthy food choices (p < .05), and the consumption of more food from the calorically-dense items (p < .05).	Ecologically-relevant impairments in subjective and objective alertness are associated with increased caloric intake and dysfunctional eating decisions. People experiencing reduced alertness after modest sleep loss may be more willing to eat food they recognize as less healthful, and appear to prefer more calorically-dense foods.	
28364493	Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages over melatonin treatment. In this study, we compare the effects of melatonin and bright light treatment with a placebo condition in children with chronic sleep onset insomnia and late melatonin onset.Eighty-four children (mean age 10.0 years, 61% boys) first entered a baseline week, after which they received melatonin (N = 26), light (N = 30), or placebo pills (N = 28) for 3 to 4 weeks. Sleep was measured daily with sleep diaries and actigraphy. Before and after treatment children completed a questionnaire on chronic sleep reduction, and Dim Light Melatonin Onset (DLMO) was measured. Results were analyzed with linear mixed model analyses.	Melatonin treatment and light therapy decreased sleep latency (sleep diary) and advanced sleep onset (sleep diary and actigraphy), although for sleep onset the effects of melatonin were stronger. In addition, melatonin treatment advanced DLMO and had positive effects on sleep latency and sleep efficiency (actigraphy data), and sleep time (sleep diary and actigraphy data). However, wake after sleep onset (actigraphy) increased with melatonin treatment. No effects on chronic sleep reduction were found.	We found positive effects of both melatonin and light treatment on various sleep outcomes, but more and stronger effects were found for melatonin treatment.	
28364473	To examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder.One hundred and eighty-two DSPD patients aged 16-64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT.	One hundred and three patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 hours later in circadian DSPD compared to non-circadian DSPD (p < .001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p < .05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64; p < .01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD.	Almost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the DBT, suggesting that the reported difficulties initiating sleep at the DBT are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.	
28364457	To determine whether interdependence in couples' sleep (sleep-wake concordance i.e., whether couples are awake or asleep at the same time throughout the night) is associated with two markers of cardiovascular disease (CVD) risk, ambulatory blood pressure (BP) and systemic inflammation.This community-based study is a cross-sectional analysis of 46 adult couples, aged 18-45 years, without known sleep disorders. Percent sleep-wake concordance, the independent variable, was calculated for each individual using actigraphy. Ambulatory BP monitors measured BP across 48 h. Dependent variables included mean sleep systolic BP (SBP) and diastolic BP (DBP), mean wake SBP and DBP, sleep-wake SBP and DBP ratios, and C-reactive protein (CRP). Mixed models were used and were adjusted for age, sex, education, race, and body mass index.	Higher sleep-wake concordance was associated with lower sleep SBP (b = -.35, SE = .01) and DBP (b = -.22, SE = .10) and lower wake SBP (b = -.26, SE = .12; all p values < .05). Results were moderated by sex; for women, high concordance was associated with lower BP. Men and women with higher sleep-wake concordance also had lower CRP values (b = -.15, SE = .03, p < .05). Sleep-wake concordance was not associated with wake DBP or sleep/wake BP ratios. Significant findings remained after controlling for individual sleep quality, duration, and wake after sleep onset.	Sleep-wake concordance was associated with sleep BP, and this association was stronger for women. Higher sleep-wake concordance was associated with lower systemic inflammation for men and women. Sleep-wake concordance may be a novel mechanism by which marital relationships are associated with long-term CVD outcomes.	
28364455	Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared electroencephalogram (EEG) and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD).Male contactin-associated protein-like 2 (Cntnap2) knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, electromyogram, body temperature, and locomotor activity. Animals were subjected to a test battery for ASD-related behaviors, followed by 24-hr EEG recordings that were analyzed for sleep-wake parameters and subjected to spectral analysis.	Cntnap2 KO rats exhibited severe motor seizures, hyperactivity, and increased consolidation of wakefulness and REM sleep. By contrast, Cntnap2 KO mice demonstrated absence seizure-like events, hypoactivity, and wake fragmentation. Although seizures observed in Cntnap2 KO rats were more similar to those in CDFE patients than in KO mice, neither model fully recapitulated the full spectrum of disease symptoms. However, KOs in both species had reduced spectral power in the alpha (9-12 Hz) range during wake, suggesting a conserved EEG biomarker.	Deletion of Cntnap2 impacts similar behaviors and EEG measures in rats and mice, but with profound differences in nature and phenotypic severity. These observations highlight the importance of cross-species comparisons to understand conserved gene functions and the limitations of single- species models to provide translational insights relevant to human diseases.	
28364448	To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration.Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases), aged 33 years on average and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of the levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1).	Levels of β-amyloid were lower in patients with type 1 narcolepsy (375.4 ± 143.5 pg/mL) and type 2 narcolepsy (455.9 ± 65.0 pg/mL) compared to controls (697.9 ± 167.3 pg/mL, p < .05). Furthermore, in patients with type 1 narcolepsy, levels of T-tau (79.0 ± 27.5 pg/mL) and P-tau181 (19.1 ± 4.3 pg/mL) were lower than in controls (162.2 ± 49.9 pg/mL and 33.8 ± 9.2 pg/mL, p < .05). Levels of α-synuclein, NF-L, and CHI3L1 in CSF from narcolepsy patients were similar to those of healthy individuals.	Six CSF biomarkers of neurodegeneration were decreased or normal in narcolepsy indicating that taupathy, synucleinopathy, and immunopathy are not prevalent in narcolepsy patients with a disease duration of 2-29 years. Lower CSF levels of β-amyloid, T-tau protein, and P-tau181 in narcolepsy may indicate that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in the central nervous system.	
28364421	To better understand the development of sleep, we characterized the development of circadian rhythms in sleep and wakefulness in the artificially-reared, isolated rat pup using an experimental design that minimized the effects of maternal separation.Neonatal rats were reared in constant conditions (dim red light) while electroencephalographic and electromyographic signals were continuously recorded for up to 3 weeks. This time period spanned the preweaned and weaned ages. The distribution of sleep-wake states was analyzed to estimate the emergence of circadian rhythms.	Overt ~24-hour rhythms in time spent awake and asleep appear by postnatal day (P)17. A marked bi-modal sleep-wake pattern was also observed, evidenced by the appearance of a pronounced ~12-hour component in the periodogram over the subsequent 3 days (P17-P21). This suggested the presence of two ~24-hour components consistent with the dual-oscillator concept. During this 3-day time window, waking bouts became longer resulting in a repartition of the duration of intervals without non-rapid-eye movement (NREM) sleep into short (<30 minutes) and longer inter-NREM sleep episodes. These longer waking bouts did not immediately result in an increase in NREM sleep delta (0.5-4.0 Hz) power, which is an index of sleep homeostasis in adult mammals. The sleep homeostatic response did not fully mature until P25.	These results demonstrate that the maturation of circadian organization of sleep-wake behavior precedes the expression of mature sleep homeostasis.	
28364414	Interest in orexin receptor antagonism as a novel mechanism of action against seizures and epilepsy has increased in recent years. Loss of orexinergic activity is associated with rapid eye movement (REM) sleep onset, and REM sleep is generally protective against seizures. This paper discusses the dynamic modulation of seizure threshold by orexin through a postulated "orexi-cortical" axis in which the specific type of orexinergic activity exquisitely regulates sleep-wake states to modify ascending subcortical influences on cortical synchronization with profound subsequent consequences on seizure threshold. This paper also explores the current state of research into experimental orexinergic modulation of seizure threshold and suggests possible future research directions to fully understand the promise and peril of orexinergic manipulation in seizures and epilepsy.
28363787	Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. In this study, we compared the effect of corannulene (non-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. First, the toxicity of graded doses of corannulene (1, 10, and 50μg/mL) was tested in developing zebrafish embryos. Corannulene showed minimal developmental toxicity only induced an epiboly delay. Further, a significant decrease in locomotion/increase in sleep was observed in larvae treated with the highest dose (50μg/mL) of corannulene while no significant locomotion alterations were induced by graphene. Finally, the effect of corannulene or graphene on the hypocretin (hcrt) system and sleep/wake regulators such as hcrt, hcrt G-protein coupled receptor (hcrtr), and arylalkylamine N-acetyltransferase-2 (aanat2) was evaluated. Corannulene increased sleep and reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behavior and gene expression patterns. These results suggest that the corannulene has the potential to cause hypnosis-like behavior in larvae and provides a fundamental comparative understanding of the effects of corannulene and graphene on biology systems.Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. Here, we compare the effect of corannulene (no-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. And we aim to investigate the effect of curvature on biological system. First, toxicity of corannulene over the range of doses (1μg/mL, 10μg/mL and 50μg/mL) was tested in developing zebrafish embryos. Corannulene has minimal developmental toxicity, only incurred epiboly delay. Subsequently, a significant decrease in locomotion/increase in sleep at the highest dose (50μg/mL) was detected in corannulene treated larvae while no significant locomotion alterations was induced by graphene. Finally, the impact of corannulene or graphene on hypocretin system and sleep/wake regulator such as hcrt, hcrtr and aanat2 was evaluated. Corannulene increased sleep, reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behaviors and gene expression patterns. This result may indicate the potential effect of corannulene to cause hypnosia-like behavior in larvae and provide the fundamental understanding for the biological effect of curvature on biology system.	
28359652	To develop a method for automated neonatal sleep state classification based on EEG that can be applied over a wide range of age.We collected 231 EEG recordings from 67 infants between 24 and 45weeks of postmenstrual age. Ten minute epochs of 8 channel polysomnography (N=323) from active and quiet sleep were used as a training dataset. We extracted a set of 57 EEG features from the time, frequency, and spatial domains. A greedy algorithm was used to define a reduced feature set to be used in a support vector machine classifier.	Performance tests showed that our algorithm was able to classify quiet and active sleep epochs with 85% accuracy, 83% sensitivity, and 87% specificity. The performance was not substantially lowered by reducing the epoch length or EEG channel number. The classifier output was used to construct a novel trend, the sleep state probability index, that improves the visualisation of brain state fluctuations.	A robust EEG-based sleep state classifier was developed. It performs consistently well across a large span of postmenstrual ages.	This method enables the visualisation of sleep state in preterm infants which can assist clinical management in the neonatal intensive care unit.	
28357049	Animals continuously alternate between sleep and wake states throughout their life. The daily organization of sleep and wakefulness is orchestrated by circadian, homeostatic, and motivational processes. Over the last decades, much progress has been made toward determining the neuronal populations involved in sleep/wake regulation. Here, we will discuss how the application of advanced in vivo tools for cell type-specific manipulations now permits the functional interrogation of different features of sleep/wake state regulation: initiation, maintenance, and structural organization. We will specifically focus on recent studies examining the roles of wake-promoting neuronal populations.
28346384	Intensive sleep re-training is a promising new therapy for chronic insomnia. Therapy is completed over a 24-h period during a state of sleep deprivation. Improvements of sleep and daytime impairments are comparable to the use of stimulus control therapy but with the advantage of a rapid reversal of the insomnia. The initial studies have been laboratory based and not readily accessible to the patient population. However, new smart phone technology, using a behavioral response to external stimuli as a measure of sleep/wake state instead of EEG determination of sleep, has made this new therapy readily available. Technological improvements are still being made allowing the therapy to provide further improvements in the effectiveness of Intensive Sleep Re-training.
28346163	The present study investigated whether the effects of sleep duration and quality on adolescent adjustment were moderated by perceived attachment to mothers and fathers.The study used a cross-sectional design.	Participants were recruited from small town and semirural communities in Alabama.	Participants were 106 adolescents (mean age=13.61 years, SD=.73; 55% girls; 28% African American, 72% European American) and their parents.	Sleep duration (minutes) and sleep quality (efficiency, number of long wake episodes) were derived using actigraphy, and subjective sleep/wake problems were derived with adolescent reports. Adolescents also reported on perceived attachment to mothers and fathers, internalizing symptoms, and self-esteem. Mothers and fathers reported on externalizing behaviors.	Path model analyses indicated that perceived attachment to parents moderated relations between adolescents' sleep quality and their adjustment. For externalizing symptoms and self-esteem, adolescents at greatest risk for maladjustment were those who reported poor quality sleep (ie, more sleep/wake problems, lower sleep efficiency) coupled with less secure attachment to parents. Conversely, adolescents who experienced better actigraphy-based sleep quality (ie, higher sleep efficiency, fewer long wake episodes) in conjunction with more secure attachment to parents experienced the lowest levels of anxiety symptoms. Less secure attachment was associated with high levels of anxiety symptoms independent of sleep quality. Similar patterns of associations emerged for attachment to mothers and fathers.	Findings highlight the importance of examining the conjoint influence of sleep and adolescent-parent relationships toward explication of adolescent's mental health.	
28346154	This 10-day study aimed to (1) assess the effectiveness of a text message-based sleep intervention and (2) determine whether the intervention was equally effective for non-Hispanic whites and racial-ethnic minority adolescents.Participants were 46 (50% female) adolescents (13-18 years; mean=15.75 years old, SD=0.98) from a public high school in the Midwest.	Participants were randomly assigned to a control or text message intervention condition. Only participants in the intervention condition received 2 text messages outlining individualized bedtime goals daily, for 8 weekdays.	All participants attended a sleep lecture, wore a sleep monitor, and completed baseline and exit surveys that assessed demographics, subjective sleep, lifestyle, and psychosocial adjustment variables.	Results of a 2 (intervention, control) × 2 (pre-intervention, postintervention) analysis of variance test revealed no significant intervention × time interaction effect (F1,38=0.020, P=.889) in the full sample. This effect, however, was significantly moderated by race-ethnicity: Results indicated a significant intervention × time × race interaction (F1,36=8.050, P=.007, partial η2=.183) such that the intervention significantly improved sleep hours (by approximately 1 hour) only among non-Hispanic whites (and not among adolescents of racial-ethnic minority status).	Adolescents from racial-ethnic minority groups may face significant barriers that interfere with their ability to successfully alter their sleep-wake patterns and maximize sleep hours.	
28343323	All living organisms that face a traumatic life event are susceptible to sleep-wake disturbances. Stress, which can result in trauma, evokes a high level of physiological arousal associated with sympathetic nervous system activation, during both sleep and wakefulness. Heredity, sex hormones, early losses, developmental factors and intra- and interpersonal conflicts, contribute to the level of baseline physiological arousal, producing either subclinical, clinical or complex clinical traits, acutely and at any time after exposure to a traumatic event. The risk of acute sleep-wake disturbances becoming disorders and syndromes depends on the type of traumatic event and all of the aforementioned factors. Taken together, with consideration for behavioural and environmental heterogeneity, in research, will aid identification and understanding of susceptibility factors in long-term sleep and wakefulness pathology after exposure to traumatic events.
28343215	The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) is a novel tool allowing for a complex assessment of biological rhythms. We compared patients with bipolar disorder (BD) and healthy control subjects (HC) using the Polish version of the BRIAN scale.Fifty-four remitted BD patients (17 males and 37 females aged 52 ± 13 years) and 54 healthy control subjects (25 males and 29 females aged 42 ± 14 years) were studied. In addition to the BRIAN scale, the Composite Scale of Morningness (CSM) and the Sleep-Wake Pattern Assessment Questionnaire (SWPAQ) were employed.	The Polish version of the BRIAN scale displayed high feasibility and consistency, showing that the patients had greater biological rhythm disturbances than the controls. After regression analysis, significant differences were obtained for the BRIAN subscales activity and predominant chronotype, and for the SWPAQ items quality of night-time sleep and ability to stay awake. We obtained positive correlations between higher BRIAN scores and morningness and eveningness, but the correlations with vigilance and the ability to stay awake (on the SWPAQ) were negative.	Using the BRIAN scale, we confirmed the greater disturbances of biological rhythm in Polish remitted bipolar patients, compared with healthy controls. The differences between these 2 groups in sleep-awake patterns were also demonstrated by the SWPAQ scores. In contrast to other studies, we were unable to confirm an evening chronotype as a discriminating factor between remitted bipolar patients and healthy subjects. This can be explained by the older age and the use of lithium by a significant proportion of the patients.	
28338525	Oxytocin neurons in the paraventricular nucleus (PVN) of the hypothalamus play an important role in food intake regulation. It has been shown that the secretion of oxytocin from the hypothalamus shows a diurnal circadian rhythmic pattern and disturbance of this pattern leads to the development of obesity. However, whether oxytocin secretion from the PVN has a diurnal pattern remains unknown. Here, we show that oxytocin secretion from the PVN does have a diurnal pattern and that the terminals of orexin neurons, the neuropeptide responsible for regulating the sleep-wake rhythm, are synapsed with PVN oxytocin neurons. Using transgenic rats selectively expressing monomeric red fluorescent protein 1 in oxytocin neurons, we found that orexin-A inhibits the activities of PVN oxytocin neurons by inhibiting glutamatergic excitatory synaptic input. These data suggest that orexin is a possible candidate to regulate the circadian rhythm of PVN oxytocin neurons. The circadian rhythmic secretion of oxytocin is considered to play an important role in maintaining homeostasis, including body weight regulation. Our present data indicate a possible contribution of orexin toward the development of circadian rhythm in PVN oxytocin neurons.
28334632	Research in older adolescents suggests insufficient sleep may increase substance use initiation risk. This study tested whether sleep duration and dysregulation of sleep-wake patterns in late-elementary school youth were prospectively associated with cigarette and alcohol use initiation and how sleep-related changes in inhibitory control mediate these relationships. Average sleep duration at 4th grade predicted 6th grade cigarette but not alcohol use, however indirect effects were identified through 5th grade inhibitory control to both cigarette and alcohol use. Indirect effects were also identified through inhibitory control for relationships between 4th grade weekend bed-time delay and 6th grade cigarette or alcohol use, and for relationships between 4th grade weekend wake-time delay and 6th grade cigarette or alcohol use. Reductions in nightly sleep increased risk of cigarette use. Findings suggest a pathway linking both reduced sleep duration and greater weekend shifting of sleep patterns to future substance use through sleep-related inhibitory control deficits.
28332250	The incidence, underlying physiopathology, features and association with lesion topography of visual hallucinations in acute stroke have scarcely been investigated.Patients with a diagnosis of acute stroke (ischaemic or haemorrhagic) in any vascular territory, admitted within 24 h after the onset of symptoms, were consecutively included in the study. Patients with a previous history of psychosis or cognitive impairment were excluded. They and/or their caregivers answered a structured hallucination and sleep questionnaire at admission, within the first 15 days and at the clinical follow-up 3-6 months after discharge. Lesion location (IMAIOS online atlas) and leukoaraiosis (Wahlund scale) were determined by magnetic resonance imaging or computed tomography scan. Subsets of patients also underwent a neuropsychological evaluation (N = 50) and an electroencephalogram (N = 33) before discharge.	In all, 77 patients with a mean age of 71 ± 12 years were included of whom 57.1% were men. The incidence of visual hallucinations was 16.7%. These hallucinations were mostly complex, in black and white and self-limited. The appearance of hallucinations was not influenced by age, sex, neuropsychological performance during admission or modified Rankin scale score at discharge. Visual hallucinations were associated with occipital cortex lesions (P = 0.04), and with sleep disturbances during and before admission (P = 0.041 and P = 0.03 respectively).	Visual hallucinations are relatively frequent in patients with acute stroke and they are self-limited. Patients with occipital lesions and sleep disturbances are more likely to suffer them.	
28332103	To describe the sleep patterns of children below 36 months in Hong Kong, and evaluate the associations between parental behaviors and childhood sleep/wake patterns.Parents of 1049 infants and toddlers completed an internet-based expanded version of the Brief Infant Sleep Questionnaire.	Total sleep duration (P<0.001), frequency (P<0.001) and duration (P<0.001) of nocturnal awakenings decreased with age, whereas the longest sleep duration (P<0.001) and nocturnal sleep duration (P<0.001) increased with age. Children who room- or bed-shared with parents had later bedtimes (P<0.001), but similar sleep duration compared with those who had a separate sleep location. Falling asleep independently was associated with longer nocturnal sleep duration (P<0.001) and less sleep awakenings (P<0.001). Full-time employment of parents was associated with shorter total sleep duration of children (P<0.001). Although breastfeeding was associated with more nocturnal awakenings (P<0.001), no association was detected between breastfeeding and shorter sleep duration in children.	As infants and toddlers develop, their sleep consolidates. Falling asleep independently was associated with longer nocturnal sleep duration and fewer sleep awakenings, whereas sleep location was not. This is an important finding, especially for families with limited living space where parent/child room- or bed-sharing cannot be avoided.	
28331380	Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD) or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism) received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism) who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light.
28329356	Determine the associations of sleep disturbances with hospitalization risk among older women.One thousand eight hundred and twenty-seven women (mean age 83.6 years) participating in Study of Osteoporotic Fractures Year 16 (Y16) examination (2002-2004) linked with Medicare and/or HMO claims. At Y16 examination, sleep/wake parameters were measured by actigraphy (total sleep time [TST], sleep efficiency [SE], sleep latency [SL], and wake after sleep onset [WASO]) and subjective sleep measures (sleep quality [Pittsburgh Sleep Quality Index] and daytime sleepiness [Epworth Sleepiness Scale]) were assessed by questionnaire. Measures except TST were dichotomized based on clinical thresholds. Incident hospitalizations were determined from claims data.	Nine hundred and seventy-six women (53%) had ≥1 hospitalization in the 3 years after the Year 16 examination. Reduced SE (odds ratio [OR] = 2.39, 95% confidence interval [CI] 1.69-3.39), prolonged SL (OR = 1.41, 95% CI 1.11-1.78), greater WASO (OR = 1.57, 95% CI 1.28-1.93), shorter TST (OR = 1.98, 95% CI 1.42-2.77) and poorer sleep quality (OR = 1.33, 95% CI 1.07-1.65) were each associated with a higher age and site-adjusted odds of hospitalization; associations were attenuated after multivariable adjustment for traditional prognostic factors with the OR for reduced SE (OR = 1.60, 95% CI 1.08-2.38) and shorter TST (OR = 1.63, 95% CI 1.12-2.37) remaining significant. Among women who were hospitalized, greater WASO (rate ratio [RR] = 1.20, 95% CI 1.04-1.37) and poorer sleep quality (RR = 1.18, 95% CI 1.02-1.35) were each associated with a greater age and site-adjusted RR of inpatient days, but associations did not persist after multivariate adjustment.	Older women with sleep disturbances have an increased risk of hospitalization partially attributable to demographics, poorer health status, and comorbidities.	
28329204	The complexity of the brain is yielding to technology. In the area of sleep neurobiology, conventional neuroscience tools such as lesions, cell recordings, c-Fos, and axon-tracing methodologies have been instrumental in identifying the complex and intermingled populations of sleep- and arousal-promoting neurons that orchestrate and generate wakefulness, NREM, and REM sleep. In the last decade, new technologies such as optogenetics, chemogenetics, and the CRISPR-Cas system have begun to transform how biologists understand the finer details associated with sleep-wake regulation. These additions to the neuroscience toolkit are helping to identify how discrete populations of brain cells function to trigger and shape the timing and transition into and out of different sleep-wake states, and how glia partner with neurons to regulate sleep. Here, we detail how some of the newest technologies are being applied to understand the neural circuits underlying sleep and wake.
28329124	Fatigue from sleep loss is a risk to physician and patient safety, but objective data on physician sleep and alertness on different duty hour schedules is scarce. This study objectively quantified differences in sleep duration and alertness between medical interns working extended overnight shifts and residents not or rarely working extended overnight shifts.Sleep-wake activity of 137 interns and 87 PGY-2/3 residents on 2-week Internal Medicine and Oncology rotations was assessed with wrist-actigraphy. Alertness was assessed daily with a brief Psychomotor Vigilance Test (PVT) and the Karolinska Sleepiness Scale.	Interns averaged 6.93 hours (95% confidence interval [CI] 6.84-7.03 hours) sleep per 24 hours across shifts, significantly less than residents not working overnight shifts (7.18 hours, 95% CI 7.06-7.30 hours, p = .007). Interns obtained on average 2.19 hours (95% CI 2.02-2.36 hours) sleep during on-call nights (17.5% obtained no sleep). Alertness was significantly lower on mornings after on-call nights compared to regular shifts (p < .001). Naps between 9 am and 6 pm on the first day post-call were frequent (90.8%) and averaged 2.84 hours (95% CI 2.69-3.00 hours), but interns still slept 1.66 hours less per 24 hours (95% CI 1.56-1.76 hours) compared to regular shift days (p < .001). Sleep inertia significantly affected alertness in the 60 minutes after waking on-call.	Extended overnight shifts increase the likelihood of chronic sleep restriction in interns. Reduced levels of alertness after on-call nights need to be mitigated. A systematic comparison of sleep, alertness, and safety outcomes under current and past duty hour rules is encouraged.	
28329120	Sleep-wake disturbances following traumatic brain injury (TBI) are increasingly recognized as a serious consequence following injury and as a barrier to recovery. Injury-induced sleep-wake disturbances can persist for years, often impairing quality of life. Recently, there has been a nearly exponential increase in the number of primary research articles published on the pathophysiology and mechanisms underlying sleep-wake disturbances after TBI, both in animal models and in humans, including in the pediatric population. In this review, we summarize over 200 articles on the topic, most of which were identified objectively using reproducible online search terms in PubMed. Although these studies differ in terms of methodology and detailed outcomes; overall, recent research describes a common phenotype of excessive daytime sleepiness, nighttime sleep fragmentation, insomnia, and electroencephalography spectral changes after TBI. Given the heterogeneity of the human disease phenotype, rigorous translation of animal models to the human condition is critical to our understanding of the mechanisms and of the temporal course of sleep-wake disturbances after injury. Arguably, this is most effectively accomplished when animal and human studies are performed by the same or collaborating research programs. Given the number of symptoms associated with TBI that are intimately related to, or directly stem from sleep dysfunction, sleep-wake disorders represent an important area in which mechanistic-based therapies may substantially impact recovery after TBI.
28327443	Attention-deficit/hyperactivity disorder (ADHD) is a common condition with comorbid insomnia reported in >70% of children and adults. These patients demonstrate delays in sleep-wake rhythms, nocturnal rise in melatonin, and early morning rise in cortisol. Given that standard psychopharmacologic treatments for ADHD often do not completely control symptoms in participants with circadian rhythm delay, we sought to test whether bright light therapy (BLT) advances circadian rhythms and further reduces ADHD symptoms over standard treatments. In addition to standard of care, participants with ADHD diagnosis underwent 1 week of baseline assessment followed by 2-weeks of 30-min morning 10,000-lux BLT beginning 3 h after mid-sleep time. Participants minimized overhead light after 4 p.m., wore an actigraphy watch, and recorded BLT time on daily sleep logs. Dim Light Melatonin Onset (DLMO) was assessed at baseline and after 2-week treatment. ADHD symptoms were measured by the ADHD-Rating Scales (ADHD-RS). BLT significantly advanced the phase of DLMO by 31 min [mean time (SEM), 20:36 (0:21) advanced to 20:05 (0:20)] and mid-sleep time by 57 min [4:37 (0:22) advanced to 3:40 (0:16); paired t-tests, p = 0.002 and 0.004, respectively). Phase advances (in DLMO or mid-sleep time) were significantly correlated with decreased ADHD-RS total scores (p = 0.027 and 0.044) and Hyperactive-Impulsive sub-scores (p = 0.014 and 0.013, respectively). Actigraphy analysis for a subset of 8 participants with significant DLMO phase advance revealed no significant changes in total sleep time, sleep efficiency, wake after sleep onset, or percent wake during sleep interval. This is the first successful use of BLT for advancing melatonin phase and improving ADHD symptoms in adults. BLT may be a complementary treatment for both delayed sleep timing and ADHD symptoms in adults.
28324298	Alzheimer's disease (AD) is increasing in prevalence and has a significant impact on caregivers and the healthcare system. One of the many physiologic process affected by AD is the circadian system, with disruption reflected in abnormalities of the sleep-wake cycle. This interaction is bidirectional, with circadian and sleep disruption influencing disease progression. Understanding the bidirectional relationship between AD and circadian disruption may allow for earlier recognition of the potential to develop dementia as well as improved targeted approaches for therapy. Therapies including melatonin and bright light therapy may be advantageous in improving sleep and circadian rhythms and preventing the progression of disease. However, unfortunately, these modalities are not curative, and additional research is needed to improve treatment options for these individuals.
28324186	Smartphones are prevalently used among adolescents; however, nighttime exposure to blue-enriched light, through electric devices, is known to induce delays of the circadian rhythm phases and poor morning somatic conditions. We therefore investigated whether evening smartphone use may affect sleep-wake cycle and cardiac autonomic nervous system (ANS) activity after awaking in dormitory students.The participants were high school students, living under dormitory rules regarding the curfew, study, meals, lights-out, and wake-up times. The students were forbidden from the use of both television and personal computer in their private rooms, and only the use of a smartphone was permitted. According to prior assessment of smartphone use, we chose age-, sex-, exercise time-matched long (n = 22, >120 min) and short (n = 14, ≤60 min) groups and compared sleep-wake cycle and physiological parameters, such as cardiac ANS activity, blood pressure, and intra-aural temperature. All measurements were performed during 6:30 to 7:00 a.m. in the dormitories.	Compared with the short group, the long group showed a significantly lower cardiac ANS activity (2727 ± 308 vs. 4455 ± 667 ms2, p = 0.030) with a tendency toward a high heart rate, in addition to later bedtimes during weekdays and more delayed wake-up times over the weekend. Blood pressure and intra-aural temperature did not differ between the groups.	In this population, evening smartphone use may be associated with altered sleep-wake cycle and a diminished cardiac ANS activity after awakening could be affecting daytime activities.	
28323455	To evaluate the performance of a multisensor sleep-tracker (ŌURA ring) against polysomnography (PSG) in measuring sleep and sleep stages.Forty-one healthy adolescents and young adults (13 females; Age: 17.2 ± 2.4 years).	Sleep data were recorded using the ŌURA ring and standard PSG on a single laboratory overnight. Metrics were compared using Bland-Altman plots and epoch-by-epoch (EBE) analysis.	Summary variables for sleep onset latency (SOL), total sleep time (TST), and wake after sleep onset (WASO) were not different between ŌURA ring and PSG. PSG-ŌURA discrepancies for WASO were greater in participants with more PSG-defined WASO (p < .001). Compared with PSG, ŌURA ring underestimated PSG N3 (~20 min) and overestimated PSG REM (~17 min; p < .05). PSG-ŌURA differences for TST and WASO lay within the ≤ 30 min a-priori-set clinically satisfactory ranges for 87.8% and 85.4% of the sample, respectively. From EBE analysis, ŌURA ring had a 96% sensitivity to detect sleep, and agreement of 65%, 51%, and 61%, in detecting "light sleep" (N1), "deep sleep" (N2 + N3), and REM sleep, respectively. Specificity in detecting wake was 48%. Similarly to PSG-N3 (p < .001), "deep sleep" detected with the ŌURA ring was negatively correlated with advancing age (p = .001). ŌURA ring correctly categorized 90.9%, 81.3%, and 92.9% into PSG-defined TST ranges of < 6 hr, 6-7 hr, > 7 hr, respectively.	Multisensor sleep trackers, such as the ŌURA ring have the potential for detecting outcomes beyond binary sleep-wake using sources of information in addition to motion. While these first results could be viewed as promising, future development and validation are needed.	
28322171	The role of dopamine in sleep-wake regulation is considered as a wakefulness-promoting agent. For the clinical treatment of excessive daytime sleepiness, drugs have been commonly used to increase dopamine release. However, sleep disorders or lack of sleep are related to several dopaminerelated disorders. The effects of dopaminergic agents, nevertheless, are mediated by two families of dopamine receptors, D1 and D2-like receptors; the first family increases adenylyl cyclase activity and the second inhibits adenylyl cyclase. For this reason, the dopaminergic agonist effects on sleep-wake cycle are complex. Here, we review the state-of-the-art and discuss the different effects of dopaminergic agonists in sleep-wake states, and propose that these receptors account for the affinity, although not the specificity, of several effects on the sleep-wake cycle.
28322083	Melanin-concentrating hormone (MCH), the neuropeptide produced mainly in the hypothalamus, plays an operative role in regulating food intake and the sleep/wake cycle. Considering that these physiological functions pursue diurnal variations, we checked whether the total hypothalamic MCH level depends on the time of the day. The aggregated MCH peptide content of the whole MCH neuron population was significantly higher at the end of the sleeping period (lights on), than at the end of the active period (lights off). This result, together with earlier observations, indicates that in contrast to the MCH gene expression, the level of MCH peptide is object of circadian variation in the hypothalamus.
28321642	We review recent evidence for circadian rhythm dysregulation in bipolar spectrum disorders (BSDs). We examine evidence for endogenous abnormalities in the biological clock and disruptions in the external entrainment of circadian rhythms in BSDs. We also address whether circadian dysregulation provides vulnerability to onset of BSD and evidence for a new integration of reward and circadian dysregulation in BSD.Relative circadian phase delay (e.g., later melatonin peak, evening chronotype) is associated with BSD, particularly in the depressive phase. More consistent evidence supports irregularity of social rhythms, sleep/wake and activity patterns, and disruptions of social rhythms by life events, as stable trait markers of BSD and potential vulnerabilities for BSD onset. Growing research supports an integrative reward/circadian model. Both endogenous abnormalities in the biological clock pacemaking function and disruptions in the external entrainment of circadian rhythms by physical and social cues are involved in BSDs. Circadian dysregulation may provide vulnerability to BSD onset.	
28318293	Yawning is a multifunctional behavior with a role in social communication. In Old World monkeys, the "tension yawn" is often used as a threat, allowing individuals to completely expose their canines. To explore the role of this phenomenon, we selected 2 closely related species-Japanese macaques (Macaca fuscata) and Tonkean macaques (M. tonkeana)-which differ primarily in terms of their tolerance levels. Japanese macaques are classified as despotic; Tonkean macaques are classified as tolerant. Both species live in multimale-multifemale societies, show a high level of sexual dimorphism, and have comparable yawning repertoires that include displaying a covered teeth yawn and an uncovered gums yawn. We found comparable baseline frequencies of the 2 yawning types and a similar distribution of these behaviors according to sex (males yawned more frequently than females). This morphological homogeneity permitted us to evaluate potential differences in the meaning of yawning as a function of social tension, aggressive contexts, and dominance hierarchy. Divergent social styles determine a functional dichotomy in the use of the covered teeth yawn and the uncovered gums yawn. The covered teeth yawn is not susceptible to social and environmental stimuli and seems to be a form of yawning mostly linked to the physiology of the sleep-wake cycle. However, the uncovered gums yawn is modulated according to different social contexts, and its use could be favored by natural selection, especially in tolerant species, which apparently require more elaborate forms of social communication. (PsycINFO Database Record
28314820	Amyloid precursor protein (App) plays a crucial role in Alzheimer's disease via the production and deposition of toxic β-amyloid peptides. App is heavily expressed in neurons, the focus of the vast majority of studies investigating its function. Meanwhile, almost nothing is known about App's function in glia, where it is also expressed, and can potentially participate in the regulation of neuronal physiology. In this report, we investigated whether Appl, the Drosophila homolog of App, could influence sleep-wake regulation when its function is manipulated in glial cells. Appl inhibition in astrocyte-like and cortex glia resulted in higher sleep amounts and longer sleep bout duration during the night, while overexpression had the opposite effect. These sleep phenotypes were not the result of developmental defects, and were correlated with changes in expression in glutamine synthetase (GS) in astrocyte-like glia and in changes in the gap-junction component innexin2 in cortex glia. Downregulating both GS and innexin2, but not either one individually, resulted in higher sleep amounts, similarly to Appl inhibition. Consistent with these results, the expression of GS and innexin2 are increased following sleep deprivation, indicating that GS and innexin2 genes are dynamically linked to vigilance states. Interestingly, the reduction of GS expression and the sleep phenotype observed upon Appl inhibition could be rescued by increasing the expression of the glutamate transporter dEaat1. In contrast, reducing dEaat1 expression severely disrupted sleep. These results associate glutamate recycling, sleep, and a glial function for the App family proteins.SIGNIFICANCE STATEMENT The amyloid precursor protein (App) has been intensively studied for its implication in Alzheimer's disease (AD). The attributed functions of App are linked to the physiology and cellular biology of neurons where the protein is predominantly expressed. Consequences on glia in AD are generally thought to be secondary effects of the pathology in neurons. Researchers still do not know whether App plays a role in glia in nonpathological conditions. We report here that glial App plays a role in physiology and in the regulation of sleep/wake, which has been shown recently to be involved in AD pathology. These results also associate glutamate recycling and sleep regulation, adding further complexity to the physiological role of App and to its implication in AD.
28314054	Research suggests that sleep disturbance is common in psoriasis. While several sleep investigations have been conducted in psoriasis populations, many have methodological shortcomings, and no study has examined multiple dimensions of sleep-wake functioning. Moreover, research has yet to be performed comprehensively examining the range of physical and psychological factors that may affect sleep in people with psoriasis.To characterize sleep disturbance using validated measures and to identify physical and psychological predictors of sleep quality in people with psoriasis.	An online survey was conducted (186 respondents; mean age 39·2 years) comprising validated measures assessing sleep [Pittsburgh Sleep; Quality Index (PSQI), Berlin Questionnaire, Pre-Sleep Arousal Scale]; chronotype (Morningness-Eveningness Questionnaire); mood (Hospital Anxiety and Depression Scale); itch (5-D Itch Scale); and psoriasis severity (Simplified Psoriasis Index). Group comparisons and regression analyses were used to examine predictors of poor sleep.	The mean PSQI score was 9·2 ± 4·3, with 76·3% scoring above the threshold for poor sleep (≥ 6 on the PSQI) and 32·5% scoring 'positive' for probable obstructive sleep apnoea (OSA). Poor sleep and high likelihood of OSA were associated with more severe psoriasis (P < 0·05; η = 0·07; η2 = 0·005). Cognitive arousal (β = 0·26, P = 0·001), itch (β = 0·26, P < 0·001) and depression (β = 0·24, P = 0·001) were the most robust predictors of poor sleep quality, which, together with somatic arousal (β = 0·17, P = 0·022), accounted for 43% of variance in PSQI scores.	Poor sleep is common in psoriasis and associated with psychological and physical factors. Rates of probable OSA are also high. Given the importance of restorative sleep for health, sleep complaints should receive greater clinical attention in the management of psoriasis.	
28306414	Pham, Luu V., Christopher Meinzen, Rafael S. Arias, Noah G. Schwartz, Adi Rattner, Catherine H. Miele, Philip L. Smith, Hartmut Schneider, J. Jaime Miranda, Robert H. Gilman, Vsevolod Y. Polotsky, William Checkley, and Alan R. Schwartz. Cross-sectional comparison of sleep-disordered breathing in native Peruvian highlanders and lowlanders. High Alt Med Biol. 18:11-19, 2017.Altitude can accentuate sleep disordered breathing (SDB), which has been linked to cardiovascular and metabolic diseases. SDB in highlanders has not been characterized in large controlled studies. The purpose of this study was to compare SDB prevalence and severity in highlanders and lowlanders.	170 age-, body-mass-index- (BMI), and sex-matched pairs (age 58.2 ± 12.4 years, BMI 27.2 ± 3.5 kg/m2, and 86 men and 84 women) of the CRONICAS Cohort Study were recruited at a sea-level (Lima) and a high-altitude (Puno, 3825 m) setting in Peru. Participants underwent simultaneous nocturnal polygraphy and actigraphy to characterize breathing patterns, movement arousals, and sleep/wake state. We compared SDB prevalence, type, and severity between highlanders and lowlanders as measured by apnea-hypopnea index (AHI) and pulse oximetry (SPO2) during sleep.	Sleep apnea prevalence was greater in highlanders than in lowlanders (77% vs. 54%, p < 0.001). Compared with lowlanders, highlanders had twofold elevations in AHI due to increases in central rather than obstructive apneas. In highlanders compared with lowlanders, SPO2 was lower during wakefulness and decreased further during sleep (p < 0.001). Hypoxemia during wakefulness predicted sleep apnea in highlanders, and it appears to mediate the effects of altitude on sleep apnea prevalence. Surprisingly, hypoxemia was also quite prevalent in lowlanders, and it was also associated with increased odds of sleep apnea.	High altitude and hypoxemia at both high and low altitude were associated with increased SDB prevalence and severity. Our findings suggest that a large proportion of highlanders remain at risk for SDB sequelae.	
28303945	Human sleep-wake cycles are entrained by both natural and artificial light-dark cycles. However, little is known regarding when and how the photoperiod changes entrain the biological clock after conception. To investigate the dependence of sleep patterns in young infants on the natural and artificial light-dark cycles, 1,302 pairs of one-month-old infants and their mothers were asked to answer a questionnaire. Birth in spring, longer daytime sleep duration, early/regular light-off times, and longer maternal nighttime sleep duration were identified as independent variables for longer infant nighttime sleep duration in both univariate and multivariate analyses. Longer maternal nighttime sleep duration was dependent on shorter naps and early/regular bed times but not on the season. We found that nighttime sleep duration depended on both natural and artificial diurnal photoperiod changes in one-month-old infants. Although sleep patterns of infants mimicked those of their mothers, nighttime sleep duration depended on the season, and was positively associated with daytime sleep duration, only in the infants. These specific variables, which render sleep patterns of the infants different from those of their mothers, might be a clue to reveal the covert acquisition process of mature circadian rhythms after birth.
28302453	This perspective binds emerging evidence on the bidirectional relationship between Alzheimer's disease (AD) and sleep disorders through a model of brain rhythm attractor breakdown. This approach explains behavioral-cognitive changes in AD across the sleep-wake cycle and supports a causal association between early brainstem tau pathology and subsequent cortical amyloid-β accumulation. Specifically, early tau dysregulation within brainstem-hypothalamic nuclei leads to breakdown of sleep-wake attractor networks, with patients displaying an attenuated range of behavioral and electrophysiological activity patterns, a "twilight zone" of constant activity between deep rest and full alertness. This constant cortical activity promotes activity-dependent amyloid-β accumulation in brain areas that modulate their activity across sleep-wake states, especially the medial prefrontal cortex. In addition, the accompanying breakdown of hippocampal-medial prefrontal cortex interplay across sleep stages could explain deficient memory consolidation through dysregulation of synaptic plasticity. Clinical implications include the potential therapeutic benefit of attractor consolidation (e.g., slow-wave sleep enhancers) in delaying AD progression.
28299422	Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABAA and GABAB receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking. By immunofluorescence, we assessed that the proportion of Mo5 neurons positively stained for GABAARs was significantly higher after sleep deprivation (SD, ~65%) than sleep control (SC, ~32%) and that the luminance of the GABAAR fluorescence was significantly higher after SD than SC and sleep recovery (SR). Although, all Mo5 neurons were positively stained for GABABRs and AChM2Rs (100%) in all groups, the luminance of these receptors was significantly higher following SD as compared to SC and SR. We conclude that the density of GABAA, GABAB and AChM2 receptors increases on Mo5 neurons during SD. The increase in these receptors would be associated with increased inhibition in the presence of GABA and ACh and thus a homeostatic down-scaling in the excitability of the Mo5 neurons after prolonged waking and resulting increased susceptibility to muscle hypotonia or atonia along with sleep.
28294708	The authors examined 28 dementia inpatients receiving treatment as usual. Beginning-to-end differences in neuropsychiatric symptoms and actigraphic sleep patterns were measured. Using a mixed-model, the authors regressed neuropsychiatric symptoms on average sleep minutes (between-subjects effect) and each night's deviation from average (within-subject effect). Sleep did not significantly differ from beginning to end of participation, whereas neuropsychiatric symptoms did. Average sleep minutes predicted average neuropsychiatric symptoms (p=0.002), but each night's deviation from the average did not predict next day's symptoms (p=0.90). These findings raise questions about the immediate benefits of treating sleep-wake disturbances on neuropsychiatric symptoms in hospitalized inpatients with dementias.
28294380	Obstructive sleep apnoea syndrome (OSAS) is associated with several sleep disorders and sleep-related problems. Therefore, the aim of this study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. In this randomised placebo-controlled trial, sixty-four OSAS patients (52·0 ± 9·6 years) were randomly assigned to an MAD, nCPAP or an intra-oral placebo appliance in a parallel design. All participants filled out the validated Dutch Sleep Disorders Questionnaire (SDQ) twice: one before treatment and one after six months of treatment. With 88 questions, thirteen scales were constructed, representing common sleep disorders and sleep-related problems. Linear mixed model analyses were performed to study differences between the groups for the different SDQ scales over time. The MAD group showed significant improvements over time in symptoms corresponding with 'insomnia', 'excessive daytime sleepiness', 'psychiatric sleep disorder', 'periodic limb movements', 'sleep apnoea', 'sleep paralysis', 'daytime dysfunction', 'hypnagogic hallucinations/dreaming', 'restless sleep', 'negative conditioning' and 'automatic behaviour' (range of P values: 0·000-0·014). These improvements in symptoms were, however, not significantly different from the improvements in symptoms observed in the nCPAP and placebo groups (range of P values: 0·090-0·897). It can be concluded that there is no significant difference between MAD and nCPAP in their positive effects on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. These beneficial effects may be a result of placebo effects.
28286917	We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.
28283102	The majority of individuals with multiple sclerosis (MS) suffer from sleep disorders. In this study, we investigated the relationship between physical activity and sleep characteristics in MS patients.Sixty MS patients were recruited in the study. Sleep characteristics were assessed using the Actisleep device while physical activity levels were assessed using mobility accelerometer.	The results showed that means (±SD) of sleep latency (SL) and sleep efficiency (ES) for MS patients were 23.89±13.23min and 87.52±76.89% respectively. The participants' total time in sleep (TST) and wake after sleep onset (WASO) were 353.25±63.98min and 83.84±42.23min respectively. With respect to physical activity levels, means (±SD) of light (LA), moderate (MA), vigorous (VA) activities and moderate to vigorous physical activity (MVPA) were 11,660.15±18,145, 212.04±148.67, 9.70±9.26 and 222.88±154.60 counts per minute, respectively. Pearson's correlation analysis showed that WASO correlated significantly with LA, MA and MVPA (P<0.05). These correlations remained significant even after accounting for age, body weight and disease severity (P<0.05).	The results show a positive relationship of physical activity with sleep parameters in individuals with MS.	
28282238	Studies on the diurnal sleep-wake rhythm of patients with lung cancer have mostly examined patients cross-sectionally, whereas the effects of lung cancer treatment over time have rarely been considered. Through long-term longitudinal tracking of patients with lung cancer, this study examined changes in their sleep-wake rhythm, sleep quality, anxiety, depressive symptoms, fatigue and quality of life (QoL) at various treatment stages. In addition, factors affecting their QoL were explored. Hierarchical linear modeling was adopted to analyze a convenience sample of 82 patients with lung cancer. The changes in their sleep-wake rhythm, sleep, mood (anxiety, depressive symptoms and fatigue) and QoL were observed at five time points: prior to treatment and at weeks 6, 12, 24 and 48 after the start of the treatment. The effects of sex, age, cancer stage, treatment type, comorbidities and time were controlled to determine the predictors of patients' QoL. The results showed that patients' sleep-wake rhythms were poor before treatments. Compared with baseline, the sleep-wake rhythms of the patients significantly improved at week 48, and anxiety significantly improved at weeks 6, 12, 24 and 48. By contrast, their fatigue became exacerbated at weeks 8 and 48. Moreover, QoL improved significantly from week 6 until the end of the treatment period. QoL was negatively affected by poor sleep quality (β = -0.69, p = 0.00) and depressive symptoms (β = -2.59, p < 0.001) and positively affected by regular sleep-wake rhythms (β = 0.23, p = 0.001). Therefore, clinical health-care professionals should focus more attention to the fatigue levels of patients with lung cancer before, during and after treatment. Health-care professionals may also need to provide such patients with health education regarding sleep hygiene and with emotional support to assist them in maintaining regular sleep-wake rhythms in order to improve their QoL.
28279596	We aimed to investigate the prevalence and severity of nonmotor symptoms (NMSs) and to identify factors affecting NMSs and the health-related quality of life of Japanese patients with Parkinson's disease (PD).A total of 1021 patients with PD who had one or more NMS and showed wearing-off under anti-parkinsonian treatment were enrolled from 35 medical centers in Japan for this observational study. The primary measurements were the Movement Disorder Society unified Parkinson's disease rating scale (MDS-UPDRS) part I and the Parkinson's Disease Questionnaire (PDQ-8). The relationships of MDS-UPDRS and PDQ-8 with the patient's clinical background and undertaken medical interventions were determined. Here, we report baseline data of our 52-week ongoing study.	The mean MDS-UPDRS part I and PDQ-8 scores were 10.9 and 7.3, respectively. The most common NMSs were constipation problems (85.4%), sleep problems (73.7%), pain and other sensations (72.7%) and daytime sleepiness (72.0%). Fatigue was an NMS that affected 79.6% of females but only 72.6% of males, whereas features of dopamine dysregulation syndrome affected only 5.6% of females and 10.8% of males. Positive correlations were found between the MDS-UPDRS part I and the PDQ-8 (p < 0.0001, r = 0.56) and between the number of NMSs and the PDQ-8 score (p < 0.0001, r = 0.47).	This study revealed distinctive patterns of NMSs in Japanese patients with PD and suggested that the prevalence and severity of NMSs vary between sexes, and that the NMSs are important factors affecting the long-term quality of life of PD patients.	
28278488	Sleep/wake-up scheduling is one of the fundamental problems in wireless sensor networks, since the energy of sensor nodes is limited and they are usually unrechargeable. The purpose of sleep/wake-up scheduling is to save the energy of each node by keeping nodes in sleep mode as long as possible (without sacrificing packet delivery efficiency) and thereby maximizing their lifetime. In this paper, a self-adaptive sleep/wake-up scheduling approach is proposed. Unlike most existing studies that use the duty cycling technique, which incurs a tradeoff between packet delivery delay and energy saving, the proposed approach, which does not us duty cycling, avoids such a tradeoff. The proposed approach, based on the reinforcement learning technique, enables each node to autonomously decide its own operation mode (sleep, listen, or transmission) in each time slot in a decentralized manner. Simulation results demonstrate the good performance of the proposed approach in various circumstances.
28276850	A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants < 0.5). In order to comprehensively evaluate variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected for multiple comparisons). In conclusion, alleles of the VNTR are expressed at the transcript level and may have a functional effect in cells expressing the PER3 gene. PER3 polymorphisms had a modest impact on selected sleep/circadian variables in our sample, suggesting that PER3 is associated with sleep and circadian function beyond VNTR polymorphisms. Further replicate analyses in larger, independent samples are recommended.
28275716	Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents.
28275701	Sleep disturbances in elderly medical inpatients are common, but their relationship to delirium and dementia has not been studied.Sleep and delirium status were assessed daily for a week in 145 consecutive newly admitted elderly acute general hospital patients using the Delirium Rating Scale-Revised-98 (DRS-R98), Diagnostic and Statistical Manual 5, and Richards-Campbell Sleep Quality Scale measures. The longitudinal relationship between DRS-R98 and Richards-Campbell Sleep Quality Scale sleep scores and delirium, also with dementia as a covariate, was evaluated using generalized estimating equation logistic regression.	The cohort was divided into delirium only, dementia only, comorbid delirium-dementia, and no-delirium/no-dementia subgroups. Mean age of total group was 80 ± 6.3, 48% were female, and 31 (21%) had dementia, 29 had delirium at admission (20%), and 27 (18.5%) experienced incident delirium. Mild sleep disturbance (DRS-R98 sleep item score ≥1) occurred for at least 1 day in all groups, whereas moderate sleep disturbance (score ≥2) occurred in significantly more of the prevalent delirium-only (81%; n = 17) cases than incident delirium-only (46%; n = 13) cases (P < .001). There were more cases with DRS-R98 sleep item scores ≥2 (P < .001) in the delirium-only group compared with the other subgroups. Severity of sleep-wake cycle disturbance over time was significantly associated with Diagnostic and Statistical Manual 5 delirium status but not with age, sex, or dementia (P < .001).	Observer-rated more severe sleep-wake cycle disturbances are highly associated with delirium irrespective of dementia status, consistent with being a core feature of delirium. Monitoring for altered sleep-wake cycle patterns may be a simple way to improve delirium detection.	
28275652	Sleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction by analyzing sleep and tau pathology throughout tauopathy disease progression in P301S human tau transgenic mice.P301S and wild-type mice were analyzed by electroencephalography (EEG)/electromyography at 3, 6, 9, and 11 months of age for sleep/wake time, EEG power, and homeostatic response. Cortical volume and tau pathology was also assessed by anti-phospho-tau AT8 staining.	P301S tau mice had significantly decreased rapid eye movement (REM) sleep at 9 months of age and decreased REM and non-REM (NREM) sleep as well as increased wakefulness at 11 months. Sleep loss was characterized by fewer wake, REM, and NREM bouts, increased wake bout duration, and decreased sleep bout duration. Decreased REM and NREM sleep was associated with increased brainstem tau pathology in the sublaterodorsal area and parafacial zone, respectively. P301S mice also showed increased EEG power at 6 and 9 months of age and decreased power at 11 months. Decreased EEG power was associated with decreased cortical volume. Despite sleep disturbances, P301S mice maintained homeostatic response to sleep deprivation.	Our results indicate that tau pathology is associated with sleep disturbances that worsen with age and these changes may be related to tau pathology in brainstem sleep regulating regions as well as neurodegeneration. Tau-induced sleep changes could affect disease progression and be a marker for therapeutic efficacy in this and other tauopathy models.	
28271579	Sleep is essential for recovery and performance in elite athletes. While actigraphy-based studies revealed suboptimal sleep in athletes, information on their subjective experience of sleep is scarce. Relatively unexplored is also the extent to which athletes' sleep is adversely affected by environmental conditions and daytime behaviours, that is sleep hygiene. This study aimed to provide insight in sleep quantity, quality and its putative association with sleep hygiene. Participants were 98 elite (youth) athletes competing at the highest (inter-)national level. Sleep quantity, quality and sleep hygiene were assessed once covering a 1-month period by using established (sub)clinical questionnaires, and repeatedly during 7 consecutive days. Sleep quality was generally healthy, although 41% of all athletes could be classified as 'poor sleeper', and 12% were identified as having a sleep disorder. Daily self-monitoring revealed sleep durations of 8:11 ± 0:45 h, but elevated wake after sleep onset of 13 ± 19 min. Sleep quality, feeling refreshed, and morning vigor were moderate at best. Regarding sleep hygiene, general measures revealed irregular sleep-wake patterns, psychological strain and activating pre-sleep behaviours. At the daily level, blue-light exposure and late-evening consumption of heavy meals were frequently reported. General sleep hygiene revealed significant associations with sleep quality (0.45 < r > 0.50; P < 0.001). Results indicate that there is ample room for optimization, specifically in onset latency and in wake after sleep onset. Subtle improvements in sleep seem possible, and optimizing sleep hygiene, such as regular sleep-wake patterns and reducing psychological strain, may facilitate this sleep upgrading process.
28270635	Sleep-wake cycle is controlled by the interplay between circadian rhythm and sleep homeostasis. Genetic studies, through the discovery of mutants with altered sleep-wake behaviors, have explored the molecular components that regulate our daily rhythms. In mammalian circadian clocks, negative-feedback loops composed of a set of transcription activators and inhibitors generate a cell-autonomous oscillation of transcriptional activity. Recent studies further discovered that such transcriptional feedback is controlled through post-translational modifications for the fine-tuning of the oscillation period. Compared to circadian clocks, the canonical molecular model for sleep homeostasis is not established yet. However, recent advances in mammalian forward and reverse genetic studies discovered several genes that regulate sleep duration. Interestingly, these genes include ion channels and kinases, which potentially modify these channels. A part of sleep-related ion channels is involved in Ca<sup>2+</sup>-dependent hyperpolarization of the neuronal membrane potential. Computational models suggest that the hyperpolarization pathway underlies the firing patterns observed in the cortical pyramidal neurons during sleep. Thus, ion channels controlling the membrane potential of the cortical neurons may be involved in sleep homeostasis.
28270491	To determine the difference in relative intraocular pressure (IOP) measured by the SENSIMED Triggerfish (TF) contact lens in flat compared with 30° head-up sleeping positions in patients with progressive primary open-angle glaucoma or normotensive glaucoma, based on recent or recurrent disc haemorrhage.Prospective, randomised, cross-over, open-label comparative study.	IOP was monitored for 24 hours using TF on two separate sessions. Patients were randomly assigned to sleep flat one night and 30° head-up the other. Outputs in arbitrary units were obtained. Sleep and wake periods were defined as 22:00-6:00 and 8:00-22:00, respectively. Mean TF values during sleep and wake periods and wake-sleep and sleep-wake slopes were calculated for each session. TF output signals were compared between positions.	Twelve subjects completed the study. Significant mean positive slopes were noted during the sleep period for both positions (p<0.01). No significant differences in the TF mean values were observed between positions (p=0.51). Six (54%) subjects had mean TF values significantly higher during the flat supine session, while four (36%) subjects had higher values during the head-up session. A significant increase in Goldmann IOP (p=0.001) and TF (p=0.02) measurements were observed after 24 hours of TF wear ('drift phenomenon').	Sleep position affects IOP as measured by TF in some patients with progressive glaucoma. The upward drift in TF output detected in >50% of the subjects requires further investigation to establish whether the increased output values over time are an artefact induced by the TF or a real change in IOP.	
28268648	Rodent models are widely used for the experimental analysis of sleep. While this is motivated by similarities in brain circuitry and electrophysiological rhythms, unlike the circadian sleep-wake cycle in humans, rodent sleep is polyphasic, containing multiple bouts of sleep and wake minutes to hours in duration over the course of a day. Each sleep bout is punctuated by several brief arousals several seconds to minutes long. Physiologically motivated mathematical models replicate the shorter timescale of arousal within sleep, but not the longer one representing prolonged wakefulness. Here, we adapt a previously published "flip-flop" model of human sleep to capture the ultradian alternation of sleep and wakefulness in mice on the longer timescale. The resulting model reproduces both the mean durations of alternating sleep and wake bouts as well as the circadian trends in their bout durations documented in our experiments on mice.
28262397	To explore the effect of depression on the sleep quality, and the circadian rhythm of ambulatory blood pressure in patients with essential hypertension.A total of 73 older patients with hypertension were screened for depression and divided into two groups. The Pittsburgh Sleep Quality Index (PSQI) and the circadian rhythm of ambulatory blood pressure were compared between the non-depressed (control) and depressed (case) group.	In the case group, 24h ambulatory SBP and DBP, and nocturnal SBP and DBP were higher than in the control group, and the circadian rhythm of non-dipper was higher (67.22% vs 40.13%，P<0.01). There was a positive correlation between PSQI and depression (r=0.432, P<0.01).	There was a significant correlation between sleep quality and depression in older patients with hypertension. Depression increases the circadian rhythm of non-dipper in older patients with hypertension.	
28262089	Similar to delirium, its subsyndromal form has been recognized as the cause of diverse adverse outcomes. Nonetheless, the nature of this subsyndromal delirium remains vastly understudied. Therefore, in the following, we evaluate the phenomenological characteristics of this syndrome versus no and full-syndromal delirium.In this prospective cohort study, we evaluated the Delirium Rating Scale-Revised, 1998 (DRS-R-98) versus the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnostic criteria and examined the diagnosis of delirium with respect to phenomenological distinctions in the intensive care setting.	Out of 289 patients, 36 with subsyndromal delirium versus 86 with full-syndromal and 167 without delirium were identified. Agreement with respect to the DSM-IV-TR diagnosis of delirium was perfect. The most common subtype in those with subsyndromal delirium was hypoactive, in contrast to mixed subtype in those with full-syndromal delirium versus no motor alterations in those without delirium. By presence and severity of delirium symptoms, subsyndromal delirium was intermediate. The ability of the DRS-R-98 items to discriminate between either form of delirium was substantial. Between subsyndromal and no delirium, the cognitive domain and sleep-wake cycle were more impaired and allowed a distinction with no delirium. Further, between full- and subsyndromal delirium, the prevalence and severity of individual DRS-R-98 items were greater. Although the differences between these two forms of delirium was substantial, the items were not very specific, indicating that the phenomenology of subsyndromal delirium is closer to full-syndromal delirium.	Phenomenologically, subsyndromal delirium was found to be distinct from and intermediate between no delirium and full-syndromal delirium. Moreover, the greater proximity to full-syndromal delirium indicated that subsyndromal delirium represents an identifiable subform of full-syndromal delirium.	
28261151	Sleep disorders (SDs) are one of the most frequent non-motor symptoms of Parkinson's disease (PD), usually increasing in frequency over the course of the disease and disability progression. SDs include nocturnal and diurnal manifestations such as insomnia, REM sleep behavior disorder, and excessive daytime sleepiness. The causes of SDs in PD are numerous, including the neurodegeneration process itself, which can disrupt the networks regulating the sleep-wake cycle and deplete a large number of cerebral amines possibly playing a role in the initiation and maintenance of sleep. Despite the significant prevalence of SDs in PD patients, few clinical trials on SDs treatment have been conducted. Our aim is to critically review the principal therapeutic options for the most common SDs in PD. The appropriate diagnosis and treatment of SDs in PD can lead to the consolidation of nocturnal sleep, the enhancement of daytime alertness, and the amelioration of the quality of life of the patients.
28255956	It is well recognized that sleep is severely disturbed in patients in intensive care units (ICU) and that this can compromise their rehabilitation potential. However, it is still difficult to objectively assess sleep quantity and quality and the determinants of sleep disturbance remain unclear. The aim of this study was therefore to evaluate carefully the impact of ICU sound intensity levels and their sources on ICU patients' sleep over a 24-h period.Sleep and sound levels were recorded in 11 ICU intubated patients who met the criteria. Sleep was recorded using a miniaturized multi-channel ambulatory recording device. Sound intensity levels and their sources were recorded with the Nox-T3 monitor. A 30-s epoch-by-epoch analysis of sleep stages and sound data was carried out. Multinomial and binomial logistic regressions were used to associate sleep stages, wakefulness and sleep-wake transitions with sound levels and their sources.	The subjects slept a median of 502.2 [283.2-718.9] min per 24 h; 356.9 [188.6-590.9] min at night (22.00-08.00) and 168.5 [142.5-243.3] during daytime (8 am-10 pm). Median sound intensity level reached 70.2 [65.1-80.3] dBC at night. Sound thresholds leading to disturbed sleep were 63 dBC during the day and 59 dBC during the night. With levels above 77 dBC, the incidence of arousals (OR 3.9, 95% CI 3.0-5.0) and sleep-to-wake transitions (OR 7.6, 95% CI 4.1-14) increased. The most disturbing noises sources were monitor alarms (OR 4.5, 95% CI 3.5-5.6) and ventilator alarms (OR 4.2, 95% CI 2.9-6.1).	We have shown, in a small group of 11 non-severe ICU patients, that sound level intensity, a major disturbance factor of sleep continuity, should be strictly controlled on a 24-h profile.	
28254633	Eveningness, a preference for later sleep-wake timing, is linked to altered reward function, which may explain a consistent association with substance abuse. Notably, the extant literature rests largely on cross-sectional data, yet both eveningness and reward function show developmental changes. We examined whether circadian preference during late adolescence predicted the neural response to reward 2 years later. A sample of 93 males reported circadian preference and completed a monetary reward fMRI paradigm at ages 20 and 22. Primary analyses examined longitudinal paths from circadian preference to medial prefrontal cortex (mPFC) and ventral striatal (VS) reward responses. We also explored whether reward responses mediated longitudinal associations between circadian preference and alcohol dependence, frequency of alcohol use, and/or frequency of cannabis use. Age 20 eveningness was positively associated with age 22 mPFC and VS responses to win, but not associated with age 22 reactivity to reward anticipation. Age 20 eveningness was indirectly related to age 22 alcohol dependence via age 22 mPFC response to win. Our findings provide novel evidence that altered reward-related brain function could underlie associations between eveningness and alcohol use problems. Eveningness may be an under-recognized but modifiable risk factor for reward-related problems such as mood and substance use disorders.
28254099	There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn-Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann-Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease.
28251921	Since the discovery of the non-image-forming visual system, tremendous research efforts have been dedicated to understanding its mechanisms and functional roles. Original functions associated with the melanopsin system include the photoentrainment of circadian sleep-wake cycles and the pupillary light reflex. Recent findings, however, suggest a much broader involvement of this system in an array of physiologic responses to light. This newfound insight into the underlying function of the non-image-forming system has revealed the many connections to human pathology and attendant disease states, including seasonal affective disorder, migraine, glaucoma, inherited mitochondrial optic neuropathy, and sleep dysregulation of aging. In this review, the authors discuss in detail the clinical implications of the melanopsin system.
28251715	Sleep-or sleep-like states-have been reported in adult and larval zebrafish using behavioural criteria. These reversible quiescent periods, displaying circadian rhythmicity, have been used in pharmacological, genetic and neuroanatomical studies of sleep-wake regulation. However, one of the important criteria for sleep, namely sleep homeostasis, has not been demonstrated unequivocally. To study rest homeostasis in zebrafish larvae, we rest-deprived 1-week-old larvae with a novel, ecologically relevant method: flow of water. Stereotyped startle responses to sensory stimuli were recorded after the rest deprivation to study arousal threshold using a high-speed camera, providing an appropriate time resolution to detect species-specific behavioural responses occurring in a millisecond time-scale. Rest-deprived larvae exhibited fewer startle responses than control larvae during the remaining dark phase and the beginning of the light phase, which can be interpreted as a sign of rest homeostasis-often used as equivalent of sleep homeostasis. To address sleep homeostasis further, we probed the adenosinergic system, which in mammals regulates sleep homeostasis. The adenosine A1 receptor agonist, cyclohexyladenosine, administered during the light period, decreased startle responses and increased immobility bouts, while the adenosine antagonist, caffeine, administered during the dark period, decreased immobility bouts. These results suggest that the regulation of sleep homeostasis in zebrafish larvae consists of the same elements as that of other species.
28251587	The thalamus plays an important role in different brain functions including memory, emotions, sleep-wake cycle, executive functions, mediating general cortical alerting responses, processing of sensory (including taste, somatosensory, visual, and auditory) information and relaying it to the cortex, and sensorimotor control. Thalamic stroke, both in isolation and in combination with infarcts involving other structures, are not rare. The functional complexity of the thalami nuclei and the not uncommon normal variations of arteries supply the thalamus induce wide variations in presentation of thalami infarcts. In patients with an unusual collection of deficits difficult to explain by a single lesion, in particular where there is impaired vigilance, thalamic disease should be considered which may mimic several different neurological conditions. By researching the literature, we found that the characteristic stroke syndrome of paramedian thalamic infarction is probably underdiagnosed. In addition to thalamic infarct, thalamic lesions can be caused by deep cerebral venous thrombosis with neuropsychological and radiological features that should be considered in the differential diagnosis of intracranial artery occlusion or bleeding, especially in young patients.
28250327	 Sleepiness is known as one of the side effects of antihistamines, and impaired performance caused by these drugs has become problematic. Among the 13 second-generation antihistamines causing sleepiness to some extent, the package inserts of 8 drugs prohibit driving, 3 stress driving with care, and 2 give no driving-related warning. It was confirmed that the description did not necessarily reflect the results of the standard deviation of lateral position measurement study, which is considered the most effective study for evaluating the effects of drugs on automobile driving. Do these descriptions reflect actual patients' sleepiness? According to a questionnaire survey involving 2000 individuals taking second-generation antihistamines, 7.3% of respondents answered that they had always become sleepy after taking antihistamines (3.1-12.5% according to the type of antihistamine), 32.8% (27.8-45.8%) had become sleepy sometimes, 9.1% (3.1-15.8%) had previously become sleepy but not anymore, and 40.9% (27.1-49.1%) had never become sleepy. In addition, 10.3% (2.4-21.1%) reported intolerable sleepiness. Patients who had experience of receiving pharmaceutical education from pharmacists numbered 1296 (64.8%), and 80.2% of them had also received driving-related explanations, which included the prohibition of driving (32.8%), stressing the need to drive with care (54.7%), and the prohibition of medication before driving (12.0%). Concerning these explanations, the proportion who paid attention on a daily basis, paid slight attention, and paid no attention was 36.7, 31.2, and 32.1%, respectively. To provide effective and safe pharmacotherapy for the increasing number of patients taking antihistamines, pharmacists should ideally improve pharmaceutical education.
28250173	The Darwinian fitness of mammals living in a rhythmic environment depends on endogenous daily (circadian) rhythms in behavior and physiology. Here, we discuss the mechanisms underlying the circadian regulation of physiology and behavior in mammals. We also review recent efforts to understand circadian flexibility, such as how the phase of activity and rest is altered depending on the encountered environment. We explain why shifting activity to the day is an adaptive strategy to cope with energetic challenges and show how this can reduce thermoregulatory costs. A framework is provided to make predictions about the optimal timing of activity and rest of non-model species for a wide range of habitats. This Review illustrates how the timing of daily rhythms is reciprocally linked to energy homeostasis, and it highlights the importance of this link in understanding daily rhythms in physiology and behavior.
28250055	Early in 1998, we (de Lecea et al., 1998) and others (Sakurai et al., 1998) described the same hypothalamic neuropeptides, respectively called the hypocretins or orexins, which were discovered using two different approaches. In December of that year, we published the subject of this commentary in the Journal of Neuroscience: a highly detailed anatomical description of the extensive axonal projections of the hypocretin/orexin neurons. Although the function of this system was unknown at the time, a large body of literature today attests that the hypocretin/orexin neuropeptides play important roles in multiple physiological functions, particularly in sleep/wake regulation. Neuroanatomical studies are rarely frontline news, but the citation rate of this paper underscores the critical nature of such basic research. Based in part on this detailed description, the hypocretin/orexin neuropeptides have since been studied in many different areas of neuroscience research, including sleep/wake regulation, feeding, addiction, reward and motivation, anxiety and depression, cardiovascular regulation, pain, migraine, and neuroendocrine regulation, including reproduction. Thus, this paper has had a surprisingly broad impact on neuroscience research, particularly since it was originally rejected by the Journal!
28243864	Relationships between symptoms of hypersomnolence, psychiatric disorders, and hypersomnia disorders (i.e., narcolepsy and idiopathic hypersomnia) are complex and multidirectional. Hypersomnolence is a common complaint across mood disorders; however, patients suffering from mood disorders and hypersomnolence rarely have objective daytime sleepiness, as assessed by the current gold standard test, the Multiple Sleep Latency Test. An iatrogenic origin of symptoms of hypersomnolence, and sleep apnea syndrome must be considered in a population of psychiatric patients, often overweight and treated with sedative drugs. On the other hand, psychiatric comorbidities, especially depression symptoms, are often reported in patients with hypersomnia disorders, and an endogenous origin cannot be ruled out. A great challenge for sleep specialists and psychiatrists is to differentiate psychiatric hypersomnolence and a central hypersomnia disorder with comorbid psychiatric symptoms. The current diagnostic tools seem to be limited in that condition, and further research in that field is warranted.
28243212	The dopamine ontogeny hypothesis for schizophrenia proposes that transient dysregulation of the dopaminergic system during brain development increases the likelihood of this disorder in adulthood. To test this hypothesis in a high-throughput animal model, we have transiently manipulated dopamine signaling in the developing fruit fly Drosophila melanogaster and examined behavioral responsiveness in adult flies. We found that either a transient increase of dopamine neuron activity or a transient decrease of dopamine receptor expression during fly brain development permanently impairs behavioral responsiveness in adults. A screen for impaired responsiveness revealed sleep-promoting neurons in the central brain as likely postsynaptic dopamine targets modulating these behavioral effects. Transient dopamine receptor knockdown during development in a restricted set of ~20 sleep-promoting neurons recapitulated the dopamine ontogeny phenotype, by permanently reducing responsiveness in adult animals. This suggests that disorders involving impaired behavioral responsiveness might result from defective ontogeny of sleep/wake circuits.
28241858	The circadian clock and the daily rhythms it produces are crucial for human health, but are often disrupted by the modern environment. At the same time, circadian rhythms may influence the efficacy and toxicity of therapeutics and the metabolic response to food intake. Developing treatments for circadian dysfunction, as well as optimizing the daily timing of treatments for other health conditions, will require a simple and accurate method to monitor the molecular state of the circadian clock.Here we used a recently developed method called ZeitZeiger to predict circadian time (CT, time of day according to the circadian clock) from genome-wide gene expression in human blood.	In cross-validation on 498 samples from 60 individuals across three publicly available datasets, ZeitZeiger predicted CT in single samples with a median absolute error of 2.1 h. The predictor trained on all 498 samples used 15 genes, only two of which are part of the core circadian clock. By then applying ZeitZeiger to 475 additional samples from the same three datasets, we quantified how the circadian clock in the blood was affected by various perturbations to the sleep-wake and light-dark cycles. Finally, we extended ZeitZeiger (1) to handle intra-individual variation by making predictions based on multiple samples taken a known time apart, and (2) to handle inter-individual variation by personalizing predictions based on samples from the respective individual. Each of these strategies improved prediction of CT by ~20%.	Our results are an important step towards precision circadian medicine. In addition, our generalizable extensions to ZeitZeiger may be applicable to the growing number of biological datasets that contain multiple observations per individual.	
28241802	Up to 33% of the general population over 50 years of age are affected by nocturnal leg cramps. Currently there are no generally accepted clinical characteristics, which identify nocturnal leg cramps. This study aims to identify these clinical characteristics and to differentiate between them and the characteristics of restless leg syndrome and periodic limb disorder.A systematic literature study was executed from December 2015 to May 2016. This study comprised of a systematic literature review of randomized clinical trials, observational studies on nocturnal and rest cramps of legs and other muscles, and other systematic and narrative reviews. Two researchers independently extracted literature data and analyzed this using a standardized reviewing protocol. Modified versions of the Cochrane Collaboration tools assessed the risk of bias. A Delphi study was conducted to assess agreement on the characteristics of nocturnal leg cramps.	After systematic and manual searches, eight randomized trials and ten observational studies were included. On the basis of these we identified seven diagnostic characteristics of nocturnal leg cramps: intense pain, period of duration from seconds to maximum 10 minutes, location in calf or foot, location seldom in thigh or hamstrings, persistent subsequent pain, sleep disruption and distress.	The seven above characteristics will enhance recognition of the condition, and help clinicians make a clear distinction between NLC and other sleep-related musculoskeletal disorder among older adults.	
28241468	Neuroimaging studies have produced seemingly contradictory findings in regards to the pathophysiology of insomnia. Although most study results are interpreted from the perspective of a "hyperarousal" model, the aggregate findings from neuroimaging studies suggest a more complex model is needed. We provide a review of the major findings from neuroimaging studies, then discuss them in relation to a heuristic model of sleep-wake states that involves three major factors: wake drive, sleep drive, and level of conscious awareness. We propose that insomnia involves dysregulation in these factors, resulting in subtle dysregulation of sleep-wake states throughout the 24 h light/dark cycle.
28241159	Impaired sleep and alertness are some of the most common nonmotor manifestations of Parkinson disease (PD) and currently have only limited treatment options. Light therapy (LT), a widely available treatment modality in sleep medicine, has not been systematically studied in the PD population.To determine the safety and efficacy of LT on excessive daytime sleepiness (EDS) associated with PD.	This randomized, placebo-controlled, clinical intervention study was set in PD centers at Northwestern University and Rush University. Participants were 31 patients with PD receiving stable dopaminergic therapy with coexistent EDS, as assessed by an Epworth Sleepiness Scale score of 12 or greater, and without cognitive impairment or primary sleep disorder. Participants were randomized 1:1 to receive bright LT or dim-red LT (controlled condition) twice daily in 1-hour intervals for 14 days. This trial was conducted between March 1, 2007, and October 31, 2012. Data analysis of the intention-to-treat population was conducted from November 1, 2012, through April 30, 2016.	The primary outcome measure was the change in the Epworth Sleepiness Scale score comparing the bright LT with the dim-red LT. Secondary outcome measures included the Pittsburgh Sleep Quality Index score, the Parkinson's Disease Sleep Scale score, the visual analog scale score for daytime sleepiness, and sleep log-derived and actigraphy-derived metrics.	Among the 31 patients (13 males and 18 females; mean [SD] disease duration, 5.9 [3.6] years), bright LT resulted in significant improvements in EDS, as assessed by the Epworth Sleepiness Scale score (mean [SD], 15.81 [3.10] at baseline vs 11.19 [3.31] after the intervention). Both bright LT and dim-red LT were associated with improvements in sleep quality as captured by mean (SD) scores on the Pittsburg Sleep Quality Index (7.88 [4.11] at baseline vs 6.25 [4.27] after bright LT, and 8.87 [2.83] at baseline vs 7.33 [3.52] after dim-red LT) and the Parkinson's Disease Sleep Scale (97.24 [22.49] at baseline vs 106.98 [19.37] after bright LT, and 95.11 [19.86] at baseline vs 99.28 [16.94] after dim-red LT). Bright LT improved several self-reported mean (SD) sleep metrics, including sleep fragmentation (number of overnight awakenings, 1.51 [1.03] at baseline vs 0.92 [0.97] after the intervention), sleep quality (sleep diary score, 3.03 [1.01] at baseline vs 3.53 [0.91] after the intervention), and ease of falling asleep (sleep diary score, 2.32 [0.89] at baseline vs 1.83 [0.88] after the intervention). Light therapy was associated with increased daily physical activity as assessed by actigraphy (average activity [SD] counts, 165.01 [66.87] at baseline vs 194.59 [87.81] after the intervention).	Light therapy was well tolerated and may be a feasible intervention for improving the sleep-wake cycles in patients with PD. Further studies are required to determine optimal parameters of LT for PD.	
28240187	Cannabinoids are derivatives that are either compounds occurring naturally in the plant, Cannabis sativa or synthetic analogs of these molecules. The first and most widely investigated of the cannabinoids is Δ9-tetrahydrocannabinol (Δ9-THC), which is the main psychotropic constituent of cannabis and undergoes significant binding to cannabinoid receptors. These cannabinoid receptors are seven-transmembrane receptors that received their name from the fact that they respond to cannabinoid compounds, including Δ9-THC. The cannabinoid receptors have been described in rat, human and mouse brains and they have been named the CB1 and CB2 cannabinoid receptors. Later, an endogenous molecule that exerts pharmacological effects similar to those described by Δ9-THC and binds to the cannabinoid receptors was discovered. This molecule, named anandamide, was the first of five endogenous cannabinoid receptor agonists described to date in the mammalian brain and other tissues. Of these endogenous cannabinoids or endocannabinoids, the most thoroughly investigated to date have been anandamide and 2-arachidonoylglycerol (2-AG). Over the years, a significant number of articles have been published in the field of endogenous cannabinoids, suggesting a modulatory profile in multiple neurobiological roles of endocannabinoids. The general consensus accepts that the endogenous cannabinoid system includes natural ligands (such as anandamide and 2- AG), receptors (CB1 and CB2), and the main enzymes responsible for the hydrolysis of anandamide and 2-AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL], respectively) as well as the anandamide membrane transporter (AMT). To date, diverse pieces of evidence have shown that the endocannabinoid system controls multiple functions such as feeding, pain, learning and memory and has been linked with various disturbances, such as Parkinson´s disease. Among the modulatory properties of the endocannabinoid system, current data indicate that the sleep-wake cycle is under the influence of endocannabinoids since the blocking of the CB1 cannabinoid receptor or the pharmacological inhibition of FAAH activity promotes wakefulness, whereas the obstruction of AMT function enhances sleep. However, no solid evidence is available regarding the role of the endocannabinoid system in an unquestionable emotional component of the sleep: Dream activity. Since dreaming is a mental activity that occurs during sleep (characterized by emotions, sensory perceptions, and bizarre components) and the endocannabinoid system modulates neurobiological processes involving consciousness, such as learning and memory, attention, pain perception, emotions and sleep, it is acceptable to hypothesize that the endocannabinoid system might be modulating dream activity. In this regard, an accumulative body of evidence in human and animal models has been reported regarding the role of the endocannabinoid system in the control of emotional states and dreams. Moreover, preliminary studies in humans have indicated that treatment with cannabinoids may decrease post-traumatic stress disorder symptoms, including nightmares.Thus, based on a review of the literature available in PubMed, this article hypothesizes a conceptual framework within which the endocannabinoid system might influence the generation of dream experiences.	
28238681	This study aimed to correlate amplitude-integrated electroencephalography findings with early outcomes, measured by mortality and neuroimaging findings, in a prospective cohort of infants at high risk for brain injury in this center in Brazil.This blinded prospective cohort study evaluated 23 preterm infants below 31 weeks of gestational age and 17 infants diagnosed with hypoxic-ischemic encephalopathy secondary to perinatal asphyxia, with gestational age greater than 36 weeks, monitored with amplitude-integrated electroencephalography in a public tertiary center from February 2014 to January 2015. Background activity (classified as continuous, discontinuous high-voltage, discontinuous low-voltage, burst-suppression, continuous low-voltage, or flat trace), presence of sleep-wake cycling, and presence of seizures were evaluated. Cranial ultrasonography in preterm infants and cranial magnetic resonance imaging in infants with hypoxic-ischemic encephalopathy were performed.	In the preterm group, pathological trace or discontinuous low-voltage pattern (p=0.03) and absence of sleep-wake cycling (p=0.019) were associated with mortality and brain injury assessed by cranial ultrasonography. In patients with hypoxic-ischemic encephalopathy, seizure patterns on amplitude-integrated electroencephalography traces were associated with mortality or brain lesion in cranial magnetic resonance imaging (p=0.005).	This study supports previous results and demonstrates the utility of amplitude-integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury.	
28235898	Narcolepsy is characterized by chronic sleepiness and cataplexy-sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine-N-oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy.SIGNIFICANCE STATEMENT Cataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control.
28235679	To better understand how sleep/wake dysregulation affects Alzheimer's disease (AD), we compared the cerebrospinal fluid (CSF) orexin and histamine/tele-methylhistamine (HA/t-MHA) levels of 82 patients (41 probable-AD-high level of evidence, 41 mild cognitive impairment MCI-due-to-AD), 24 other neurologic disorders (OND) and 24 controls. We determined the relationships between these biomarkers, the CSF AD biomarkers concentrations, and the clinical sleep profile. CSF orexin-A but not HA/t-MHA levels were higher in MCI and AD than OND and controls. CSF orexin-A is correlated to CSF amyloid-β42in MCI and AD, independently of age, gender, MMSE, total-tau/phosphorylated-tau, HA or sleep parameters. Nighttime sleep duration was longer in MCI and AD patients than controls. In MCI, nighttime sleep duration negatively correlated with CSF amyloid-β42 and MMSE. To conclude, CSF orexin-A but not HA/t-HMA was upregulated in AD and correlated with amyloid-β42 level. Our data suggested a change in the sleep-wake pattern at an early stage of the disease that needs further investigation to deeply explain the mechanistic interplay between sleep and Alzheimer.

28231463	Sleep remains one of the most mysterious yet ubiquitous animal behaviors. We review current perspectives on the neural systems that regulate sleep/wake states in mammals and the circadian mechanisms that control their timing. We also outline key models for the regulation of rapid eye movement (REM) sleep and non-REM sleep, how mutual inhibition between specific pathways gives rise to these distinct states, and how dysfunction in these circuits can give rise to sleep disorders.
28231027	Sleep disorders are prevalent in Parkinson's disease but underreported in clinical settings. The contribution of sleep disorders to health-related quality of life (HRQOL) for patients with this degenerative neurological disease are not well known.To evaluate the impact of insomnia symptoms, obstructive sleep apnea (OSA), and poor sleep quality on HRQOL in a cohort of patients with idiopathic Parkinson's disease.	We enrolled a convenience sample of 66 adults seen in the University of Miami Movement Disorders Clinic between July 2011 and June 2013. Participants completed validated questionnaires to determine insomnia symptoms, OSA risk, depression, anxiety, and HRQOL. All patients underwent unattended polysomnography to confirm OSA. Results were compared for those with and without insomnia symptoms. Principal component and regression analyses were performed to evaluate determinants of HRQOL.	Participants were predominately Hispanic males with mild to moderate Parkinson's disease. Insomnia symptoms were reported for 46% of the study subjects. OSA (apnea-hypopnea index, ≥5) was noted in 47%, with a mean apnea-hypopnea index of 8.3 ± 11.0. Fairly bad to very bad sleep quality was reported by 21% of the participants. Insomnia (r = 0.71; P < 0.001), daytime sleepiness (r = 0.36; P = 0.003), depression symptoms (r =  0.44; P < 0.001), and anxiety symptoms (r = 0.33; P = 0.006) were significant correlates of poor sleep quality. OSA, severity of Parkinson's disease, and dopaminergic therapy were not. In the principal component analysis, sleep quality was a significant component of the "psychological factor" that in turn was a significant determinant of overall HRQOL.	
28229310	Non-24-h sleep-wake disorder (non-24) is a circadian rhythm disorder occurring in 55-70% of totally blind individuals (those lacking conscious light perception) in which the 24-h biological clock (central, hypothalamic, circadian pacemaker) is no longer synchronized, or entrained, to the 24-h day. Instead, the overt rhythms controlled by the biological clock gradually shift progressively earlier or later (free run) in accordance with the clock's near-24-h period, resulting in a recurrent pattern of daytime hypersomnolence and night-time insomnia. Orally administered melatonin and the melatonin agonist tasimelteon have been shown to entrain (synchronize) the circadian clock, resulting in improvements in night-time sleep and daytime alertness. We review the basic principles of circadian rhythms necessary to understand and treat non-24. The time of melatonin or tasimelteon administration must be considered carefully. For most individuals, those with circadian periods longer than 24 h, low-dose melatonin should be administered about 6 h before the desired bedtime, while in a minority, those with circadian periods shorter than 24 h (more commonly female individuals and African-Americans), melatonin should be administered at the desired wake time. Small doses (e.g., 0.5 mg of melatonin) that are not soporific would thus be preferable. Administration of melatonin or tasimelteon at bedtime will entrain individuals with non-24 but at an abnormally late time, resulting in continued problems with sleep and alertness. To date, tasimelteon has only been administered 1 h before the target bedtime in patients with non-24. Issues of cost, dose accuracy, and purity may figure into the decision of whether tasimelteon or melatonin is chosen to treat non-24. However, there are no head-to-head studies comparing efficacy, and studies to date show comparable rates of treatment success (entrainment).
28228567	To evaluate the association between sleep duration and the risk of incident dementia and brain aging.Self-reported total hours of sleep were examined in the Framingham Heart Study (n = 2,457, mean age 72 ± 6 years, 57% women) as a 3-level variable: <6 hours (short), 6-9 hours (reference), and >9 hours (long), and was related to the risk of incident dementia over 10 years, and cross-sectionally to total cerebral brain volume (TCBV) and cognitive performance.	We observed 234 cases of all-cause dementia over 10 years of follow-up. In multivariable analyses, prolonged sleep duration was associated with an increased risk of incident dementia (hazard ratio [HR] 2.01; 95% confidence interval [CI] 1.24-3.26). These findings were driven by persons with baseline mild cognitive impairment (HR 2.83; 95% CI 1.06-7.55) and persons without a high school degree (HR 6.05; 95% CI 3.00-12.18). Transitioning to sleeping >9 hours over a mean period of 13 years before baseline was associated with an increased risk of all-cause dementia (HR 2.43; 95% CI 1.44-4.11) and clinical Alzheimer disease (HR 2.20; 95% CI 1.17-4.13). Relative to sleeping 6-9 hours, long sleep duration was also associated cross-sectionally with smaller TCBV (β ± SE, -1.08 ± 0.41 mean units of TCBV difference) and poorer executive function (β ± SE, -0.41 ± 0.13 SD units of Trail Making Test B minus A score difference).	Prolonged sleep duration may be a marker of early neurodegeneration and hence a useful clinical tool to identify those at a higher risk of progressing to clinical dementia within 10 years.	
28228241	Intracerebroventricular injection of NPS reduces the duration of the ketamine- or thiopental-induced loss of the righting reflex in rats. But the specific EEG activities are unknown. We therefore sought to examine the effects of the NPS-NPSR system on anesthetic-induced characteristics of EEG power spectra and sleep-wake profiles. NPS alone or together with an NPSR antagonist was injected intracerebroventricularly, whereas the propofol (50mg/kg) or ketamine (100mg/kg) was administrated intraperitoneally. NPS (1 or 2nmol) significantly reduced the amount of propofol-induced EEG delta activity and slow wave states (SWS). NPS (1 or 5nmol) significantly reduced the amount of ketamine-induced SWS and EEG delta activity. Cortical EEG power spectral analysis showed that, in saline-pretreated rats, propofol induced a marked increase in delta (0.5-4Hz) activity, decrease in theta (4.5-8.5Hz) activity, and decrease in high frequency activity (14.5-60Hz), while, in rats pretreated with 1nmol of NPS, the duration of delta activity was reduced, while its spectral pattern was not changed. Whereas injection of ketamine into saline-pretreated rats induced a marked increase in delta (0.5-4Hz) activity, a moderate increase in theta (4.5-8.5Hz) activity, and a marked decrease in high frequency (14.5-60Hz) activity. However, delta activity was reduced while theta activity increased under pretreatment with 1nmol of NPS. The inhibitory effect of NPS on anesthetic-induced SWS was characterized by a reduced SWS episode duration with no significant change in either episode number or latency to SWS. [D-Val5]NPS, an NPSR antagonist (20nmol), significantly attenuated the arousal-promoting effect of 1nmol of NPS, but had no effect on SWS when injected alone. We speculate that NPS significantly reduces anesthetic-induced SWS and EEG slow activity by selective activation of the NPSR, which, in turn, would trigger subsequent arousal pathways.
28228148	Depression following acute coronary syndrome (ACS) constitutes a serious and debilitating problem. Approximately one in five patients will develop significant depression following ACS and less severe depressive symptoms are even more frequent. Furthermore, anxiety symptoms and sleep-wake disturbances are frequent. The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS."The effect of MElatonin and Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms.	Previously, only selective serotonin reuptake inhibitors (SSRIs) have been investigated in a primary preventive setup in patients following ACS. However, SSRIs are associated with several side effects. An ideal intervention would constitute the highest degree of prevention of depressive symptoms with the lowest risk of side effects. In this regard, melatonin may have advantages due to its low toxicity as well as its proven anxiolytic and hypnotic effects.	
28224427	In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease (PD), 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). It was found that poor sleep quality (77.11%) and excessive daytime sleepiness (32.34%) were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency (SE) was significantly decreased (P<0.01), and sleep latency (SL) and the arousal index (AI) were increased (P<0.05) in the PD group as compared with those in the control group. SE and total sleep time (TST) were positively correlated with the Hoehn and Yahr (H&Y) stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group (P<0.05). Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.
28223099	In the current study we set out to determine the effects of morpholino oligonucleotide (MO) knock-down of kcna2 on sleep-wake cycles in zebrafish. The results were compared to a non-overlapping MO injection, Dec2, who's mutant is also linked with a short sleep phenotype. Four groups of fish were used in the experiment: naïve fish, and fish injected with either control, kcna2, or Dec2 MO. All groups underwent 24-h behavioral monitoring of sleep-wake cycles at four and seven days-post-fertilization (dpf). First, we established an immobility dependent, sleep related, increase in arousal thresholds at both 4 and 7 dpf. Secondly, we show that kcna2 MO injected fish exhibit significantly less sleep behavior than controls and naïve fish, whereas Dec2 MO injections had similar but less severe effects. Finally, using kcna2 MO injected fish only, we turn to local field recordings at the level of the telencephalon and tectum opticum and rule out that the knock-down resulted in a non-specific increase in neural excitability that would mask sleep behavior.
28218891	Diagnosis and treatment of circadian rhythm sleep-wake disorders both require assessment of circadian phase of the brain's circadian pacemaker. The gold-standard univariate method is based on collection of a 24-hr time series of plasma melatonin, a suprachiasmatic nucleus-driven pineal hormone. We developed and validated a multivariate whole-blood mRNA-based predictor of melatonin phase which requires few samples. Transcriptome data were collected under normal, sleep-deprivation and abnormal sleep-timing conditions to assess robustness of the predictor. Partial least square regression (PLSR), applied to the transcriptome, identified a set of 100 biomarkers primarily related to glucocorticoid signaling and immune function. Validation showed that PLSR-based predictors outperform published blood-derived circadian phase predictors. When given one sample as input, the R2 of predicted vs observed phase was 0.74, whereas for two samples taken 12 hr apart, R2 was 0.90. This blood transcriptome-based model enables assessment of circadian phase from a few samples.
28217760	Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep wake cycle and is higher during wakefulness and lower during sleep. This fluctuation is lost with Aβ deposition, likely due to its sequestration into amyloid plaques. As such, Aβ is believed to play a significant role in the development of sleep disturbances in the preclinical and clinical phase of AD. In addition to Aβ, the influence of tau AD pathology is likely important to the sleep disturbances observed in AD. Abnormal tau is the earliest observable AD-like pathology in the brain with abnormal tau phosphorylation in many sleep regulating regions such as the locus coeruleus, dorsal raphe, tuberomammillary nucleus, parabrachial nucleus, and basal forebrain prior to the appearance of amyloid or cortical tau pathology. Furthermore, human tau mouse models exhibit AD-like sleep disturbances and sleep changes are very common in other tauopathies including frontotemporal dementia and progressive supranuclear palsy. Together these observations suggest that tau pathology can induce sleep disturbances and may play a large role in the sleep disruption seen in AD. To elucidate the relationship between sleep and AD it will be necessary to not only understand the role of amyloid but also tau and how these two pathologies, together with comorbid pathology such as alpha-synuclein, interact and affect sleep regulation in the brain.
28215256	Adolescents and adults who are evening-types exhibit shorter sleep duration and more sleep problems than individuals with an earlier chronotype. We hypothesized that already at a preschool age, evening-types would exhibit more sleep problems relative to children who are morning or intermediate chronotypes. The aim of this study was to examine the association between chronotype and sleep problems among preschool children.We studied a subset of typically-developing 4.5-year-olds taking part in the Growing Up in Singapore Towards healthy Outcomes birth cohort study (n = 244). The Children's Chronotype Questionnaire (CCTQ) was used to categorize children into morning-, intermediate-, and evening-types. Sleep problems were measured using the Children's Sleep Habits Questionnaire (CSHQ), with higher scores corresponding to greater sleep problems. The relation between chronotype, sleep-wake timing, and nocturnal sleep time was also evaluated in a subsample of 117 children using actigraphy recordings with parent-reported sleep diaries.	After controlling for potential confounders (maternal education, child's sex, birth order, and ethnicity), a significant main effect of chronotype on sleep problems was observed, in which evening-types exhibited greater CSHQ scores compared to morning- and intermediate-types (all p < 0.001). Actigraphy data in the subsample confirmed that evening-types had later bedtimes (p < 0.001) and get-up times (p = 0.02) during weekdays and weekends, but shorter nocturnal sleep time (p = 0.034) only during weekdays, compared to children who had earlier chronotypes.	In preschool children, sleep problems were greater in evening-types compared to morning- and intermediate-types, suggesting that chronotype could be a contributing factor to sleep disturbances in early childhood.	
28215246	Previous neuroimaging studies have shown subtle structural changes of the brain in various sleep disorders, suggesting detrimental effects of disrupted sleep-wake cycle on brain structures. We aimed to identify structural changes in shift workers relative to day workers. We hypothesized that brain structures belonging to sleep-wake modulation may be altered in shift workers.Nineteen male shift workers (median age, 21 years) and 19 male day workers (median age, 21 years) voluntarily participated in the current study. Sleep questionnaires were obtained from all participants and compared between the groups. Voxel-based morphometry was used to compare regional gray matter volume between shift workers and day workers (corrected p < 0.05 with small volume correction). Separate correlation analyses were performed between regional gray matter volume change and scores of Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index (Pearson's correlation, p < 0.05).	Compared to day workers, shift workers had higher scores of Beck Depression Inventory-II, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. Compared to day workers, shift workers had a significant gray matter volume reduction in the pontomesencephalic tegmentum. Regional volume of the pontomesencephalic tegmentum negatively correlated with Pittsburgh Sleep Quality Index global score.	We observed that pontomesencephalic tegmentum volume was reduced in shift workers compared to day workers and that the smaller pontomesencephalic tegmentum volume was related to the poorer sleep quality. Our preliminary findings may be related to chronic disruption of circadian rhythm or decreased exposure to bright light in shift workers.	
28215242	To examine the effects of a modest delay (15 min) in school start time (SST) on adolescent sleep patterns, mood, and behaviors.Two secondary schools in Hong Kong with a total of 1173 students (intervention: n = 617; comparison school n = 556) completed both baseline and follow-up questionnaires. School start time was delayed by 15 min, from 7:45 a.m. to 8:00 a.m., in the intervention school. The comparison school maintained their regular SST at 7:55 a.m. Students' sleep-wake patterns, daytime sleepiness, and mental and behavioral aspects were assessed by validated questionnaires before and after the intervention.	Students in the intervention school significantly delayed their weekday wake-up time (p < 0.001) and increased their total time in bed (p < 0.001) when compared to students in the comparison school. Both groups experienced a delay in their weekday bedtime. The students in the intervention school showed improved mental health [General Health Questionnaire (GHQ) score, p = 0.015], better prosocial behaviors (p = 0.009), better peer relationships (p < 0.001), greater attentiveness (p < 0.001), less emotional problems (p = 0.002), and less behavioral difficulties (p < 0.001) as measured by Strengths and Difficulties Questionnaire (SDQ).	A modest delay (15 min) in school start time can increase adolescent sleep with corresponding improvement in mood and behaviors. Current findings have significant implications for education policy, suggesting that school administrators and policy makers should systematically consider delaying school start time to promote sleep and health among school-aged adolescents.	ChiCTR-TRC-12002798. The trial protocol can be accessed at: http://www.chictr.org/en/proj/show.aspx?proj=3955.	
28215235	Delayed sleep-wake phase disorder (DSWPD) is associated with a delayed timing of circadian rhythms, and this delay is suggested to be the basis of the disorder. However, this has been questioned due to frequent relapses following treatment based on this aetiology. Recent studies have emerged suggesting personality factors may contribute to sleep patterns in DSWPD. The aim of this study was to further investigate circadian and personality factors in DSWPD patients as well as patients with non-24-h sleep-wake rhythm disorder (N24SWD) relative to control sleepers.This sample consisted of 16 DSWPD (age = 21.1 ± 2.8, 10 m, 7 f), and three N24SWD patients (age = 24.0 ± 4.4, 2 m, 1 f). Controls were seven males and seven females (age = 23.4 ± 5.9). Before starting an 80-h modified constant routine, eligible participants' sleep patterns were monitored for a week and they completed a personality questionnaire (NEO PI-R). An ultradian routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the timing of endogenous circadian temperature and melatonin rhythms.	As compared with controls, DSWPD patients reported higher neuroticism, significantly lower extraversion, conscientiousness and agreeableness. Similarly, N24SWD patients' patterns of personality traits were similar to that of DSWPD. Conscientiousness, in particular, was associated with phase timings of circadian rhythms as well as sleep measures and lifestyle factors within the DSWPD group.	These findings suggest that circadian rhythm sleep-wake disorders (CRSWDs) may not only stem from circadian abnormalities but personality factors may also drive lifestyle choices, including sleep timing.	
28215031	Sleep disorders represent a significant comorbidity in the heart failure population, and there is mounting evidence that treatment of sleep disorders such as obstructive sleep apnea can significantly improve cardiac function. However, the link between these two disorders is still not entirely clear.Recently, a novel neurohormonal pathway has been elucidated involving signaling molecules now collectively known as the orexins, which have been implicated in regulating autonomic function during sleep/wake cycles. Further evidence has mounted that orexin signaling is deeply perturbed in the setting of sleep disorders, and furthermore that abnormal orexin signaling may be implicated in the pathology of heart failure. The orexin signaling pathway represents an enticing novel target for both the treatment of sleep disorders as well as heart failure, and may represent one facet of the "missing link" between these two prevalent and often comorbid diseases.	
28207519	Sleep disturbance is a common symptom in CC patients, and it is positively related to greater somatic and psychiatric symptoms.The participants were 126 adult outpatients with CC. The measures were: constipation-Constipation Scoring System (CSS) and Patient Assessment of Constipation-Symptoms (PAC-SYM); sleep-Pittsburgh Sleep Quality Index (PSQI); anxiety-General Anxiety Disorder-7 (GAD-7); depression-Patient Health Questionnaire-9 (PHQ-9); and QOL-Patient Assessment of Constipation Quality of Life (PAC-QOL) and SF-36. Patients were divided into sleep-disorder and normal-sleep groups by their PSQI scores.	The sleep-disorder group had significantly higher rates of incomplete defecation and blockage and higher CSS scores, PAC-SYM total scores, and PAC-SYM rectal-item scores than the normal-sleep group. GAD-7 and PHQ-9 scores were significantly higher in patients with poor sleep. Furthermore, sleep disorders, depression, and anxiety were all positively correlated with constipation severity. "Worry/anxiety" score of PAC-QOL scale was significantly higher and scores for seven SF-36 subscales were significantly lower in patients with poor sleep. In addition, correlation analyses showed significant negative relations between QOL and constipation, sleep disturbance, anxiety as well as depression. However, multiple regression revealed that PAC-QOL was positively associated with severe constipation and SF-36 was negatively associated with anxiety and depression. But sleep disturbance was not the independent risk factor for QOL of CC patients.	Sleep disorders may worsen the physical- and mental health of CC patients. Sleep disturbance may lower CC patients' QOL indirectly through the combined effects of anxiety, depression, and constipation.	
28190167	Studies have shown that experimental fasting can affect cognitive function, sleep, and wakefulness patterns. However, the effects of experimental fasting cannot be generalized to fasting during Ramadan due to its unique characteristics. Therefore, there has been increased interest in studying the effects of fasting during Ramadan on sleep patterns, daytime sleepiness, cognitive function, sleep architecture, and circadian rhythm.In this review, we critically discuss the current research findings in those areas during the month of Ramadan.	Available data that controlled for sleep/wake schedule, sleep duration, light exposure, and energy expenditure do not support the notion that Ramadan intermittent fasting increases daytime sleepiness and alters cognitive function. Additionally, recent well-designed studies showed no effect of fasting on circadian rhythms. However, in non-constrained environments that do not control for lifestyle changes, studies have demonstrated sudden and significant delays in bedtime and wake time.	Studies that controlled for environmental factors and sleep/wake schedule reported no significant disturbances in sleep architecture. Nevertheless, several studies have consistently reported that the main change in sleep architecture during fasting is a reduction in the proportion of REM sleep.	
28189461	Actical® actigraphy is commonly used to monitor athlete sleep. The proprietary software, called Actiware®, processes data with three different sleep-wake thresholds (Low, Medium or High), but there is no standardisation regarding their use. The purpose of this study was to examine validity and bias of the sleep-wake thresholds for processing Actical® sleep data in team sport athletes.Validation study comparing actigraph against accepted gold standard polysomnography (PSG).	Sixty seven nights of sleep were recorded simultaneously with polysomnography and Actical® devices. Individual night data was compared across five sleep measures for each sleep-wake threshold using Actiware® software. Accuracy of each sleep-wake threshold compared with PSG was evaluated from mean bias with 95% confidence limits, Pearson moment-product correlation and associated standard error of estimate.	The Medium threshold generated the smallest mean bias compared with polysomnography for total sleep time (8.5min), sleep efficiency (1.8%) and wake after sleep onset (-4.1min); whereas the Low threshold had the smallest bias (7.5min) for wake bouts. Bias in sleep onset latency was the same across thresholds (-9.5min). The standard error of the estimate was similar across all thresholds; total sleep time ∼25min, sleep efficiency ∼4.5%, wake after sleep onset ∼21min, and wake bouts ∼8 counts.	Sleep parameters measured by the Actical® device are greatly influenced by the sleep-wake threshold applied. In the present study the Medium threshold produced the smallest bias for most parameters compared with PSG. Given the magnitude of measurement variability, confidence limits should be employed when interpreting changes in sleep parameters.	
28188139	To explore if gender difference in sleep quality is due to higher prevalence of depression in females, and whether socio-demographic and lifestyle factors have a differential effect on sleep quality in males and females.Youth self-reports and the Pittsburgh Sleep Quality Index were used to assess sleep quality and associated risk factors. Logistic regression analyses were used to analyze the association between various risk factors and poor sleep quality.	Reports from 3,778 young adults (20.6±0.86 years) indicate a higher prevalence of poor sleep quality in females than males (65.1% vs. 49.8%). It seems that gender difference in poor sleep is independent of depression, socio-demographics, and lifestyle factors, since the higher odds of poor sleep quality in females was robust to adjust for depression, socio-demographics, and lifestyle factors (OR: 1.53, 95% CI: 1.23-1.90). Lifestyle factors (eg, smoking) (OR 1.91; 95% CI 1.05-3.46) were associated with sleep quality in only males.	Our findings indicate that female vulnerability to poor sleep quality should be explored beyond psycho-social disparities. Perhaps, exploring if the female predisposition to poor sleep quality originates at the biological level could lead to the answer.	

28181975	This study sought to examine the effect of auricular acupressure therapy on the stress and sleep status of middle-aged women in South Korea. A quasi-experimental pretest/posttest control group design was employed. The study sample consisted of 67 middle-aged women (experimental: 35 samples; control: 32 samples) in Seoul, South Korea. Auricular acupressure therapy including the auricular acupressure needle on the skin paper tape was applied on an ear for 2 weeks, 2 times per week. The acupoints were Gyogam, Sinmun, Bushin, Naebunbi, and Pijilha. For the placebo control group, only the skin paper tape without the auricular acupressure needle was applied on the same acupoints. Measures were a stress scale, cortisol level in blood, and a sleep status scale. The findings showed that there were significant differences on stress (physical: t = 2.170, P < .033; psychological: t = 2.117, P < .037), cortisol level in blood (t = 2.277, P < .025), and sleep status (t = -3.127, P < .004). Health care providers should consider providing auricular acupressure therapy as an alternative method for reducing physical and psychological stress, cortisol level in blood, and sleep disturbance of middle-aged women in South Korea.
28181924	This study examined sleep patterns and sleep problems in relation to smoking and alcohol use in Chinese adolescents. A questionnaire survey of 2090 adolescent students was conducted in Lijin County, Shandong, China. A self-administered questionnaire was used to collect the data. After adjustment for demographics and internalizing and externalizing problems, poor sleep quality was associated with increased risk of smoking (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.24-5.40), alcohol use (OR, 2.65; 95% CI, 2.81-3.89), and getting drunk (OR, 2.81; 95% CI, 1.72-4.57); sleeping 7 hours (OR, 1.64; 95% CI, 1.20-2.43) and sleeping 6 hours or less per night on weekdays (OR, 1.97; 95% CI, 1.25-3.10) were significantly associated with increased risk for alcohol use, and sleeping 6 hours or less per night on weekends (OR, 2.09; 95% CI, 1.18-3.70) were significantly associated with increased risk for getting drunk; and hypnotic medication use was significantly associated with ever smoking (OR, 1.80; 95% CI, 1.08-2.99). These findings highlight the potential role of sleep intervention in the prevention of adolescent substance use.
28181718	We studied sleep in a rural population in Madagascar to (i) characterize sleep in an equatorial small-scale agricultural population without electricity, (ii) assess whether sleep is linked to noise levels in a dense population, and (iii) examine the effects of experimentally introduced artificial light on sleep timing.Using actigraphy, sleep-wake patterns were analyzed for both daytime napping and nighttime wakefulness in 21 participants for a sum total of 292 days. Functional linear modeling was used to characterize 24-h time-averaged circadian patterns and to investigate the effect of experimentally introduced mobile field lights on sleep timing. We also obtained the first polysomnography (PSG) recordings of sleep in a traditional population.	In every measure of sleep duration and quality, the Malagasy population experienced shorter and lower quality sleep when compared to similarly measured postindustrial values. The population slept for a total of 6.5 h per night and napped during 89% of recorded days. We observed a peak in activity after midnight for both sexes on 49% of nights, consistent with segmented sleep. Access to mobile field lights had no statistical effect on nighttime sleep timing. From PSG, we documented relatively short rapid eye movement (14%), poor sleep efficiency (66%), and high wake after sleep onset (162 min).	Sleep in this population is segmented, similar to the "first" sleep and "second" sleep reported in the historical record. Moreover, although average sleep duration and quality were lower than documented in Western populations, circadian rhythms were more stable across days.	
28178395	Sleep pattern has been shown to be associated with type 2 diabetes mellitus. Here, we investigated the difference in bedtime, waking time and estimated sleep duration in type 2 diabetes mellitus patients with or without visceral fat accumulation, using a questionnaire on sleep patterns. The study participants were 59 Japanese type 2 diabetes mellitus patients (men/women 34/25, age 64.5 ± 12.1 years). Visceral fat accumulation was defined as estimated visceral fat area ≥100 cm2 . The patients with visceral fat accumulation (n = 40) showed significantly later bedtime (23.51 ± 01.27 h in the [+] group vs 22.49 ± 01.23 h in the [-] group) and shorter estimated sleep duration (6.6 ± 1.4 h in the [+] group vs 7.9 ± 1.0 h in the [-] group) on weekdays, compared with those without (n = 19). Later bedtime and shorter estimated sleep duration existed in the type 2 diabetes mellitus patients with visceral fat accumulation, compared with those without.
28173758	Sleep is regulated by two main processes. The circadian process provides a 24-h rhythm and the homeostatic process reflects sleep pressure, which increases in the course of wakefulness and decreases during sleep. Both of these processes undergo major changes during development. For example, sleep homeostasis, measured by means of electroencephalogram (EEG) slow-wave activity (SWA, EEG power between 0.5 and 4.5 Hz), peaks around puberty and decreases during adolescence. In humans and rats these changes have been related to cortical maturation. We aimed to explore whether additional parameters as state dynamic (dynamic of sleep/wake behavior) parameters of movement velocity, trajectories and micro-arousals provide markers of rat maturation. The state dynamics reflect the stability of sleep within a specific sleep stage. We applied a state space technique (SST), a quantitative and unbiased method, based on frequency band ratios of the EEG to analyze the development of different sleep/wake states and state dynamics between vigilance states. EEG of recording electrodes at the frontal and parietal lobe were analyzed using conventional scoring criteria and SST.We found that movement velocity, trajectories between sleep states and micro-arousals changed as an inverse U-shaped curve across maturation. At all ages, movement velocity over the frontal lobe is higher compared to the parietal lobe, while the number of trajectories and micro-arousals are reduced. Furthermore, we showed that SWA correlates negatively with movement velocity and the number of micro-arousals. The velocity in the parietal lobe correlates positively with the number of micro-arousals. As for SWA, trajectories seem primarily to depend on sleep homeostasis regulatory mechanisms while the movement velocity seems to be modulated by other sleep regulators like the circadian rhythms.	New insights in sleep/wake state dynamics are established with the SST, because trajectories, micro-arousals and velocities are not evident by traditional scoring methods. These dynamic measures may represent new indicators for changes in sleep regulatory processes across maturation.	
28169087	Individuals with psychotic disorders experience disruptions to both the sleep and circadian components of the sleep/wake cycle. Recent evidence has supported a role of sleep disturbances in emerging psychosis. However, less is known about how circadian rhythm disruptions may relate to psychosis symptoms and prognosis for adolescents with clinical high-risk (CHR) syndromes. The present study examines circadian rest/activity rhythms in CHR and healthy control (HC) youth to clarify the relationships among circadian rhythm disturbance, psychosis symptoms, psychosocial functioning, and the longitudinal course of illness.Thirty-four CHR and 32 HC participants were administered a baseline evaluation, which included clinical interviews, 5days of actigraphy, and a sleep/activity diary. CHR (n=29) participants were re-administered clinical interviews at a 1-year follow-up assessment.	Relative to HC, CHR youth exhibited more fragmented circadian rhythms and later onset of nocturnal rest. Circadian disturbances (fragmented rhythms, low daily activity) were associated with increased psychotic symptom severity among CHR participants at baseline. Circadian disruptions (lower daily activity, rhythms that were more fragmented and/or desynchronized with the light/dark cycle) also predicted severity of psychosis symptoms and psychosocial impairment at 1-year follow-up among CHR youth.	Circadian rhythm disturbances may represent a potential vulnerability marker for emergence of psychosis, and thus, rest/activity rhythm stabilization has promise to inform early-identification and prevention/intervention strategies for CHR youth. Future studies with longer study designs are necessary to further examine circadian rhythms in the prodromal period and rates of conversion to psychosis among CHR teens.	
28162920	Post-operative patients experience sleep disturbances. Animal studies demonstrate that general anaesthesia (GA) can disrupt circadian rhythms and cause changes in the molecular clock, indicating that anaesthesia contributes to post-operative circadian disruption. Here we review the effect of anaesthesia on the circadian clock and its rhythms in order to summarise current findings outline commonalities between studies and propose mechanisms by which effects may be mediated.1) GA has strong effects on the main neurotransmitter systems linked with circadian control (Gamma aminobutyric acid/N-methyl-D-aspartate (GABA/NMDA)) and may act by interfering with light-entrainment of the clock. 2) Expression of the core clock gene per2 is inhibited by GA (possibly via a NMDA/glycogen synthase kinase 3β (GSK3β) pathway). 3) GA's effect on circadian rhythms appears greatest when administered during animals' active phases 4) GA may have different effects when administered under free-running and entrained conditions. 5) Anaesthesia may mimic the mechanism involved in adaptation of the clock to changes in daylength. There is agreement that GA can strongly affect the circadian clock. How anaesthesia-induced changes in the molecular clock lead to changes in behaviour remains unclear. The answer, and what it may mean for patients post-operatively, will rely on systematic studies at molecular, behavioural, and clinical levels using standardised protocols.	
28160289	Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1 (GDM1)." Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin-ir (0.63-0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin-ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin-ir RGCs, which most likely are involved in different functions.
28160224	This study aimed to examine the behavioural sleep-wake rhythm in 36 adults with autism spectrum disorder (ASD) and to determine the prevalence of circadian sleep-wake rhythm disorders compared to age- and sex-matched controls. Participants completed an online questionnaire battery, a 14-day sleep-wake diary and 14-day actigraphy assessment. The results indicated that a higher proportion of adults with ASD met criteria for a circadian rhythm sleep-wake disorder compared to control adults. In particular, delayed sleep-wake phase disorder was particularly common in adults with ASD. Overall the findings suggest that individuals with ASD have sleep patterns that may be associated with circadian rhythm disturbance; however factors such as employment status and co-morbid anxiety and depression appear to influence their sleep patterns.

28159099	Sleep disorders and neurologic illness are common and burdensome in their own right; when combined, they can have tremendous negative impact at an individual level as well as societally. The socioeconomic burden of sleep disorders and neurologic illness can be identified, but the real cost of these conditions lies far beyond the financial realm. There is an urgent need for comprehensive care and support systems to help with the burden of disease. Further research in improving patient outcomes in those who suffer with these conditions will help patients and their families, and society in general.
28159098	The burden of narcolepsy is likely the result of 2 main aspects: the clinical difficulties and disability incurred as a direct effect of the disorder and the socioeconomic burden. The clinical burden includes the symptoms, diagnosis, comorbidities, treatment, and even mortality that can be associated with narcolepsy. Lifelong therapy is necessary for these patients. Effective treatment results in long-term benefits from both patient and societal perspectives by improving clinical outcomes, potentially enabling improved education and increased employment and work productivity, and quality of life. Thus, reducing the time to appropriate management results in improved outcomes in these patients.
28159095	There are normal changes to sleep architecture throughout the lifespan. There is not, however, a decreased need for sleep and sleep disturbance is not an inherent part of the aging process. Sleep disturbance is common in older adults because aging is associated with an increasing prevalence of multimorbidity, polypharmacy, psychosocial factors affecting sleep, and certain primary sleep disorders. It is also associated with morbidity and mortality. Because many older adults have several factors from different domains affecting their sleep, these complaints are best approached as a multifactorial geriatric health condition, necessitating a multifaceted treatment approach.
28159094	Pediatric disorders tend to affect the immediate support unit, adults and children. High costs for direct consumption of medical care are offset by early diagnosis and treatment of pediatric sleep disorders. Pediatric sleep disorders are underdiagnosed and undertreated. Attention-deficit/hyperactivity disorder may result from insufficient or fragmented sleep. Delaying school start time resulted in decreased car crashes in teen drivers and improved mood.
28159093	Sleep disorders may interact with the law, making awareness important. Insufficient sleep and obstructive sleep apnea (OSA) are prevalent and associated with excessive sleepiness. Patients with excessive sleepiness may have civil or criminal liability if they fall asleep and cause a motor vehicle accident. Awareness of screening and treatment of OSA is increasing in certain industries. Parasomnia associated sleep-related violence represents a challenge to clinicians, who may be called on to consider parasomnia as a contributing, mitigating, or exculpatory factor in criminal proceedings. Improving access to sleep medicine care is an important aspect in reducing the consequences of sleep disorders.
28159089	Biological needs for sleep are met by engaging in behaviors that are largely influenced by the environment, social norms and demands, and societal influences and pressures. Insufficient sleep duration and sleep disorders such as insomnia and sleep apnea are highly prevalent in the US population. This article outlines some of these downstream factors, including cardiovascular and metabolic disease risk, neurocognitive dysfunction, and mortality, as well as societal factors such as age, sex, race/ethnicity, and socioeconomics. This review also discusses societal factors related to sleep, such as globalization, health disparities, public policy, public safety, and changing patterns of use of technology.
28155201	The sleep-wake cycle is a biological phenomena under the orchestration of neurophysiological, neurochemical, neuroanatomical, and genetical mechanisms. Moreover, homeostatic and circadian processes participate in the regulation of sleep across the light-dark period. Further complexity of the understanding of the genesis of sleep engages disturbances which have been characterized and classified in a variety of sleep-wake cycle disorders. The most prominent sleep alterations include insomnia as well as excessive daytime sleepiness. On the other side, several human diseases have been linked with direct changes in DNA, such as chromatin configuration, genomic imprinting, DNA methylation, histone modifications (acetylation, methylation, ubiquitylation or sumoylation, etc.), and activating RNA molecules that are transcribed from DNA but not translated into proteins. Epigenetic theories primarily emphasize the interaction between the environment and gene expression. According to these approaches, the environment to which mammals are exposed has a significant role in determining the epigenetic modifications occurring in chromosomes that ultimately would influence not only development but also the descendants' physiology and behavior. Thus, what makes epigenetics intriguing is that, unlike genetic variation, modifications in DNA are altered directly by the environment and, in some cases, these epigenetic changes may be inherited by future generations. Thus, it is likely that epigenetic phenomena might contribute to the homeostatic and/or circadian control of sleep and, possibly, have an undescribed link with sleep disorders. An exciting new horizon of research is arising between sleep and epigenetics since it represents the relevance of the study of how the genome learns from its experiences and modulates behavior, including sleep.
28154744	Photic and non-photic environmental factors are suggested to modulate the development of circadian rhythms in infants. Our aim is to evaluate the development of biological rhythms (circadian or ultradian) in newborns in transition from Neonatal Intensive Care Units (NICU) to home and along the first 6 months of life, to identify masking and entraining environment factors along development. Ten newborns were evaluated in their last week inside the NICU and in the first week after being delivered home; 6 babies were also followed until 6 months of corrected age. Activity, recorded with actimeters, wrist temperature and observed sleep and feeding behavior were recorded continuously along their last week inside the NICU and in the first week at home and also until 6 months of corrected age for the subjects who remained in the study. Sleep/wake and activity/rest cycle showed ultradian patterns and the sleep/wake was strongly influenced by the 3 h feeding schedule inside the NICU, while wrist temperature showed a circadian pattern that seemed no to be affected by environmental cycles. A circadian rhythm emerges for sleep/wake behavior in the first week at home, whereas the 3 h period vanishes. Both activity/rest and wrist temperature presented a sudden increase in the contribution of the circadian component immediately after babies were delivered home, also suggesting a masking effect of the NICU environment. We found a positive correlation of postconceptional age and the increase in the daily component of activity and temperature along the following 6 months, while feeding behavior became arrhythmic.
28151835	Strategies directed at the prevention of disabling pain have been suggested as a public health priority, making early identification of youth at risk for poor outcomes critical. At present, limited information is available to predict which youth presenting with acute pain are at risk for persistence. The aims of this prospective longitudinal study were to identify biopsychosocial factors in the acute period that predict the transition to persistent pain in youth with new-onset musculoskeletal (MSK) pain complaints. Participants were 88 children and adolescents (age 10-17 years) presenting to the emergency department (n = 47) or orthopedic clinic (n = 41) for evaluation of a new MSK pain complaint (<1 month duration). Youth presented for 2 study visits (T1 ≤1 month post pain onset; T2 = 4-month follow-up) during which they completed questionnaires (assessing pain characteristics, psychological factors, sleep quality) and participated in a laboratory task assessing conditioned pain modulation. Regression analyses tested T1 predictors of longitudinal pain outcomes (pain persistence, pain-related disability, quality of life [QOL]). Results revealed approximately 35% of youth had persistent pain at 4-month follow-up, with persistent pain predicted by poorer conditioned pain modulation and female sex. Higher depressive symptoms at T1 were associated with higher pain-related disability and poorer QOL at T2. Findings highlight the roles of depressive symptoms and pain modulation in longitudinally predicting pain persistence in treatment-seeking youth with acute MSK pain and suggest potential mechanisms in the transition from acute to chronic MSK pain in children and adolescents.
28148557	As kidney disease progresses, patients often experience a variety of symptoms. A challenge for the nephrologist is to help determine if these symptoms are related to advancing CKD or the effect of various comorbidities and/or medications prescribed. The clinician also must decide the timing of dialysis initiation. The initiation of dialysis can have a variable effect on quality of life measures and the alleviation of uremic signs and symptoms, such as anorexia, fatigue, cognitive impairment, depressive symptoms, pruritus, and sleep disturbances. Thus, the initiation of dialysis should be a shared decision-making process among the patient, the family and the nephrology team; information should be provided, in an ongoing dialogue, to patients and their families concerning the benefits, risks, and effect of dialysis therapies on their lives.
28145903	Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.

28140399	Temporal organization of physiology is critical for human health. In the past, humans experienced predictable periods of daily light and dark driven by the solar day, which allowed for entrainment of intrinsic circadian rhythms to the environmental light-dark cycles. Since the adoption of electric light, however, pervasive exposure to nighttime lighting has blurred the boundaries of day and night, making it more difficult to synchronize biological processes. Many systems are under circadian control, including sleep-wake behavior, hormone secretion, cellular function and gene expression. Circadian disruption by nighttime light perturbs those processes and is associated with increasing incidence of certain cancers, metabolic dysfunction and mood disorders. This review focuses on the role of artificial light at night in mood regulation, including mechanisms through which aberrant light exposure affects the brain. Converging evidence suggests that circadian disruption alters the function of brain regions involved in emotion and mood regulation. This occurs through direct neural input from the clock or indirect effects, including altered neuroplasticity, neurotransmission and clock gene expression. Recently, the aberrant light exposure has been recognized for its health effects. This review summarizes the evidence linking aberrant light exposure to mood.
28132583	This review describes the evolving role of oral hormone therapy (HT) for treating menopausal symptoms and preventing osteoporosis, focusing on conjugated estrogens/bazedoxifene (CE/BZA). Estrogens alleviate hot flushes and prevent bone loss associated with menopause. In nonhysterectomized women, a progestin should be added to estrogens to reduce the risk of endometrial cancer. Use of HT declined since the Women's Health Initiative (WHI) studies showed that HT does not prevent coronary heart disease (CHD) and that conjugated estrogens/medroxyprogesterone acetate increased the risk of invasive breast cancer after nearly 5 years of use. However, re-analyses of the WHI data suggest that some risks (eg, CHD, all-cause mortality) may be reduced when HT is initiated in women <60 years of age and <10 years since menopause, compared with later. CE/BZA is the first menopausal HT without a progestogen for nonhysterectomized women. Instead, BZA, a selective estrogen receptor modulator, in combination with CE, protects against estrogenic effects on uterine and breast tissue. Data from 5 large, randomized clinical trials show that CE/BZA reduces hot flush frequency/severity, prevents bone loss, reduces bone turnover, improves the vaginal maturation index and ease of lubrication, and improves some measures of sleep and menopause-specific quality of life. In studies of up to 2 years, there was no increase in endometrial hyperplasia, vaginal bleeding, breast density, or breast pain/tenderness compared with placebo. Venous thromboembolism and stroke are risks of all estrogen-based therapies. The choice of HT should be individualized, with consideration of the risk/benefit profile and tolerability of therapy, as well as patient preferences.

28131197	Nocturnal hypokinesia is a common night-time symptom in patients with Parkinson's disease (PD). However, there is still little understanding of the nature, and variations of severity of this symptom.To evaluate the severity of nocturnal hypokinesia and sleep positions in PD patients using multisite wearable sensors.	Nocturnal parameters and sleep positions in 18 PD couples were assessed and compared using wearable sensors (limbs and trunk) for one night in their homes. Nocturnal parameters included number, velocity, acceleration, degree, limb movements and the number of times they got out of bed.	PD patients had significantly fewer episodes of turns in bed than their spouses (p=0.043), which was associated with significantly slower speed (p=0.005), acceleration (p=0.005) and fewer degrees (p=0.017). When we split the night into the first and second half, significant findings were mainly demonstrated in the second half of the night, including significantly fewer turns (p=0.02) with smaller degrees (p=0.017), slower speed (p=0.005) and acceleration (p=0.007). No significant differences in these parameters were shown in the first half of the night except for smaller degrees of turn in bed in PD patients (p=0.028) and slower acceleration (p=0.037). In addition, PD patients spent significantly more time in a supine position compared to their spouses (p=0.031) with significantly less time in a prone position (p=0.041).	Nocturnal hypokinesia gets worse as the night progresses. Treatment of nocturnal hypokinesia should aim at providing a continuous dopaminergic delivery that can achieve a sustained therapeutic level of dopamine throughout the night.	

28129305	Seventy-three women with posttraumatic stress disorder (PTSD) resulting from rape or physical assault participated in a loud-tone procedure, while skin conductance (SC), heart rate, and electromyogram responses were recorded. Pearson correlations were examined between each psychophysiological response and Clinician-Administered PTSD Scale (CAPS) symptom scores. Significant correlations were adjusted for each remaining individual PTSD symptom score. Heart rate response (HRR) significantly correlated with CAPS total score and with CAPS nightmares. The relationship between HRR and nightmares remained significant after controlling for each of the other 16 individual PTSD symptoms, for the remaining reexperiencing cluster, and for CAPS total score. The zero-order correlations between SC response and nightmares and between electromyography response and nightmares were both not significant. The association of nightmares with larger HRR in the absence of an association with larger SC response likely reflects reduced parasympathetic tone. Thus, our findings indirectly support a role for reduced parasympathetic tone in PTSD nightmares.
28128994	Differences between the so-called larks and owls representing the opposite poles of morningness-eveningness dimension are widely known. However, scientific consensus has not yet been reached on the methodology for ranking and typing people along other dimensions of individual variation in their sleep-wake pattern. This review focused on the history and state-of-the-art of the methodology for self-assessment of individual differences in more than one trait or adaptability of the human sleep-wake cycle. The differences between this and other methodologies for the self-assessment of trait- and state-like variation in the perceived characteristics of daily rhythms were discussed and the critical issues that remained to be addressed in future studies were highlighted. These issues include a) a failure to develop a unidimensional scale for scoring chronotypological differences, b) the inconclusive results of the long-lasting search for objective markers of chronotype, c) a disagreement on both number and content of scales required for multidimensional self-assessment of chronobiological differences, d) a lack of evidence for the reliability and/or external validity of most of the proposed scales and e) an insufficient development of conceptualizations, models and model-based quantitative simulations linking the differences between people in their sleep-wake pattern with the differences in the basic parameters of underlying chronoregulatory processes. It seems that, in the nearest future, the wide implementation of portable actigraphic and somnographic devices might lead to the development of objective methodologies for multidimensional assessment and classification of sleep-wake traits and adaptabilities.
28127845	Sleep problems in people with dementia are common and place a high burden on caregivers. Although hypnotic agents are often used to treat sleep disturbances, their use is associated with a considerable number of high-risk side-effects such as daytime sleepiness, amnesia, and an increased frequency of falling. The administration of bright light therapy (BLT) in the morning was a non-pharmacological remedy that was expected to treat sleep disorders in patients with dementia by entraining the circadian rhythm to ameliorate disturbances to the normal sleep-wake cycle. However, there are some unsolved issues related to the application of BLT, including the types of dementia for which it is effective and its efficacy in the different stages of cognitive decline and dementia. Furthermore, a protocol for effective BLT has not yet been proposed.In this study, we explored the efficacy of BLT in the treatment of 17 participants, including those with Alzheimer's type dementia (AD) (n = 8), vascular dementia (n = 4), and dementia with Lewy bodies (n = 5). Patients sat in front of the light box for 1 h/day from 0900 to 1000. The patients underwent treatment every day for 2 weeks.	BLT led to the improvement of sleep disturbance in four participants, all of whom were AD patients. The four AD patients showed a shorter duration of illness and/or had mild to moderate AD.	BLT could be an effective strategy for treating dementia patients, depending on their type and grade of their dementia. To confirm this hypothesis, it would be necessary to study a larger number of cases. Non-pharmacological therapies for sleep disorders should be emphasized as a safe form of treatment for patients with dementia.	
28124114	A growing body of evidence suggests that dopamine plays a role in sleep-wake regulation, but the dopamine-producing brain areas that control sleep-wake states are unclear. In this study, we chemogenetically activated dopamine neurons in the ventral midbrain of mice to examine the role of these neurons in sleep-wake regulation. We found that activation of dopamine neurons in the ventral tegmental area (VTA), but not in the substantia nigra, strongly induced wakefulness, although both cell populations expressed the neuronal activity marker c-Fos after chemogenetic stimulation. Analysis of the pattern of behavioral states revealed that VTA activation increased the duration of wakefulness and decreased the number of wakefulness episodes, indicating that wakefulness was consolidated by VTA activation. The increased wakefulness evoked by VTA activation was completely abolished by pretreatment with the dopamine D2/D3 receptor antagonist raclopride, but not by the D1 receptor antagonist SCH23390. These findings indicate that the activation of VTA dopamine neurons promotes wakefulness via D2/D3 receptors.
28123823	Sleep problems represent a worldwide health concern but their prevalence and impacts are unknown in most non-European/North American countries. This study aimed to evaluate sleep-wake patterns, sleep quality and potential correlates of poor sleep in a sample of the urban Georgian population.Analyses are based on 395 volunteers (267 females, 128 males, aged 20-60 years) of the Georgia Somnus Study. Subjects completed the Pittsburgh Sleep Quality Index (PSQI) and the Beck Depression Inventory-Short Form. Sociodemographic information and self-reported height and weight were collected.	43% of subjects had poor sleep quality (PSQI > 5). Further, 41% had low sleep efficiency, 27.6% slept 6 hours or less, 32.4% went to bed after midnight, 27.6% snored, 10.6% were taking sleep medication, and 26.8% had sleep maintenance problems as occurring three or more times a week. The latest bedtime, rise time, and gender effect on these variables were found in the age group 20-29 years. PSQI global score showed a significant age but not gender difference. The economic status and the depression score were two significant predictors of sleep quality.	Poor sleep quality has a high prevalence and is strongly linked to the economic status. Study findings call for a global assessment of sleep problems in countries where sleep disturbances represent an insufficiently recognized public health issue.	
28119579	Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin (Lf) and milk fat globule membrane (MFGM) will reduce the negative physiological impacts of stress. Male F344 rats, postnatal day (PND) 24, received a diet with prebiotics, Lf and MFGM (test) or a calorically matched control diet. Fecal samples were collected on PND 35/70/91 for 16S rRNA sequencing to examine microbial composition and, in a subset of rats; Lactobacillus rhamnosus was measured using selective culture. On PND 59, biotelemetry devices were implanted to record sleep/wake electroencephalographic (EEG). Rats were exposed to an acute stressor (100, 1.5 mA, tail shocks) on PND 87 and recordings continued until PND 94. Test diet, compared to control diet, increased fecal Lactobacillus rhamnosus colony forming units (CFU), facilitated non-rapid eye movement (NREM) sleep consolidation (PND 71/72) and enhanced rapid eye movement (REM) sleep rebound after stressor exposure (PND 87). Rats fed control diet had stress-induced reductions in alpha diversity and diurnal amplitude of temperature, which were attenuated by the test diet (PND 91). Stepwise multiple regression analysis revealed a significant linear relationship between early-life Deferribacteres (PND 35) and longer NREM sleep episodes (PND 71/72). A diet containing prebiotics, Lf and MFGM enhanced sleep quality, which was related to changes in gut bacteria and modulated the impact of stress on sleep, diurnal rhythms and the gut microbiota.
28119195	The associations of moderate alcohol consumption, sleep duration, and tobacco smoking with coronary heart disease (CHD) among patients with type 2 diabetes mellitus (T2D) are not clearly clarified. The aims of the study were to evaluate the associations of lifestyle factors, hypertension, obesity, depression and sleep duration with CHD development among patients with T2D, and particularly, to examine the gender differences in risk factors for CHD.A total of 2335 T2D adults were selected from the 2012 National Health Interview Survey. Weighted univariate and multiple logistic regression analyses were used to estimate the odds ratios with 95% confidence intervals.	The CHD prevalence among patients with T2D was 14.2% (18.1% and 10.4% for males and females, respectively), which increased with age (10.3% and 19.6% for age groups 18-64 and 65+, respectively). After adjusting for other factors, weighted logistic regression analyses showed that CHD among patients with T2D was significantly associated with being male, older age, past smoking, long sleep duration, hypertension, and high cholesterol level. Furthermore, the significant association of older age, past smoking, hypertension and high cholesterol level were observed particularly in males, while the association of long sleep duration with CHD was only observed in females. Hypertension was associated with CHD for both genders.	Gender, age, past smoking, long sleep duration, hypertension and high cholesterol level were significantly associated with CHD among T2D patients; however, such associations differed by gender. Such gender disparities should be considered in the prevention and treatment of T2D.	
28118871	Accelerometry can be a practical replacement for polysomnography in large observational studies. This review discusses the need for sleep characterization in large observational studies, exemplified by the practices of the ongoing German National Cohort study. After brief descriptions of the physical principles and state-of-the-art accelerometer devices and an overview of public data analysis algorithms for sleep-wake differentiation, we demonstrate that the spectral properties of acceleration data provide additional features that can be exploited. This leads to a periodogram-based sleep detection algorithm. Finally, we address issues of data handling and quality assurance in large cohort studies.
28117135	Sleep problems are common, reported by a quarter of parents with children under the age of 5 years, and have been associated with poor behavior, worse school performance, and obesity, in addition to negative secondary effects on maternal and family well-being. Yet, it has been shown that pediatricians do not adequately address sleep in routine well-child visits, and underdiagnose sleep issues. Pediatricians receive little formal training in medical school or in residency regarding sleep medicine. An understanding of the physiology of sleep is critical to a pediatrician׳s ability to effectively and confidently counsel patients about sleep. The biological rhythm of sleep and waking is regulated through both circadian and homeostatic processes. Sleep also has an internal rhythmic organization, or sleep architecture, which includes sleep cycles of REM and NREM sleep. Arousal and sleep (REM and NREM) are active and complex neurophysiologic processes, involving both neural pathway activation and suppression. These physiologic processes change over the life course, especially in the first 5 years. Adequate sleep is often difficult to achieve, yet is considered very important to optimal daily function and behavior in children; thus, understanding optimal sleep duration and patterns is critical for pediatricians. There is little experimental evidence that guides sleep recommendations, rather normative data and expert recommendations. Effective counseling on child sleep must account for the child and parent factors (child temperament, parent-child interaction, and parental affect) and the environmental factors (cultural, geographic, and home environment, especially media exposure) that influence sleep. To promote health and to prevent and manage sleep problems, the American Academy of Pediatrics (AAP) recommends that parents start promoting good sleep hygiene, with a sleep-promoting environment and a bedtime routine in infancy, and throughout childhood. Thus, counseling families on sleep requires an understanding of sleep regulation, physiology, developmental patterns, optimal sleep duration recommendations, and the many factors that influence sleep and sleep hygiene.
28116784	Parkinson's disease (PD) and multiple system atrophy (MSA) are disorders associated with α synuclein-related neurodegeneration. Nonmotor symptoms are common hallmarks of these disorders, and disturbances of the sleep-wake cycle are among the most common nonmotor symptoms. It is only recently that sleep disturbances have received the attention of the medical and research community. Significant progress has been made in understanding the pathophysiology of sleep and wake disruption in alphasynucleinopathies during the past few decades. Despite these advancements, treatment options are limited and frequently associated with problematic side effects. Further studies that center on the development of novel treatment approaches are very much needed. In this article, the author discusses the current state of the management of disturbed sleep and alertness in PD and MSA. © 2017 International Parkinson and Movement Disorder Society.
28114147	Hemodialysis (HD) patients are less active than their healthy counterparts. They are often plagued with sleep disorders that affect the quality of their sleep. Our aim was to objectively quantify activity and sleep quality among HD patients in a suburban HD population.Activity and sleep parameters were measured using a commercially available activity tracker in 29 HD patients from Baton Rouge, LA, USA. Patients in the feedback group received their activity and sleep data at each dialysis treatment. In addition, questionnaires were administered at the beginning and end of the study period. Patients were stratified based on activity levels and sleep quality.	Patients walked an average of 5,281 steps/day and slept 370.5 min/night. Informing patients about their daily number of steps taken, did not increase activity. Only 3% of the population followed were active, defined as walking more than 10,000 steps per day. Patients walked significantly less on dialysis days compared to the other days of the week. Many of the patients experienced poor sleep quality, with patients in the first shift experiencing the greatest disturbance to their sleep/wake cycle.	Patients in a suburban environment walked much less than those in a previously studied urban population. They rarely met the recommended goal of 10,000 steps/day, even on non-dialysis days. Interventions to increase physical activity may target any day of the week, particularly HD days. Prospective, long-term studies are needed to evaluate the use of activity trackers in dialysis patients and their impact on physical activity.	
28105535	Orexin-A and orexin-B (Ox-A, Ox-B) are neuropeptides produced by a small number of neurons that originate in the hypothalamus and project widely in the brain. Only discovered in 1998, the orexins are already known to regulate several behaviours. Most prominently, they help to stabilise the waking state, a role with demonstrated significance in the clinical management of narcolepsy and insomnia. Orexins bind to G-protein-coupled receptors (predominantly postsynaptic) of two subtypes, OX1R and OX2R. The primary effect of Ox-OXR binding is a direct depolarising influence mediated by cell membrane cation channels, but a wide variety of secondary effects, both pre- and postsynaptic, are also emerging. Given that inhibitory GABAergic neurons also influence orexin-regulated behaviours, crosstalk between the two systems is expected, but at the cellular level, little is known and possible mechanisms remain unidentified. Here, we have used an expression system approach to examine the feasibility, and nature, of possible postsynaptic crosstalk between Ox-A and the GABAA receptor (GABAAR), the brain's main inhibitory neuroreceptor. When HEK293 cells transfected with OX1R and the α1, β1, and γ2S subunits of GABAAR were exposed to Ox-A, GABA-induced currents were inhibited, in a calcium-dependent manner. This inhibition was associated with increased phosphorylation of the β1 subunit of GABAAR, and the inhibition could itself be attenuated by (1) kinase inhibitors (of protein kinase C and CaM kinase II) and (2) the mutation, to alanine, of serine 409 of the β1 subunit, a site previously identified in phosphorylation-dependent regulation in other pathways. These results are the first to directly support the feasibility of postsynaptic crosstalk between Ox-A and GABAAR, indicating a process in which Ox-A could promote phosphorylation of the β1 subunit, reducing the GABA-induced, hyperpolarising current. In this model, Ox-A/GABAAR crosstalk would cause the depolarising influence of Ox-A to be boosted, a type of positive feedback that could, for example, facilitate the ability to abruptly awake.
28104063	Sleep complaints and sleep disturbances are common in depression; however, the association of sleep duration and subjective sleep quality has been rarely investigated. Thus, subjective sleep quality and sleep duration were analyzed in depressed inpatients. Questionnaire data comprising clinical and sleep-related questions were sampled over a one-year period from adult inpatients with depressive syndromes. Sleep duration and items related to sleep quality were analyzed by means of group comparisons (sleep duration categories) and correlation analyses. Data of 154 patients (age 58.2±17.0 years, 63.6% women) were analyzed. Mean sleep duration was 7.2±2.1 h (16.9% of patients were below and 7.1% above age-specific recommendations), 25-40% of patients reported almost always daytime sleepiness, non-restorative sleep, attention deficits, or memory complaints with significant correlations between all variables (P<0.05). Sleep duration and sleep quality indicators showed significant curvilinear associations (quadratic contrast, P<0.05); i.e. extremely low and high sleep durations were associated with unfavorable sleep quality and subjective cognitive impairment. Non-recommended low or high sleep durations occur in a substantial proportion of patients with depression, and both were associated with poor sleep quality and subjectively impaired cognitive functions. Clinicians should be aware of these relationships. During hospitalization, a more individualized sleep-wake schedule should be applied.
28102151	Research evidence increasingly points to the large impact of sleep disturbances on public health. Many aspects of sleep are heritable and genes influencing traits such as timing, EEG characteristics, sleep duration, and response to sleep loss have been identified. Notably, large-scale genome-wide analyses have implicated numerous genes with small effects on sleep timing. Additionally, there has been considerable progress in the identification of genes influencing risk for some neurological sleep disorders. For restless legs syndrome, implicated variants are typically in genes associated with neuronal development. By contrast, genes conferring risk for narcolepsy function in the immune system. Many genetic variants associated with sleep disorders are also implicated in neurological disorders in which sleep abnormalities are common; for example, variation in genes involved in synaptic homoeostasis are implicated in autism spectrum disorder and sleep-wake control. Further investigation into pleiotropic roles of genes influencing both sleep and neurological disorders could lead to new treatment strategies for a variety of sleep disturbances.
28100870	Periodic leg movements during sleep (PLM) are characterized by regularly recurring movement of the legs during sleep. Although PLM is common and a predictor of death in patients with chronic heart failure, the clinical significance of PLM in hospitalized patients with a reduced left ventricular ejection fraction (LVEF) following acute decompensated heart failure (ADHF) remains unknown.Methods and Results:After initial improvement of acute signs and symptoms of ADHF, 94 consecutive patients with reduced LVEF who underwent polysomnography were enrolled. They were divided into 2 groups based on the presence or absence of severe PLM defined as PLM index ≥30. The risks for clinical events, composite of all-cause death and rehospitalization, were assessed using a stepwise multivariable Cox proportional model including variables showing P<0.10 in univariate analyses. Severe PLM was observed in 21 patients (22%). At a median follow-up of 5.2 months, 30 patients experienced clinical events (32%). In the multivariable analysis, the presence of severe PLM was significantly associated with increasing clinical events (hazard ratio, 2.16; 95% confidence interval, 1.03-4.54; P=0.042) independent of hemoglobin level and the severity of sleep-disordered breathing.In hospitalized patients with systolic dysfunction following ADHF, severe PLM was prevalent and significantly associated with increased risk of death and/or rehospitalization.	
28094998	Both impulsivity and sleep disturbance have been associated with heavy alcohol use among young adults; yet studies to date have not examined their interactive effects. The current study aimed to determine if adequate sleep moderates the association between impulsive personality traits and alcohol use among young adults. College students (N = 568) who had been mandated to alcohol treatment following violation of campus alcohol policy provided information regarding alcohol use and related consequences, impulsive personality traits (measured using the UPPS Impulsive Behavior Scale), and perception of sleep adequacy as part of a larger intervention trial. Higher urgency, lower premeditation, and higher sensation-seeking predicted greater levels of alcohol consumption, while higher urgency predicted more alcohol-related consequences. As hypothesized, there was a significant interaction between premeditation and sleep adequacy in the prediction of drinks per week; in contrast to hypotheses, however, premeditation was associated with drinking only among those reporting adequate (rather than inadequate) sleep. Specifically, the tendency to premeditate was associated with less drinking among those who reported adequate sleep and was not associated with drinking among those reporting inadequate sleep. Sensation-seeking and urgency are associated with greater alcohol involvement among young adults, regardless of sleep adequacy. Conversely, the ability to plan ahead and anticipate the consequences of one's behaviors (premeditation) is only protective against heavy drinking among individuals receiving adequate sleep. With replication, these findings may inform alcohol prevention and intervention efforts. (PsycINFO Database Record
28092792	Curiosity, the tendency to engage in novel and challenging opportunities, may be an important source of resilience for those at risk for suicide. We hypothesized that curiosity would have a buffering effect against risk conferred by multiple sources of distress, whereby curiosity would be associated with reduced suicidal ideation and increased coping efficacy. As part of a larger intervention trial designed to improve coping skills and reduce suicidal ideation, 117 military veterans with suicidal ideation completed measures of curiosity and distress (perceived stress, depression, anxiety, and sleep disturbances) at baseline, and completed measures of suicidal ideation and coping efficacy (to stop negative thoughts, to enlist support from friends and family) at baseline and 3-, 6-, and 12-week follow up. Growth curve models showed that curiosity moderated the association between distress and suicidal ideation at baseline and that curiosity moderated the association between distress and increased coping efficacy to stop negative thoughts over time. Findings suggest that curiosity may buffer against the effect of heightened levels of distress on suicidal ideation and help facilitate stronger gains in coping efficacy over time. Additional work should further examine the role of curiosity as a protective factor for veterans with suicidal ideation.
28089853	Using a rat model of chronic sleep restriction (CSR) featuring periodic sleep deprivation with slowly rotating wheels (3h on/1h off), we previously observed that 99h of this protocol induced both homeostatic and allostatic (adaptive) changes in physiological and behavioural measures. Notably, the initial changes in sleep intensity and attention performance gradually adapted during CSR despite accumulating sleep loss. To identify brain regions involved in these responses, we used FosB/ΔFosB immunohistochemistry as a marker of chronic neuronal activation. Adult male rats were housed in motorized activity wheels and underwent the 3/1 CSR protocol for 99h, or 99h followed by 6 or 12days of recovery. Control rats were housed in home cages, locked activity wheels, or unlocked activity wheels that the animals could turn freely. Immunohistochemistry was conducted using an antibody that recognized both FosB and ΔFosB, and 24 brain regions involved in sleep/wake, autonomic, and limbic functions were examined. The number of darkly-stained FosB/ΔFosB-immunoreactive cells was increased immediately following 99h of CSR in 8/24 brain regions, including the medial preoptic and perifornical lateral hypothalamic areas, dorsomedial and paraventricular hypothalamic nuclei, and paraventricular thalamic nucleus. FosB/ΔFosB labeling was at control levels in all 8 brain areas following 6 or 12 recovery days, suggesting that most of the immunoreactivity immediately after CSR reflected FosB, the more transient marker of chronic neuronal activation. This region-specific induction of FosB/ΔFosB following CSR may be involved in the mechanisms underlying the allostatic changes in behavioural and physiological responses to CSR.
28084629	Postpartum sleep and fatigue have bidirectional relationships with depressive symptoms and challenge women's everyday functioning. The everyday process of managing postpartum sleep and fatigue in the context of depressive symptoms remains unexplored. We conducted a grounded theory study with a sample of 19 women who screened positive on the Postpartum Depression Screening Scale (PDSS™) Short Form at 3 weeks postpartum. Women completed semi-structured in-home interviews and the full PDSS and Modified Fatigue Symptoms Checklist at 1, 3, and 6 months postpartum. The sample was on average 27 years old, with 2.8 children, and 63% were African-American. They described a basic social process of Finding a Routine Together, during which women's experiences with their infants progressed from Retreating at month 1 toward Finding a New Normal at month 6. In their work to Find a Routine Together, mothers' patterns of change over time were continuous, gradual, or prolonged. Their progress was influenced by depressive symptoms, social support, work and daycare, stability in social circumstances, and underlying stressors. This study's findings suggest the need to allocate resources and tailor interventions to meet the needs of women who are most vulnerable to the health effects of ongoing persistent severe fatigue, disordered sleep, and sub-clinical and clinical levels of depressive symptoms. © 2017 Wiley Periodicals, Inc.
28084151	Enuresis results in behavioural disorder in children. This study investigated the behavioural disorders in children possessing primary enuresis.In this cross-sectional study, 100 children with primary enuresis were referred to children's hospital Khorramabad; the census method was used in this study. Data were collected using a short screening instrument for enuresis psychological problems, the reliability and validity of which have been confirmed in previous studies. First, a questionnaire was used to assess academic failure, anxiety, behavioural disorders, sleep, and psychological disorders. Results obtained were compared in terms of gender and age. Statistical analyses using inferential and descriptive statistics including Chi-square and Fisher test were employed.	The average age of children was 8.46 years. Sixty-six per cent of participants were male and the rest of them were female. Ninety per cent of subjects were between the age range of 1-9 years, and 10% were over 10 years old. Forty-three per cent of children suffered from anxiety disorders and 34% had sleep disorders, 4% also suffered from academic failure. Among behavioural disorders, hyperactivity and restlessness were the most common disorders, and they were significantly higher in nine boys. Headache, obsessive, and sleep disorders were more common in children above 10. There was a significant correlation between eating disorders, headache, sleep disorders, and strange movements in males, while feelings of sadness were more common in females.	Social personality development in children with enuresis can be improved by informing parents of enuresis.	
28083705	The aim of this randomized placebo-controlled trail was to compare the effects of an objectively titrated mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) and an intraoral placebo device on symptoms of psychological distress in OSA patients.In a parallel design, 64 mild/moderate OSA patients (52.0 ± 9.6 years) were randomly assigned to an objectively titrated MAD, nCPAP, or an intraoral placebo appliance. All patients filled out the Symptom Checklist-90-Revised twice: one before treatment and one after 6 months of treatment. The Symptom Checklist-90-Revised is a multidimensional symptom inventory designed to measure symptomatic psychological distress over the past week. Linear mixed model analyses were performed to study differences between the therapy groups for the different dimensions of the Symptom Checklist-90-Revised over time.	The MAD group showed significant improvements over time in the dimensions "somatization," "insufficiency of thinking and acting," "agoraphobia," "anxiety," "sleeping problems," and "global severity index" (F = 4.14-16.73, P = 0.048-0.000). These improvements in symptoms of psychological distress were, however, not significantly different from those observed in the nCPAP and placebo groups (P = 0.374-0.953).	There is no significant difference between MAD, nCPAP, and an intraoral placebo appliance in their beneficial effects on symptoms of psychological distress.	The improvement in psychological distress symptoms in mild/moderate OSA patients under MAD or nCPAP treatment may be explained by a placebo effect.	
28082331	Sleep complaints are consistently cited as the most prominent health and well-being problem in Arctic and Antarctic expeditions, without clear evidence to identify the causal mechanisms. The present investigation aimed at studying sleep and determining circadian regulation and mood during a 4-mo Antarctic summer expedition. All data collection was performed during the continuous illumination of the Antarctic summer. After an habituation night and acclimatization to the environment (3 wk), ambulatory polysomnography (PSG) was performed in 21 healthy male subjects, free of medication. An 18-h profile (saliva sampling every 2 h) of cortisol and melatonin was assessed. Mood, sleepiness, and subjective sleep quality were assessed, and the psychomotor vigilance task was administered. PSG showed, in addition to high sleep fragmentation, a major decrease in slow-wave sleep (SWS) and an increase in stage R sleep. Furthermore, the ultradian rhythmicity of sleep was altered, with SWS occurring mainly at the end of the night and stage R sleep at the beginning. Cortisol secretion profiles were normal; melatonin secretion, however, showed a severe phase delay. There were no mood alterations according to the Profile of Mood States scores, but the psychomotor vigilance test showed an impaired vigilance performance. These results confirm previous reports on "polar insomnia", the decrease in SWS, and present novel insight, the disturbed ultradian sleep structure. A hypothesis is formulated linking the prolonged SWS latency to the phase delay in melatonin.NEW & NOTEWORTHY The present paper presents a rare body of work on sleep and sleep wake regulation in the extreme environment of an Antarctic expedition, documenting the effects of constant illumination on sleep, mood, and chronobiology. For applied research, these results suggest the potential efficiency of melatonin supplementation in similar deployments. For fundamental research, these results warrant further investigation of the potential link between melatonin secretion and the onset of slow-wave sleep.
28079475	To observe the effects of hyperbaric oxygen (HBO2) therapy on the treatment of sleep disorders and its safety in children with cerebral palsy (CP).A total of 71 recruited children were divided into two groups based on age: group 1, aged between 2 and 4 years; and group 2, aged between 4 and 6 years. The effects of HBO2 therapy on sleep quality were observed.	The total sleep items (TSIs) were significantly different in the two groups between pre-HBO2, post 10 HBO2 sessions, and post 20 HBO2 sessions (p < 0.01). A total of 15/38 (39.5%) participants in group 1 and 8/21 (38.0%) in group 2 presented difficulty in falling asleep; 17/38 (44.7%) in group 1 and 4/21 (19.0%) in group 2 had a short duration of sleep during the night; and 20/38 (52.6%) in group 1 and 11/21 (52.4%) in group 2 woke up easily in the night. No significant difference in the average TSIs in 59 participants was found after 10 HBO2 sessions. Eight participants had insomnia after the first 5 sessions, and three in group 2 had nocturnal hyperkinesia after 15 sessions. A seizure during decompression was observed in 2/59 participants (2/419 sessions).	These results indicate that HBO2 therapy is beneficial to improve sleep and is safe for children with CP; however, further studies are necessary to explore the mechanisms of HBO2 on sleep.	
28078839	Located within the ascending reticular activating system are nuclei which release neurotransmitters such as acetylcholine, serotonin, dopamine, and norepinephrine. These nuclei have widespread projections that extend into the limbic system and throughout cortex. Activation of these neurotransmitters during awake states leads to arousal, while inhibition leads to the loss of consciousness experienced during slow-wave sleep. Previously, we proposed a mechanism in which cardiorespiratory synchronization may underlie the widespread hyperpolarization that occurs throughout the brain during slow-wave sleep. We further propose that a similar homeostatic mechanism may be involved in sleep-wake transitions and maintaining various arousal states including rapid eye movement sleep, waking, and anxiety. Widespread depolarization associated with more rapid, shallow breathing and desynchronized cardiorespiratory oscillatory activity may underlie waking, anxiety, and rapid eye movement sleep states. The exact voltage values of these widespread membrane potential changes remain unknown and possibly highly variable between different neural areas and cell types. Here, we place these consciousness states on a spectrum of approximated widespread membrane potential values with anxiety states being the most depolarized, followed by waking states, and rapid eye movement sleep. We propose that although these widespread membrane potential changes are minor, they may underlie transitions between and maintenance of varying levels of arousal. Further research on these mechanisms could provide insights into how the brain functions. This homeodynamic arousal mechanism involves the established feed-forward and feedback signaling between the ascending reticular activating system and the hypothalamus, as well as the modulation by cardiorespiratory oscillatory feedback from the body. Understanding the basic mechanisms responsible for the states of sleep, waking, and anxiety could lead to better treatment options in health and disease.
28077269	Individual differences in ability to overcome desire to fall asleep cannot be accurately predicted from subjective and objective measurements of sleepiness level. Previously, we showed that an exponential buildup of sleep pressure during prolonged wakefulness can be accurately traced with electroencephalographic (EEG) indexes, such as Spectral Sleep Pressure Component (SSPC) score and score on the 2nd principal component (2PC) of the EEG spectrum. The anterior-posterior gradients in SSPC and 2PC scores were calculated as the differences between frontal and occipital scores and examined as possible correlates of individual's ability to overcome desire of falling asleep. Fifteen young and 15 older adults participated in two identically designed sleep deprivation experiments. After, at least, 12hours of wakefulness, resting EEG recordings were obtained from frontal and occipital derivations with 2-h intervals during 26-50hours. Due to irresistible desire to sleep, 11 young and 5 older adults completed <25 required EEG recordings. SSPC and 2PC scores were computed and, by subtracting occipital scores from frontal scores, the anterior-posterior gradients in SSPC and 2PC scores were calculated on one-min intervals of 5-min eyes closed EEG records. The analysis of these anterior-posterior gradients revealed their age-related difference and association with the number of completed EEG recording sessions (13-25). This association remained significant after accounting for age, alertness-sleepiness level, minute of eyes closed recording, and day of experiment. It seems that the anterior-posterior gradients in the EEG indexes of sleep pressure are the objective correlates of individual's ability to overcome desire to fall asleep.
28076377	From photosynthetic bacteria to mammals, the circadian clock evolved to track diurnal rhythms and enable organisms to anticipate daily recurring changes such as temperature and light. It orchestrates a broad spectrum of physiology such as the sleep/wake and eating/fasting cycles. While we have made tremendous advances in our understanding of the molecular details of the circadian clock mechanism and how it is synchronized with the environment, we still have rudimentary knowledge regarding its connection to help regulate diurnal physiology. One potential reason is the sheer size of the output network. Diurnal/circadian transcriptomic studies are reporting that around 10% of the expressed genome is rhythmically controlled. Zebrafish is an important model system for the study of the core circadian mechanism in vertebrate. As Zebrafish share more than 70% of its genes with human, it could also be an additional model in addition to rodent for exploring the diurnal/circadian output with potential for translational relevance. Here we performed comparative diurnal/circadian transcriptome analysis with established mouse liver and other tissue datasets. First, by combining liver tissue sampling in a 48h time series, transcription profiling using oligonucleotide arrays and bioinformatics analysis, we profiled rhythmic transcripts and identified 2609 rhythmic genes. The comparative analysis revealed interesting features of the output network regarding number of rhythmic genes, proportion of tissue specific genes and the extent of transcription factor family expression. Undoubtedly, the Zebrafish model system will help identify new vertebrate outputs and their regulators and provides leads for further characterization of the diurnal cis-regulatory network.
28075423	INTRODUCTION Slow breathing training (SBT) has been proposed as a new nonpharmacologic treatment in patients with chronic heart failure (CHF). OBJECTIVES The aim of this study was to assess the effects of SBT on exercise capacity, hemodynamic parameters, and sleep respiratory patterns in a relatively large sample of CHF patients. PATIENTS AND METHODS A crossover open study was conducted. Patients completed, in a random order, 10- to 12‑week SBT, with 2 15‑minute sessions of device‑guided SBT each day, reaching 6 breaths/ min, and a 10- to 12‑week follow‑up under standard care. Clinical data collection, polysomnography, echocardiography, 6‑minute walk test (6MWT), and laboratory tests were performed. RESULTS A total of 96 patients (74 men, 22 women) in New York Heart Association classes I-III, with an average age of 65 years and an ejection fraction (EF) of 31%, completed the study. Home‑based SBT was safe. After training, EF and 6MWT distance improved (EF: 31.3% ±7.3% vs 32.3% ±7.7%; P = 0.030; 6MWT: 449.9 ±122.7 m vs 468.3 ±121.9 m; P <0.001), and the apnea-hypopnea index decreased (5.6 [interquartile range (IQR), 2.1; 12.8] vs. 5.4 [IQR, 2.0; 10.8]; P = 0.043). CONCLUSIONS SBT improved physical capacity and systolic heart function; it also diminished sleep disturbances. The results support the benefits of SBT as a novel component of cardiorespiratory rehabilitation programs in patients with CHF.
28072860	Hyperbilirubinemia is a common cause for irreversible neuronal influence in the brain of term newborns, while the feature of neurological symptoms associated with hyperbilirubinemia has not been well characterized yet. In the present study, we examined a total of 203 neonates suffering from hyperbilirubinemia with a bedside amplitude-integrated Electroencephalography (aEEG) device, in order to determine whether there is any special change in sleep-wake cycles (SWCs). Among these patients, 14 cases showed no recognizable SWCs with the total serum bilirubin (TSB) level at 483.9-996.2 μmol/L; 75 cases exhibited reduced SWCs with the TSB level at 311.2-688.5 μmol/L; and the rest cases had the normal SWCs. The number of the normal SWCs occurrence had a significant negative correlation with the increased TSB level in a non-linear manner (r = -0.689, p <0.001). In addition, the increased TSB reshaped the structure of SWC by narrowing down the broadband and broadening the narrowband. Spearman's correlation analysis indicated a significant negative correlation between the TSB level and the ratio of broadband (r = -0.618, p < 0.001), a significant positive correlation between the TSB level and the narrowband ratio (r = 0.618, p < 0.001), respectively. Furthermore, the change of SWC seemed like a continuous phenomenon, and the hyperbilirubinemia caused SWC changes was fit into a loess model in this paper. In summary, the hyperbilirubinemia influenced SWC of term newborns significantly at a non-linear manner, and these results revealed the feature of the neurological sequela that is associated with TSB.
28072446	Few studies have investigated the effects of preoperative dexamethasone in acute surgical patients. This study examined the effects of 8 mg dexamethasone administered intravenously 30 min before surgery for suspected acute appendicitis.A multicentre, parallel-group, double-blind, placebo-controlled study was conducted at two university hospitals in Denmark. Adults undergoing laparoscopic surgery for suspected appendicitis were eligible for inclusion. Participants, healthcare staff and investigators were blinded until all data analysis had been done. The primary outcome was the incidence of postoperative nausea and vomiting (PONV) during the first postoperative day. Secondary outcomes were pain, fatigue, sleep, opioid consumption, use of antiemetics, quality of recovery and duration of convalescence. Analysis was done according to the intention-to-treat principle.	A total of 120 patients were enrolled; 57 patients in the dexamethasone group and 59 in the placebo group were eligible for primary analysis. In the dexamethasone group, 47 (95 per cent c.i. 35 to 60) per cent of patients experienced PONV compared with 63 (50 to 74) per cent) in the placebo group. The absolute risk reduction in PONV was 15 (-3 to 33) per cent in favour of the dexamethasone group (P = 0·098). Patients in the dexamethasone group had less pain at rest (difference in score on visual analogue scale (VAS) 9 (95 per cent c.i. 1 to 17) mm; P = 0·024), were less fatigued (difference in VAS score 7 (0 to 14) mm; P = 0·038), used fewer opioids (absolute risk reduction 17 (2 to 33) per cent; P = 0·033) and had better quality of recovery (difference in QoR-15 score 13 (4 to 22); P = 0·006) during the first postoperative day. There was no difference in postoperative complications (P = 0·595).	
28071711	Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3-/- mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3-/-) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3-/- mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3-/- nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3-/- phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light.


28066802	To describe the development and psychometric evaluation of the Children's Sleep-Wake Scale (CSWS), a caregiver-report measure of behavioral sleep quality in 2- to 8-year-old children.Five studies using independent samples were completed to generate, refine, and finalize the item pool, as well as to confirm the factor structure and to assess the reliability and validity of the CSWS.	Field.	CSWS, sleep diary, and actigraphy.	Confirmatory factor analysis supported the theoretically proposed 5-factor structure (Going to Bed, Falling Asleep, Maintaining Sleep, Reinitiating Sleep, Returning to Wakefulness). The final questionnaire included 25 items, with items rated on a 6-point scale (Never, Once in Awhile, Sometimes, Quite Often, Frequently-if not Always, and Always); higher scores indicate better sleep quality. We found excellent internal consistency reliability for subscales and the total scale (α = .81-α = .91), strong test-retest reliability (r = 0.67-r = 0.84; all P values < .001), moderate-to-strong correlations between CSWS subscale scores and corresponding parental diary ratings (r = 0.58-r = 0.72; all P values < .001), and weak-to-moderate correlations between CSWS subscales and actigraphic measures (r = 0.38-r = 0.61; all P values < .001). CSWS subscale scores discriminated 4 extreme groups, thus supporting the construct validity of the scale.	These collective findings indicate that the CSWS has adequate reliability and validity for research instruments and suggest that it is a convenient tool for assessing behavioral sleep quality in preschool-aged and school-aged children.	
28066710	This prospective uncontrolled study evaluated the effect of low-dose adjunctive perampanel therapy (4 mg/day for 3 months) on the sleep-wake cycle and daytime somnolence in adult patients (n = 10) with focal seizures. A > 50% reduction in the number of seizures was reported in 80% of the study patients; treatment had no significant effect on any sleep parameters as evident by the Maintenance of Wakefulness Test, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale scores. Two patients reported dizziness with treatment. In conclusion, low-dose perampanel may improve seizure control without affecting the sleep characteristics or daytime somnolence in patients with epilepsy.
28066138	Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAA receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABAA-ergic systems, and can be useful in the treatment of insomnia.
28065514	Childhood obesity has emerged as an important public health problem in the United States and other countries in the world. Currently 1 in 3 children in the United States is afflicted with overweight or obesity. The increasing prevalence of childhood obesity is associated with emergence of comorbidities previously considered to be "adult" diseases including type 2 diabetes mellitus, hypertension, nonalcoholic fatty liver disease, obstructive sleep apnea, and dyslipidemia. The most common cause of obesity in children is a positive energy balance due to caloric intake in excess of caloric expenditure combined with a genetic predisposition for weight gain. Most obese children do not have an underlying endocrine or single genetic cause for their weight gain. Evaluation of children with obesity is aimed at determining the cause of weight gain and assessing for comorbidities resulting from excess weight. Family-based lifestyle interventions, including dietary modifications and increased physical activity, are the cornerstone of weight management in children. A staged approach to pediatric weight management is recommended with consideration of the age of the child, severity of obesity, and presence of obesity-related comorbidities in determining the initial stage of treatment. Lifestyle interventions have shown only modest effect on weight loss, particularly in children with severe obesity. There is limited information on the efficacy and safety of medications for weight loss in children. Bariatric surgery has been found to be effective in decreasing excess weight and improving comorbidities in adolescents with severe obesity. However, there are limited data on the long-term efficacy and safety of bariatric surgery in adolescents. For this comprehensive review, the literature was scanned from 1994 to 2016 using PubMed using the following search terms: childhood obesity, pediatric obesity, childhood overweight, bariatric surgery, and adolescents.
28064405	Reports of sleep disturbances in attention deficit hyperactivity disorder (ADHD) are common in both children and adults; however, the aetiology of such disturbances is poorly understood. One potentially important mechanism which may be implicated in disrupted sleep in ADHD is the circadian clock, a known key regulator of the sleep/wake cycle. In this systematic review, we analyse the evidence for circadian rhythm changes associated with ADHD, as well as assessing evidence for therapeutic approaches involving the circadian clock in ADHD. We identify 62 relevant studies involving a total of 4462 ADHD patients. We find consistent evidence indicating that ADHD is associated with more eveningness/later chronotype and with phase delay of circadian phase markers such as dim light melatonin onset and delayed sleep onset. We find that there is evidence that melatonin treatment may be efficacious in addressing ADHD-related sleep problems, although there are few studies to date addressing other chronotherapeutic approaches in ADHD. There are only a small number of genetic association studies which report linkages between polymorphisms in circadian clock genes and ADHD symptoms. In conclusion, we find that there is consistent evidence for circadian rhythm disruption in ADHD and that such disruption may present a therapeutic target that future ADHD research might concentrate explicitly on.
28063234	Cross-cultural sleep research is critical to deciphering whether modern sleep expression is the product of recent selective pressures, or an example of evolutionary mismatch to ancestral sleep ecology. We worked with the Hadza, an equatorial, hunter-gatherer community in Tanzania, to better understand ancestral sleep patterns and to test hypotheses related to sleep segmentation.We used actigraphy to analyze sleep-wake patterns in thirty-three volunteers for a total of 393 days. Linear mixed effects modeling was performed to assess ecological predictors of sleep duration and quality. Additionally, functional linear modeling (FLM) was used to characterize 24-hr time averaged circadian patterns.	Compared with post-industrialized western populations, the Hadza were characterized by shorter (6.25 hr), poorer quality sleep (sleep efficiency = 68.9%), yet had stronger circadian rhythms. Sleep duration time was negatively influenced by greater activity, age, light (lux) exposure, and moon phase, and positively influenced by increased day length and mean nighttime temperature. The average daily nap ratio (i.e., the proportion of days where a nap was present) was 0.54 (SE = 0.05), with an average nap duration of 47.5 min (SE = 2.71; n = 139).	This study showed that circadian rhythms in small-scale foraging populations are more entrained to their ecological environments than Western populations. Additionally, Hadza sleep is characterized as flexible, with a consistent early morning sleep period yet reliance upon opportunistic daytime napping. We propose that plasticity in sleep-wake patterns has been a target of natural selection in human evolution.	
28062427	Sleep problems in toddlers occur in ∼40% of children and increase the likelihood of postnatal depression. Most sleep training in toddlers requires contact with a trained professional, and requires a parent to ignore their child's cries, causing distress to many children and parents, increasing attrition and leaving families untreated and at risk. This case study reports success in significantly ameliorating sleep reluctance and bedtime fears in a sleep disturbed toddler with a history of trauma. It uses a novel use of bedtime behaviour management with some positive reinforcement techniques, called the Boss of My Sleep book: a non-cry, online (thus readily and cheaply available without a trained professional) sleep intervention. The system was successful immediately and was sustained after 6 months. The Boss of My Sleep book shows promise as a sleep intervention in toddlers, particularly for those parents who do not want to use cry intensive methods.
28057302	Sleep disorders in humans are increasingly appreciated to be not only widespread but also detrimental to multiple facets of physical and mental health. Recent work has begun to shed light on the mechanistic basis of sleep disorders like insomnia, restless legs syndrome, narcolepsy, and a host of others, but a more detailed genetic and molecular understanding of how sleep goes awry is lacking. Over the past 15 years, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation. More recently, powerful genetic approaches in the fly have been applied toward studying primary human sleep disorders and other disease states associated with dysregulated sleep. In this review, we discuss the contribution of Drosophila to the landscape of sleep biology, examining not only fundamental advances in sleep neurobiology but also how flies have begun to inform pathological sleep states in humans.
28050973	Automated behavioral state classification can benefit next generation implantable epilepsy devices. In this study we explored the feasibility of automated awake (AW) and slow wave sleep (SWS) classification using wide bandwidth intracranial EEG (iEEG) in patients undergoing evaluation for epilepsy surgery.Data from seven patients (age [Formula: see text], 4 women) who underwent intracranial depth electrode implantation for iEEG monitoring were included. Spectral power features (0.1-600 Hz) spanning several frequency bands from a single electrode were used to train and test a support vector machine classifier.	Classification accuracy of 97.8  ±  0.3% (normal tissue) and 89.4  ±  0.8% (epileptic tissue) across seven subjects using multiple spectral power features from a single electrode was achieved. Spectral power features from electrodes placed in normal temporal neocortex were found to be more useful (accuracy 90.8  ±  0.8%) for sleep-wake state classification than electrodes located in normal hippocampus (87.1  ±  1.6%). Spectral power in high frequency band features (Ripple (80-250 Hz), Fast Ripple (250-600 Hz)) showed comparable performance for AW and SWS classification as the best performing Berger bands (Alpha, Beta, low Gamma) with accuracy  ⩾90% using a single electrode contact and single spectral feature.	Automated classification of wake and SWS should prove useful for future implantable epilepsy devices with limited computational power, memory, and number of electrodes. Applications include quantifying patient sleep patterns and behavioral state dependent detection, prediction, and electrical stimulation therapies.	
28049647	The suprachiasmatic nucleus (SCN) is the principal circadian clock of the brain, directing daily cycles of behavior and physiology. SCN neurons contain a cell-autonomous transcription-based clockwork but, in turn, circuit-level interactions synchronize the 20,000 or so SCN neurons into a robust and coherent daily timer. Synchronization requires neuropeptide signaling, regulated by a reciprocal interdependence between the molecular clockwork and rhythmic electrical activity, which in turn depends on a daytime Na+ drive and nighttime K+ drag. Recent studies exploiting intersectional genetics have started to identify the pacemaking roles of particular neuronal groups in the SCN. They support the idea that timekeeping involves nonlinear and hierarchical computations that create and incorporate timing information through the interactions between key groups of neurons within the SCN circuit. The field is now poised to elucidate these computations, their underlying cellular mechanisms, and how the SCN clock interacts with subordinate circadian clocks across the brain to determine the timing and efficiency of the sleep-wake cycle, and how perturbations of this coherence contribute to neurological and psychiatric illness.
28045199	Breast cancer is the cancer most frequently diagnosed in women worldwide. Even though survival rates are continually increasing, breast cancer is often associated with long-term psychological distress, chronic pain, fatigue and impaired quality of life. Yoga comprises advice for an ethical lifestyle, spiritual practice, physical activity, breathing exercises and meditation. It is a complementary therapy that is commonly recommended for breast cancer-related impairments and has been shown to improve physical and mental health in people with different cancer types.To assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment.	We searched the Cochrane Breast Cancer Specialised Register, MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), Indexing of Indian Medical Journals (IndMED), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal and Clinicaltrials.gov on 29 January 2016. We also searched reference lists of identified relevant trials or reviews, as well as conference proceedings of the International Congress on Complementary Medicine Research (ICCMR), the European Congress for Integrative Medicine (ECIM) and the American Society of Clinical Oncology (ASCO). We applied no language restrictions.	Randomised controlled trials were eligible when they (1) compared yoga interventions versus no therapy or versus any other active therapy in women with a diagnosis of non-metastatic or metastatic breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances.	Two review authors independently collected data on methods and results. We expressed outcomes as standardised mean differences (SMDs) with 95% confidence intervals (CIs) and conducted random-effects model meta-analyses. We assessed potential risk of publication bias through visual analysis of funnel plot symmetry and heterogeneity between studies by using the Chi2 test and the I2 statistic. We conducted subgroup analyses for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention.	We included 24 studies with a total of 2166 participants, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias.Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life (pooled SMD 0.22, 95% CI 0.04 to 0.40; 10 studies, 675 participants), reduced fatigue (pooled SMD -0.48, 95% CI -0.75 to -0.20; 11 studies, 883 participants) and reduced sleep disturbances in the short term (pooled SMD -0.25, 95% CI -0.40 to -0.09; six studies, 657 participants). The funnel plot for health-related quality of life was asymmetrical, favouring no therapy, and the funnel plot for fatigue was roughly symmetrical. This hints at overall low risk of publication bias. Yoga did not appear to reduce depression (pooled SMD -0.13, 95% CI -0.31 to 0.05; seven studies, 496 participants; low-quality evidence) or anxiety (pooled SMD -0.53, 95% CI -1.10 to 0.04; six studies, 346 participants; very low-quality evidence) in the short term and had no medium-term effects on health-related quality of life (pooled SMD 0.10, 95% CI -0.23 to 0.42; two studies, 146 participants; low-quality evidence) or fatigue (pooled SMD -0.04, 95% CI -0.36 to 0.29; two studies, 146 participants; low-quality evidence). Investigators reported no serious adverse events.Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression (pooled SMD -2.29, 95% CI -3.97 to -0.61; four studies, 226 participants), anxiety (pooled SMD -2.21, 95% CI -3.90 to -0.52; three studies, 195 participants) and fatigue (pooled SMD -0.90, 95% CI -1.31 to -0.50; two studies, 106 participants) in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life (pooled SMD 0.81, 95% CI -0.50 to 2.12; two studies, 153 participants) or sleep disturbances (pooled SMD -0.21, 95% CI -0.76 to 0.34; two studies, 119 participants). No trial adequately reported safety-related data.Three studies that compared yoga versus exercise presented very low-quality evidence showing no short-term effects on health-related quality of life (pooled SMD -0.04, 95% CI -0.30 to 0.23; three studies, 233 participants) or fatigue (pooled SMD -0.21, 95% CI -0.66 to 0.25; three studies, 233 participants); no trial provided safety-related data.	Moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.	
28045131	Morningness-eveningness (M/E) is an individual trait related to a person's sleep-wake cycle and preference for morning or evening hours. The "environment hypothesis" suggests that M/E is dependent on environmental factors, such as latitude, mean average temperature and photoperiod. We here analyzed a large number of datasets to assess this effect based on a systematic review. Data were from a total of 87 datasets and 35,589 individuals based on 28 countries. Partial correlations correcting for age revealed significant relationships between M/E and latitude, mean yearly temperature, photoperiod and sunset. Evening orientation was related to higher latitude, longer days and later sunset. Morning orientation was related to higher average temperatures. Percentage of females and sunrise time had no significant influence. These variables (sunset, temperature, photoperiod) were then input in a general linear model. The full model showed an influence of age and of sunset on CSM scores, but not of photoperiod and average temperature. Sunset, therefore, seems to be the most important statistical predictor for the observed latitudinal gradient.
28042731	To investigate the association between physical fitness, obesity, health related quality of life (HRQoL) and sleep disturbance in 463 community-dwelling older Spanish women (66-91 years of age).Cross-sectional study.	Sleep disturbance was assessed with the Jenkins Sleep Scale. Active and sedentary behaviors were recorded by standardized questionnaires. HRQoL was assessed with the EuroQoL-5D. Anthropometric measurements were obtained using standardized techniques. Body fat was measured using bioelectrical impedance. Physical fitness was evaluated by a set of eight tests.	Sleep disturbance was reported by 45.1% of women, being associated with higher body mass index (p < 0.05) and waist circumference (p < 0.01). Presence of insomnia was inversely associated with physical fitness. Women in the upper tertile of fitness index had 92.0% lower risk of sleep disturbance as compared to the lower tertile (p = 0.08), while women in the highest tertile of upper body strength had 76.4% lower risk of sleep disturbance as compared to the lower tertile (p < 0.05). Women without sleep disturbance showed better HRQoL.	Sleep disturbance was associated with central obesity, lower physical fitness and reduced HRQoL. Interventions involving weight management and improvement of physical fitness may contribute to better sleep quality in older women.	
28039375	The pedunculopontine tegmental (PPT) nucleus has long been implicated in the regulation of cortical activity and behavioral states, including rapid eye-movement (REM) sleep. For example, electrical stimulation of the PPT region during sleep leads to rapid awakening, whereas lesions of the PPT in cats reduce REM sleep. Though these effects have been linked with the activity of cholinergic PPT neurons, the PPT also includes intermingled glutamatergic and GABAergic cell populations, and the precise roles of cholinergic, glutamatergic, and GABAergic PPT cell groups in regulating cortical activity and behavioral state remain unknown. Using a chemogenetic approach in three Cre-driver mouse lines, we found that selective activation of glutamatergic PPT neurons induced prolonged cortical activation and behavioral wakefulness, whereas inhibition reduced wakefulness and increased non-REM (NREM) sleep. Activation of cholinergic PPT neurons suppressed lower-frequency electroencephalogram rhythms during NREM sleep. Last, activation of GABAergic PPT neurons slightly reduced REM sleep. These findings reveal that glutamatergic, cholinergic, and GABAergic PPT neurons differentially influence cortical activity and sleep/wake states.More than 40 million Americans suffer from chronic sleep disruption, and the development of effective treatments requires a more detailed understanding of the neuronal mechanisms controlling sleep and arousal. The pedunculopontine tegmental (PPT) nucleus has long been considered a key site for regulating wakefulness and REM sleep. This is mainly because of the cholinergic neurons contained in the PPT nucleus. However, the PPT nucleus also contains glutamatergic and GABAergic neurons that likely contribute to the regulation of cortical activity and sleep-wake states. The chemogenetic experiments in the present study reveal that cholinergic, glutamatergic, and GABAergic PPT neurons each have distinct effects on sleep/wake behavior, improving our understanding of how the PPT nucleus regulates cortical activity and behavioral states.	
28039311	To assess the association between sleep structure and cognitive impairment in the general population.Data stemmed from 580 participants aged >65 years of the population-based CoLaus/PsyCoLaus study (Lausanne, Switzerland) who underwent complete sleep evaluation (HypnoLaus). Evaluations included demographic characteristics, personal and treatment history, sleep complaints and habits (using validated questionnaires), and a complete polysomnography at home. Cognitive function was evaluated using a comprehensive neuropsychological test battery and a questionnaire on the participant's everyday activities. Participants with cognitive impairment (global Clinical Dementia Rating [CDR] scale score > 0) were compared with participants with no cognitive impairment (global CDR score = 0).	The 291 participants with a CDR score > 0 (72.5 ± 4.6 years), compared to the 289 controls with CDR = 0 (72.1 ± 4.6 years), had significantly more light (stage N1) and less deep (stage N3) and REM sleep, as well as lower sleep efficiency, higher intrasleep wake, and higher sleepiness scores (all p < 0.05). Sleep-disordered breathing was more severe in participants with cognitive impairment with an apnea/hypopnea index (AHI) of 18.0 (7.8-35.5)/h (p50 [p25-p75]) (vs 12.9 [7.2-24.5]/h, p < 0.001), and higher oxygen desaturation index (ODI). In the multivariate analysis after adjustments for confounding variables, the AHI and the ODI ≥4% and ≥6% were independently associated with cognitive impairment.	Participants aged >65 years with cognitive impairment have higher sleepiness scores and a more disrupted sleep. This seems to be related to the occurrence of sleep-disordered breathing and the associated intermittent hypoxia.	
28028196	Endogenous extracellular adenosine level fluctuates in an activity-dependent manner and with sleep-wake cycle, modulating synaptic transmission and short-term plasticity. Hebbian-type long-term plasticity introduces intrinsic positive feedback on synaptic weight changes, making them prone to runaway dynamics. We previously demonstrated that co-occurring, weight-dependent heterosynaptic plasticity can robustly prevent runaway dynamics. Here we show that at neocortical synapses in slices from rat visual cortex, adenosine modulates the weight dependence of heterosynaptic plasticity: blockade of adenosine A1 receptors abolished weight dependence, while increased adenosine level strengthened it. Using model simulations, we found that the strength of weight dependence determines the ability of heterosynaptic plasticity to prevent runaway dynamics of synaptic weights imposed by Hebbian-type learning. Changing the weight dependence of heterosynaptic plasticity within an experimentally observed range gradually shifted the operating point of neurons between an unbalancing regime dominated by associative plasticity and a homeostatic regime of tightly constrained synaptic changes. Because adenosine tone is a natural correlate of activity level (activity increases adenosine tone) and brain state (elevated adenosine tone increases sleep pressure), modulation of heterosynaptic plasticity by adenosine represents an endogenous mechanism that translates changes of the brain state into a shift of the regime of synaptic plasticity and learning. We speculate that adenosine modulation may provide a mechanism for fine-tuning of plasticity and learning according to brain state and activity.SIGNIFICANCE STATEMENT Associative learning depends on brain state and is impaired when the subject is sleepy or tired. However, the link between changes of brain state and modulation of synaptic plasticity and learning remains elusive. Here we show that adenosine regulates weight dependence of heterosynaptic plasticity: adenosine strengthened weight dependence of heterosynaptic plasticity; blockade of adenosine A1 receptors abolished it. In model neurons, such changes of the weight dependence of heterosynaptic plasticity shifted their operating point between regimes dominated by associative plasticity or by synaptic homeostasis. Because adenosine tone is a natural correlate of activity level and brain state, modulation of plasticity by adenosine represents an endogenous mechanism for translation of brain state changes into a shift of the regime of synaptic plasticity and learning.
28027860	Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy with seizures arising mainly during sleep and characterized by complex, often bizarre, motor behavior or sustained dystonic posturing. First described in 1981, it was initially considered a motor disorder of sleep and was named nocturnal paroxysmal dystonia (NPD). The unusual seizure semiology, onset during sleep, and often uninformative scalp EEG and brain MRI make it difficult to distinguish NPD attacks from other non-epileptic nocturnal paroxysmal events, namely parasomnias. The long-debated epileptic origin of the condition was finally demonstrated in 1990 and the term NFLE introduced. Even though many aspects of parasomnias and NFLE have been clarified in the last two decades, the differential diagnosis remains a challenge for clinicians. To address controversial issues and define the diagnostic criteria for NFLE, a Consensus Conference was held in Bologna, Italy in 2014. Major points of agreement emerged on: (i) the relationship of the seizures with sleep and not with the circadian pattern of seizure occurrence; (ii) the possible extrafrontal origin of hypermotor seizures, without substantial differences in seizure semiology. In the wake of the Consensus, the syndrome was renamed Sleep-Related Hypermotor Epilepsy (SHE).
28027399	Rapid eye movement (REM) sleep dysregulation is a symptom of many neuropsychiatric disorders, yet the mechanisms of REM sleep homeostatic regulation are not fully understood. We have shown that, after REM sleep deprivation, the pedunculopontine tegmental nucleus (PPT) plays a critical role in the generation of recovery REM sleep. In this study, we used multidisciplinary techniques to show a causal relationship between brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the PPT and the development of REM sleep homeostatic drive. Rats were randomly assigned to conditions of unrestricted sleep or selective REM sleep deprivation (RSD) with PPT microinjections of vehicle control or a dose of a TrkB receptor inhibitor (2, 3, or 4 nmol K252a or 4 nmol ANA-12). On experimental days, rats received PPT microinjections and their sleep-wake physiological signals were recorded for 3 or 6 h, during which selective RSD was performed in the first 3 h. At the end of all 3 h recordings, rats were killed and the PPT was dissected out for BDNF quantification. Our results show that K252a and ANA-12 dose-dependently reduced the homeostatic responses to selective RSD. Specifically, TrkB receptor inhibition reduced REM sleep homeostatic drive and limited REM sleep rebound. There was also a dose-dependent suppression of PPT BDNF up-regulation, and regression analysis revealed a significant positive relationship between REM sleep homeostatic drive and the level of PPT BDNF expression. These data provide the first direct evidence that activation of BDNF-TrkB signaling in the PPT is a critical step for the development of REM sleep homeostatic drive.
28019041	The sleep homeostatic Process S reflects the build-up of sleep pressure during waking and its dissipation during sleep. Process S is modelled as a saturating exponential function during waking and a decreasing exponential function during sleep. Slow wave activity is a physiological marker for non-rapid eye movement (non-REM) sleep intensity and serves as an index of Process S. There is considerable interindividual variability in the sleep homeostatic responses to sleep and sleep deprivation. The aim of this study was to investigate whether interindividual differences in Process S are trait-like. Polysomnographic recordings of 8 nights (12-h sleep opportunities, 22:00-10:00 hours) interspersed with three 36-h periods of sustained wakefulness were performed in 11 healthy young adults. Empirical mean slow wave activity per non-REM sleep episode at episode mid-points were used for parameter estimation. Parameters of Process S were estimated using different combinations of consecutive sleep recordings, resulting in two to three sets of parameters per subject. Intraclass correlation coefficients were calculated to assess whether the parameters were stable across the study protocol and they showed trait-like variability among individuals. We found that the group-average time constants of the build-up and dissipation of Process S were 19.2 and 2.7 h, respectively. Intraclass correlation coefficients ranged from 0.48 to 0.56, which reflects moderate trait variability. The time constants of the build-up and dissipation varied independently among subjects, indicating two distinct traits. We conclude that interindividual differences in the parameters of the dynamics of the sleep homeostatic Process S are trait-like.
28017605	The suprachiasmatic nucleus (SCN) is the central circadian clock in mammals. It is entrained by light but resistant to temperature shifts that entrain peripheral clocks [1-5]. The SCN expresses many functionally important neuropeptides, including vasoactive intestinal peptide (VIP), which drives light entrainment, synchrony, and amplitude of SCN cellular clocks and organizes circadian behavior [5-16]. The transcription factor LHX1 drives SCN Vip expression, and cellular desynchrony in Lhx1-deficient SCN largely results from Vip loss [17, 18]. LHX1 regulates many genes other than Vip, yet activity rhythms in Lhx1-deficient mice are similar to Vip-/- mice under light-dark cycles and only somewhat worse in constant conditions. We suspected that LHX1 targets other than Vip have circadian functions overlooked in previous studies. In this study, we compared circadian sleep and temperature rhythms of Lhx1- and Vip-deficient mice and found loss of acute light control of sleep in Lhx1 but not Vip mutants. We also found loss of circadian resistance to fever in Lhx1 but not Vip mice, which was partially recapitulated by heat application to cultured Lhx1-deficient SCN. Having identified VIP-independent functions of LHX1, we mapped the VIP-independent transcriptional network downstream of LHX1 and a largely separable VIP-dependent transcriptional network. The VIP-independent network does not affect core clock amplitude and synchrony, unlike the VIP-dependent network. These studies identify Lhx1 as the first gene required for temperature resistance of the SCN clockworks and demonstrate that acute light control of sleep is routed through the SCN and its immediate output regions.
28012092	The hypothalamic Hypocretin/Orexin (Hcrt) neurons secrete two Hcrt neuropeptides. These neurons and peptides play a major role in the regulation of feeding, sleep wake cycle, reward-seeking, addiction, and stress. Loss of Hcrt neurons causes the sleep disorder narcolepsy. The zebrafish has become an attractive model to study the Hcrt neuronal network because it is a transparent vertebrate that enables simple genetic manipulation, imaging of the structure and function of neuronal circuits in live animals, and high-throughput monitoring of behavioral performance during both day and night. The zebrafish Hcrt network comprises ~16-60 neurons, which similar to mammals, are located in the hypothalamus and widely innervate the brain and spinal cord, and regulate various fundamental behaviors such as feeding, sleep, and wakefulness. Here we review how the zebrafish contributes to the study of the Hcrt neuronal system molecularly, anatomically, physiologically, and pathologically.
28012089	Alzheimer's disease (AD) is the most frequent age-related dementia. It prevalently causes cognitive decline, although it is frequently associated with secondary behavioral disturbances. AD neurodegeneration characteristically produces a remarkable destruction of the sleep-wake cycle, with diurnal napping, nighttime arousals, sleep fragmentation, and REM sleep impairment. It was recently hypothesized that the orexinergic system was involved in AD pathology. Accordingly, recent papers showed the association between orexinergic neurotransmission dysfunction, sleep impairment, and cognitive decline in AD. Orexin is a hypothalamic neurotransmitter which physiologically produces wakefulness and reduces REM sleep and may alter the sleep-wake cycle in AD patients. Furthermore, the orexinergic system seems to interact with CSF AD biomarkers, such as beta-amyloid and tau proteins. Beta-amyloid accumulation is the main hallmark of AD pathology, while tau proteins mark brain neuronal injury due to AD pathology. Investigations so far suggest that orexinergic signaling overexpression alters the sleep-wake cycle and secondarily induces beta-amyloid accumulation and tau-mediated neurodegeneration. Therefore, considering that orexinergic system dysregulation impairs sleep-wake rhythms and may influence AD pathology, it is hypothesized that orexin receptor antagonists are likely potential preventive/therapeutic options in AD patients.
28011945	Orexins A (OXA) and B (OXB) control energy homeostasis by regulating food intake, energy expenditure and sleep-wake cycle. Several studies showed that OXA stimulates insulin secretion and proliferation of beta cells. However, mechanisms of action are still not well understood. Here, we investigated whether ERK and transient receptor potential channels (TRPs) play a role in mediating the effect of OXA on cell growth, insulin production, and secretion using the established INS-1E cell line. Cell proliferation was measured using BrdU assay. Insulin mRNA expression was detected by real-time PCR. Insulin secretion was assessed using ELISA. Intracellular calcium levels were measured using fluorescence calcium imaging (fura-2/AM). Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was detected by Western blot. TRP channel activity was blocked by lanthanum (III) chloride (La3+; 100 - 300 μM) or ruthenium red (RuR; 10 μM). OXA (100 nM) stimulated INS-1E cell proliferation, insulin secretion, intracellular Ca2+ concentration and ERK1/2 phosphorylation, without changing insulin mRNA expression. Inhibition of ERK1/2 by 10 μM U0126 attenuated OXA-stimulated INS-1E cell proliferation. Blockade of TRP channel activity by La3+ or RuR rendered OXA ineffective at modulating Ca2+ regulation and insulin release. In contrast, the L-type channel blocker nifedipine (10 μM) failed to affect OXA-stimulated insulin release. Taken together, OXA increases INS-1E cell proliferation via ERK1/2-dependent mechanism. Furthermore, OXA stimulates insulin secretion from INS-1E cells. TRPs are relevant for OXA-stimulated insulin secretion and intracellular calcium regulation.
28009416	Chronic kidney disease (CKD) patients have more frequent sleep disorders and cardiovascular disease than normals. Since arterial stiffness as a risk factor of atherosclerosis can be evaluated with pulse wave velocity (PWV), we aimed to investigate the prevalance of sleep quality (SQ) and the relationship between SQ and risk factors of atherosclerosis and whether there is a relationship between SQ and PWV (the indicator of arterial stiffness) in predialysis CKD patients.This cross-sectional study was carried out in CKD patients followed at the Nephrology Department in Konya, Turkey, between November 2014 and March 2015. A total of 484 CKD patients were screened. Of the 484 patients, 285 patients were excluded. The remaining 199 CKD patients without cardiovascular disease at stage 3, 4, and 5 (predialysis) were included in the final study. The SQ of the patients was evaluated by the Pittsburgh Sleep Quality Index (PSQI). PWV was measured by using a single-cuff arteriography device (Mobil-O-Graph PWA, a model pulse wave analysis device; IEM).	A total of 199 predialysis CKD patients were included in the study, 73 of whom (36.7 %) were 'poor sleepers' (global PSQI &gt;5). Patients with poor SQ were older than those with good SQ (p = 0.077). SQ was worse in female patients compered to male patients (p = 0.001). SQ was worse in obese patients. As laboratory parameters, serum phosphorus, LDL cholesterol, and triglycerides levels correlated positively with SQ (respectively; r = 0.245, p&amp;0.001; r = 0.142, p = 0.049; r = 0.142, p = 0.048). The indicator of arterial stiffness, PWV, was higher in patients with poor SQ (p = 0.033). Hyperphosphatemia and female gender are determined as risk factors for poor SQ in multivariate analysis (p = 0.049, ExpB = 1.477; p = 0.009, ExpB = 0,429, respectively).	Our study showed for the first time that there is a relationship between SQ and risk factors of atherosclerosis in predialysis CKD patients.	
28008257	A woman was diagnosed with non-24-hour sleep-wake syndrome and depressive symptoms. Her depressive symptoms did not respond to standard doses of several antidepressants or mood stabilizers. Furthermore, her sleep-wake cycle remained non-entrained despite treatment with a melatonin-related drug, vitamin B12, and phototherapy. Ultimately, her sleep-wake rhythm was restored to a 24-hour pattern with a low dose of valproic acid, and her depressive symptoms tended to improve as a result of synchronization without antidepressants. Low-dose valproic acid appears to be one of the effective means of entraining circadian rhythms in patients with non-24-hour sleep-wake syndrome, which in turn likely improves associated depressive symptoms.
28003503	To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI).This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score.	Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses.	Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI.	

27998295	Severe mental illness (SMI) is common, chronic and difficult to treat. Sleep and circadian dysfunctions are prominent correlates of SMI, yet have been minimally studied in ways that reflect the complexity of the sleep problems experienced. Prior treatment studies have been disorder-focused-they have treated a specific sleep problem in a specific diagnostic group. However, real life sleep and circadianproblems are not so neatly categorized, particularly in SMI where features of insomnia overlap with hypersomnia, delayed sleep phase and irregular sleep-wake schedules. Accordingly, the aim of this studyprotocol is to test the hypothesis that a Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) will improve functional impairment, disorder-focused symptoms and sleep and circadian functioning. Participants across DSM diagnoses and across common sleep and circadian problems are eligible. The elements of TranS-C are efficacious across SMI in research settings with research-based providers. The next step is to test TranS-C in a community setting. Accordingly, this study is being conducted within Alameda County Behavioral Health Care Services (ACBHCS), the Community Mental Health Centre (CMHC) for Alameda County.120 adults diagnosed with SMI and sleep and circadian dysfunction within ACBHCS will be randomly allocated to TranS-C (n = 60) or 6-months of Usual Care followed by Delayed Treatment with TranS-C (UC-DT; n = 60). TranS-C is modularized and delivered across eight to twelve 50-minute, weekly, individual sessions. All participants will be assessed before and immediately following treatment and again 6 months later. Primary analysis will examine whether TranS-C significantly improves functional impairment, disorder-specific symptoms and sleep and circadian functioning, relative to UC-DT. Exploratory analysis will examine whether improvements in sleep and circadian functioning predict reduction in functional impairment and disorder-specific symptoms, and whether the intervention effects are mediated by improved sleep and circadian functioning and moderated by previously reported risk factors (demographics, symptom severity, medications, psychiatric and medical comorbidity).	This trial tests an important and understudied mechanism-dysregulated sleep and circadian rhythms-in SMI, a novel transdiagnostic treatment approach, in a community setting so as to contribute to the goal of bridging the gap between research and practice.	
27996307	Human genetic studies have implicated specific genes that constitute the molecular clock in the manifestation of bipolar disorder (BD). Among the clock genes involved in the control system of circadian rhythms, CLOCK 3111 T/C and Period3 (PER3) influence core psychopathological features of mood disorders, such as patterns of sleep, rest, and activity, diurnal preference, cognitive performances after sleep loss, age at the onset of the illness, and response to antidepressant treatment. Furthermore, several studies pointed out that bipolar symptomatology is associated with dysfunctions in white matter (WM) integrity, suggesting these structural alterations as a possible biomarker of the disorder. We hypothesise that CLOCK and PER3 polymorphisms could be potential factors affecting WM microstructure integrity in bipolar patients. The relationship between these clock genes and DTI measures of WM integrity in a sample of 140 (53 M; 87 F) patients affected by BD type I was studied. Tract-based spatial statistics analyses on DTI measures of WM integrity were performed for each clock gene polymorphism, between the genetic groups. We accounted for the effect of nuisance covariates known to influence WM microstructure: age, sex, lithium treatment, age at the onset of the illness, and the number of illness episodes. We found that compared to T homozygotes, CLOCK C carriers showed a widespread increase of the mean diffusivity in several WM tracts. Compared with PER35/5 homozygotes, PER34/4 homozygotes showed significantly increased radial diffusivity and reduced fractional anisotropy in several brain WM tracts. No significant difference was observed between heterozygotes and the other subgroups. Altogether, this pattern of results suggests WM disruption in CLOCK C carrier and in PER34 homozygotes. Sleep promotes myelination and oligodendrocyte precursor cell proliferation and associates with higher expression of genes coding for phospholipid synthesis and myelination in oligodendrocytes. These clock genes play a pivotal role in maintaining circadian rhythms and the sleep-wake cycle. Thus, it may be suggested that CLOCK rs1801260*C and PER34/4 influence myelination processes by regulating sleep quality and quantity.
27995604	Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).	We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.	Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.	We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.	Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.	
27992761	Very little is known about the characteristics of sleep related (SR) crashes occurring on low speed roads compared with current understanding of the role of sleep in crashes occurring on high speed roads e.g. motorways. To address this gap, analyses were undertaken to identify the differences and similarities between (1) SR crashes occurring on roads with low (≤60km/h) and high (≥100km/h) speed limits, and (2) SR crashes and not-SR crashes occurring on roads with low speed limits.Police reports of all crashes occurring on low and high speed roads over a ten year period between 2000 and 2009 were examined for Queensland, Australia. Attending police officers identified all crash attributes, including 'fatigue/fell asleep', which indicates that the police believe the crash to have a causal factor relating to falling asleep, sleepiness due to sleep loss, time of day, or fatigue. Driver or rider involvement in crashes was classified as SR or not-SR. All crash-associated variables were compared using Chi-square tests (Cramer's V=effect size). A series of logistic regression was performed, with driver and crash characteristics as predictors of crash category. A conservative alpha level of 0.001 determined statistical significance.	There were 440,855 drivers or riders involved in a crash during this time; 6923 (1.6%) were attributed as SR. SR crashes on low speed roads have similar characteristics to those on high speed roads with young (16-24y) males consistently over represented. SR crashes on low speed roads are noticeably different to not-SR crashes in the same speed zone in that male and young novice drivers are over represented and outcomes are more severe. Of all the SR crashes identified, 41% occurred on low speed roads.	SR crashes are not confined to high speed roads. Low speed SR crashes warrant specific investigation because they occur in densely populated areas, exposing a greater number of people to risk and have more severe outcomes than not-SR crashes on the same low speed roads.	
27992627	Recent studies found that the concentration of amyloid-β (Aβ) fluctuates with the sleep-wake cycle. Although the amplitude of this day/night pattern attenuates with age and amyloid deposition, to our knowledge, the association of Aβ kinetics (ie, production, turnover, and clearance) with this oscillation has not been studied.To determine the association between Aβ kinetics, age, amyloid levels, and the Aβ day/night pattern in humans.	We measured Aβ concentrations and kinetics in 77 adults aged 60 to 87 years with and without amyloid deposition by a novel precise mass spectrometry method at the Washington University School of Medicine in St Louis, Missouri. We compared findings of 2 orthogonal methods, enzyme-linked immunosorbent assay and mass spectrometry, to validate the day/night patterns and determine more precise estimates of the cosinor parameters. In vivo labeling of central nervous system proteins with stable isotopically labeled leucine was performed, and kinetics of Aβ40 and Aβ42 were measured.	Serial cerebrospinal fluid collection via indwelling lumbar catheter over 36 to 48 hours before, during, and after in vivo labeling, with a 9-hour primed constant infusion of 13C6-leucine.	The amplitude, linear increase, and other cosinor measures of each participant's serial cerebrospinal fluid Aβ concentrations and Aβ turnover rates.	Of the 77 participants studied, 46 (59.7%) were men, and the mean (range) age was 72.6 (60.4-87.7) years. Day/night patterns in Aβ concentrations were more sharply defined by the precise mass spectrometry method than by enzyme-linked immunosorbent assay (mean difference of SD of residuals: Aβ40, -7.42 pM; P < .001; Aβ42, -3.72 pM; P < .001). Amyloid deposition diminished day/night amplitude and linear increase of Aβ42 but not of Aβ40. Increased age diminished day/night amplitude of both Aβ40 and Aβ42. After controlling for amyloid deposition, amplitude of Aβ40 was positively associated with production rates (r = 0.42; P < .001), while the linear rise was associated with turnover rates (r = 0.28; P < .05). The amplitude and linear rise of Aβ42 were both associated with turnover (r = -0.38; P < .001) and production (r = 0.238; P < .05) rates.	Amyloid deposition is associated with premature loss of normal Aβ42 day/night patterns in older adults, suggesting the previously reported effects of age and amyloid on Aβ42 amplitude at least partially affect each other. Production and turnover rates suggest that day/night Aβ patterns are modulated by both production and clearance mechanisms active in sleep-wake cycles and that amyloid deposition may impair normal circadian patterns. These findings may be important for the designs of future secondary prevention trials for Alzheimer disease.	
27990327	This review summarizes recent developments relevant to the treatment of circadian rhythm sleep-wake disorders. The clinical practice guidelines for the treatment of intrinsic circadian rhythm sleep-wake disorders is described, followed by recent treatment studies for delayed sleep-wake phase disorder, non-24 hour sleep-wake disorder, irregular sleep-wake disorder and shift work. New methods to estimate circadian phase, including home saliva collection to estimate the dim light melatonin onset, circadian questionnaires and general rules to guide light and exogenous melatonin treatments are described. New developments in light treatment are detailed, including light flashes during sleep and wearable light devices. Substances such as caffeine and alcohol, and devices such as electronic tablets are also considered for their potential to shift circadian timing. Finally, an update on melatonin supplements in the US is discussed, along with the controversy surrounding the use of melatonin supplements in patients with prediabetes or diabetes.
27988352	Orexins, also known as hypocretins, play a regulatory role in the sleep-wake cycle by activating orexin receptors. Previous animal studies have shown that sleep deprivation can elevate orexinergic peptide levels. However, the relationship between insomnia disorder and orexin-A levels in humans has not been explored. In the current study, we examined plasma orexin-A levels in patients with insomnia disorder and in normal sleepers. We also studied the possible mechanisms underlying changes in orexin-A levels between the study groups; this included investigations of prepro-orexin and orexin receptor gene polymorphisms as well as exploration of other variables. We measured plasma orexin-A levels in 228 patients with insomnia disorder and 282 normal sleepers. The results indicated that the patients with insomnia disorder had significantly higher orexin-A levels than normal sleepers (63.42±37.56 vs. 54.84±23.95pg/ml). A positive relationship was detected between orexin-A level and age in patients with insomnia disorder. Orexin-A levels were elevated in relation to course of insomnia, as well as in relation to increased Insomnia Severity Index score. None of the evaluated prepro-orexin gene single nucleotide polymorphisms were informative between the two study populations. After sequencing all orexin receptor exons, one variation (rs2271933) in the OX1R gene and one variation (rs2653349) in the OX2R gene were found. However, no significant differences were found in either genotypic or allelic frequency distributions between the two study groups. It is suggested that the increased plasma orexin-A levels in patients with insomnia disorder are associated with the course and severity of insomnia, but not with prepro-orexin and orexin receptor gene polymorphisms.

27977578	Parkinson disease (PD) is usually accompanied by numerous nonmotor symptoms (NMS), such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunctions, and sensory disturbances. However, it is not clear that the factors influencing the occurrence of NMS and its sequence with motor symptoms (MS).We conducted comprehensive assessments of NMS by using 13 scales in 1119 PD patients.A total of 70.8% PD patients present NMS. Olfactory dysfunction tends to occur in PD patients with older age, more severe depression, sleep problems, and autonomic dysfunctions. Older patients are more likely to have olfactory dysfunction before MS than younger patients. Rapid eye movement behavior disorder is more prone to happen in patients with older age, older onset age, more severe depression, sleep problems, and autonomic dysfunctions. Patients with rapid eye movement behavior disorder before MS are older in onset age than after group.Olfactory dysfunction, constipation, rapid eye movement behavior disorder, and depression, as early warning NMSs of PD, connected to each other. There is a clinical heterogeneity that older patients are more likely to have NMS before MS, while younger patients are opposite.
27976622	There are many reasons to take into consideration the sleep disorders in the elderly. The sleep quality degrades with age and is strongly affected by medical conditions, intrinsic sleep disorders, or by a combination of these factors. Other age-related conditions such as severe dementia, dependence or living in institution worsen sleep disturbances in older people. When living alone elderly people, being cognitively impaired and medically disabled, may not be able to complain about sleep problems. Sleep disorders are thus underdiagnosed, unmarked, and insufficiently investigated in the elderly. In this heterogeneous population, sleep assessment should include a global geriatric approach and be individually adapted for each subject. The sleep interview must specially include medical comorbidities, medication uses, and aged-related changes of lifestyle such as retirement, loss of spouse, hospitalization or institutionalization. In the elderly with loss of autonomy, standard sleep assessment is not always adequate and must be replaced by shorter, simpler or observation-based tests such as the Sleep disorders inventory, Observation-based nocturnal sleep inventory, Observation and interview based diurnal sleepiness inventory. When sleep log is impossible, actimetry is an excellent alternative for studying sleep-wake rhythm. Ventilatory polygraphy is a simpler test for detecting sleep apnea than polysomnography. Utilization of sophisticated investigations should be discussed when the feasibility and usefulness is limited.
27965397	Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterised by complex motor enactment of dreams and is a potential prodromal marker of Parkinson's disease (PD). Of note, patients with PD observed during RBD episodes exhibit improved motor function, relative to baseline states during wake periods. Here, we review recent epidemiological and mechanistic findings supporting the prodromal value of RBD for PD, incorporating clinical and electrophysiological studies. Explanations for the improved motor function during RBD episodes are evaluated in light of recent publications. In addition, we present preliminary findings describing changes in the activity of the basal ganglia across the sleep-wake cycle that contribute to our understanding of RBD.
27964860	To characterize the patterns of light exposure and physical activity level and assess their relationship with sleep quality and depressive symptoms in adults with delayed sleep-wake phase disorder (DSWPD).42 DSWPD (22 female, mean age 34.5 y) and 26 (±4 years) age-and-sex-matched controls (12 female, mean age 33.4 y) underwent seven days of light and activity monitoring.	Individuals with DSWPD had significantly delayed bed times and wake times, but similar sleep duration compared to controls. Subjective sleep quality (Pittsburgh Sleep Quality Index (PSQI)) was poorer in DSWPDs compared to controls. Those with DSWPD had significantly more activity and light exposure late at night (2:00-4:00) and significantly less activity and light exposure in the morning (8:00-11:00). Total 24 h levels of light and activity were not significantly different between DSWPD and controls. However, the DSWPD group had significantly more light exposure than controls 22 h after waking, during their sleep period. Later light exposure correlated with higher depression scores [Beck Depression Index (BDI)] and poorer sleep quality (PSQI).	The light exposure patterns observed in DSWPD likely contribute to and perpetuate the chronically delayed sleep and wake phase in these patients. In addition, increased light exposure during the sleep period may also contribute to the poor sleep quality and mood disorders that are common in these individuals.	
27957554	People differ in their sleep-wake behavior. This individual difference is conceptualized in different aspects, such as wake up times, bed times, times of peak performance, as well as in morning affect. A total of 14,987 visitors of an exhibition in the LWL State Museum of Natural History, Münster (Germany), did the survey on chronotype and gave their consent that these data can be used for a scientific study. Age groups were coded into 5-year bins. Mean age (mean ± SD) was 28.2 ± 17.5 years. There were 8075 females (54%) and 6912 males in the sample. The German version of the rMEQ (reduced Morningness-Eveningness-Questionnaire) was used for data collection. The data showed clear age effects. Younger children are more morning oriented and become rapidly evening oriented during puberty, while the more attenuated turn towards morningness occurs from the age of 20 years. Then between the ages 25 to 30 morningness-eveningness remained rather stable. Significant gender differences existed in the reproductive age, i.e., the age groups 20 to 50 (corresponding to the age 16-50 years). In other age groups, no gender differences could be detected. Seasonal effects were also found. Chronotype score was lowest during the summer months (and more evening oriented). Based on the single item analysis of the five questions of the rMEQ, we found age group differences in all items. Gender differences occurred in all items except item 1, which deals with the preferred wake-up time. Men always scored significantly lower (i.e. more evening oriented) than women except in item 2 (tiredness after awakening). Seasonal effects were only significant in item 3, which is related to preferred bed times. People showed a later bed time preference during summer. The classification of chronotypes according to the cut-off scores provided by Adan and Almirall (1991) and by using the 20/80 percentile provided identical cut-off scores (values of 11 and below for evening types and 18 and above for morning types).
27939122	To investigate systematically the associations of sleep patterns with a range of mental disorders and other outcomes among a nationally representative sample of US adolescents.Using the National Comorbidity Survey Adolescent Supplement, a nationally representative cross-sectional survey of 10 123 US adolescents 13-18 years of age, we assessed associations between adolescent-reported sleep patterns (tertiles of weeknight bedtime, weeknight sleep duration, weekend bedtime delay, and weekend oversleep) and past-year mental disorders based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, smoking, injury, suicidality, and perceived mental and physical health, assessed via direct diagnostic interview.	The average weeknight bedtime was at 22:37 and sleep duration was 7.72 hours. Average weekend bedtime delay was 1.81 hours and average weekend oversleep was 1.17 hours. Later weeknight bedtime, shorter weeknight sleep duration, greater weekend bedtime delay, and both short and long periods of weekend oversleep were associated with increased odds of mood, anxiety, substance use, and behavioral disorders, as well as suicidality, tobacco smoking, and poor perceived mental and physical health. ORs ranged from 1.27 to 2.15. The only outcomes not associated with any sleep patterns were past-year injury and eating disorder.	Suboptimal sleep patterns were associated with an array of mental disorders and other health-related outcomes among adolescents. Abnormal sleep patterns may serve as markers of prodromal or untreated mental disorders among adolescents, and may provide opportunities for prevention and intervention in mental disorders.	
27935421	This study examined sleep-wake habits and subjective jet-lag ratings of 55 German junior rowers (n = 30 male, 17.8 ± 0.5 years) before and during the World Rowing Junior Championships 2015 in Rio de Janeiro, Brazil. Athletes answered sleep logs every morning, and Liverpool John Moore's University Jet-Lag Questionnaires each evening and morning. Following an 11-h westward flight with 5-h time shift, advanced bedtimes (-1 h, P < .001, ηp2 = 0.68), reduced sleep onset latency (P = .002, ηp2 = 0.53) and increased sleep duration (P < .001, ηp2 = 0.60) were reported for the first two nights. Jet-lag symptoms peaked upon arrival but were still present after 6 days. Sleep quality improved (P < .001, ηp2 = 0.31) as well as some scales of the Recovery-Stress Questionnaire for Athletes. Participation was successful as indicated by 11 of 13 top 3 placings. Overall, the initial desynchronisation did not indicate negative impacts on competition performance. As travel fatigue probably had a major effect on perceptual decrements, sleep during travel and time to recover upon arrival should be emphasised. Coaches and practitioners should consider higher sleep propensity in the early evening by scheduling training sessions and meetings until the late afternoon.
27931914	Sleep is known to be markedly disturbed in patients with depression, but in patients with schizophrenia these problems are underestimated. This research aimed to determine if a relationship existed between sleep problems in patients with schizophrenia and with depression and their reduced working memory (WM) performance. Thirty outpatients with schizophrenia, 30 outpatients with depression, and 30 healthy control participants were enrolled in this study. All participants completed a sleep questionnaire (i.e., Pittsburgh Sleep Quality Index (PSQI)), two simple WM tasks tapping only its storage component (i.e., digit span forward and backward task), and two complex WM tasks tapping both its storage and processing components (i.e., letter-number sequencing and reading span task). The results showed that neither psychiatric group differed from the healthy controls on simple WM tasks. Patients with schizophrenia did not differ from those with depression in the performance of simple or complex WM tasks. However, patients with schizophrenia, and, to a lesser degree, patients with depression performed significantly worse than the healthy control participants on complex WM tasks, which was visible in lower WM scores for patients with depression and in slower information processing, as well, for patients with schizophrenia. Finally, a significant negative relationship was found between the PSQI score and the reading span task scores; thus, participants with worse performance tended to report more sleep problems. To conclude, sleep needs to receive more priority when treating patients with depression and especially patients with schizophrenia because better sleep improves (working) memory performance and daily functioning.
27931262	Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation.We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test.	We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state.	Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.	
27931030	Cytokines play an integral role in sleep/wake regulation. The objective of this study was to identify how total sleep deprivation affects cytokine levels.Male C57BL/6 mice were subjected to 48 h of total sleep deprivation produced by brief rotation of activity wheels or 3 different controls: home cage, a sedentary wheel, or forced activity. In addition, the serum levels of cytokines were analyzed using a mouse magnetic bead-based multiplex immunoassay.	The concentrations of some cytokines (fibroblast growth factor-basic [FGF-basic], leukemia inhibitory factor [LIF], and monokine induced by interferon-γ [MIG]) decreased significantly after total sleep deprivation. However, other cytokines (macrophage colony-stimulating factor, macrophage inflammatory protein-2, platelet-derived growth factor-bb, vascular endothelial growth factor) did not show any significant difference. Serum corticosterone levels did not differ significantly among the groups.	The biochemical mechanisms responsible for sleep regulation are very complex. These results suggest the involvement of 3 cytokines (FGF-basic, LIF, and MIG) in sleep/wake regulation.	
27930498	The aim of this systematic review was to identify published articles that evaluated the use of prazosin for treating nightmares in children and adolescents who have posttraumatic stress disorder (PTSD).A literature search was conducted of PubMed, MEDLINE, EMBASE, Cochrane Collaboration, and PsycINFO databases for published articles in any language that evaluated the use of prazosin for treating nightmares in the context of PTSD in children and adolescents using the following key words: PTSD, nightmares, prazosin, children, adolescents, trauma, and sleep.	A total of 9 published articles related to the use of prazosin for treatment of nightmares in PTSD in children and adolescents were identified. Six of the 9 articles that met our inclusion criteria were case reports. All of these 6 case reports showed marked improvement in nightmares when prazosin was used, although at a generally lower dose when compared with its use in adults, with dosing ranging from 1 to 4 mg/d.	Prazosin has shown promising outcomes in treating nightmares associated with PTSD in children and adolescents, although this has not been well studied. Future placebo-controlled trials are needed to assess the efficacy and safety of prazosin in treating PTSD-related nightmares in children and adolescents.	
27929109	The circadian clock governs virtually all processes in the human body, including sleep-wake behaviour. Circadian misalignment describes the off-set between sleep-wake cycles and clock-regulated physiology. This strain is predominantly caused by external (societal) demands including shift work, early school start times and fast travels across time zones. Sleeping at the 'wrong' internal time can jeopardise health and safety, and we therefore need a good quantification of this phenomenon. Here, we propose a novel method to quantify the mistiming of sleep-wake rhythms and demonstrate its versatility in day workers and shift workers. Based on a single time series, our Composite Phase Deviation method unveils distinct, subject- and schedule-specific geometries ('islands and pancakes') that illustrate how modern work times interfere with sleep. With increasing levels of circadian strain, the resulting shapes change systematically from small, connected forms to large and fragmented patterns. Our method shows good congruence with published measures of circadian misalignment (i.e., Inter-daily Stability and 'Behavioural Entrainment'), but offers added value as to its requirements, e.g., being computable for sleep logs and questionnaires. Composite Phase Deviations will help to understand the mechanisms that link 'living against the clock' with health and disease on an individual basis.
27927175	To examine the effectiveness and acceptability of an 8-week individual tailored cognitive behavioural therapy (CBT) intervention for the treatment of depressive symptoms in those newly diagnosed with multiple sclerosis.The current study presents a pilot, parallel group randomized controlled trial (RCT) with an allocation ratio of 1:1 conducted in a large research and teaching hospital in Melbourne, Australia. 30 individuals with a mean age of 36.93 years (SD = 9.63) who were newly diagnosed with multiple sclerosis (MS) (X = 24.87 months, SD = 15.61) were randomized to the CBT intervention (n = 15) or treatment as usual (TAU) (n = 15). The primary outcome was level of depressive symptoms using the Beck Depression Inventory-II (BDI-II). Secondary outcomes were level of anxiety, fatigue and pain impact, sleep quality, coping, acceptance of MS illness, MS related quality of life, social support, and resilience. Tertiary outcomes were acceptability and adherence to the intervention.	Large between group treatment effects were found for level of depressive symptoms at post and at 20 weeks follow-up (d = 1.66-1.34). There were also small to large group treatment effects for level of anxiety, fatigue and pain impact, sleep quality, MS related quality of life, resilience, and social support at post and at 20 weeks follow-up (d = 0.17-1.63). There were no drop-outs and participants completed all treatment modules. All participants reported the treatment as 'very useful', and most (73.4%) reported that the intervention had addressed their problems 'completely'.	These data suggest that the tailored early intervention is appropriate and clinically effective for the treatment of depressive symptoms in those newly diagnosed with MS. A larger RCT comparing the CBT intervention with an active comparative treatment with longer term follow-up and cost effectiveness analyses is warranted. The pilot trial has been retrospectively registered on 28/04/2016 with the ISRCTN registry (trial ID ISRCTN10423371).	
27925052	Night eating syndrome (NES) is characterized by caloric intake ≥ 25% of total daily after dinner and/or by two or more weekly nocturnal awakenings accompanied by food ingestion. Causes of NES are not entirely clear and seem to involve a desynchronization between the circadian rhythms of food ingestion and sleep, resulting in a delayed pattern of food intake. Estimates of the prevalence of NES in the general population are around 1.5%, and although much higher frequencies have been described in obese individuals, a causal relationship between NES and obesity is not clearly established. Since the first NES reports, several treatment modalities have been proposed, although, in many cases, the evidence is still insufficient and there is no consensus on the ideal approach. In order to conduct a critical review of proposed treatments for NES since its original description, a systematic search of articles published in journals indexed in Medline/Pubmed database in the period 1955-2015 was performed. Seventeen articles addressing non-pharmacological and pharmacological therapies met the selection criteria. Based on the articles analyzed, we conclude that serotonergic agents and psychological interventions, particularly cognitive behavioral therapy, have been shown to be effective for the treatment of NES. A combination of non-pharmacological and pharmacological therapies must be considered in future studies on the treatment of these patients.
27923424	Interest in orexin receptor antagonism as a novel mechanism of action against seizures and epilepsy has increased in recent years. Loss of orexinergic activity is associated with REM sleep onset, and REM sleep is generally protective against seizures. This paper discusses the dynamic modulation of seizure threshold by orexin through a postulated "orexi-cortical" axis in which the specific type of orexinergic activity exquisitely regulates sleep-wake states to modify ascending subcortical influences on cortical synchronization with profound subsequent consequences on seizure threshold. This paper also explores the current state of research into experimental orexinergic modulation of seizure threshold, and suggests possible future research directions to fully understand the promise and peril of orexinergic manipulation in seizures and epilepsy.
27923187	To describe sleep EEG patterns of neonates, and infants with microcephaly due to congenital Zika virus (ZikV) syndrome.A descriptive case series of EEGs performed in a cohort of neonates with microcephaly monitored from October 2015 to February 2016 at a University Hospital in Northeast Brazil. Infants were investigated following an established protocol that includes EEG, neuroimaging studies, PCR and specific antibodies for ZikV detection.	EEGs (n=37) from 37 infants were reviewed. Age at investigation varied from 1 to 5months (mean=2.6). Diffuse low voltage (n=7), background asymmetry (n=6) and modified hypsarrhythmia with or without burst-suppression (n=11), were the main background abnormalities identified. Interictal EEG abnormalities were identified in 23 recordings (62%) and localized as focal frontal (n=8) or occipital (n=2) spikes/sharp, multifocal spikes/sharp waves (n=13). Electrographic seizures without clinical manifestation were identified in 4 recordings and characterized as focal pseudo rhythmic pattern. Further findings were focal high amplitude slow waves that were registered in the frontal (n=3) or occipital (n=1) regions.	Different types of EEG abnormalities were encountered with a predominance of interictal epileptogenic activity and hypsarrhythmia.	Sleep EEGs in congenital Zika virus syndrome are consistently abnormal even in infants who have not yet developed epilepsy.	

27922144	This study aimed to determine the sleep patterns and dysfunctions in children with learning problems in comparison against a local population-based sample.Parents of 200 children with learning problems and 372 parents of a local population-based sample of typically developing (TD) children were recruited to complete a questionnaire on their child's sleep patterns and sleep problems. The Children's Sleep Habits Questionnaire (CSHQ) is a validated parent-reported sleep screening questionnaire that contains 54 items identifying sleep behaviours in children.	The mean age of the sample was 4.2 years (SD: 1.4; range, 2 to 6 years). Sleep duration was similar between the 2 groups. The difference in mean CSHQ subscale scores between children with learning problems and TD children was significant for sleep-disordered breathing (1.3 vs 1.2, P = 0.001). Among children with learning problems, 36.5% snored (vs 26.6% of TD children), 30.5% had noisy breathing (vs 18.8%), and 9.0% (vs 4.6%) experienced difficulty breathing 2 or more times a week. Children with learning problems woke up in a more irritable mood (P = 0.01), had more difficulty in getting out of bed (P <0.001), and took a longer time to be alert (P <0.001). They exhibited fewer behaviours of daytime drowsiness (P = 0.009). Among this group of children, 15.0% of parents reported that their child had a sleep problem compared to 9.0% in the TD group.	Sleep breathing disorders and symptoms of morning sleepiness are more prevalent in children with learning problems. Symptoms of daytime lethargy are similar between the 2 groups. We suggest that a simple outpatient screening targeted at these problems be instituted in the initial workup of any child with learning difficulties.	
27919403	Narcolepsy, a disorder of rapid eye movement (REM) sleep, is characterized by excessive daytime sleepiness and cataplexy, a loss of muscle tone triggered by emotional stimulation. Current narcolepsy pharmacotherapeutics include controlled substances with abuse potential or drugs with undesirable side effects. As partial agonists at trace amine-associated receptor 1 (TAAR1) promote wakefulness in mice and rats, we evaluated whether TAAR1 agonism had beneficial effects in two mouse models of narcolepsy.In the first experiment, male homozygous B6-Taar1tm1(NLSLacZ)Blt (Taar1 knockout) and wild-type mice were surgically implanted to record electroencephalogram, electromyogram, locomotor activity, and body temperature, and the efficacy of the TAAR1 agonist, RO5256390, on sleep/wake and physiological parameters was determined. In the second experiment, the effects of the TAAR1 full agonist RO5256390 and partial agonist RO5263397 on sleep/wake, locomotor activity, body temperature, and cataplexy were assessed in two mouse narcolepsy models.	RO5256390 profoundly reduced rapid eye movement sleep in wild-type mice; these effects were eliminated in Taar1 knockout mice. The TAAR1 partial agonist RO5263397 also promoted wakefulness and suppressed nonrapid eye movement sleep. Both compounds reduced body temperature in the two narcolepsy models at the highest doses tested. Both TAAR1 compounds also mitigated cataplexy, the pathognomonic symptom of this disorder, in the narcolepsy models. The therapeutic benefit was mediated through a reduction in number of cataplexy episodes and time spent in cataplexy.	These results suggest TAAR1 agonism as a new therapeutic pathway for treatment of this orphan disease. The common underlying mechanism may be the suppression of rapid eye movement sleep.	
27918895	In recent years, a labile sleep-wake cycle has been implicated as a cause for dissociative experiences, and studies show that dissociation is elevated following sleep deprivation. Dissociative individuals may find it harder to regulate sleepiness in the face of sleep disruption. Although there is significant variability in reactions to sleep deprivation, research on trait predictors is scarce. The present study examined the ability of trait dissociation to prospectively predict sleepiness following sleep loss and recovery sleep. Two high-functioning samples, namely, Remotely Piloted Aircraft officers (N=29) and Air Force jet pilots (N=57) completed state and trait questionnaires assessing sleep and dissociation before and after full or partial sleep loss. Dissociative absorption was a consistent predictor of an increase in sleepiness following sleep loss and following recovery sleep, controlling for baseline sleepiness levels. We discuss the findings in light of a difficulty to regulate and monitor consciousness states.
27917740	Overlap between neuropsychiatric symptoms of dementia and delirium complicates diagnosis of delirium superimposed on dementia (DSD). This study sought to examine differences in delirium presentation and outcomes between DSD patients with and without pre-existing behavioral and psychological symptoms of dementia (BPSD).This was a prospective cohort study of older adults with DSD admitted to a specialized delirium unit (December 2010-August 2012). We collected data on demographics, comorbidities, illness severity, delirium precipitants, and cognitive and functional scores. Delirium severity was assessed using Delirium Rating Scale Revised-98 (DRS-R-98) and Cognitive Assessment Method severity score (CAM-sev). Patients were categorized as DSD-BPSD+ and DSD-BPSD- based on elicited behavioral and psychological disturbances.	We recruited 174 patients with DSD (84.4 +/-7.4 years) with 37 (21.3%) having BPSD. At presentation, delirium severity and symptom frequency on DRS-R98 were similar, but DSD-BPSD+ more often required only a single precipitant (40.5% vs. 21.9%, p = 0.07), and had significantly longer delirium duration (median days: 7 vs. 5, p < 0.01). At delirium resolution, DSD-BPSD+ exhibited significant improvement in sleep-wake disturbances (89.2% vs. 54.1%, p < 0.01), affect lability (81.1% vs. 56.8%, p = 0.05), and motor agitation (73% vs. 40.5%, p < 0.01), while all non-cognitive symptoms except motor retardation were improved in DSD-BPSD-. Pharmacological restraint was more prevalent (62.2% vs. 40.1%, p = 0.03), and at higher doses (chlorpromazine equivalents 0.95 +/-1.8 vs. 0.40 +/-1.2, p < 0.01) in DSD-BPSD+.	BPSD may increase vulnerability of dementia patients to delirium, with subsequent slower delirium recovery. Aggravation of sleep disturbance, labile affect, and motor agitation should raise suspicion for delirium among these patients.	
27912885	Sleep disorders have been found to be associated with hypertension in both cross-sectional and longitudinal epidemiological studies. Tetrandrine, a major component of Stephania tetrandra, is well known as an antihypertensive agent. The anti-hypertension mechanism mainly relies on its L-type calcium channel blocking property. In the previous study, tetrandrine revealed both anti-hypertension and hypnotic effects in spontaneously hypertensive rats (SHRs).This study aims to elucidate whether the antihypertensive mechanism of tetrandrine in SHRs is relevant to its hypnotic effect.	Sleep-wake behavior of the SHRs was detected by electroencephalography (EEG) and electromyography (EMG) recordings. Blood pressure was measured by noninvasive blood pressure tail cuff test. Immunohistochemistry was performed to evaluate the noradrenergic neuronal activity. The level of norepinephrine (NE) was detected by HPLC-ECD.	Amlodipine (100mg/kg, i.g.), the well-known L-type Ca2+ channel blockers (CCBs) exhibited remarkable antihypertensive activities in SHRs, but did not show effects on sleep of SHRs. Tetrandrine (30 and 60mg/kg/day, i.g.) significantly suppressed blood pressure of SHRs. Meanwhile, tetrandrine (60mg/kg/day, i.g.) remarkably increased non-rapid eye movement sleep (NREMS) time, bouts and mean duration. The hypnotic effect of tetrandrine was potentiated by prazosin (0.5mg/kg, i.p.) but attenuated by yohimbine (2mg/kg, i.p.). Administration of tetrandrine (60mg/kg/day, i.g.) not only significantly decreased c-Fos positive ratio of noradrenergic neurons in the locus coeruleus (LC), but also significantly decrease NE in the endogenous sleep-wake regulating pathways including LC, hypothalamus and ventrolateral preoptic nucleus (VLPO).	In spite of a good potency in blocking L-type Ca2+ channel, the hypnotic effects of tetrandrine may be related to its suppressing effects on the noradrenergic system other than to block calcium channels. As a multi-targets drug, tetrandrine might be favorable to the hypertension patients who suffered poor sleep.	
27912882	Radix Polygalae, the dried root of Polygala tenuifolia, has been extensively used as a traditional Chinese medicine for promoting intelligence and tranquilization. Polygalasaponins extracted from the root of P. tenuifolia possess evident anxiolytic and sedative-hypnotic activities. Previous studies have reported that tenuifolin was a major constituent of polygalasaponins.The currently study aims to investigate the hypnotic effect and possible mechanism of tenuifolin in freely moving mice.	The hypnotic effects of tenuifolin (20, 40 and 80mg/kg, p.o.) were assessed by electroencephalographic (EEG) and electromyographic (EMG) analysis. Double-staining immunohistochemistry test was performed to evaluate the neuronal activity of sleep-wake regulating brain areas. High performance liquid chromatograph- electrochemical detection (HPLC-ECD) and ultrafast liquid chromatography-mass spectrometry (UFLC-MS) were used for the detection of neurotransmitters. Locomotor activity was measured by Open-field Test.	Tenuifolin at doses of 40 and 80mg/kg (p.o.) significantly prolonged the total sleep time by increasing the amount of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, associated with the significant increase in the bouts of episodes respectively. After administration of tenuifolin, the cortical EEG power spectral densities during NREM and REM sleep were similar to that of natural sleep (vehicle) and thus compatible with physiological sleep. Double-immunohistochemistry staining test showed that tenuifolin increased the c-Fos positive ratios of GABAergic NREM sleep-promoting neurons in ventrolateral preoptic area (VLPO), cholinergic REM sleep-promoting neurons in laterodorsal tegmental area (LDT) and pontomesencephalic tegmental area (PPT) and decreased the c-Fos positive ratios in wake-promoting neurons (locus coeruleus (LC) and perifornical area (Pef)). Neurotransmitter detections revealed that tenuifolin significantly reduced the noradrenaline (NA) levels in LC, VLPO, PPT and LDT, elevated the GABA levels in VLPO, LC and Pef and increased the acetylcholine (Ach) levels in LDT and PPT. In addition, tenuifolin did not cause any change to locomotor activity.	Taken together, these results provide the first experimental evidence of the significant sleep-enhancing effect of tenuifolin in mice. This effect appears to be mediated, at least in part, by the activation of GABAergic systems and/or by the inhibition of noradrenergic systems. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant P. tenuifolia in the development of phytomedicines with hypnotic properties.	
27912106	Due to the limited cognitive and communicative abilities of adults with intellectual disabilities (ID), current treatment options for depression are often limited to lifestyle changes and pharmacological treatment. Bright light therapy (BLT) is an effective intervention for both seasonal and non-seasonal depression in the general population. BLT is an inexpensive, easy to carry out intervention with minimal side effects. However, knowledge on its anti-depressant effect in adults with ID is lacking. Obstacles in realizing a controlled intervention study in this particular study population may have contributed to this lack. To study the effect of BLT on depression in this population, it is necessary to successfully execute a multicenter randomized controlled trial (RCT). Therefore, the study protocol and the management of anticipated obstacles regarding this trial are presented.
27909991	Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences. Alcohol abuse and addiction have major social and economic consequences and cause significant morbidity and mortality worldwide. Currently available therapeutics are inadequate, outlining the need for alternative treatments. Detailed knowledge of the neurocircuitry and brain chemistry responsible for aberrant behavior patterns should enable the development of novel pharmacotherapies to treat addiction. Therefore it is important to expand our knowledge and understanding of the neural pathways and mechanisms involved in alcohol seeking and abuse. The orexin (hypocretin) neuropeptide system is an attractive target, given the recent FDA and PMDA approval of suvorexant for the treatment of insomnia. Orexin is synthesized exclusively in neurons located in the lateral (LH), perifornical (PEF), and dorsal medial (DMH) hypothalamus. These neurons project widely throughout the neuraxis with regulatory roles in a wide range of behavioral and physiological responses, including sleep-wake cycle neuroendocrine regulation, anxiety, feeding behavior, and reward seeking. Here we summarize the literature to date, which have evaluated the interplay between alcohol and the orexin system.
27909987	The discovery of the orexin system represents the single major progress in the sleep field of the last three to four decades. The two orexin peptides and their two receptors play a major role in arousal and sleep/wake cycles. Defects in the orexin system lead to narcolepsy with cataplexy in humans and dogs and can be experimentally reproduced in rodents. At least six orexin receptor antagonists have reached Phase II or Phase III clinical trials in insomnia, five of which are dual orexin receptor antagonists (DORAs) that target both OX1 and OX2 receptors (OX2Rs). All clinically tested DORAs induce and maintain sleep: suvorexant, recently registered in the USA and Japan for insomnia, represents the first hypnotic principle that acts in a completely different manner from the current standard medications. It is clear, however, that in the clinic, all DORAs promote sleep primarily by increasing rapid eye movement (REM) and are almost devoid of effects on slow-wave (SWS) sleep. At present, there is no consensus on whether the sole promotion of REM sleep has a negative impact in patients suffering from insomnia. However, sleep onset REM (SOREM), which has been documented with DORAs, is clearly an undesirable effect, especially for narcoleptic patients and also in fragile populations (e.g. elderly patients) where REM-associated loss of muscle tone may promote an elevated risk of falls. Debate thus remains as to the ideal orexin agent to achieve a balanced increase in REM and non-rapid eye movement (NREM) sleep. Here, we review the evidence that an OX2R antagonist should be at least equivalent, or perhaps superior, to a DORA for the treatment of insomnia. An OX2R antagonist may produce more balanced sleep than a DORA. Rodent sleep experiments show that the OX2R is the primary target of orexin receptor antagonists in sleep modulation. Furthermore, an OX2R antagonist should, in theory, have a lower narcoleptic/cataplexic potential. In the clinic, the situation remains equivocal, since OX2R antagonists are in early stages: MK-1064 has completed Phase I, and MIN202 is currently in clinical Phase II/III trials. However, data from insomnia patients have not yet been released. Promotional material suggests that balanced sleep is indeed induced by MIN-202, whereas in volunteers MK-1064 has been reported to act similarly to DORAs.
27905361	В последние годы большое внимание уделяется немоторным симптомам болезни Паркинсона (БП), среди которых расстройства сна и бодрствования занимают ведущее место. Дневная сонливость (ДС) встречается у 30-55% больных в зависимости от длительности и стадии заболевания и ведет к выраженной социальной дезадаптации больного. ДС имеет мультифакторную природу, и выявление причин ее возникновения имеет большое значение для терапии. Рассматриваются основные факторы развития ДС при БП, описаны ключевые моменты патогенеза первичной ДС, приведены алгоритмы диагностики ДС и методы ее коррекции.В последние годы большое внимание уделяется немоторным симптомам болезни Паркинсона (БП), среди которых расстройства сна и бодрствования занимают ведущее место. Дневная сонливость (ДС) встречается у 30—55% больных в зависимости от длительности и стадии заболевания и ведет к выраженной социальной дезадаптации больного. ДС имеет мультифакторную природу, и выявление причин ее возникновения имеет большое значение для терапии. Рассматриваются основные факторы развития ДС при БП, описаны ключевые моменты патогенеза первичной ДС, приведены алгоритмы диагностики ДС и методы ее коррекции.	For the recent years, a special attention is given to the non-motor symptoms of Parkinson's disease, including sleep/wake disorders representing one of the leading symptoms. Daytime sleepiness occurs in 30-55% of patients depending on duration and stage of the disease, leading to severe maladjustment. This symptom seems to be multifactorial by nature and identification of it's causes could have a great importance for the therapy. The main factors of the development of daytime sleepiness in Parkinson's disease and key points of the pathogenesis of «primary» daytime sleepiness are discussed. Diagnostic methods and treatment opportunities are considered as well.	
27903128	OBJECTIVE One of the more serious risks in the treatment of third ventricle craniopharyngiomas is represented by hypothalamic damage. Recently, many papers have reported the expansion of the indications for the endoscopic endonasal approach (EEA) to be used for these tumors as well. The aim of this study was to assess the outcome of sleep-wake cycle and body core temperature (BCT), both depending on hypothalamic control, in patients affected by craniopharyngiomas involving the third ventricle that were surgically treated via an EEA. METHODS All consecutive adult patients with craniopharyngiomas that were treated at one center via an EEA between 2014 and 2016 were prospectively included. Each patient underwent neuroradiological, endocrinological, and ophthalmological evaluation; 24-hour monitoring of the BCT rhythm; and the sleep-wake cycle before surgery and at follow-up of at least 6 months. RESULTS Ten patients were included in the study (male/female ratio 4:6, mean age 48.6 years, SD 15.9 years). Gross-total resection was achieved in 8 cases. Preoperative BCT rhythm was pathological in 6 patients. After surgery, these disturbances resolved in 2 cases, improved in another 3, and remained the same in 1 patient; also, 1 case of de novo onset was observed. Before surgery the sleep-wake cycle was pathological in 8 cases, and it was restored in 4 patients at follow-up. After surgery the number of patients reporting diurnal naps increased from 7 to 9. CONCLUSIONS The outcome of the sleep-wake cycle and BCT analyzed after EEA in this study is promising. Despite the short duration of the authors' experience, they consider these results encouraging; additional series are needed to confirm the preliminary findings.
27896948	Chronic partial sleep deprivation (SD) by environmental noise exposure increases weight gain and feeding in rodents, which contrasts weight loss after acute SD by physical methods. This study tested whether acute environmental noise exposure reduced sleep and its effect on weight gain, food intake, physical activity, and energy expenditure (EE). It was hypothesized that acute exposure would (1) increase weight gain and feeding and (2) reduce sleep, physical activity, and EE (total and individual components); and (3) behavioral changes would persist throughout recovery from SD.Three-month old male Sprague-Dawley rats slept ad libitum, were noise exposed (12-h light cycle), and allowed to recover (36 h). Weight gain, food intake, sleep/wake, physical activity, and EE were measured.	Acute environmental noise exposure had no effect on feeding, increased weight gain (P < 0.01), and reduced sleep (P < 0.02), physical activity (P < 0.03), total EE (P < 0.05), and several components (P < 0.05). Reductions in EE and physical activity persisted during recovery.	Reductions in EE during sleep, rest, and physical activity reduce total EE and contribute to weight gain during acute SD and recovery from SD. These data emphasize the importance of increasing physical activity after SD to prevent obesity.	
27895820	Synchrony of biological processes with environmental cues developed over millennia to match growth, reproduction and senescence. This entails a complex interplay of genetic, metabolic, chemical, light, hormonal and hedonistic factors across life forms. Sleep is one of the most prominent rhythms where such a match is established. Over the past 100 years or so, it has been possible to disturb the synchrony between sleep-wake cycle and environmental cues. Development of electric lights, shift work and continual accessibility of the internet has disrupted this match. As a result, many non-communicable diseases such as obesity, insulin resistance, type 2 diabetes, coronary artery disease and malignancies have been attributed in part to such disruption. In this presentation a review is made of the origin and evolution of sleep studies, the pathogenic mediators for such asynchrony, clinical evidence and relevance and suggested management options to deal with the disturbances.

27887821	The relationship between sleep disorders and Internet addiction has been little work. Given the importance of these disorders, we felt it appropriate to make a synthesis of available data and to establish causality or accountability between Internet addiction and the onset of sleep disorders.A literature review was then performed. We selected scientific articles in English and French, published between 1987 and 2016 by consulting the databases Medline, Embase, PsycINFO and Google Scholar. The words used alone or in combination are as follows: addiction, dependence, Internet, behavioral addiction, sleep.	A computer screen light inhibits melatonin secretion and acts as a real external desynchronizer circadian rhythm resulting in a withdrawal syndrome or syndrome sleep phase delay when the stress of social awakening is suppressed.	We assume here that the specific treatment of addictive disorders have an influence on sleep disorders.	
27886007	Alterations of the sleep-wake cycle are common features of neurodegenerative dementia.To study differences in sleep-wake profiles in dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and healthy controls.	30 DLB and 32 AD patients, and 33 healthy elderly participants were studied. Patients were evaluated for global cognitive impairment, extrapyramidal signs, fluctuations of attention, and behavioral disorders. A comprehensive sleep-wake profile was obtained including a set of questionnaires [Pittsburgh Sleep Quality Index (PSQI), REM Sleep Behavior Disorder Single-Question screen (RBD1Q), Epworth Sleepiness Scale (ESS)] and 12-day sleep diaries.	Patients were matched for age, gender, and disease severity. DLB patients showed more severe daytime somnolence/dysfunction due to somnolence, and a higher proportion of RBD-like symptoms (70%) compared to AD and controls (p < 0.001), regardless of the presence of psychoactive drug treatment. As for sleep timing, DLB patients had a greater number of daytime naps and longer night sleep, with the latter being associated with use of clonazepam. The severity of fluctuations was associated with the presence of RBD (Clinician Assessment of Fluctuation score = RBD+: 5.2±3.7; RBD-: 2.1±3.2, p = 0.04). AD patients reported the best sleep-wake profile, while healthy controls declared the poorest sleep quality, although sleep timing and the quality of wakefulness were comparable between AD and controls.	RBD and daytime fluctuations of attention may coexist in DLB and even reciprocally potentiate each other. Self-reports of sleep quality may lead to an underestimation of sleep disturbances in AD, possibly influenced by anosognosia, compared to normal elderly individuals who complain mainly of insomnia.	
27884699	Cell adhesion molecules (CAMs) play essential roles in the central nervous system, where some families are involved in synaptic development and function. These synaptic adhesion molecules (SAMs) are involved in the regulation of synaptic plasticity, and the formation of neuronal networks. Recent findings from studies examining the consequences of sleep loss suggest that these molecules are candidates to act in sleep regulation. This review highlights the experimental data that lead to the identification of SAMs as potential sleep regulators, and discusses results supporting that specific SAMs are involved in different aspects of sleep regulation. Further, some potential mechanisms by which SAMs may act to regulate sleep are outlined, and the proposition that these molecules may serve as molecular machinery in the two sleep regulatory processes, the circadian and homeostatic components, is presented. Together, the data argue that SAMs regulate the neuronal plasticity that underlies sleep and wakefulness.
27884682	The anatomical and functional mapping of lateral hypothalamic circuits has been limited by the numerous cell types and complex, yet unclear, connectivity. Recent advances in functional dissection of input-output neurons in the lateral hypothalamus have identified subset of inhibitory cells as crucial modulators of both sleep-wake states and metabolism. Here, we summarize these recent studies and discuss the multi-tasking functions of hypothalamic circuitries in integrating sleep and metabolism in the mammalian brain.
27884398	To determine the feasibility of using slow-paced respiration therapy to treat symptoms in women with pulmonary arterial hypertension (PAH).People with PAH report increased dyspnea, fatigue and sleep disturbance that can impair health-related quality of life (HRQOL).	Ten women with PAH received 8-weeks of daily, 15 min sessions using slow-paced respiration therapy via the RESPeRATE™ device. Participants had baseline and follow up assessments including plasma norepinephrine and interleukin-6 (IL-6), self-report questionnaires to measure dyspnea, fatigue, depressive symptoms, sleep and HRQOL along with 7-day actigraphy and sleep diaries.	The mean age was 50 years. Adherence to the intervention was 92%. There was decrease in median IL-6 levels [1.3 ± 0.5 to 1.1 ± 0.4, 95% CI (0.03-0.43)] over the study period. Sleep disturbance decreased, depressive symptoms decreased and HRQOL scores decreased (higher scores indicate worse HRQOL).	In this pilot study, slow-paced respiration therapy is feasible in patients with PAH and may improve symptoms and lower IL-6.	
27883169	Physical functioning is a key factor in independent living, and its preclinical state assessment and monitoring during the subject's normal life would be beneficial.The aim of the study is to analyse associations between ambulatory measured physical activity behaviour and sleep patterns (wrist actigraphy) and self-reported difficulties in performing activities of daily living. Participants, setting and design: 36 residents in assisted living facilities and nursing homes (average age=80.4±9.0 years) without dementia in free living conditions participated. Actigraphic monitoring is integrated with the facilities' social alarm system.	Indices on activity level, activity rhythm, sleep pattern and external stimuli response of sleep-wake behaviours were extracted from the actigraph data and correlated (Spearman rank-order correlation) with activities of daily living measures. Bonferroni correction for multiple comparisons was applied.	Activity level (ρ=-0.49, p<0.05) and night-time activity variance (ρ=-0.69, p<0.01) had correlation with the activities of daily living scores. The similarity of subject-wise activity pattern to facility common activities had a trend with activities of daily living (ρ=-0.44, p<0.1). In longitudinal case analysis, sleep and activity patterns were found to be associated with local weather variables.	Activity patterns as measured by actigraphy may provide objective information on older people's behaviour related to functioning state and its changes in nursing home and assisted living facility settings. However, variance between individuals was large in this dataset which decreases the reliability of the results. Furthermore, external stimuli such as weather and facility-related activities can affect subjects' activity and sleep behaviour and should be considered in the related studies as well.	
27882644	Converging evidence identifies that the offspring of parents with bipolar disorder (BD), individuals at clinical high risk of BD, and young people with recent onset BD may differ from other clinical cases or healthy controls in terms of sleep-wake profiles. However, it is possible that these differences may reflect current mental state, subtype of mood disorder, or familial traits. This study aimed to determine objective and subjective sleep-wake profiles in individuals aged 15-25 years with a current major depressive episode, in relation to familial traits.Frequency matching was employed to ensure that each individual with a confirmed family history of BD (FH+) could be compared to four controls who did not have a familial mood disorder (FH-). Pre-selected objective actigraphy and subjective Pittsburgh Sleep Quality Index (PSQI) ratings were compared using one-way analysis of variance (ANOVA) and applying the Benjamini-Hochberg (BH) correction for false discoveries.	The sample comprised 60 individuals with a mean age of 19 years. The FH+ (n=12) and FH- groups (n=48) differed on three key sleep parameters: mean sleep duration on week nights (P=.049), variability in waking after sleep onset (P=.038), and daily disturbances (PSQI dimension of sleep disturbance and daytime dysfunction; P=.01).	The sleep profiles we identified in this study, especially the daily disturbances phenotype, provide support for research into endophenotypes for BD. Also, the findings may offer the opportunity for more tailored, personalized interventions that target specific components of the sleep-wake cycle in individuals with a family history of BD.	
27881627	To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.	We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26-14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31-5.85, p = 0.008) were associated with TR.	Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.	
27871441	There is increasing evidence that essential tremor (ET) is a complex and heterogeneous disorder with nonmotor features including cognitive deficits and sleep problems. We are unaware of a study that has examined sleep deficits in ET across the full spectrum of cognitive presentations. Cross-sectional (baseline) data on self-reported nighttime sleep dysfunction and excessive daytime sleepiness were collected using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) in 96 ET cases enrolled in a prospective study. Cases underwent a comprehensive neuropsychological assessment, and were classified as ET with normal cognition (ET-NC), ET with mild cognitive impairment (ET-MCI), and ET with dementia (ET-D). PSQI scores did not significantly differ across the three ET cognitive groups (p=0.22). ESS scores were highest (more daytime sleepiness) in the ET-MCI group, followed by the ET-D and ET-NC groups, respectively (p=0.016). We examined sleep dysfunction across the cognitive spectrum in ET. We demonstrate for the first time that excessive daytime sleepiness is greater in ET-MCI than ET-NC. Unpredicted low ESS scores in the dementia group raises two possibilities: a self-report bias related to cognitive impairment and/or the possibility that currently undefined pathological heterogeneity in ET may map onto multiple presentations of non-motor deficits.
27867309	Objective. To test the gender differences in tenderness, impact of fibromyalgia, health-related quality of life, fatigue, sleep quality, mental health, cognitive performance, pain-cognition, and positive health in Spanish fibromyalgia patients and in age-matched nonfibromyalgia individuals from the same region. To test the optimal cut-off score of the different tender points for women and men. Methods. A total of 405 (384 women) fibromyalgia versus 247 (195 women) nonfibromyalgia control participants from southern Spain (Andalusia) took part in this cross-sectional study. The outcomes studied were assessed by means of several tests. Results. In the fibromyalgia group, men showed better working memory than women (all, P < 0.01), whereas sleep latency was lower in women compared to men (P = 0.013). In the nonfibromyalgia group, men showed higher pain threshold in all the tender points (all, P < 0.01), except in right and left lateral epicondyle. Furthermore, men showed better working memory than women (all, P < 0.01), whereas memory performance was better in women compared to men (all, P ≤ 0.01). Conclusion. The results of the present study do not support consistent evidence of gender differences in fibromyalgia-related symptoms. However, it seems that detriment of some symptoms (especially pain) in fibromyalgia men compared with their nonfibromyalgia counterparts is greater than those of fibromyalgia women compared with their nonfibromyalgia peers.
27864941	This study investigated whether sex, age, income and any comorbidity affect subsequent epilepsy development in migraineurs.A total of 4915 men diagnosed with migraine who were aged older than 20 years were identified as the study cohort. A total of 4882 female migraineurs were included in the comparison cohort. We calculated the adjusted hazard ratio (aHR) for the risk of epilepsy in the two cohorts after adjustment for age and comorbidity. Kaplan-Meier analysis was used to analyse the cumulative epilepsy incidence, and the log-rank test was used to estimate the differences between the two cumulative incidence curves.	The risk of epilepsy was 2·31-fold higher in male migraineurs than in female migraineurs. The income-specific analysis showed that the risk of epilepsy was high in migraineurs with a low monthly income [aHR: 2·73 for 15 000-25 000 new Taiwan dollar (NTD; approximately 500-833 USD) and aHR: 2·71 for < 15 000 NTD]. Among patients with one or more comorbidity, a 2·48-fold (95% confidence interval: 1·65-3·74) high risk of epilepsy was noted in male migraineurs, regardless of the presence of head injury. Additional analyses revealed that male migraineurs aged 65 years or older had the highest risk of epilepsy.	Migraineurs have an increased risk of subsequent epilepsy. Male sex, old age and low income may interact with migraine and result in a high risk of epilepsy in migraineurs.	
27861713	Sleep disturbances are common during pregnancy, yet underdiagnosed and under-investigated. We evaluated sleep quality during pregnancy and assessed associated factors, especially depressive and anxiety symptoms.A total of 78 healthy pregnant women from the FinnBrain Birth Cohort Study were studied twice prospectively during pregnancy (in mid-pregnancy and late pregnancy). Sleep quality was evaluated by the Basic Nordic Sleep Questionnaire, depressive symptoms by the Edinburgh Postnatal Depression Scale, and anxiety symptoms by the State-Trait Anxiety Inventory.	Poor general sleep quality, difficulty falling asleep, the number of nocturnal awakenings per night, and too-early morning awakenings increased in late pregnancy compared with mid-pregnancy (all p-values < 0.020). The total insomnia score (p < 0.001) and sleep latency increased (p = 0.005), but sleep duration and preferred sleep duration did not change. Women tended to snore more often in late pregnancy, but apneas remained rare. Almost one-fourth of the women reported both morning and daytime sleepiness, but the frequencies did not increase during the follow up. In late pregnancy, depressive and anxiety symptoms were cross-sectionally related to sleep disturbances, but depressive or anxiety symptoms in mid-pregnancy were not associated with sleep disturbances in late pregnancy.	We found deterioration in sleep quality across pregnancy. However, no increase in negative daytime consequences was found, presumably indicating a compensatory capacity against sleep impairment. Additionally, depressive and anxiety symptoms and sleep disturbances were only cross-sectionally associated. Our study calls for further research on the factors that influence sleep disturbances during pregnancy.	
27860347	The aim of this article was to examine the associations between having had a sinus infection (SI) and BMI and physical activity (PA), diet quality, stress and/or sleep. A total of 2915 adults from the National Health and Nutrition Examination Survey 2005-2006 were examined. Logistic regression analysis was used to examine the association between having had an SI with BMI and PA, diet quality, stress or sleep. As these factors are known to influence one another, a fully adjusted model with PA, diet quality, stress and sleep was also constructed to examine their independent associations with having had an SI. Overall, 15.5 ± 1.2% of the population report having had an SI in the past year. In all models, individuals with obesity were approximately twice as likely to have had an SI compared to those of normal weight (P < 0.05). While PA and diet quality were not significantly associated with having had an SI (P > 0.05), individuals with stress and sleep troubles were also twice as likely to have had an SI (P < 0.05) independent of BMI. In the fully adjusted model, only the associations for BMI and sleep troubles remained significant (P < 0.05). Results from this study suggest that obesity and sleep troubles, but not PA, quality of diet and stress, are associated with having had an SI. As interactions exist between obesity, immune system factors and exposure to infectious disease(s), more research is necessary to understand the directionality of these relationships.
27858874	Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome.Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients' psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome.	The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013-0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000-0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome.	We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders.	
27857011	The purpose of this study was to develop an Allergic Rhinitis-Specific Quality of Life (ARSQOL) scale and verify its validity and reliability.ARSQOL was developed in 5 steps. Items for the preliminary instrument of ARSQOL were developed through a literature review and deep interviews with allergic rhinitis patients. Face validity with Content Validity Index (CVI), construct validity using factor analysis, and known group comparison, criterion validity test using correlation between ARSQOL and total nasal symptoms score (TNSS) were conducted to evaluate the validity of ARSQOL. Cronbach's α was used to evaluate the reliability of ARSQOL.	CVI for the items in the final ARSQOL were .92. Five factors including discomfort associated with nasal symptoms (4 items), physical function (7 items), mental function (5 items), sleep disorder and social function (4 items), and problems of daily life (6 items) were identified through factor analysis and these five factors explained 66.6% of the total variance. The correlation coefficient between TNSS and the total score of life quality was -.69. In the group comparison, the persistent allergic rhinitis group showed lower ARSQOL scores than the intermittent patient group, and moderate to the severe allergic rhinitis patient group presented poorer ARSQOL than the mild symptom patient group. The Cronbach's α reliability coefficient was .95.	Results show that the ARSQOL has good reliability and validity and thus ARSQOL is a useful scale for clinical practices and research as a measure of quality of life in adults with allergicr hinitis.	
27855749	We investigate how characteristics of sleep-wake dynamics in humans are modified by narcolepsy, a clinical condition that is supposed to destabilize sleep-wake regulation. Subjects with and without cataplexy are considered separately. Differences in sleep scoring habits as a possible confounder have been examined.Four groups of subjects are considered: narcolepsy patients from China with (n=88) and without (n=15) cataplexy, healthy controls from China (n=110) and from Europe (n=187, two nights each). After sleep stage scoring and calculation of sleep characteristic parameters, the distributions of wake-episode durations and sleep-episode durations are determined for each group and fitted by power-laws (exponent α) and by exponentials (decay time τ).	We find that wake duration distributions are consistent with power laws for healthy subjects (China: α=0.88, Europe: α=1.02). Wake durations in all groups of narcolepsy patients, however, follow the exponential law (τ=6.2-8.1 min). All sleep duration distributions are best fitted by exponentials on long time scales (τ=34-82 min).	We conclude that narcolepsy mainly alters the control of wake-episode durations but not sleepepisode durations, irrespective of cataplexy. Observed distributions of shortest wake and sleep durations suggest that differences in scoring habits regarding the scoring of short term sleep stages may notably influence the fitting parameters but do not affect the main conclusion.	
27853240	Apterous (Ap), the best studied LIM-homeodomain transcription factor in Drosophila, cooperates with the cofactor Chip (Chi) to regulate transcription of specific target genes. Although Ap regulates various developmental processes, its function in the adult brain remains unclear. Here, we report that Ap and Chi in the neurons expressing PDF, a neuropeptide, play important roles in proper sleep/wake regulation in adult flies. PDF-expressing neurons consist of two neuronal clusters: small ventral-lateral neurons (s-LNvs) acting as the circadian pacemaker and large ventral-lateral neurons (l-LNvs) regulating light-driven arousal. We identified that Ap localizes to the nuclei of s-LNvs and l-LNvs. In light-dark (LD) cycles, RNAi knockdown or the targeted expression of dominant-negative forms of Ap or Chi in PDF-expressing neurons or l-LNvs promoted arousal. In contrast, in constant darkness, knockdown of Ap in PDF-expressing neurons did not promote arousal, indicating that a reduced Ap function in PDF-expressing neurons promotes light-driven arousal. Furthermore, Ap expression in l-LNvs showed daily rhythms (peaking at midnight), which are generated by a direct light-dependent mechanism rather than by the endogenous clock. These results raise the possibility that the daily oscillation of Ap expression in l-LNvs may contribute to the buffering of light-driven arousal in wild-type flies.
27852301	Poor sleep quality is common in rheumatoid arthritis (RA) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). The increasing prevalence of poor sleep in RA patients is associated with adverse demographic, clinical, and psychological characteristics. However, there are currently no known reported studies related to the effects of sleep quality on HRQoL in RA patients from China. This cross-sectional study aims to evaluate the contributors of poor sleep and the effects of sleep quality on HRQoL in Chinese RA patients.A self-report survey was administered to 131 RA patients and 104 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. RA patients completed the Hospital Anxiety and Depression Scale for anxiety and depression, the 28-joint Disease Activity Score for disease activity, the 10 cm Visual Analog Scale for pain, the Health Assessment Questionnaire-Disability Index for functional capacity and the Short Form 36 health survey for HRQoL. Blood samples were taken to gain some biochemical indicators (e.g., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide). Independent samples t-tests, Chi square analysis, logistic regression modeling and linear regression were used to analyze these data.	Our results found that the prevalence of poor sleep (PSQI ≥ 5) was 78.6% and the mean global score of PSQI was 7.93 (SD 3.98) in patients, which were significantly higher than the controls (18.7% and 3.88 (SD 1.89), respectively). There were significant correlations among synthetic disease-modifying antirheumatic drugs, erythrocyte sedimentation rate, pain, disease activity, functional capacity, anxiety/depression and sleep quality in RA patients. Meanwhile, logistic regression models identified disease activity and depression as predictors of poor sleep quality. Poor RA sleepers had impaired HRQoL than good RA sleepers, and sleep quality was independently and significantly associated with social function and mental components summary.	The majority of Chinese RA patients suffered from poor sleep, which significantly impairs their HRQoL. The data suggested the need for holistic assessment and management of RA patients and the importance of objective interventions to improve their sleep quality and finally to improve their HRQoL.	
27851868	Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant caregiver distress, increased healthcare costs, and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population.To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia, through identification and analysis of all relevant randomised controlled trials (RCTs).	We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, in March 2013 and again in March 2016, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, sundowning.	We included RCTs that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline. Trials could also include non-pharmacological interventions, as long as both drug and placebo groups had the same exposure to them.	Two review authors independently extracted data on study design, risk of bias, and results from the included study reports. We obtained additional information from study authors where necessary. We used the mean difference as the measure of treatment effect, and where possible, synthesized results using a fixed-effect model.	We found six RCTs eligible for inclusion for three drugs: melatonin (222 participants, four studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), trazodone (30 participants, one study), and ramelteon (74 participants, one study, no peer-reviewed publication, limited information available).The participants in the trazodone study and almost all participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. Only two studies made a systematic assessment of adverse effects. Overall, the evidence was at low risk of bias, although there were areas of incomplete reporting, some problems with participant attrition, related largely to poor tolerance of actigraphy and technical difficulties, and a high risk of selective reporting in one trial that contributed very few participants. The risk of bias in the ramelteon study was unclear due to incomplete reporting.We found no evidence that melatonin, at doses up to 10 mg, improved any major sleep outcome over 8 to 10 weeks in patients with AD who were identified as having a sleep disturbance. We were able to synthesize data for two of our primary sleep outcomes: total nocturnal sleep time (mean difference (MD) 10.68 minutes, 95% CI -16.22 to 37.59; N = 184; two studies), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; N = 184; two studies). From single studies, we found no difference between melatonin and placebo groups for sleep efficiency, time awake after sleep onset, or number of night-time awakenings. From two studies, we found no effect of melatonin on cognition or performance of activities of daily living (ADL). No serious adverse effects of melatonin were reported in the included studies. We considered this evidence to be of low quality.There was low-quality evidence that trazodone 50 mg given at night for two weeks improved total nocturnal sleep time (MD 42.46 minutes, 95% CI 0.9 to 84.0; N = 30; one study), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; N = 30; one study) in patients with moderate-to-severe AD, but it did not affect the amount of time spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6; N = 30; one study), or the number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8; N = 30; one study). No effect was seen on daytime sleep, cognition, or ADL. No serious adverse effects of trazodone were reported.Results from a phase 2 trial investigating ramelteon 8 mg administered at night were available in summary form in a sponsor's synopsis. Because the data were from a single, small study and reporting was incomplete, we considered this evidence to be of low quality in general terms. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or eight weeks (end of treatment) in patients with mild-to-moderate AD. The synopsis reported few significant differences from placebo for any sleep, behavioural, or cognitive outcomes; none were likely to be of clinical significance. There were no serious adverse effects from ramelteon.	We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in dementia. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in dementia, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin (up to 10mg) helped sleep problems in patients with moderate to severe dementia due to AD. There was some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in dementia. Systematic assessment of adverse effects is essential.	
27849327	The aim of this study was to determine the sleep quality of patients treated at burn center.The present study is descriptive research conducted between January 2014 and July 2015 at a university hospital. The study included 36 patients (32 male, 4 female; mean age 26.69±9.63; range 19 to 60 years). Patient information form and Pittsburgh Sleep Quality Index (PSQI) were used to collect data. SPSS software (version 22.0; SPSS Inc., Chicago, IL, USA) was used for the analysis of the data, and statistical significance was regarded as p<0.05 in all analyses.	Burn injuries of 50% of the patients were due to flash burn that occurred in the house. Complications developed in 52.8% of the patients. PSQI score average of the patients was 9.30±4.03 and 86.5% of them suffer from poor sleep quality. It was found that there was a statistically significant correlation (p<0.05) between Pittsburgh Sleep Quality averages and patient being in the intensive care unit (ICU), education level, percentage of area burned, length of time that had passed since the burn, and medication (antidepressant or antipsychotic).	The sleep quality of patients in the study was found to be of poor degree. It is known that after burn injury, sufficient sleep enhances the function of natural defense cells, protein synthesis, and release of growth hormones, thereby healing the burn injuries. Information about patient sleep quality and sleep problems can lead to the development of nursing care for patients suffering from burns.	
27845651	Poor sleep is increasingly being recognised as an important prognostic parameter of health. For those with suspected sleep disorders, patients are referred to sleep clinics which guide treatment. However, sleep clinics are not always a viable option due to their high cost, a lack of experienced practitioners, lengthy waiting lists and an unrepresentative sleeping environment. A home-based non-contact sleep/wake monitoring system may be used as a guide for treatment potentially stratifying patients by clinical need or highlighting longitudinal changes in sleep and nocturnal patterns. This paper presents the evaluation of an under-mattress sleep monitoring system for non-contact sleep/wake discrimination. A large dataset of sensor data with concomitant sleep/wake state was collected from both younger and older adults participating in a circadian sleep study. A thorough training/testing/validation procedure was configured and optimised feature extraction and sleep/wake discrimination algorithms evaluated both within and across the two cohorts. An accuracy, sensitivity and specificity of 74.3%, 95.5%, and 53.2% is reported over all subjects using an external validation dataset (71.9%, 87.9% and 56%, and 77.5%, 98% and 57% is reported for younger and older subjects respectively). These results compare favourably with similar research, however this system provides an ambient alternative suitable for long term continuous sleep monitoring, particularly amongst vulnerable populations.
27845162	Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61μg/5μl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5μl; n=6). Microinjection of either NEI (61ng/0.2μl: n=7), MCH (100ng/0.2μl: n=6) or GABA (250mM/0.2μl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG.
27844033	The sodium leak channel, a Na+-permeable, nonselective cation channel, is widely expressed in the nervous system, contributing a basal Na+-leak conductance and regulating neuronal excitability. A 3-year-old girl, heterozygous for a de novo missense mutation in NALCN (c.956C>T; p.Ala319Val) predicted to be deleterious, presented from birth with: stimulus-induced, episodic contractures of the limbs and face with associated respiratory distress; distal arthrogryposis; severe axial hypotonia; and severe global developmental delay (CLIFAHDD syndrome). In infancy, she manifested a reversed sleep-wake rhythm, nocturnal life-threatening respiratory rhythm disturbances with central apnea. Sevoflurane sensitivity caused respiratory depression and cardiac arrest.
27836462	Attention deficit/hyperactivity disorder (ADHD) is frequently associated with comorbid aggression and sleep disturbances. The sleep/wake cycle is under the control of the circadian system which is moderated by clock genes. Clock genes can regulate the transcription of monoamine oxidase A, which is involved in the degradation of monoamines. Disturbances in monoamine interaction with clock genes in those with monoamine gene polymorphisms may regulate susceptibility of ADHD and comorbid aggression/sleep disturbances. While monoamines influence circadian rhythm and clock gene expression, circadian rhythm components modulate aggressive behavior, and altered clock genes expression have been associated with ADHD. We propose a mechanism by which circadian rhythm and clock gene expression may influence ADHD and comorbid aggression through the modulation of neurotransmitters. The role of clock genes in ADHD patients with comorbid aggression awaits further research; therefore we also indicate directions for future studies to help increase understanding of the underlying mechanisms in ADHD with comorbid aggression and sleep disturbances.
27835722	Brexpiprazole is a serotonin-dopamine activity modulator. We evaluated the effects of adjunctive treatment with brexpiprazole on sleep disturbances in patients with DSM-IV-TR major depressive disorder (MDD) and inadequate response to antidepressant treatment.This study was conducted between September 27, 2013, and August 19, 2014. Patients with inadequate response to antidepressant treatment and sleep disturbances continued treatment with their current antidepressant for 2 weeks. Patients still having inadequate response and sleep efficiency less than 85% measured by baseline polysomnography (PSG) received 8-week open-label treatment with their current antidepressant treatment and adjunctive brexpiprazole (target dose: 3 mg/d). Assessments included PSG recordings and scales of insomnia severity, depressive symptoms, and daytime alertness and functioning. Changes from baseline to week 8 were analyzed.	Forty-four patients were treated. Improvements (P < .05) measured by PSG and Consensus Sleep Diary for Morning, respectively, were observed in sleep efficiency (10.4 and 15.4 percentage points), total sleep time (49.0 and 84.5 min), sleep onset latency (-19.7 and -42.6 min), wake-time after sleep onset (-26.4 and -48.0 min), and latency to persistent sleep (-24.9 min, PSG only). Insomnia Severity Index (ISI) total score was improved (-9.2), as was daytime sleepiness (-2.1) as measured by the Epworth Sleepiness Scale (ESS) total score and morning sleepiness (-9.2) as measured by the Bond-Lader Visual Analog Scale (all P < .05). Reaction time was slightly decreased (-0.2 sec-1) by treatment (P < .05). Depressive symptoms improved (Montgomery-Asberg Depression Rating Scale [MADRS]: -16.0 and Clinical Global Impressions-Severity [CGI-S]: -1.8), as did functioning (-8.4) assessed by the Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (all P < .05). Improvements in depressive symptoms were dependent on sleep (as assessed by ISI) (P < .0001) and improvements in daytime alertness (as assessed by ESS) were dependent on improvements in ISI (P = .009). No new safety concerns were observed compared to previous brexpiprazole studies.	In patients with inadequate response to antidepressant treatment and sleep disturbances treated with adjunctive brexpiprazole, physiologic measures of sleep and daytime alertness were improved.	
27834148	There is a general consensus that sleep-wake cycle is controlled by neuroanatomical, neurochemical and molecular systems as well as by homeostatic and circadian complex networks. The research has shown that a molecular element that could be displaying a relevant role in the modulation of sleep is the peroxisome proliferator-activated receptor alpha (PPARα), which belongs to the family of nuclear receptor ligand-activated transcription factors that includes PPARβ/δ and PPARγ. A growing body of evidence supports the notion that PPARα is activated by natural ligands such as the anorexic lipid mediator oleoylethanolamide (OEA) or synthetic compounds including Wy14643 whereas antagonists like MK-886 block the neurobiological outcomes of PPARα. More recently, studies have reported the permissive role of PPARα by modulating diverse neurobiological functions such as inflammation, metabolic disorders, learning, degenerative diseases and sleep. Remarkably, this nuclear receptor has been described in sleep-related brain regions leading to the hypothesis that PPARα might be involved in sleep modulation inasmuch as activation of this protein promotes a robust enhancement of wakefulness while reduces sleep. In this minireview, the emerging evidence of the putative role of PPARα in sleep control is highlighted. Even though the data are derived from new areas of research, there are many reasons to believe that understanding and appreciation of PPARα functions may provide knowledge of possible mechanisms of action activated by this nuclear receptor in sleep modulation. Moreover, novel insights of therapeutic intervention for sleep disorders might be visualized targeting the function of PPARα in sleep abnormalities.
27828694	To consolidate the evidence from the literature to evaluate the role of prazosin in the treatment of posttraumatic stress disorder (PTSD).Major databases, including PubMed, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO, and Scopus, were searched through August 2015 for studies reporting the role of prazosin in the treatment of PTSD with no language constraints. Keywords included (PTSD OR posttraumatic stress OR posttraumatic stress OR nightmares) AND prazosin.	Of 402 screened articles, 6 studies were included in the systematic review and meta-analysis.	Two reviewers independently extracted relevant data (study characteristics, type of intervention, outcome measures, and follow-up) from the included studies using a standardized data extraction form. Only randomized controlled trials comparing prazosin to a placebo or control group in patients with PTSD were included.	The patients with PTSD receiving prazosin showed significant improvement in nightmares (standardized mean difference [SMD] = 1.01; 95% CI, 0.72-1.30), overall PTSD symptoms (SMD = 0.77; 95% CI, 0.48-1.06), and clinical global improvement (SMD = 0.94; 95%, CI 0.6-1.29) compared to the placebo/control group. Prazosin improved sleep quality (SMD = 0.87; 95% CI, 0.55-1.19), hyperarousal symptoms (SMD = 1.04; 95% CI, 0.23-1.84), dream content (SMD = 1.33; 95% CI, 0.69-1.97), and total sleep time (60.98 minutes; 95% CI, 18.69-103.26). Prazosin was fairly well tolerated. Minor side effects were reported, which were similar between the prazosin and placebo groups.	This study suggests that prazosin improves nightmares and overall PTSD symptoms including hyperarousal, sleep disturbances, total sleep time, and sleep quality.	
27827298	The prevalence of sleep disturbances among patients with Parkinson's disease (PD) is estimated to occur in 37% to 98% of patients. Sleep disturbances have been associated with a reduced quality of life for patients with PD. The objective of this study was to assess the impact of rasagiline treatment on the severity of sleep disturbances among patients with idiopathic PD.In this open-label, multicentre study, 110 adult patients with idiopathic PD were treated with rasagiline either as monotherapy or as adjunct therapy. The primary endpoint was the change in severity of sleep disturbances, assessed with the PD Sleep Scale from baseline to month 2. Exploratory endpoints included change in daytime sleepiness, assessed with the Epworth Sleep Scale, treatment satisfaction measured with the Treatment Satisfaction Questionnaire for Medication, patient's overall improvement or deterioration over time measured with the Clinical Global Impression of Improvement, tolerability, and safety.	Patients treated with rasagiline as mono- or adjunct therapy showed a statistically significant improvement in sleep quality after 2 months. There was no change in daytime sleepiness. Overall, patients were satisfied with rasagiline treatment with a mean Treatment Satisfaction Questionnaire for Medication [standard deviation] total score at month 2 of 68% [16.1]. At the end of study, 64 patients (65.9%) were judged, by the investigator, as being at least minimally improved from baseline on the Clinical Global Impression of Improvement. Rasagiline was safe and well-tolerated.	Rasagiline as mono- or adjunct-therapy may improve sleep experience in patients with PD in the short term.	
27823835	Fatigue and sleep disorders are frequently reported in patients affected by Multiple Sclerosis (MS) but the causes and the relationship are not yet fully understood. This study aimed at evaluating their prevalence, at determining the relationships between clinical findings of MS and the occurrence of sleep disorders and at investigating the relations between sleep disorders and fatigue.One hundred and two MS patients were enrolled in the study. They were analyzed on both their clinical features (type of MS, disease duration, clinical severity, type of treatment, presence of spinal demyelinating lesions) and specific scales scores (Expanded Disability Status Scale, Modified Fatigue Impact Scale - MFIS, Self-Administered Anxiety Scale - SAS, Beck's Depression Inventory - BDI, Pittsburgh Sleep Quality Index - PSQI, Epworth Sleepiness Scale - ESS, and the Berlin's questionnaire for Obstruction Sleep Apnea Syndrome - OSAS).	Patients with poor sleep quality are more frequently fatigued (p=0.001), have higher MFIS global scores (p<0.001), higher prevalence of RLS symptoms (p=0.049), and show higher scores at BDI (p=0.017) and SAS (p≤0.001). Conversely patients with fatigue show older age (p=0.005), higher prevalence of sleepiness (p=0.021), higher prevalence of RLS symptoms (p=0.030), higher prevalence of poor sleep quality (p<0.001) with higher PSQI scores (p<0.001), higher scores on the BDI (p<0.001) and SAS (p≤0.001).	This study shows that MS is associated with a high prevalence of sleep complaints, including subjectively poor sleep quality, excessive daytime sleepiness, RLS and symptoms of OSAS. Further, it demonstrated a strict relation between fatigue and sleep disorders. Finally, it underlines their relationship with anxiety and depression in MS patients.	
27823734	This follow-up study aimed to evaluate risk factors for menopausal sleep disturbances already identifiable before menopause.At baseline, all 81 women were premenopausal. At year-five follow-up, 27 of the women were premenopausal, 40 postmenopausal, and 14 postmenopausal and using hormone therapy. We used the Basic Nordic Sleep Questionnaire to study sleep; additional questionnaires evaluated risk factors for sleep impairment.	Sleep quality differed only marginally between the groups. The following baseline variables were associated with impaired sleep quality at follow-up: depressive symptoms increased the risk of nocturnal awakenings (OR 1.16 (95%CI 1.02-1.32), p=0.025), morning tiredness (OR 1.22 (95%CI 1.06-1.40), p=0.007), daytime tiredness (OR 1.24 (95%CI 1.06-1.44), p=0.007) and propensity to fall asleep during work or leisure time (OR 1.18 (95%CI 1.01-1.37), p=0.036). Personal crises increased the risk of longer sleep latency (OR 5.46 (95%CI 1.13-26.32), p=0.035) and of propensity to fall asleep when not active (OR 5.41 (95%CI 1.42-20.83), p=0.014). Use of medications affecting the CNS increased the risk of worse general sleep quality (OR 11.44 (95% CI 1.07-121.79), p=0.044). Perceived impaired general health (OR 2.87 (95%CI 1.04-7.94), p=0.043) and frequent night sweats (OR 10.50 (95%CI 2.25-49.01), p=0.003) increased the risk of difficulty falling asleep.	Various premenopausal health-related factors seem to predict poor sleep in menopausal transition. Menopause itself appears to have only minor effects. Thus, it is essential to identify high-risk women to allow timely interventions that may prevent the development of sleep disturbances at menopause.	
27823726	Sleep disorders are common but underdiagnosed conditions, which are associated with obesity. In Colombia, the distribution of sleep disorders remains unclear. We aimed to describe the distribution of sleep disorders, according to demographic, geographic and anthropometric characteristics, in adult Colombian populations.A multicenter study was conducted with 5474 participants recruited from three Colombian cities at different altitudes. A two-stage cluster sampling method was applied. Participants' mean age was 40.2 years and 53.8% were female. Collected data included demographic information and anthropometric characteristics of adiposity such as body mass index, neck circumference and waist circumference, as well as participants' scores on five scales used to assess sleep disorders. Disorders included sleepiness, obstructive sleep apnea (OSA), insomnia, poor sleep quality and restless legs syndrome; the scales were the Epworth Sleepiness Scale, Berlin questionnaire, STOP-Bang questionnaire, Pittsburgh Sleep Quality Index and diagnostic criteria for the restless legs syndrome set out by the International Restless Legs Syndrome Study Group.	Nearly two-thirds of the population reported at least one sleep disorder according to their results on the five scales (59.6% [95%CI 57.4; 61.81)]. This proportion was similar by sex. Prevalence of overweight was 34.8% and of obesity was 14.4%. Sleep disorders were more frequent among those aged 65 years or more (91.11 [95%CI 86.1; 94.43]), those who were obese (83.71% [95%CI 78.94; 87.56]) and those who resided in the cities at the lowest altitude (72.4% [95%CI 70.2; 74.5]). Waist circumference showed a stronger association with sleep disorders among women than among men.	Sleep disorders are common in Colombia, irrespective of sex and geographical location. They are associated with obesity. Abdominal obesity could explain the high frequency of sleep disorders among women. We believe that this part of the study will substantially contribute to the understanding of sleep disorders. Further research is needed to identify key factors behind the high prevalence rates of sleep disorders and obesity in Colombia.	
27822929	Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure.
27822641	The purpose of this study was to evaluate the relationships between screen time (ST), nighttime sleep duration, and behavioural problems in a sample of preschool children in China. A sample of 8900 children aged 3-6 years was enrolled from 35 kindergartens, in four cities, in two provinces, in China to evaluate the relationships between ST, nighttime sleep duration, and behavioural problems. Children's ST and nighttime sleep duration were assessed by questionnaires completed by parents or guardians. Behavioural problems were assessed using the Strengths and Difficulties Questionnaire (SDQ), and the Clancy Autism Behaviour Scale (CABS). Multivariate analysis was used to assess the associations between ST, nighttime sleep duration, and behavioural problems. The total SDQ and CABS scores were higher in children with ST ≥2 h/day and sleep duration <9.15 h/day (a P < 0.001 for all). After adjusting for potential confounders, children with ST ≥2 h/day had a significantly increased risk of having total difficulties, emotional symptoms, conduct problems, hyperactivity, peer problems, and prosocial problems, as well as behavioural symptoms of autism spectrum disorder. Similar results were found in children with sleep duration <9.15 h/day. No significantly increased risk of emotional symptoms was observed for short sleep duration. Preschool children with more ST and short nighttime sleep duration were significantly more likely to have behavioural problems. These results may contribute to a better understanding of prevention and intervention for psychosocial problems in children.
27822504	Unraveling the roles of distinct neuron types is a fundamental challenge to understanding brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons has been only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). These cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performing ex vivo patch-clamp recordings from nNOS+ neurons in Nos1-CreER;Ai9 mice, we observed that nNOS+ neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization, and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS+ neurons are activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin [5-hydroxytryptamine (5-HT)] neurons, which are involved in sleep-wake regulation, innervate nNOS+ neurons. Bath application of 5-HT hyperpolarizes nNOS+ neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS+ cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links among mood, sleep deprivation, and 5-HT, the recruitment of paracapsular nNOS+ neurons following high sleep pressure may represent an important mechanism in emotional regulation.
27822283	Inadequate sleep hygiene may result in difficulties in daily functioning; therefore, reliable scales for measuring sleep hygiene are important.The purpose of this study was to assess the psychometric properties of the Persian version of the Sleep Hygiene Index (SHI).	From April 2014 to May 2015, 1280 subjects, who were selected by cluster random sampling in Kermanshah province, filled out the SHI, Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). A subset of the participants (20%) repeated the SHI after a four to six-week interval to measure test-retest reliability. Then, we computed the Pearson product-moment correlation coefficients of SHI against PSQI, ESS and ISI, to demonstrate the construct validity of the SHI. The factor structure of the SHI was evaluated by explanatory factor analysis.	The interclass correlation coefficient was 0.89, and SHI was found to have good test-retest reliability (r = 0.89, P < 0.01). The SHI was positively correlated with the total score of the PSQI (r = 0.60, P < 0.01), ESS (r = 0.62, P < 0.01) and ISI (r = 0.60, P < 0.01). Exploratory factor analysis extracted three factors, namely "sleep-wake cycle behaviors" (four items), "bedroom factors" (three items), and "behaviors that affect sleep" (six items).	The Persian version of the SHI can be considered a reliable tool for evaluating sleep hygiene in the general population.	
27821764	Sleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state, such as sleep deprivation (SD) or arousal, can phase shift the circadian clock. Here we demonstrate that the level of wakefulness is critical for this arousal resetting of the circadian clock. Specifically, drowsy animals with significant power in the 7- to 9-Hz band of their EEGs do not exhibit phase shifts in response to a mild SD procedure. We then show that treatments that both produce arousal and reset the phase of circadian clock activate (i.e., induce Fos expression in) the basal forebrain. Many of the activated cells are cholinergic. Using retrograde tract tracing, we demonstrate that cholinergic cells activated by these arousal procedures project to the circadian clock in the suprachiasmatic nuclei (SCN). We then demonstrate that arousal-induced phase shifts are blocked when animals are pretreated with atropine injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal-induced phase shifting. Finally, we demonstrate that electrical stimulation of the substantia innominata of the basal forebrain phase shifts the circadian clock in a manner similar to that of our arousal procedures and that these shifts are also blocked by infusions of atropine to the SCN. These results establish a functional link between the major forebrain arousal center and the circadian system.
27819459	Our goal was to examine the association between marital conflict and nocturnal blood pressure dipping (NBP) in Iraq/Afghanistan healthy veterans and their partners and to determine whether sleep disturbances mediate such associations.The sample consisted of 25 heterosexual couples comprised of male veterans and their female civilian spouses/partners. Blood pressure was measured across 48 hr, and NBP was calculated as the ratio of sleep/wake mean arterial pressure (MAP). Marital conflict was assessed by questionnaire. Sleep was assessed via in-home polysomnography (PSG). Posttraumatic stress disorder (PTSD) diagnosis was determined via clinician interview and was included as a covariate in all analyses, along with body mass index, age, gender, and deployment characteristics.	Higher marital conflict was associated with higher MAP ratios (β = .74, p < .01), with the effect stronger among women (β = -0.68, p < .05, for gender interaction). Among women only, for each SD increase in marital conflict there was a .82 increase in MAP ratio (p < .01). This association was reduced to nonsignificance after adjustment for PSG-assessed sleep efficiency.	Consistent with limited prior work in civilian samples, higher marital conflict in military couples was associated with blunted NBP, particularly among women. These findings highlight the importance of considering the health and well-being of both veterans and their partners in the aftermath of war, as well as the importance of considering nighttime physiological pathways that are relevant to cardiovascular disease risk. (PsycINFO Database Record	
27819313	Jet travel and night shift work produce large changes in when people sleep, work and eat; a challenge that was not encountered during most of our evolution. Successful adaptation would require the internal, master, circadian clock to make large phase shifts to reduce the circadian misalignment between circadian rhythms and the times for sleep, work and meals. We compared African-Americans and non-Hispanic European-Americans in how much their circadian clocks shifted after a 9 hour phase delay of the light/dark, sleep/wake and meal schedule, which has similarities to flying west or sleeping in the daytime after night shifts. We also measured their free-running circadian periods using a forced desynchrony protocol with a 5-h day. European-Americans had longer free-running periods and larger phase delays than African-Americans. Correlations (among all subjects, just African-Americans and just European-Americans) showed that longer circadian periods were associated with larger phase delays. Larger phase delays, facilitated by longer circadian periods, reduce jet lag after westward travel and make it easier to work night shifts and sleep during the daytime after night work. On the other hand, a shorter circadian period, which makes one more of a morning-type person, is better for most people given our early-bird dominated society.
27818086	Substantial research attention has been devoted to understanding the importance and impact of sleep in children and adolescents. Traditionally, this has focused on mean sleep variables (e.g., a child's "typical" or average sleep duration), yet research increasingly suggests that intraindividual variability (IIV) of sleep/wake patterns (sometimes referred to as sleep variability or night-to-night variability) regularly occurs and may have implications for adjustment. A systematic search of five electronic databases identified 52 empirical studies published between 2000 and 2015 that examined correlates of sleep IIV in children and adolescents, with a recent increase in the publication rate of such studies. Identified studies were often atheoretical and included post hoc analyses, though IIV in select aspects of sleep does appear to be associated with increasing age/pubertal status, non-White race, physical and neurodevelopmental conditions (e.g., attention-deficit/hyperactivity disorder; autism), psychopathology symptoms (e.g., anxiety, depression, inattention), body weight, stress, aspects of cognitive functioning, and poorer sleep functioning/habits. The limited intervention work examining sleep IIV in adolescents is promising, though studies are needed using more rigorous intervention designs. Clinical sleep recommendations may not only need to address overall sleep duration and sleep habits but also the stability of sleep duration and timing. It will be important for future research examining sleep IIV in children and adolescents to use a developmental framework in advancing theory pertaining to the causes, mechanisms, moderators, and outcomes of sleep IIV in youth, and a conceptual model is proposed to help guide such efforts.
27816835	Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients.89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength.	23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue.	The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients.	
27816011	Airline pilots' sleep and on-duty alertness are important focus areas in commercial aviation. Until now, studies pertaining to this topic have mainly focused on specific characteristics of flights and thus a comprehensive picture of the matter is not well established. In addition, research knowledge of what airline pilots actually do to maintain their alertness while being on duty is scarce. To address these gaps in research knowledge, we conducted a field study on a representative sample of the airline pilots of a medium-sized airline. The sample consisted of 90 pilots, of whom 30 flew long-haul (LH) routes, 30 short-haul (SH) routes, and 30 flew both. A total of 86 pilots completed the measurements that lasted for almost two months per pilot. The measurements resulted in a total of 965 flight duty periods (FDPs) including SH flights and 627 FDPs including LH flights. During the measurement periods, sleep was measured by a diary and actigraphs, on-duty alertness by the Karolinska Sleepiness Scale (KSS) in all flight phases, and on-duty alertness management strategies by the diary. Results showed that SH and LH FDPs covering the whole domicile night (00:00-06:00 at home base) were most consistently associated with reduced sleep-wake ratio and subjective alertness. Approximately every 3rd FDP falling into this category involved a reduced sleep-wake ratio (1:3 or lower) and every 2nd a reduced level of subjective alertness (KSS rating 8-9 in at least one flight phase). The corresponding frequencies for the SH and LH FDPs that partly covered the domicile night were every 10th and every 5th FDP and for the pure non-night FDPs every 30th and every 36th FDP, respectively. The results also showed that the pilots tended to increase the use of effective on-duty alertness management strategies (consuming alertness-promoting products and taking strategic naps) in connection with the FDPs that overlapped the domicile night. Finally, the results showed that the frequency of flights involving reduced subjective alertness depended on how alertness was assessed. If it was assessed solely in the flight phase just before starting the landing procedures (top of descent) the phenomenon was less frequent than if the preceding cruise phase was also taken into account. Our results suggest that FDPs covering the whole domicile night should be prioritised over the other FDPs in fatigue management, regardless of whether an FDP is a short-haul or a long-haul. In addition, the identification of fatigue in flight operations requires one to assess pilots' alertness across all flight phases, not only at ToD. Due to limitations in our data, these conclusions can, however, be generalise to only LH FDPs during which pilots can be expected to be well acclimatised to the local time at their home base and SH night FDPs that include at least 3h of flying in the cruise phase.
27812851	Affective disorders in young people have been associated with disruptions in circadian rhythms, including abnormalities in secretion of the pineal hormone melatonin. Previous research reports relationships between pineal gland volumes, melatonin secretion, and sleep-wake cycles, but the relationship between these factors has not been explored in affective disorders. This study aimed to characterize these factors and explore associations with mood symptoms and functioning in a sample of young people with affective disorders. Pineal volume from magnetic resonance imaging and melatonin assay from evening dim-light saliva collection were evaluated in 50 individuals (15-30 years old; 72 % female) with bipolar, depressive, or anxiety disorders. Actigraphy monitoring was also conducted for approximately two weeks to derive sleep-wake measures. Pineal volume was associated with melatonin secretion across the evening, replicating previous findings in psychiatrically healthy individuals. Pineal volume was smaller in participants in which melatonin onset was not detected. Timing of melatonin secretion was related to sleep timing, but amount of melatonin and pineal volume were not related to any sleep-wake measures. A shorter phase angle between onset of melatonin secretion and sleep onset was associated with longer total sleep time. Lower melatonin levels were associated with poorer social and occupational functioning. Although pineal volume is not directly related to sleep disturbances or symptoms, melatonin may influence both sleep-wake cycles and functioning in the early stages of affective disorder. Causal links remain to be established, however, treatments that target circadian rhythms may be useful in improving functioning in young people with affective disorders.
27812308	The aim of the study was to examine basal hypothalamic-pituitary-adrenal (HPA) axis activity and to determine associations of various covariates (gender, sleep-wake rhythm, demographic, academic, life style and health-related characteristics) with altered daily salivary cortisol profiles in late adolescence.The total analytic sample consisted of 903 Croatian secondary school students aged 18 - 21 years (median 19 years). Salivary cortisol was sampled at home at three time points over the course of one week and its concentrations were measured by using the enzyme immunoassay.	In comparison to males, female students had a higher cortisol awakening response (CAR) (median 4.69, IQR 10.46 and median 3.03, IQR 8.94, respectively; P < 0.001), a steeper ("healthier") diurnal cortisol slope (DCS) (median 0.51, IQR 0.55 and median 0.44, IQR 0.51, respectively; P = 0.001), and a greater area under curve with respect to ground (AUCG) (median 206.79, IQR 111.78 and median 191.46, IQR 104.18, respectively; P < 0.001). Those students who woke-up earlier and were awake longer, had a higher CAR (P < 0.001), a flatter ("less healthy") DCS (P < 0.001), and a greater AUCG (P < 0.001), than students who woke-up later and were awake shorter. Less consistent but still significant predictors of salivary cortisol indexes were age, school behaviour, friendship, diet healthiness and drug abuse.	Gender and sleep-wake up rhythm were major determinants of the altered daily salivary cortisol profiles in late adolescence. The predictive power of other covariates, although less clear, has a potential for identifying vulnerable subgroups such as male drug users and females without a best friend.	
27810175	Light plays an important role in the synchronization of the internal biological clock and the environmental day/night pattern. Thus, absence of vision is often associated with both increases in reported sleep disturbances and incidence of free-running circadian rhythms. In this study we discuss variability in the sleep-wake pattern between blind and normal-sighted individuals.Thirty-day actigraphy recordings were collected from 11 blind individuals without residual light perception and 11 age- and sex-matched normal-sighted controls. From these recordings, we extracted parameters of sleep and wake, including episodes of rest, day-time and night-time sleep periods, and the number of awakenings throughout sleep. A measure of sleep efficiency was derived from these measures for each night-time sleep episode. We also examined complementary measures of sleep quality, using the Pittsburgh Sleep Quality Index, and chronotype, using the Morningness-Eveningness Questionnaire.	Although no group differences were found when averaging over the entire recording period, we found a greater variability throughout the 30-days in both sleep efficiency and timing of the night-time sleep episode in blind participants as compared to sighted control participants. We also confirm previous reports of reduced sleep quality in blind individuals. Notably, the variability in sleep efficiency and in the timing of sleep correlated with the severity of sleep disturbances.	The timing and physiology of sleep are strongly dependent on the endogenous circadian phase; therefore, observed findings support the hypothesis of free-running circadian rhythms as a dominant factor for the sleep disturbances experienced in blindness.	
27663355	The relationship between functional brain images and performances in narcoleptic patients and controls is a new field of investigation. We studied 71 young, type 1 narcoleptic patients and 20 sex- and age-matched control individuals using brain positron emission tomography (PET) images and neurocognitive testing. Clinical investigation was carried out using sleep-wake evaluation questionnaires; a sleep-wake study was conducted with actigraphy, polysomnography, multiple sleep latency test (MSLT), and blood tests (with human leukocyte antigen typing). The continuous performance test (CPT) and Wisconsin card sorting test (WCST) were administered on the same day as the PET study. PET data were analyzed using Statistical Parametric Mapping (version 8) software. Correlation of brain imaging and neurocognitive function was performed by Pearson's correlation. Statistical analyses (Student's t-test) were conducted with SPSS version-18. Seventy-one narcoleptic patients (mean age: 16.15 years, 41 boys (57.7%)) and 20 controls (mean age: 15.1 years, 12 boys (60%)) were studied. Results from the CPT and WCST showed significantly worse scores in narcoleptic patients than in controls (P < 0.05). Compared to controls, narcoleptic patients presented with hypometabolism in the right mid-frontal lobe and angular gyrus (P < 0.05) and significant hypermetabolism in the olfactory lobe, hippocampus, parahippocampus, amygdala, fusiform, left inferior parietal lobe, left superior temporal lobe, striatum, basal ganglia and thalamus, right hypothalamus, and pons (P < 0.05) in the PET study. Changes in brain metabolic activity in narcoleptic patients were positively correlated with results from the sleepiness scales and performance tests. Young, type 1 narcoleptic patients face a continuous cognitive handicap. Our imaging cognitive test protocol can be useful for investigating the effects of treatment trials in these patients.
27647493	The 5-HT6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD). The high affinity and selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on cortical function using two in vivo electrophysiological methods. Neuronal network oscillations in the frontal cortex were measured during electrical stimulation of the brainstem nucleus pontis oralis (nPO) in the anesthetized rat and by an electroencephalogram (EEG) in the awake, freely moving rat. In conjunction with the EEG study, we investigated the effects of idalopirdine and donepezil on sleep-wake architecture using telemetric polysomnography. Idalopirdine (2 mg/kg i.v.) increased gamma power in the medial prefrontal cortex (mPFC) during nPO stimulation. Donepezil (0.3 and 1 mg/kg i.v.) also increased cortical gamma power and pretreatment with idalopirdine (2 mg/kg i.v.) potentiated and prolonged the effects of donepezil. Similarly, donepezil (1 and 3 mg/kg s.c.) dose-dependently increased frontal cortical gamma power in the freely moving rat and pretreatment with idalopirdine (10 mg/kg p.o.) augmented the effect of donepezil 1 mg/kg. Analysis of the sleep-wake architecture showed that donepezil (1 and 3 mg/kg s.c.) dose-dependently delayed sleep onset and decreased the time spent in both REM and non REM sleep stages. In contrast, idalopirdine (10 mg/kg p.o.) did not affect sleep-wake architecture nor the effects of donepezil. In summary, we show that idalopirdine potentiates the effects of donepezil on frontal cortical gamma oscillations, a pharmacodynamic biomarker associated with cognition, without modifying the effects of donepezil on sleep. The increased cortical excitability may contribute to the procognitive effects of idalopirdine in donepezil-treated AD patients.
27605426	Sleep-wake disturbances (SWD) are common nonmotor symptoms (NMS) and have a great impact on quality of life of patients with Parkinson's disease (PD). Deep brain stimulation (DBS) is an established treatment in PD. While the beneficial effects of DBS on cardinal PD motor symptoms are indisputable, the data for several NMS, including sleep-wake functions, are limited and often controversial. Our primary objective was to review the literature on the impact of DBS on sleep-wake functions in patients with PD. A systematic review of articles, published in PubMed between January 1st, 2000 and December 31st, 2015 was performed to identify studies addressing the evolution of sleep-wake functions after DBS in patients with PD. Only 38 of 208 studies, involving a total of 1443 subjects, met the inclusion criteria. Most of them reported a positive effect of subthalamic DBS on sleep quality and consequently on quality of life. Seven studies used polysomnography to objectively assess sleep parameters. The data concerning subthalamic DBS and wake functions are controversial and studies using objective, laboratory-based measures for the assessment of wake functions are lacking. Very few studies assessed the impact of other DBS targets (e.g. pallidal stimulation) on SWD. Further prospective observational DBS studies assessing subjectively and objectively specific sleep-wake parameters in patients with PD are needed.
27403929	Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry.We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND.	Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models.	In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46-0.83), free T, and SHBG with AHI were rendered nonsignificant after multivariable adjustment. In multivariable analyses, ASD was associated with Epworth Sleepiness Scale (β-coefficient per SD increase in ASD: -0.71; 95% CI: -1.18 to -0.25). In women, multivariable analyses showed positive associations of dehydroepiandrosterone-sulphate with wake after sleep onset (β-coefficient: .16; 95% CI 0.03-0.28) and of E2 and E2 to TT ratio with Epworth Sleepiness Scale. Additionally, free T and SHBG were associated with AHI in multivariable models among premenopausal women.	The present cross-sectional, population-based study observed sex-specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness. However, multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep.	
27807182	To investigate the relationship between hypothalamic D3 dopamine receptor availability and severity of sleep problems in Parkinson disease (PD).Twelve patients were assessed with PET and the high-affinity dopamine D3 receptor radioligand [11C]-propyl-hexahydro-naphtho-oxazin ([11C]-PHNO). Severity of sleep problems was rated with appropriate subitems of the Unified Parkinson's Disease Rating Scale part I (patient questionnaire) and the Epworth Sleepiness Scale.	We found that lower dopamine D3 receptor availability measured with [11C]-PHNO PET was associated with greater severity of excessive daytime sleepiness but not with problems of falling asleep or insomnia.	In our cohort of patients with PD, the occurrence of excessive daytime sleepiness was linked to reductions in hypothalamic dopamine D3 receptor availability. If these preliminary findings are confirmed in larger cohorts of patients with polysomnographic characterization, selective pharmacologic modulation of the dopaminergic D3 system could be used to increase daytime alertness in patients with PD.	
27118763	We describe a 70-year-old man who, after a viral encephalitis associated with pneumonia, progressively developed a parkinsonism associated with lethargy. Encephalitis manifested with persistent hiccups, seizures and impairment of consciousness. After 2 weeks, the initial neurologic symptoms subsided and the patient progressively developed movement disorders (rigidity and bradykinesia, resistant to L-DOPA), lethargy and behavioral hypersomnia. Magnetic resonance imaging showed thalamic and hippocampal signal abnormalities, immunohistochemistry on a mouse brain substrate revealed serum autoantibodies binding to the brainstem neuropil. Polysomnographic monitoring was consistent with a very severe disruption of sleep: the sleep-wake cycle was fragmented, and the NREM-REM ultradian cycle was irregular. Intravenous immune globulin therapy resulted in the complete reversal of the movement and the sleep disorders. Our observation confirms that parkinsonism and sleep disorders may be consequences of encephalitis, that an immune-mediated pathogenesis is likely, and, consequently, that immunotherapy can be beneficial in these patients. The polysomnographic monitoring suggests that lethargia, rather than a mere hypersomnia, is the result of a combination between sleep disruption and altered motor control.
27798423	Review of recent literature pertaining to frequency, associations, mechanisms, and overall significance of sleep--wake disturbances (SWD) in the premotor and early phase of Parkinson's disease.SWD are frequent in Parkinson's disease and their prevalence increases with disease progression. Recent studies confirm previous findings that SWD can appear as initial manifestation of Parkinson's disease even decades before motor signs appear and highlight their clinical associations in these early stages. More intriguingly, new evidence underpins their role as risk factors, predictors, or even as driving force for the neurodegenerative process. As our understanding of sleep--wake neurobiology increases, new hypotheses emerge concerning the pathophysiology of SWD in early Parkinson's disease stages involving dopaminergic and nondopaminergic mechanisms.	SWD are predictors for the development of parkinsonian syndromes including Parkinson's disease. This may offer the opportunity of developing new preventive strategies and interventions at an early stage of this neurodegenerative disease.	
26324072	To assess which laboratory and clinical factors are associated with fatigue in patients with terminal cancer.We evaluated 51 patients with advanced incurable solid tumors using the Chalder Fatigue Questionnaire (CFQ) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale for fatigue; the Pittsburgh Sleep Quality Index (PSQI-BR) for sleep quality; the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression; the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire, Version 3.0 (QLQ C-30); and Functional Assessment of Cancer Therapy (FACT) for quality of life. We also analyzed several inflammatory markers and the modified Glasgow prognostic score (mGPS).	We observed severe fatigue in 19 (38%) patients (FACIT-F score >36). There was a significant correlation between fatigue as evaluated by the CFQ and quality of sleep and between the CFQ mental fatigue subscale scores and TNF-α level. When fatigue was evaluated using the FACIT-F scale, we observed a significant association between fatigue and anxiety/depression, quality of sleep, mGPS, and hemoglobin levels. Fatigue measured both with the CFQ and FACIT-F scale correlated with poor quality of life according to the EORTC QLQ C-30.	In patients with advanced cancer, fatigue is a common symptom associated with the presence of inflammation, poor quality of sleep, depression/anxiety, and poor quality of life.	
27694264	As cluster headache (CH) is often referred to as "suicide headache," we wanted to assess the prevalence of depression in CH patients, and to investigate determinants of depression such as sleep disturbances.In a cross-sectional, web-based, validated questionnaire study among 462 well-defined CH patients and 177 controls, we diagnosed CH according to the ICHD-III. We assessed depression using the Hospital Anxiety and Depression Scale (HADS-D) and the Center for Epidemiologic Studies Depression scale (CES-D) with supplementary questions to assess lifetime depression. Data were analyzed with logistic and linear regression models.	Lifetime depression showed almost 3 times higher odds in CH patients (n = 462) than controls (n = 177) (odds ratio 2.77; 95% confidence interval 1.70-4.51). Chronic (n = 67) vs episodic (n = 394) patients had a higher prevalence of lifetime depression and more sleeping problems. Current depression was associated with having active attacks (last attack <1 month) (adjusted p = 0.02), but no effect remained after correction for sleep disturbances.	CH is associated with an almost 3 times increased odds of lifetime depression. Current depression is highly prevalent in patients with active disease, in part related to sleep disturbances due to current nocturnal attacks.	
27647451	Sleep is increasingly recognized as an important lifestyle contributor to health. However, this has not always been the case, and an increasing number of Americans choose to curtail sleep in favor of other social, leisure, or work-related activities. This has resulted in a decline in average sleep duration over time. Sleep duration, mostly short sleep, and sleep disorders have emerged as being related to adverse cardiometabolic risk, including obesity, hypertension, type 2 diabetes mellitus, and cardiovascular disease. Here, we review the evidence relating sleep duration and sleep disorders to cardiometabolic risk and call for health organizations to include evidence-based sleep recommendations in their guidelines for optimal health.
27631554	Sleep disturbances are associated with type 2 diabetes; therefore, the amelioration of sleep may improve metabolic disorders. To investigate this possibility, we here examined the effects of suvorexant, an antiinsomnia drug targeting the orexin system, on sleep and glucose metabolism in type 2 diabetic mice. Diabetic db/db mice had a longer wakefulness time during the resting period, as compared with nondiabetic db/m+ control mice. The single or 7-day administration of suvorexant at lights-on (ie, the beginning of the resting phase) increased nonrapid eye movement sleep time during the resting phase and, as a consequence, reduced awake time. The daily resting-phase administration of suvorexant for 2-4 weeks improved impaired glucose tolerance in db/db mice without affecting body weight gain, food intake, systemic insulin sensitivity, or serum insulin, and glucagon levels. No changes were detected in the markers of lipid metabolism and inflammation, such as the hepatic triglyceride content and Tnf-α mRNA levels in liver and adipose tissues. The improving effect of suvorexant on glucose tolerance was associated with a reduction in the expression levels of hepatic gluconeogenic factors, including phosphoenolpyruvate carboxykinase and peroxisome proliferator-activated receptor-γ coactivator-1α in the liver in the resting phase. In contrast, the daily awake-phase administration of suvorexant had no beneficial effect on glucose metabolism. These results suggest that the suvorexant-induced increase of sleep time at the resting phase improved hepatic glucose metabolism in db/db mice. Our results provide insight into the development of novel pharmacological interventions for type 2 diabetes that target the orexin-operated sleep/wake regulatory system.
27797160	Central sleep apnoea (CSA) - the temporary absence or diminution of ventilatory effort during sleep - is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne-Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, that is elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via continuous positive airway pressure (CPAP), tracheostomy or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep-wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, that is low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, for example CPAP improves lung volume (plant gain), stimulants reduce the alveolar-inspired PCO2 difference and supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalized interventions for CSA.
27793660	A reduction in the activity of GABAA receptors, particularly α5 subunit-containing GABAA receptors (α5GABAARs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABAARs (Gabra5-/-) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the behavioral task. The aim of this study was to examine the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5-/- mice and wild-type mice. In addition, since some individuals with ASD can exhibit elevated innate immune response, mice were treated with lipopolysaccharide (LPS; 125mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed. The results showed that Gabra5-/- mice (n=3) exhibited elevated 0-2Hz EEG activity during all sleep-wake states (all p<0.04), decreased 8-12Hz EEG activity during REM sleep (p=0.04), and decreased sleep spindles under baseline conditions compared to wild-type controls (n=4) (all p≤0.03). Alterations in EEG activity and sleep-wake behavior were identified in Gabra5-/- mice following treatment with LPS, however these changes were similar to those in wild-type mice. Our findings support the hypothesis that reduced α5GABAAR activity contributes to an ASD phenotype. The results also suggest that Gabra5-/- mice may serve as an animal model for ASD, as assessed through EEG activity and sleep-wake behaviors.
27769744	Pannexins are membrane channel proteins that play a role in a number of critical biological processes (Panchin et al., 2000; Shestopalov, Panchin, 2008). Among other cellular functions, pannexin hemichannels serve as purine nucleoside conduits providing ATP efflux into the extracellular space (Dahl, 2015), where it is rapidly degraded to adenosine. Pannexin1 (Panx1) is abundantly expressed in the brain and has been shown to contribute to adenosine signaling in nervous system tissues (Prochnow et al., 2012). We hypothesized that pannexin1 may contribute to sleep-wake cycle regulation through extracellular adenosine, a well-established paracrine factor in slow wave sleep. To investigate this link, EEG and movement activity throughout the light/dark cycle were compared in Panx1-/- and Panx1+/+ mice. We found a significant increase in waking and a correspondent decrease in slow wave sleep percentages in the Panx1-/- animals. These changes were especially pronounced during the dark period. Furthermore, we found a significant increase in movement activity of Panx1-/- mice. These findings are consistent with the hypothesis that extracellular adenosine is relatively depleted in Panx1-/- animals due to the absence of the ATP-permeable hemichannels. At the same time, sleep rebound after a 6-h sleep deprivation remained unchanged in Panx1-/- mice as compared to the control animals. Behavioral tests revealed that Panx1-/- mice were significantly faster during their descent along the vertical pole but more sluggish during their run through the horizontal pole as compared to the control mice.
27611586	The purpose of the current study was to explore the cerebral areas involved in nightmare disorder.Fifteen nightmare disorder patients and 15 healthy volunteers were invited to undergo resting-state functional magnetic resonance imaging and to complete the Nightmare Experience Questionnaire.	The nightmare disorder patients scored higher on the Physical Effect and Horrible Stimulation scales, had higher values of regional homogeneity in clusters within the left anterior cingulate cortex and right inferior parietal lobule, and lower regional homogeneity values within the left superior and inferior frontal gyri and bilateral middle occipital gyri. Physical Effect was negatively correlated with regional homogeneity values in anterior cingulate cortex and inferior parietal lobule in the nightmare disorder group, and was positively correlated with regional homogeneity value in the inferior frontal gyrus in the healthy control group.	To our best knowledge, this is the first neuroimaging study on nightmare disorder, and we have characterized the cerebral activities underlying altered hyperarousal and emotion regulation in nightmare disorder at resting-state.	
27453368	To evaluate the predictive value of pre- and postoperative amplitude-integrated electroencephalography (aEEG) on neurodevelopmental outcomes in children operated for congenital heart disease (CHD).Prospectively enrolled cohort of 60 infants with CHD who underwent cardiac surgery with cardiopulmonary bypass in the first 3 months of life. Infants with a genetic comorbidity were excluded. aEEG was assessed for 12 hours pre- and 48 hours postoperatively. Background pattern was classified by the use of standard categories, and the presence of seizures and sleep-wake cycles (SWCs) was noted. Outcome at 1 and 4 years of age was assessed with standardized developmental tests.	Preoperatively, infants either showed continuous normal voltage (n = 56) or discontinuous normal voltage (n = 4). Postoperatively, abnormal background pattern (flat trace, burst suppression, or continuous low voltage) was detected in 7 (12%), discontinuous normal voltage in 37 (61%), and continuous normal voltage in 16 (27%) infants. Nineteen infants (32%) did not return to normal SWCs within the recording period. Seizures were detected in 4 infants preoperatively and in another 4 postoperatively. After we controlled for surgical and postoperative risk factors, abnormal postoperative background pattern and lack of return to SWCs independently predicted poorer intelligence quotient at 4 years (P = .03 and P = .04 respectively) but was not related to motor outcome.	aEEG is a useful bedside tool that helps to predict outcome in infants undergoing open-heart surgery for CHD. Abnormal postoperative background pattern and lack of return to SWCs are markers for subsequent impaired cognitive development.	
27787717	The Gi/o protein-coupled histamine H3 receptor is distributed throughout the central nervous system including areas like cerebral cortex, hippocampus and striatum with the density being highest in the posterior hypothalamus, i.e. the area in which the histaminergic cell bodies are located. In contrast to the other histamine receptor subtypes (H1, H2 and H4), the H3 receptor is located presynaptically and shows a constitutive activity. In detail, H3 receptors are involved in the inhibition of histamine release (presynaptic autoreceptor), impulse flow along the histaminergic neurones (somadendritic autoreceptor) and histamine synthesis. Moreover, they occur as inhibitory presynaptic heteroreceptors on serotoninergic, noradrenergic, dopaminergic, glutamatergic, GABAergic and perhaps cholinergic neurones. This review shows for four functions of the brain that the H3 receptor represents a brake against the wake-promoting, anticonvulsant and anorectic effect of histamine (via postsynaptic H1 receptors) and its procognitive activity (via postsynaptic H1 and H2 receptors). Indeed, H1 agonists and H3 inverse agonists elicit essentially the same effects, at least in rodents; these effects are opposite in direction to those elicited by brain-penetrating H1 receptor antagonists in humans. Although the benefit for H3 inverse agonists for the symptomatic treatment of dementias is inconclusive, several members of this group have shown a marked potential for the treatment of disorders associated with excessive daytime sleepiness. In March 2016, the European Commission granted a marketing authorisation for pitolisant (WakixR) (as the first representative of the H3 inverse agonists) for the treatment of narcolepsy.
27783860	Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA). Although OSA is almost exclusively a human disorder, animal models help unveil the basic principles governing the impact of sleep on breathing and upper airway muscle activity. This article discusses the neuroanatomy, neurochemistry, and neurophysiology of the different neuronal systems whose activity changes with sleep-wake states, such as the noradrenergic, serotonergic, cholinergic, orexinergic, histaminergic, GABAergic and glycinergic, and their impact on central respiratory neurons and upper airway motoneurons. Observations of the interactions between sleep-wake states and upper airway muscles in healthy humans and OSA patients are related to findings from animal models with normal upper airway, and various animal models of OSA, including the chronic-intermittent hypoxia model. Using a framework of upper airway motoneurons being under concurrent influence of central respiratory, reflex and state-dependent inputs, different neurotransmitters, and neuropeptides are considered as either causing a sleep-dependent withdrawal of excitation from motoneurons or mediating an active, sleep-related inhibition of motoneurons. Information about the neurochemistry of state-dependent control of upper airway muscles accumulated to date reveals fundamental principles and may help understand and treat OSA. © 2016 American Physiological Society. Compr Physiol 6:1801-1850, 2016.
27658486	Trace amine-associated receptor 1 (TAAR1) agonists have been shown to have procognitive, antipsychotic-like, anxiolytic, weight-reducing, glucose-lowering, and wake-promoting activities. We used Taar1 knockout (KO) and overexpressing (OE) mice and TAAR1 agonists to elucidate the role of TAAR1 in sleep/wake. EEG, EMG, body temperature (Tb), and locomotor activity (LMA) were recorded in Taar1 KO, OE, and WT mice. Following a 24 h recording to characterize basal sleep/wake parameters, mice were sleep deprived (SD) for 6 h. In another experiment, mice were given three doses of the TAAR1 partial agonist RO5263397, caffeine, or vehicle p.o. Baseline wakefulness was modestly increased in OE compared with WT mice. Baseline theta (4.5-9 Hz) and low gamma (30-60 Hz) activity was elevated in KO compared with OE mice in NREM and REM sleep. Following SD, both KO and OE mice exhibited a homeostatic sleep rebound. In WT mice, RO5263397 increased waking and reduced NREM and REM sleep, decreased gamma power during wake and NREM, and decreased Tb without affecting LMA; these effects were absent in KO mice and potentiated in OE mice. In contrast, caffeine increased wake time, NREM gamma power, and LMA in all strains compared with vehicle; this effect was attenuated in KO and potentiated in OE mice. TAAR1 overexpression modestly increases wakefulness, whereas TAAR1 partial agonism increases wakefulness and also reduces NREM and also REM sleep. These results indicate a modulatory role for TAAR1 in sleep/wake and cortical activity and suggest TAAR1 as a novel target for wake-promoting therapeutics.
27780283	Background The aim of this study is to investigate through polysomnography sleep quality in children with rolandic epilepsy and compare sleep variables between these children and healthy controls. Methods Our study population included 15 children with rolandic epilepsy and 27 healthy children who underwent overnight polysomnography. Parameters about sleep architecture and sleep respiratory events were recorded and analyzed. The level of statistical significance was set at 0.05. Results Patients and controls did not differ in basic epidemiological traits. The percentage of sleep stage rapid eye movement was significantly lower in the epilepsy group. Moreover, the mean value of the obstructive apnea index and the obstructive apnea-hypopnea index was significantly higher in children with rolandic epilepsy compared with healthy children. Longest apnea duration and basal Spo 2 during sleep had also the trend to be higher and lower, respectively, in children with epilepsy. Conclusions Children with rolandic epilepsy exhibit alterations in sleep architecture, as well as in sleep respiratory patterns. Therefore, sleep quality should be routinely considered in the long-term follow-up of these children.
27778159	Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.
27777343	It has been estimated that the prevalence of Alzheimer disease (AD) and related dementias will triple by 2035, unless effective interventions or treatments are found for the neurodegenerative disease. Understanding sleep changes as a marker for both AD risk and progression is a burgeoning area of investigation. Specifically, there is emerging evidence that both sleep disturbances and the APOE ε4 allele are associated with increased dementia risk. Previous research has suggested that in AD, individuals carrying the APOE ε4 allele have decreased sleep quality compared to individuals without the APOE ε4 allele. This observational trial aimed to determine if healthy older adults with the risk allele (APOE ε4+) have more sleep complaints or evidence of objective sleep disruption compared to healthy older adults without the risk allele (APOE ε4-).Within the larger Brain in Motion study, a subset of participants completed at-home polysomnography (PSG) and actigraphy sleep assessment. Subjective sleep complaints were determined using the Pittsburgh Sleep Quality Index.	This investigation found a significant relationship between presence of APOE ε4 allele and objective sleep disturbances measured by both actigraphy and PSG, but not subjective sleep complaints in a healthy population screened for dementia.	These data suggest that the influence of APOE ε4 allele on objective sleep quality may precede subjective sleep complaints in individuals at increased risk for dementia.	
27292821	Willis-Ekbom disease/restless legs syndrome (WED/RLS) seems to be a frequent cause of intractable chronic insomnia (ICI) but is under-recognized in children/adolescents with neurodevelopmental conditions (NDCs), as many patients do not have the ability to express the underlying "urge-to-move". In light of this, we aim to develop a protocol for behavioral observations supporting the diagnosis of WED/RLS.We investigated 26 pediatric patients (age 1-16 years, median 8) with NDCs, ICI and evidence of familial WED/RLS employing (1) "emplotted narratives" for description of the various "urge-to-move" presentations and (2) self-description and "behavioral observations" during a "suggested clinical immobilization test" (SCIT).	Parental narratives reflected typical WED/RLS-related "urge-to-move" symptoms during day-, bed-, and nighttime in all patients. Fifteen out of 26 patients could describe the "urge-to-move" during the SCIT. Ten out of 26 patients, unable to describe their symptoms due to cognitive disabilities, showed patterns of "relieving-movements" upon observation. Sensory processing abnormalities were reported in all patients, with tactile sensitivities (26/26) (including shifted pain threshold) as the most common sensory domain.	"Emplotted narratives" and structured "behavioral observations" support recognition of familial WED/RLS associated movement patterns and provide a useful tool for the diagnosis of WED/RLS in children with NDCs in a clinical office setting.	
27776398	The selective melatonin receptor agonism effect of ramelteon is useful for insomnia. Here we wanted to present a refractory chronic migraine case, who had significant improvements in migraine after using ramelteon. The possible mechanism for the ramelteon in the migraine relief might be related to melatonin effects.
27776397	Apart from sleep wake disorders, nowadays, modafinil is being prescribed for several psychiatric disorders including depression. Despite being reported as to be having very low abuse potential, cases of modafinil dependence had come to the limelight. In this case report, we describe a 35 year old man with bipolar affective disorder while in remission who developed modafinil dependence and later on, had hypersexuality when he increased the dose of modafinil from 400 to 1,000 mg/day. Existing literature suggests that modafinil when taken above prescribed doses can cause many side effects ranging from nausea, vomiting to psychotic exacerbation and mania. However, hypersexuality as a side effect of modafinil overuse is not commonly seen. The exact pathophysiological mechanism of modafinil induced hypersexuality is not clear. Clinicians should be aware of possibility of modafinil leading to dependence and this rare significant side effect of modafinil.
27773516	To develop nomogram for prediction of postoperative delirium (POD) in patients undergoing ablative and reconstruction surgery for head and neck cancer.Total 341 patients were retrospectively analyzed, and clinical variables in preoperative, intraoperative and postoperative periods were compared between delirium group (n = 89) and non-delirium group (n = 252). Multivariate logistic regression, receiver operating characteristics curve, and area under the curve (AUC) were used to generate and test a nomogram, which performance was evaluated by 10-fold cross validation (CV) procedure.	In univariate and multivariate analysis, age, history of psychiatric disorder, marital status, preoperative numeric rating scale for pain, ASA classification, and ICU stay period were identified as significant risk factors. Using these factors, nomogram for predicting the POD was developed and it showed sensitivity of 61.8%, specificity of 75.4%, PPV of 47.0%, and NPV of 84.8% (Youden's index of 0.372). In 10-fold cross validation set, corresponding values were 44.9%, 84.1%, 50.0% and 81.2% (Youden's index of 0.337). AUC was comparable between two sets (0.7407 and 0.6898).	Proposed nomogram showed fair discriminative power for POD risk in head and neck cancer patients undergoing major surgery.	
27772641	Diminished health-related quality of life (HRQoL) is common in dialysis patients and associated with increased risks for morbidity and mortality. Patients may present limitations in both physical and mental HRQoL. Poor physical HRQoL may be defined by limited physical function, role limitations due to physical health, dissatisfaction with physical ability, and impaired mobility. Sleep disorders such as obstructive sleep apnea, restless legs, and fatigue are typical manifestations of poor physical HRQoL in dialysis patients. Poor mental HRQoL may be defined by depressive thinking, lack of positive affect, anxiety, and feelings of social isolation. The prevalence of depression is high in dialysis patients. Intensive hemodialysis (HD) can positively address HRQoL. In 3 randomized clinical trials, relative to conventional HD, intensive HD increased physical and mental component summary scores from the 36-Item Short-Form Health Survey (SF-36), although individual treatment effects of daily nocturnal HD were not statistically significant. In another large prospective study, initiation of short daily HD therapy was followed after 12 months by improvements in all SF-36 domains, sleep quality, and restless legs symptoms. In a small study of nocturnal HD, apnea and hypopnea episodes per hour decreased by almost 70% after conversion from conventional HD. Intensive HD is also associated with a large reduction in postdialysis recovery time. In contrast, 2 randomized clinical trials failed to demonstrate statistically significant effects of intensive HD on the Beck Depression Inventory score despite a significant decrease in Beck Depression Inventory score in the prospective study of short daily HD. Furthermore, intensive HD may not improve objective physical performance and can increase burden on caregivers in the home setting. In conclusion, intensive HD potentially can address both physical and mental aspects of poor HRQoL relative to conventional HD. However, more studies are needed to understand the effects of intensive HD, including specific schedules, on HRQoL.

27638459	The Neurological Fatigue Index (NFI-MS) is the only known perceived fatigue scale to include questions that consider the contribution of sleep quality to symptoms of fatigue in people with multiple sclerosis (MS). However, the relationship between the NFI-MS and sleep quality measures is unknown. This study aimed to explore the relationship between the NFI-MS and self-reported and objective sleep quality. Understanding the relationship between perceived fatigue and sleep quality measures could encourage a wider use of the NFI-MS in research and clinical settings.Fifty-one participants took part in this cross-sectional study (mean age: 47 ± 10.1 years old). Participants completed the NFI-MS to assess perceived fatigue, the Pittsburgh Sleep Quality Index to asses sleep quality, and the Epworth Sleepiness Scale to assess daytime sleepiness. The participants wore an actigraph device one week on the dominant wrist to objectively quantify sleep quality.	Higher perceived fatigue is significantly associated with poorer self-reported sleep quality and excessive daytime sleepiness, but not with objective sleeps quality.	The NFI-MS can be easily administered in clinical and research settings to assess the impact of sleep on perceived fatigue in the MS population.	
27594095	Sleep-wake behavior exhibits diurnal rhythmicity, rebound responses to acute total sleep deprivation (TSD), and attenuated rebounds following chronic sleep restriction (CSR). We investigated how these long-term patterns of behavior emerge from stochastic short-term dynamics of state transition. Male Sprague-Dawley rats were subjected to TSD (1day×24h, N=9), or CSR (10days×18h TSD, N=7) using a rodent walking-wheel apparatus. One baseline day and one recovery day following TSD and CSR were analyzed. The implications of the zero sum principle were evaluated using a Markov model of sleep-wake state transition. Wake bout duration (a combined function of the probability of wake maintenance and proportional representations of brief and long wake) was a key variable mediating the baseline diurnal rhythms and post-TSD responses of all three states, and the attenuation of the post-CSR rebounds. Post-NREM state transition trajectory was an important factor in REM rebounds. The zero sum constraint ensures that a change in any transition probability always affects bout frequency and cumulative time of at least two, and usually all three, of wakefulness, NREM and REM. Neural mechanisms controlling wake maintenance may play a pivotal role in regulation and dysregulation of all three states.
27770521	The interaction between different brain structures could be crucial to predicting seizure occurrence, threshold and spread. Moreover, the sleep-wake cycle and electrical activity of brain structures in different phases of sleep could significantly affect the pattern and extent of seizure spread, and therefore the characteristics of epileptic activity. In this animal model using 15 Wistar rats, we show that the duration of hippocampal seizures, induced by electrical stimulation of the hippocampus, is significantly increased during slow sleep. Moreover, decreasing the electrical activity of the neocortex by cooling of the cortical surface or induction of cortical spreading depression also caused an increase in hippocampal seizure duration. Conversely, warming the cortical surface triggered a remission in spreading depression, in turn restoring the duration of epileptic episodes. Our data suggest that the neocortex probably exerts a tonic inhibitory influence on hippocampal seizures. Thus, cortico-hippocampal interaction could be an important component in the manifestation and generalization of limbic seizures.
27770406	Although the comorbidity of migraine and restless legs syndrome (RLS) has been well-documented, the association between RLS and migraine frequency has yet to be elucidated. The present study aims to evaluate the prevalence of RLS among individuals who experience low-frequency, high-frequency, or chronic migraine presenting with and without aura.We conducted a cross-sectional, case-controlled study involving 505 participants receiving outpatient headache treatment. Standardized questionnaires were administered to collect information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were categorized into low-frequency (1-8/month), high-frequency (9-14/month), and chronic (≥15/month) headache groups. RLS was diagnosed according to the criteria outlined by the International RLS Study Group (IRLSSG). The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality and identify symptoms of anxiety and depression. Associations between migraine frequency and RLS prevalence were investigated using multivariate linear and logistic regression.	Univariate analysis revealed an effect of migraine frequency on RLS prevalence (p = 0.026), though this effect did not persist following adjustment for baseline characteristics (p = 0.256). The trend was robust in patients whose migraines presented with auras (p univariate = 0.002; p multivariate = 0.043) but not in those without auras (p univariate and p multivariate > 0.05). Higher anxiety [odds ratio (OR) = 1.18, p = 0.019] and sleep disturbance (OR = 1.17, p = 0.023) scores were associated with higher RLS prevalence.	Higher migraine frequency correlates with a higher prevalence of RLS, particularly among patients with auras.	
27769202	A disturbed circadian rhythm seems to be a causal factor in the occurrence of depressive disorders in patients with Parkinson's disease (PD). The circadian rhythm can be restored with light. Therefore, Bright Light Therapy (BLT) might be a new treatment option for depression in PD patients.In this double-blind controlled trial, 84 subjects with idiopathic PD are randomized to either BLT or a control light condition. The BLT condition emits white light with an intensity of 10,000 Lux, while the control device emits dim white light of 200 Lux, which is presumed to be too low to influence the circadian rhythm. Subjects receive 30 min of home treatment twice daily for three months. Timing of treatment is based on the individual chronotype. After finishing treatment, subjects enter a follow-up period of six months. The primary outcome of the study is the severity of depressive symptoms, as measured with the Hamilton Depression Rating Scale. Secondary outcomes are alternative depression measures, objective and subjective sleep measures, and salivary melatonin and cortisol concentrations. For exploratory purposes, we also assess the effects on motor symptoms, global cognitive function, comorbid psychiatric disorders, quality of life and caregiver burden. Data will be analyzed using a linear mixed models analysis.	Performing a placebo-controlled trial on the effects of BLT in PD patients is challenging, as the appearance of the light may provide clues on the treatment condition. Moreover, fixed treatment times lead to an improved sleep-wake rhythm, which also influences the circadian system. With our study design, we do not compare BLT to placebo treatment, i.e. an ineffective control treatment. Rather, we compare structuring of the sleep-wake cycle in both conditions with additional BLT in the experimental condition, and additional dim light in the control condition. Participants are not informed about the exact details of the two light devices and the expected therapeutic effect, and expectancies are rated prior to the start of treatment. Ideally, the design of a future study on BLT should include two extra treatment arms where BLT and control light are administered at random times.	
27634227	Monoamines are key neuromodulators involved in a variety of physiological and pathological brain functions. Classical studies using physiological and pharmacological tools have revealed several essential aspects of monoaminergic involvement in regulating the sleep-wake cycle and influencing sensory responses but many features have remained elusive due to technical limitations. The application of optogenetic tools led to the ability of monitoring and controlling neuronal populations with unprecedented temporal precision and neurochemical specificity. Here, we focus on recent advances in revealing the roles of some monoamines in brain state control and sensory information processing. We summarize the central position of monoamines in integrating sensory processing across sleep-wake states with an emphasis on research conducted using optogenetic techniques. Finally, we discuss the limitations and perspectives of new integrated experimental approaches in understanding the modulatory mechanisms of monoaminergic systems in the mammalian brain.
27689595	Australia's mineral, resource and infrastructure sectors continues to expand as operations in rural and remote locations increasingly rely on fly-in, fly-out or drive-in, drive-out workforces in order to become economically competitive. The issues in effectively managing these workforces are becoming more apparent with reported high amounts of turnover and concerns for safety and performance. The issues presented include a range of physical, mental, psychosocial, safety and community challenges.This review aims to consolidate a range of research conducted to communicate potential challenges for industry in relation to a wide variety of issues when engaging and using FIFO/DIDO workforces which includes compressed working schedule design (work schedules), working hours, fatigue, safety performance, employee wellbeing, turnover, psychosocial relationships and community concerns.	A comprehensive literature review was performed using EBSCOhost, PubMed and google scholar, with a focus on FIFO or DIDO workforces engaged within the resources sector. Search terms were kept broad in order to capture all national and international research conducted and included: "fly-in, fly-out" "FIFO" "DIDO" "drive-in, drive-out" "mining". There was no date restriction included in the search.	Many of the studies were focused on sleep quality, fatigue and the influence of lowered safety performance while at work, presenting an increased risk for health and safety. These issues may be exacerbated for the FIFO workforce when linked to additional research surrounding the extended periods of absence from families influencing workers personal relationships, psychological wellbeing, job satisfaction and the reported high amounts of turnover within the industry. Taken together, this presents a unique implication for the management and continued use of FIFO workforces when considering balancing safety and performance with economic viability of production and operations.	The issues of long working hours, fatigue, turnover and job satisfaction are not new to the management of workers. However, FIFO workforces appear to be at an increased risk physically and mentally due to a culmination of other influences, such as extended and frequent periods of absence from friends and families which contribute to feelings of isolation and lowered psychological wellbeing. FIFO workers and their families, engage in a unique lifestyle, rarely are other workers subjected to long hours and compressed work weeks while separated or isolated from their families for extended periods of time. Recently, FIFO interest has shifted to understanding the influences on employee engagement, satisfaction, retention and safety. Considering the management of FIFO workforces from a holistic perspective incorporating all of the issues impacting on these workers may assist to ensure the challenges associated with FIFO employment are understood, addressed and communicated to workers and their families is crucial for safety and health.	
27450579	Adolescence is a time of tremendous adjustment and includes changes in cognition, emotion, independence, social environment, and physiology. One of the most consistent changes exhibited by human adolescents is a dramatic delay in the daily timing of the sleep-wake cycle. This delay is strongly correlated with pubertal maturation and is believed to be influenced by gonadal hormone-induced changes in the neural mechanisms regulating sleep and/or circadian timing. Data from both human and non-human animals indicate that developmental changes in the intrinsic period of the circadian mechanism or its sensitivity to light are not adequate to explain adolescent changes in the daily timing of sleep and wakefulness. Rather, current evidence suggests that pubertal changes in the homeostatic drive to sleep and/or behaviorally induced changes in the amount and/or timing of light exposure permit adolescents to stay up later in the evening and cause them to wake up later in the morning.
27763782	Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.
27762290	Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed male Wistar rats to either a 12 h light (150-200lux):12 h dark (LD) schedule or a 12 h light (150-200 lux):12 h dim white light (5 lux) (LDim) schedule. LDim acutely decreased the amplitude of daily rhythms of REM and NREM sleep, with a further decrease over the following days. LDim diminished the rhythms of 1) the circadian 16-19 Hz frequency domain within the NREM sleep EEG, and 2) SCN clock gene expression. LDim also induced internal desynchronization in locomotor activity by introducing a free running rhythm with a period of ~25 h next to the entrained 24 h rhythm. LDim did not affect body weight or glucose tolerance. In conclusion, we introduce the first rodent model for disturbed circadian control of sleep due to LAN. We show that internal desynchronization is possible in a 24 h L:D cycle which suggests that a similar desynchronization may explain the association between LAN and human insomnia.
27762251	To review the available scientific literature about the effects on health by occupational exposure to noise.A systematic review of the retrieved scientific literature from the databases MEDLINE (via PubMed), ISI-Web of Knowledge (Institute for Scientific Information), Cochrane Library Plus, SCOPUS, and SciELO (collection of scientific journals) was conducted. The following terms were used as descriptors and were searched in free text: "Noise, Occupational," "Occupational Exposure," and "Occupational Disease." The following limits were considered: "Humans," "Adult (more than 18 years)," and "Comparative Studies."	A total of 281 references were retrieved, and after applying inclusion/exclusion criteria, 25 articles were selected. Of these selected articles, 19 studies provided information about hearing disturbance, four on cardiovascular disorders, one regarding respiratory alteration, and one on other disorders.	It can be interpreted that the exposure to noise causes alterations in humans with different relevant outcomes, and therefore appropriate security measures in the work environment must be employed to minimize such an exposure and thereby to reduce the number of associated disorders.	
27760892	To understand sleep mechanisms and develop treatments for sleep disorders, investigations using animal models are essential. The sleep architecture of rodents differs from that of diurnal mammals including humans and non-human primates. Sleep studies have been conducted in non-human primates; however, these sleep assessments were performed on animals placed in a restraint chair connected via the umbilical area to the recording apparatus. To avoid restraints, cables, and other stressful apparatuses and manipulations, telemetry systems have been developed. In the present study, sleep recordings in unrestrained cynomolgus monkeys (Macaca fascicularis) and common marmoset monkeys (Callithrix jacchus) were conducted to characterize normal sleep. For the analysis of sleep-wake rhythms in cynomolgus monkeys, telemetry electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG) signals were used. For the analysis of sleep-wake rhythms in marmosets, telemetry EEG and EOG signals were used. Both monkey species showed monophasic sleep patterns during the dark phase. Although non-rapid eye movement (NREM) deep sleep showed higher levels at the beginning of the dark phase in cynomolgus monkeys, NREM deep sleep rarely occurred during the dark phase in marmosets. Our results indicate that the use of telemetry in non-human primate models is useful for sleep studies, and that the different NREM deep sleep activities between cynomolgus monkeys and common marmoset monkeys are useful to examine sleep functions.
27760137	Autosomal dominant lateral temporal epilepsy (ADTLE) is a focal epilepsy syndrome caused by mutations in the LGI1 gene, which encodes a secreted protein. Most ADLTE-causing mutations inhibit LGI1 protein secretion, and only a few secretion-positive missense mutations have been reported. Here we describe the effects of four disease-causing nonsynonymous LGI1 mutations, T380A, R407C, S473L, and R474Q, on protein secretion and extracellular interactions. Expression of LGI1 mutant proteins in cultured cells shows that these mutations do not inhibit protein secretion. This finding likely results from the lack of effects of these mutations on LGI1 protein folding, as suggested by 3D protein modelling. In addition, immunofluorescence and co-immunoprecipitation experiments reveal that all four mutations significantly impair interaction of LGI1 with the ADAM22 and ADAM23 receptors on the cell surface. These results support the existence of a second mechanism, alternative to inhibition of protein secretion, by which ADLTE-causing LGI1 mutations exert their loss-of-function effect extracellularly, and suggest that interactions of LGI1 with both ADAM22 and ADAM23 play an important role in the molecular mechanisms leading to ADLTE.
27758126	Improvement in sleep, emotional distress, and health-related quality-of-life (QoL) accompanied the improvement in dizziness symptoms after vestibular rehabilitation. Persistent sleep disturbance could prevent improvements in self-perceived handicap due to chronic dizziness and anxiety.The present study investigated prospectively the effects of intervention for dizziness (vestibular rehabilitation) on sleep disturbance, and the relationship between improvements in dizziness symptoms and improvements in sleep disturbance after the intervention.	The participants of this study were 127 chronic dizziness inpatients with comorbid sleep disturbance (Pittsburgh sleep quality index [PSQI-J] global score ≥6). Participants completed the Dizziness Handicap Inventory (DHI, three sub-scales: Physical, Emotional, and Functional), PSQI-J, Hospital Anxiety and Depression Scale (HADS), and SF-8 (health-related QoL), and underwent gravity center fluctuation measurement before (time 1) and 1 month after (time 2) an in-hospital rehabilitation program.	All measured variables were significantly improved at time 2, compared to time 1. At time 2, 80.31% of patients still reported sleep disturbance. Analysis of covariance showed that chronic dizziness patients with sleep disturbance at time 2 had significantly higher DHI total, DHI-physical, and HADS-anxiety scores at time 2 than patients without sleep disturbance at time 2, after adjusting for these scores at time 1.	
27756691	Sleep is regulated by several brain structures, neurotransmitters and neuromodulators. Endocannabinoids (eCBs) are a group of lipids with modulatory activity in the brain and bind mainly to cannabinoid receptors CB1R and CB2R, thereby modulating several brain functions, (memory, mood, food intake, pain perception). Oleoylethanolamide and palmitoylethanolamide belong to the N-acylethanolamides (NAEs) family, another type of active endogenous lipids. They bind to the peroxisome proliferator-activated receptor α but not to CB1R, thereby modulating food satiety, inflammation and pain. Both eCBs and NAEs seem to be regulating the sleep-wake cycle. Our objective is to analyze the experimental evidence published in the literature and to discuss if eCBs and NAEs are actually sleep modulators. Studies suggested 1. eCBs and NAEs are under circadian control. 2. NAEs promote wake. 3. eCBs promote non-rapid-eye movement. 4. eCBs also promote rapid-eye-movement sleep by interacting with melanin-concentrating hormone neurons in the lateral hypothalamus. 5. The pharmacological blockade of the CB1R reduces sleep while increasing wake. 6. eCBs restore sleep in a model of insomnia in rats.
27412379	Limited data exist about sleep quality for patients with advanced cancer in phase 1 clinical trials. Poor sleep quality is often not captured as an adverse event, and its association with fatigue, one of the most frequently reported adverse events, is not documented routinely. This article describes sleep quality and its relation with fatigue, symptom burden, and mood in patients recruited from an early-phase clinic for targeted therapy.Sleep, fatigue, symptom burden, and mood were assessed with the Pittsburgh Sleep Quality Index (PSQI), the Brief Fatigue Inventory, the MD Anderson Symptom Inventory (MDASI), and the Brief Profile of Mood States, respectively; the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was determined from medical records.	The sample (n = 256) was 51.2% female, 90% had an ECOG PS of 0 or 1, and the mean age was 58 ± 0.8 years. Poor sleepers (global PSQI score > 5) constituted 64% of the sample. In separate multiple regression models, poor sleepers had higher levels of fatigue (P < .001), symptom burden (P < .001), and overall mood disturbance (P < .001) than good sleepers. Also, compared with good sleepers, poor sleepers had greater fatigue-related and symptom-related interference with daily activities (all P values < .001). The MDASI disturbed-sleep item correlated well with the global PSQI score (Pearson's r = 0.679, P < .001), and this suggests its usefulness as a patient-reported outcome screener of sleep quality in early-phase clinical trials clinics.	Poor sleep quality was a significant problem in the current study and was associated with greater fatigue, symptom burden, and mood disturbance. Sleep quality should be routinely assessed in patients with advanced cancer who are participating in early-phase clinical trials. Cancer 2016;122:3401-3409. © 2016 American Cancer Society.	
27753070	This study examined the direct and interactive effects of infants' respiratory sinus arrhythmia (RSA) and maternal depressive symptoms (MDS) during the first 6 months of life in the prediction of children's sleep problems at age 18 months. Participants included 156 children and their mothers who were followed from 3 to 18 months of age. At ages 3 and 6 months, infants' cardiac activity was recorded at rest and during the still-face paradigm, a mother-child social challenge task, and estimates of infant baseline RSA (RSAB) and RSA withdrawal (RSAW) were calculated. Mothers reported about their depressive symptoms at 3, 6, and 18 months, and about infants' sleep problems at age 18 months. Less RSAW and higher levels of MDS predicted more sleep problems at age 18 months. Additionally, RSAB moderated the link between MDS and children's sleep problems such that MDS were related to more sleep problems only for infants with high levels of RSAB. Results illustrate the importance of RSA as both a direct predictor and a moderator of maternal influences in the prediction of early sleep problems.
27751589	To examine the effects of paroxetine supplementation on hot flashes and sleep in gynecological cancer survivors.In a randomized, double-blind, placebo-controlled study, postmenopausal women with a prior history of stage 0-III gynecological cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 7.5mg oral paroxetine or placebo daily for 16weeks. Sleep and hot flashes were assessed at baseline, week 4 and week 16.	Eighty women (91%) completed the study. We found out a statistically significant difference in weekly reductions in VMS frequency and severity for paroxetine 7.5mg than for placebo on week 4 and 16. Regarding sleep characteristics, the analysis of data through week 16 reported a statistically significant reduction in the number of nighttime awakenings attributed to VMS among participants receiving paroxetine than among participants receiving placebo on baseline and weeks. The duration of sleep per night increased significantly more among participants receiving paroxetine than among those receiving placebo at all post baseline time points. No significant differences in sleep-onset latency were noted between the two treatment arms during the course of the study. Paroxetine was well-tolerated with a high level of compliance. In our cohort of patients, no serious adverse events have been reported.	This is the first randomized placebo-controlled study in gynecological cancer survivors that demonstrates that paroxetine significantly reduces hot flashes in weekly frequency and severity and the number of nighttime awakenings attributed to vasomotor symptoms, increasing sleep duration.	
27751212	To study the background patterns and sleep-wake cycles (SWC) on amplitude-integrated electroencephalography (aEEG) in preterm infants with different grades of periventricular-intraventricular hemorrhage (PIVH).Fifty-six preterm infants with a gestational age between 25 and 33 weeks who were diagnosed with PIVH and 31 gestational age-matched normal preterm without ICH were enrolled. According to Papile staging criteria, the infants with PIVH were subdivided into mild group (grades I and II) and moderate-severe group (grades III and IV). The results of the aEEG were compared between groups.	The moderate-severe PIVH group showed a decreased continuity of the voltage, an increased loss rate of SWC, and a lower aEEG score than the mild PIVH and control groups (P<0.017). There were no significant differences in these parameters between the mild PIVH and control groups.	The changes of background patterns and SWCs may be associated with the severity of PIVH in preterm infants.	
27617688	Significant advances have been made in our understanding of subcortical processes related to anesthetic- and sleep-induced unconsciousness, but the associated changes in cortical connectivity and cortical neurochemistry have yet to be fully clarified.Male Sprague-Dawley rats were instrumented for simultaneous measurement of cortical acetylcholine and electroencephalographic indices of corticocortical connectivity-coherence and symbolic transfer entropy-before, during, and after general anesthesia (propofol, n = 11; sevoflurane, n = 13). In another group of rats (n = 7), these electroencephalographic indices were analyzed during wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep.	Compared to wakefulness, anesthetic-induced unconsciousness was characterized by a significant decrease in cortical acetylcholine that recovered to preanesthesia levels during recovery wakefulness. Corticocortical coherence and frontal-parietal symbolic transfer entropy in high γ band (85 to 155 Hz) were decreased during anesthetic-induced unconsciousness and returned to preanesthesia levels during recovery wakefulness. Sleep-wake states showed a state-dependent change in coherence and transfer entropy in high γ bandwidth, which correlated with behavioral arousal: high during wakefulness, low during SWS, and lowest during REM sleep. By contrast, frontal-parietal θ connectivity during sleep-wake states was not correlated with behavioral arousal but showed an association with well-established changes in cortical acetylcholine: high during wakefulness and REM sleep and low during SWS.	Corticocortical coherence and frontal-parietal connectivity in high γ bandwidth correlates with behavioral arousal and is not mediated by cholinergic mechanisms, while θ connectivity correlates with cortical acetylcholine levels.	
27552653	Alterations in thalamic γ-aminobutyric acid-mediated signaling are thought to underlie the increased frontal α-β frequency electrocortical activity that signals anesthetic-induced loss of consciousness with γ-aminobutyric acid receptor type A (GABAAR)-targeting general anesthetics. The general anesthetic etomidate elicits phasic extrasynaptic GABAAR activation ("spillover" inhibition) at thalamocortical neurons in vitro. We hypothesize that this action of etomidate at the thalamus is sufficient to trigger an increase in frontal α-β frequency electrocortical activity and that this effect of etomidate is fully recapitulated by enhanced thalamic spillover inhibition in vivo.We recorded electrocortical activity and sleep-wake behavior in freely behaving wild-type (n = 33) and extrasynaptic δ-subunit-containing GABAAR knockout mice (n = 9) during bilateral microperfusion of the thalamus with etomidate and/or other pharmacologic agents that influence GABAAR or T-type Ca channel activity.	Microperfusion of etomidate into the thalamus elicited an increase in α-β frequency electrocortical activity that occurred only during non-rapid-eye-movement (REM) sleep (11.0 ± 11.8% and 16.0 ± 14.2% greater 8 to 12- and 12 to 30-Hz power, respectively; mean ± SD; both P < 0.031) and was not affected by blockade of thalamic T-type Ca channels. Etomidate at the thalamus also increased spindle-like oscillations during non-REM sleep (4.5 ± 2.4 spindle per minute with etomidate vs. 3.2 ± 1.7 at baseline; P = 0.002). These effects of etomidate were fully recapitulated by enhanced thalamic extrasynaptic GABAAR-mediated spillover inhibition.	These findings identify how a prototypic GABAAR-targeting general anesthetic agent can elicit the characteristic brain wave pattern associated with anesthetic hypnosis when acting at the thalamus by promoting spillover inhibition and the necessity of a preexisting non-REM mode of activity in the thalamus to generate this effect.	
27455435	To determine (1) the presence of fatigue symptoms and predictors of fatigue after childhood brain injury and examine (2) the feasibility, reliability, and validity of a multidimensional fatigue measure (PedsQL Multidimensional Fatigue Scale [MFS]) obtained from parent and child perspectives.Emergency and intensive care units of a hospital in Melbourne, Australia.	Thirty-five families (34 parent-proxies and 32 children) aged 8 to 18 years (mean child age = 13.29 years) with traumatic brain injury (TBI) of all severities (27 mild, 5 moderate, and 3 severe) admitted to the Royal Children's Hospital.	Longitudinal prospective study. Fatigue data collected at 6-week follow-up (mean = 6.9 weeks).	Postinjury child- and parent-rated fatigue (PedsQL MFS), mood, sleep, and pain based on questionnaire report: TBI severity (mild vs moderate/severe TBI).	A score greater than 2 standard deviations below healthy control data indicated the presence of abnormal fatigue, rates of which were higher compared with normative data for both parent and child reports (47% and 29%). Fatigue was predicted by postinjury depression and sleep disturbance for parent, but not child ratings. Fatigue, as rated by children, was not significantly predicted by TBI severity or other symptoms. The PedsQL MFS demonstrated acceptable measurement properties in child TBI participants, evidenced by good feasibility and reliability (Cronbach α values >0.90). Interrater reliability between parent and child reports was poor to moderate.	Results underscore the need to assess fatigue and associated sleep-wake disturbance and depression after child TBI from both parent and child perspectives.	
27749086	Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has long been recognized that this 24-hour rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. In the past decade, secondary circadian clocks based on the same molecular machinery as the central master pacemaker were found in other brain areas as well as in most peripheral tissues, including the adrenal glands. Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects. The robust rhythm in circulating glucocorticoid levels has been recognized as a major internal synchronizer of the circadian system. The present review examines the scientific foundation of these novel advances and their implications for health and disease prevention and treatment.
27748246	It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information.We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference.	We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training.	These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM.	
27192425	Sleep disturbance is an important contributor to poor quality of life in rheumatic disorders. This study aims to test whether clinical, autoimmune and psychological factors are associated with sleep disturbance in systemic sclerosis (SSc) compared to rheumatoid arthritis (RA) patients and controls.101 female subjects (SSc=33, RA=34, healthy controls=34) participated in this observational, cross-sectional, parallel group study. Sleep disturbance was assessed with the Pittsburgh Sleep Quality Index (PSQI). Other assessments included the visual analogue scale (VAS) for pain, 36-item Short-Form Health Survey (SF-36), Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Clinical parameters, therapeutic regimen, and serologic status were recorded.	In SSc patients, PSQI scores were higher than in RA patients and controls. Linear regression analysis showed that in SSc patients PSQI scores was associated with BDI, disease duration, modified Rodnan skin score and VAS, while DAS28 and BDI were associated with PSQI scores in RA patients. Anti-Scl70 and ANA positive SSc patients showed higher PSQI scores compared to those ANA positive only, while no differences were observed in RA patients classified according to rheumatoid factor positivity. SSc patients treated with immunosuppressants had lower PSQI scores compared to those not on therapy, whereas only corticosteroid treatment was significantly associated with higher PSQI scores in RA patients. RA patients with disease activity higher than moderate (DAS28≥3.2) had higher PSQI scores than those with lower than moderate (DAS28<3.2).	Longitudinal studies are needed to identify disease-specific patterns associated with sleep disturbances and the influence on sleep function induced by immunosuppressive therapy among rheumatic patients.	
27742297	The goal of this study was to evaluate the sleep quality and daytime sleepiness of patients eligible for liver transplants.A cross-sectional prospective study was conducted on liver transplant candidates from a transplant center in the interior of São Paulo State. The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale questionnaires were applied to obtain demographic and clinical characteristics and to assess sleep quality and daytime sleepiness.	The mean (±SD) score on the Epworth Sleepiness Scale of the 45 liver transplantation candidates was 7.00 ± 2.83 points, with 28.89% having scores >10 points, indicating excessive daytime sleepiness. The mean score on the Pittsburgh Sleep Quality Index was 6.64 ± 4.95 points, with 60% of the subjects showing impaired sleep quality, with scores >5 points. The average sleep duration was 07:16 h. Regarding sleep quality self-classification, 31.11% reported poor or very poor quality. It is noteworthy that 73.33% of patients had to go to the bathroom, 53.33% woke up in the middle of the night, and 40.00% reported pain related to sleeping difficulties. Comparison of subjects with good and poor sleep quality revealed a significant difference in time to sleep (P = .0002), sleep hours (P = .0003), and sleep quality self-classification (P = .000072).	Liver transplant candidates have a compromised quality of sleep and excessive daytime sleepiness. In clinical practice, we recommend the evaluation and implementation of interventions aimed at improving the sleep and wakefulness cycle, contributing to a better quality of life.	
27739821	We present a universal model of brain tissue microstructure that dynamically links osmosis and diffusion with geometrical parameters of brain extracellular space (ECS). Our model robustly describes and predicts the nonlinear time dependency of tortuosity (λ=sqrt[D/D^{*}]) changes with very high precision in various media with uniform and nonuniform osmolarity distribution, as demonstrated by previously published experimental data (D = free diffusion coefficient, D^{*} = effective diffusion coefficient). To construct this model, we first developed a multiscale technique for computationally effective modeling of osmolarity in the brain tissue. Osmolarity differences across cell membranes lead to changes in the ECS dynamics. The evolution of the underlying dynamics is then captured by a level set method. Subsequently, using a homogenization technique, we derived a coarse-grained model with parameters that are explicitly related to the geometry of cells and their associated ECS. Our modeling results in very accurate analytical approximation of tortuosity based on time, space, osmolarity differences across cell membranes, and water permeability of cell membranes. Our model provides a unique platform for studying ECS dynamics not only in physiologic conditions such as sleep-wake cycles and aging but also in pathologic conditions such as stroke, seizure, and neoplasia, as well as in predictive pharmacokinetic modeling such as predicting medication biodistribution and efficacy and novel biomolecule development and testing.
27739621	African trypanosomes induce sleeping sickness. The parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. During the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. Historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. The brain, however, is a strictly controlled and immune-privileged area that is completely surrounded by a dense barrier that covers the blood vessels: this is the blood-brain barrier. It is known that some immune cells are able to cross this barrier, but this requires a sophisticated mechanism and highly specific cell-cell interactions that have not been observed for trypanosomes within the mammalian host. Interestingly, trypanosomes injected directly into the brain parenchyma did not induce an infection. Likewise, after an intraperitoneal infection of rats, Trypanosoma brucei brucei was not observed within the brain, but appeared readily within the cerebrospinal fluid (CSF) and the meninges. Therefore, the parasite did not cross the blood-brain barrier, but the blood-CSF barrier, which is formed by the choroid plexus, i.e. the part of the ventricles where CSF is produced from blood. While there is no question that trypanosomes are able to invade the brain to induce a deadly encephalopathy, controversy exists about the pathway involved. This review lists experimental results that support crossing of the blood-brain barrier and of the blood-CSF barrier and discuss the implications that either pathway would have on infection progress and on the survival strategy of the parasite. For reasons discussed below, we prefer the latter pathway and suggest the existence of an additional distinct meningeal stage, from which trypanosomes could invade the brain via the Virchow-Robin space thereby bypassing the blood-brain barrier. We also consider healthy carriers, i.e. people living symptomless with the disease for up to several decades, and discuss implications the proposed meningeal stage would have for new anti-trypanosomal drug development. Considering the re-infection of blood, a process called relapse, we discuss the likely involvement of the newly described glymphatic connection between the meningeal space and the lymphatic system, that seems also be important for other infectious diseases.
27739157	While several methods have been used to restrict the sleep of experimental animals, it is often unclear whether these different forms of sleep restriction have comparable effects on sleep-wake architecture or functional capacity. The present study compared four models of sleep restriction, using enforced wakefulness by rotation of cylindrical home cages over 11 h in male Wistar rats. These included an electroencephalographic-driven 'Biofeedback' method and three non-invasive methods where rotation was triggered according to a 'Constant', 'Decreasing' or random protocol based upon the 'Weibull' distribution fit to an archival Biofeedback dataset. Sleep-wake architecture was determined using polysomnography, and functional capacity was assessed immediately post-restriction with a simple response latency task, as a potential homologue of the human psychomotor vigilance task. All sleep restriction protocols resulted in sleep loss, behavioural task disengagement and rebound sleep, although no model was as effective as real-time electroencephalographic-Biofeedback. Decreasing and Weibull protocols produced greater recovery sleep than the Constant protocol, mirrored by comparably poorer simple response latency task performance. Increases in urinary corticosterone levels following Constant and Decreasing protocols suggested that stress levels may differ between protocols. Overall, these results provide insight into the value of choosing a specific sleep restriction protocol, not only from the perspective of animal welfare and the use of less invasive procedures, but also translational validity. A more considered choice of the physiological and functional effects of sleep-restriction protocols in rodents may improve correspondence with specific types of excessive daytime sleepiness in humans.
27737865	Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old woman with bipolar disorder experiencing a life event while wearing an actigraph to measure sleep-wake parameters. The night after the life event the woman had sleep later and shorter sleep duration. Adequate response of both the woman and the treating psychiatrist resulted in two normal nights with the use of 1 mg lorazepam, possibly preventing further mood disturbances. Ambulatory assessment of the biological rhythm can function as an add-on to regular signalling plans for prevention of episodes in patients with bipolar disorder. More research should be conducted to validate clinical applicability, proper protocols and to understand underlying mechanisms.
27737315	The objective of this study was to evaluate the alterations in sleep and circadian parameters during the aging process. The study sample comprises volunteers older than 18 up to 90 years of age that answered the Pittsburgh Sleep Quality Index (PSQI) and the Horne and Östberg circadian preference questionnaire. We observed that the shift to morningness with increasing age is associated with a significant worsening in sleep quality. We discuss that this sleep profile characterized by morningness and worse sleep quality observed in elderly, when compared to younger people, reflects not necessarily a pathological state, but an expected profile for this age group.

27736199	Chronotype is a stable trait presenting one's circardian preference. Since chronotype disturbances are common in patients with affective disorders, our aim is to evaluate chronotypes related to affective temperaments, measured with the temperament evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A). The study included 618 subjects (151 men and 467 women) within the framework of web-based design. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Sleep Wake Pattern Assessment Questionnaire (SWPAQ), and the TEMPS-A scale. Multiple regression models revealed that after controlling for age and gender: irritable and cyclothymic temperaments were negatively associated with total CSM score, CSM morning affect and circadian preference components, Sleepability (S), Vigilance (V), Wakeability (W) and positively with Morningness (M) and Eveningness (E) subscales of SWPAQ; anxious temperament was negatively associated with total CSM scores, CSM morning affect and with S, V, W subscales of SWPAQ; depressive temperament was negatively associated with Falling asleep, S, V, W subscales of SWPAQ; hyperthymic temperament was positively associated with CSM morning affect and V, W and negatively with M subscales of SWPAQ. The results show distinctiveness of the associations between hyperthymic temperament and circadian preferences, compared to all other TEMPS-A temperaments (depressive, cyclothymic, irritable and anxious). In the CMS scale, only hyperthymic temperament was related to morning affect. In the SWPAQ scale, hyperthymic temperament was the only one associated with earlier morningness (earlier wake up time preference), increased parameters of vigor - wakeability, vigilance, and also the only one not associated with decreased plasticity of circadian rhythm (sleepability and falling asleep). Results also point to some similarities between cyclothymic and irritable temperaments in some aspects of the chronotype.
27734337	Sleep is tightly regulated by the circadian clock and homeostatic mechanisms. Although the sleep/wake cycle is known to be associated with structural and physiological synaptic changes that benefit the brain, the function of sleep is still debated. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate various functions including feeding, reward, sleep, and wake. Continuous imaging of single neuronal circuits in live animals is vital to understanding the role of sleep in regulating synaptic dynamics, and the transparency of the zebrafish model enables time-lapse imaging of single synapses during both day and night. Here, we use the gephyrin (Gphnb) protein, a central inhibitory synapse organizer, as a fluorescent post-synaptic marker of inhibitory synapses. Double labeling showed that Gphnb-tagRFP and collybistin-EGFP clusters co-localized in dendritic inhibitory synapses. Using a transgenic hcrt:Gphnb-EGFP zebrafish, we showed that the number of inhibitory synapses in the dendrites of Hcrt neurons was increased during development. To determine the effect of sleep on the inhibitory synapses, we performed two-photon live imaging of Gphnb-EGFP in Hcrt neurons during day and night, under light/dark and constant light and dark conditions, and following sleep deprivation (SD). We found that synapse number increased during the night under light/dark conditions but that these changes were eliminated under constant light or dark conditions. SD reduced synapse number during the night, and the number increased during post-deprivation daytime sleep rebound. These results suggest that rhythmic structural plasticity of inhibitory synapses in Hcrt dendrites is independent of the circadian clock and is modulated by consolidated wake and sleep.
27733204	Because the world population is aging, it has become increasingly important to focus on and meet the healthcare needs of elderly individuals. This study aims to evaluate the relationships among common symptoms experienced by the elderly, including fatigue, pain, sleep disturbance, indigestion, and depression/anger/anxiety, and to assess how these symptoms affect health-related quality of life (HRQoL) in the elderly population after adjusting for sociodemographic characteristics and diagnosed diseases.In a cross-sectional study conducted in 2014 in a rural area of Korea, we extracted data on 1328 elderly individuals aged 60 years or older. Their HRQoL was assessed using the EuroQol Five-Dimension (EQ-5D) questionnaire. The pairwise associations between each symptom and the influence of the symptoms on HRQoL were measured using logistic regression and multiple regression analysis.	Each symptom was positively correlated with the other symptoms. The strongest association was observed between fatigue and pain (adjusted odds ratio = 8.127), and the weakest correlation was observed between sleep and indigestion (adjusted odds ratio = 2.521). Of the individuals experiencing symptoms other than sleep disturbance, those who reported comorbid symptoms tended to report higher symptom severity and a higher prevalence of symptoms persisting for ≥ 3 days compared with individuals who reported only one symptom. The number of symptoms was significantly correlated with the EQ-5D index (Spearman correlation coefficient = -0.370, p < 0.01) and the EQ Visual Analog Scale (EQ VAS) scores (Spearman correlation coefficient = -0.226, p < 0.01). Fatigue, pain, and sleep disturbance showed negative effects on all dimensions of EQ-5D. In multiple regression analysis, fatigue (β = -0.073, p < 0.01), pain (β = -0.140, p < 0.01), sleep disturbance (β = -0.061, p < 0.05), and depression/anger/anxiety (β = -0.065, p < 0.05) showed significant independent effects on the EQ-5D index when we adjusted for socioeconomic characteristics and diagnosed diseases.	Fatigue, pain, sleep disturbance, and depression/anger/anxiety were correlated with one another, and they presented significant independent effects on the HRQoL of elderly individuals. Thus, multidisciplinary healthcare programs are required to address these common symptoms.	
27728899	We sought to investigate the temporal patterns and sleep-wake cycle-related epileptiform discharges (EDs) in genetic generalized epilepsies (GGEs).We studied 24-hour ambulatory electroencephalography (EEG) recordings of patients with GGE, diagnosed and classified according to the International League against Epilepsy criteria. We manually coded the type of discharge, time of occurrence, duration, and arousal state of each ED. We employed mixed effects Poisson regression modeling to study the temporal distribution of epileptiform discharges. Additionally, we used multinomial regression analysis to explore the significance of the relationship between different states of arousal and types of epileptiform discharges.	We analyzed 6923 EDs from 105 abnormal 24-hour EEGs. Mixed effects Poisson regression analysis demonstrated significant changes in ED counts across time blocks. This distribution was largely influenced by the state of arousal. Generalized fragments (duration<2s) and focal discharges were more frequent during non-REM sleep while paroxysms (duration≥2s) were more frequent in wakefulness. Overall, 67% of epileptiform discharges occurred in non-REM sleep and only 33% occurred in wakefulness. Twenty-four patients (23%) had ED exclusively in sleep. Epileptiform discharges peaked from 23:00 through 07:00h.	There is a time-of-day dependency of ED with a significant influence exerted by the state of arousal. Our observations suggest that the generation of epileptiform discharges is not a random process but is the result of complex interactions among biological rhythms such as the sleep-wake cycle and the intrinsic circadian pacemaker. High density of ED in sleep suggests that 24-hour EEG recording with the capture of natural sleep may be more useful than routine EEG to diagnose GGE.	
27726500	Although numerous studies have documented the effects of sleep loss on executive control (EC) and related abilities, research examining the impact of early EC on subsequent sleep problems is lacking. Therefore, the current study reports on a longitudinal investigation of EC in preschool as a predictor of sleep-wake problems and daytime sleepiness in early adolescence.The participants were 141 children (48.6% female) recruited from the community for a longitudinal study spanning preschool through early adolescence, with an oversampling for high sociodemographic risk (34.1% based on eligibility for public medical insurance, free or reduced lunch status, or family income-to-needs below the federal poverty line).	Participants completed a battery of developmentally appropriate tasks assessing major aspects of EC (working memory, inhibitory control, flexible shifting) during a laboratory visit at age 4 years, 6 months. Participants also completed a follow-up session in early adolescence (between ages 11 years and 13.5 years; mean age = 11.82 years, SD = .62 years), during which they completed self-report measures of sleep-wake problems and daytime sleepiness.	Structural equation modeling results indicate that preschool EC (represented by a single latent construct) significantly negatively predicted both sleep-wake problems and daytime sleepiness in early adolescence, with poorer EC predicting greater subsequent sleep problems.	Poorer EC abilities during the critical period of preschool may be a risk factor for later sleep problems in adolescence. Given that EC appears to be modifiable, early interventions to promote EC development may help prevent subsequent sleep problems and promote long-term health trajectories.	
27723712	В последние годы большое внимание уделяется немоторным симптомам болезни Паркинсона (БП), среди которых расстройства сна и бодрствования занимают ведущее место. Дневная сонливость (ДС) встречается у 30—55% больных в зависимости от длительности и стадии заболевания и ведет к выраженной социальной дезадаптации больного. ДС имеет мультифакторную природу, и выявление причин ее возникновения имеет большое значение для терапии. Рассматриваются основные факторы развития ДС при БП, описаны ключевые моменты патогенеза первичной ДС, приведены алгоритмы диагностики ДС и методы ее коррекции.For the recent years, a special attention is given to the non-motor symptoms of Parkinson's disease, including sleep/wake disorders representing one of the leading symptoms. Daytime sleepiness occurs in 30-55% of patients depending on duration and stage of the disease, leading to severe maladjustment. This symptom seems to be multifactorial by nature and identification of it's causes could have a great importance for the therapy. The main factors of the development of daytime sleepiness in Parkinson's disease and key points of the pathogenesis of «primary» daytime sleepiness are discussed. Diagnostic methods and treatment opportunities are considered as well.	
27721205	We study emerging phenomena in binary neural networks where, with a probability c synaptic intensities are chosen according with a Hebbian prescription, and with probability (1-c) there is an extra random contribution to synaptic weights. This new term, randomly taken from a Gaussian bimodal distribution, balances the synaptic population in the network so that one has 80%-20% relation in E/I population ratio, mimicking the balance observed in mammals cortex. For some regions of the relevant parameters, our system depicts standard memory (at low temperature) and non-memory attractors (at high temperature). However, as c decreases and the level of the underlying noise also decreases below a certain temperature Tt, a kind of memory-frustrated state, which resembles spin-glass behavior, sharply emerges. Contrary to what occurs in Hopfield-like neural networks, the frustrated state appears here even in the limit of the loading parameter α→0. Moreover, we observed that the frustrated state in fact corresponds to two states of non-vanishing activity uncorrelated with stored memories, associated, respectively, to a high activity or Up state and to a low activity or Down state. Using a linear stability analysis, we found regions in the space of relevant parameters for locally stable steady states and demonstrated that frustrated states coexist with memory attractors below Tt. Then, multistability between memory and frustrated states is present for relatively small c, and metastability of memory attractors can emerge as c decreases even more. We studied our system using standard mean-field techniques and with Monte Carlo simulations, obtaining a perfect agreement between theory and simulations. Our study can be useful to explain the role of synapse heterogeneity on the emergence of stable Up and Down states not associated to memory attractors, and to explore the conditions to induce transitions among them, as in sleep-wake transitions.
27718590	Workplace bullying (WPB) has recently received much attention in society. Research on WPB in athletic training practice settings is limited.To determine the prevalence of WPB in the secondary school setting and explore the factors related to it.	Mixed-methods study.	Secondary school.	A total of 567 athletic trainers (women = 322 [56.8%], men = 245 [43.2%]), aged 36.5 ± 11.1 years with 11.9 ± 9.5 years of experience took part in phase I. Ten participants (7 women and 3 men), aged 39.3 ± 10.1 years with 14.3 ± 8.3 years of experience, took part in phase II.	For the online survey, we used the previously validated and reliable (Cronbach α = .84) Athletic Training Workplace Environment Survey, which included the Negative Acts Questionnaire-Revised. The prevalence of WPB was measured with descriptive statistics, and χ2 analyses were used to compare differences between groups (ie, females and males, perpetrators' titles). The interview data were examined using an inductive content analysis.	Of the participants, 44 (7.8%) were empirically identified as targets of bullying, though a higher percentage (12.4%, n = 70) self-identified as bullying targets. Men and women did not differ with respect to having experienced WPB, but more perpetrators were male (71.6%, n = 48) than female (28.4%, n = 19; χ21 = 12.55, P = <.001). We also observed a difference in perpetrators' titles, with the vast majority of bullies being coaches or administrators (χ26 = 33.82, P = <.001). Lack of administrator support and discrimination were antecedents of bullying. Stress, depression, and sleep disturbances were reported consequences. Participants coped with bullying by avoidance and role refocusing.	Bullying was experienced by a small percentage of athletic trainers in the secondary school setting, a contrast to the findings in the collegiate practice setting.	
27718103	Impaired sleep patterns are common symptoms of Alzheimer's disease (AD). Cellular mechanisms underlying sleep disturbance in AD remain largely unknown. Here, using a Drosophila Aβ42 AD model, we show that Aβ42 markedly decreases sleep in a large population, which is accompanied with postdevelopmental axonal arborization of wake-promoting pigment-dispersing factor (PDF) neurons. The arborization is mediated in part via JNK activation and can be reversed by decreasing JNK signaling activity. Axonal arborization and impaired sleep are correlated in Aβ42 and JNK kinase hemipterous mutant flies. Image reconstruction revealed that these aberrant fibers preferentially project to pars intercerebralis (PI), a fly brain region analogous to the mammalian hypothalamus. Moreover, PDF signaling in PI neurons was found to modulate sleep/wake activities, suggesting that excessive release of PDF by these aberrant fibers may lead to the impaired sleep in Aβ42 flies. Finally, inhibition of JNK activation in Aβ42 flies restores nighttime sleep loss, decreases Aβ42 accumulation, and attenuates neurodegeneration. These data provide a new mechanism by which sleep disturbance could be induced by Aβ42 burden, a key initiator of a complex pathogenic cascade in AD.
27715325	The relationship between sleep duration and obesity in adolescents is inconclusive. This may stem from a more complex relationship between sleep and obesity than previously considered. Shifts toward evening preferences, later sleep-wake times and irregular sleep-wake patterns are typical during adolescence but their relationship to body mass index (BMI) has been relatively unexplored. This cross-sectional study examined associations between sleep duration, midpoint of sleep and social jet lag (estimated from 7 days of continuous actigraphy monitoring), and morningness/eveningness with BMIs (BMI z-scores) and waist-to-height ratios in 14-17-year-old adolescents. Seventy participants were recruited from ninth and tenth grades at a public high school. Participants' characteristics were as follows: 74% female, 75% post-pubertal, 36% Hispanic, 38% White, 22% Black, 4% Asian and 64% free/reduced lunch participants with a mean age of 15.5 (SD, 0.7). Forty-one percent of the participants were obese (BMI ≥ 95th percentile); 54% were abdominally obese (waist-to-height ratio ≥ 0.5). Multivariable general linear models were used to estimate the association between the independent variables (school night sleep duration, free night sleep duration, midpoint of sleep (corrected), social jet lag and morningness/eveningness) and the dependent variables (BMI z-scores and waist-to-height ratios). Social jet lag is positively associated with BMI z-scores (p < 0.01) and waist-to-height ratios (p = 0.01). Midpoint of sleep (corrected) is positively associated with waist-to-height ratios (p = 0.01). After adjusting for social jet lag, school night sleep duration was not associated with waist-to-height ratios or BMI z-scores. Morningness/eveningness did not moderate the association between sleep duration and BMI z-scores. Findings from this study suggest that chronobiological approaches to preventing and treating obesity may be important for accelerating progress in reducing obesity rates in adolescents.
27715321	Night work is associated with a large range of acute health problems and possibly also health consequences in the long run. Yet, only very few field studies specifically investigate the effects of consecutive night shift on key physiological regulatory systems. In this field study, we investigated the effects of consecutive night shifts on three hormones, melatonin, cortisol, and testosterone, among police officers at work. More specifically, the aim was to investigate how the diurnal rhythms of melatonin, cortisol, and testosterone responded to two, four, and seven consecutive night shifts and a corresponding number of days for recovery. The study was part of the "In the Middle of the Night" project and included 73 male police officers from five different police districts. The participants were exposed to three intervention conditions: "2+2": two consecutive night shifts followed by two consecutive day recovery days; "4+4": four consecutive night shifts followed by four consecutive recovery days; "7+7": seven consecutive night shifts followed by seven consecutive recovery days. On the last day with night shift and the last recovery day in each intervention, the participants collected saliva samples every 4th hour when awake. The diurnal rhythms of melatonin, cortisol, and testosterone were all affected differently by an increasing number of consecutive night shifts: the amplitude of the melatonin rhythm was suppressed by 4.9% per day (95% CI 1.4-8.2% per day; p = 0.006). The diurnal rhythm of cortisol phase was delayed with an increasing number of night shifts by 33 min/day (95% CI 18-48 min per day; p ≤ 0.001), but did not show any changes in amplitude. For the diurnal rhythm of testosterone, there was no effect of the number of consecutive night shifts and the diurnal rhythm completely followed the sleep/wake cycle. We found that there were no differences in the rhythms of melatonin, cortisol, and testosterone after 2, 4, and 7 recovery days, respectively. In conclusion, we found signs of desynchronization in terms of suppressed amplitude of melatonin and phase delay of salivary cortisol as a consequence of the increasing number of consecutive night shifts among police officers at work. Lack of synchronization has been suggested as a possible mechanism linking night work to disease, but this remains to be determined.
27711189	Nasal airflow is greater in one nostril than in the other because of transient asymmetric nasal passage obstruction by erectile tissue. The extent of obstruction alternates across nostrils with periodicity referred to as the nasal cycle. The nasal cycle is related to autonomic arousal and is indicative of asymmetry in brain function. Moreover, alterations in nasal cycle periodicity have been linked to various diseases. There is therefore need for a tool allowing continuous accurate measurement and recording of airflow in each nostril separately. Here we provide detailed instructions for constructing such a tool at minimal cost and effort. We demonstrate application of the tool in 33 right-handed healthy subjects, and derive several statistical measures for nasal cycle characterization. Using these measures applied to 24-hour recordings we observed that: 1: subjects spent slightly longer in left over right nostril dominance (left = 2.63 ± 0.89 hours, right = 2.17 ± 0.89 hours, t(32) = 2.07, p < 0.05), 2: cycle duration was shorter in wake than in sleep (wake = 2.02 ± 1.7 hours, sleep = 4.5 ± 1.7 hours, (t(30) = 5.73, p < 0.0001). 3: slower breathing was associated with a more powerful cycle (the extent of difference across nostrils) (r = 0.4, p < 0.0001), and 4: the cycle was influenced by body posture such that lying on one side was associated with greater flow in the contralateral nostril (p < 0.002). Finally, we provide evidence for an airflow cycle in each nostril alone. These results provide characterization of an easily obtained measure that may have diagnostic implications for neurological disease and cognitive state.
27709845	This study aimed to investigate the effect of facing complaining customer and suppressed emotion at worksite on sleep disturbance among working population. We enrolled 13,066 paid workers (male = 6,839, female = 6,227, age < 65 years) in the 3rd Korean Working Condition Survey (2011). The odds ratio (OR) and 95% confidence intervals (CI) for sleep disturbance occurrence were calculated using multiple logistic regression models. Among workers in working environments where they always engage complaining customers had a significantly higher risk for sleep disturbance than rarely group (The OR [95% CI]; 5.46 [3.43-8.68] in male, 5.59 [3.30-9.46] in female workers). The OR (95% CI) for sleep disturbance was 1.78 (1.16-2.73) and 1.63 (1.02-2.63), for the male and female groups always suppressing their emotions at the workplace compared with those rarely group. Compared to those who both rarely engaged complaining customers and rarely suppressed their emotions at work, the OR (CI) for sleep disturbance was 9.66 (4.34-20.80) and 10.17 (4.46-22.07), for men and women always exposed to both factors. Sleep disturbance was affected by interactions of both emotional demands (engaging complaining customers and suppressing emotions at the workplace). The level of emotional demand, including engaging complaining customers and suppressing emotions at the workplace is significantly associated with sleep disturbance among Korean working population.
27709844	Sleep is an important component in our lives as it is necessary throughout one's entire life span. This study was conducted to elucidate whether there are gender differences in sleep quality and what factors can affect sleep quality in community-dwelling elderly Koreans. A total of 382 subjects (175 males and 207 females) were recruited among elderly aged 45 or over who participated in the 2010 Hallym Aging Study (HAS). They were invited to a general hospital and were evaluated for socioeconomic status, smoking history, and various clinical measures. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). A higher score indicates poorer subjective sleep quality, (PSQI global score > 5 suggests sleep disturbance). After adjusting for potential covariates, our results show that alcohol increases the odds for poor sleep (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.11-10.10) in males. In females, lack of exercise was the major risk factor of poor sleep as they are 4.46 times more likely to suffer from low sleep quality than those who exercise regularly (95% CI=1.56-13.75). Stress was also a risk factor for poor sleep. It was 5.60 times higher in the "always have stress" group than the "do not have stress" group (95% CI = 1.54-20.34). Thus, alcohol consumption is associated with men's sleep quality, while exercise and stress level affect women's.
27707084	Sleep disturbances commonly occur after traumatic brain injury (TBI) and may predispose patients to epileptic seizures. We hypothesized that unprovoked seizure occurrence post-TBI depends on the sleep-wake cycle, and that the electrographic characteristics of a given sleep stage provide biomarkers for post-traumatic epilepsy (PTE). We show, in a rat lateral fluid percussion model, that 92% of spontaneous generalized seizures occur during the transition from stage III to rapid eye movement sleep. Moreover, a reduction in spindle duration and dominant frequency during the transition stage present as specific and sensitive noninvasive biomarkers for experimentally induced PTE with generalized electrographic seizures.
27698681	Pain and anxiety are the most common neurological responses to many harmful or noxious stimuli and their management clinically is often challenging. Many of the frequently used morphine-based drugs, non-steroid anti-inflammatory drugs and acetaminophen, while efficient for treating pain, lead to patients suffering from several unwanted side effects. Melatonin, produced from the pineal body is a hormone of darkness, is involved in the control of circadian rhythms, and exerts a number of pharmacological effects. Melatonin mediates its actions through MT1/MT2 melatonin receptors on the cell membrane and also through RZR/ROR nuclear orphan receptors. Chronic pain syndromes are often associated with the desynchronization of circadian and biological rhythms, which also cause disturbances in the sleep-wake cycle. Melatonin-mediated analgesic effects seem to involve β-endorphins, GABA receptor, opioid receptors and the nitric oxide-arginine pathway. The effectiveness of melatonin as an analgesic and anxiolytic agent has been demonstrated in various animal models of pain and this led to the use of melatonin clinically in different pathological conditions and also in patients undergoing surgery. Melatonin was found to be effective in many of these cases as an anxiolytic and analgesic agent, indicating its clinical application.
27698557	Age-related cognitivee decline is a growing public health concern worldwide. More than a quarter of adults with cognitive impairment experience sleep disturbance. The objective of this pilot study was to evaluate the preliminary effects of tai chi qigong (TCQ) on improving the night-time sleep quality of older adults with cognitive impairment.Older adults with cognitive impairment who complain of sleep disturbance.	A randomized controlled trial with two groups. Fifty-two subjects were recruited from two district elderly community centers and randomly assigned to either the TCQ group (n=27) or the control group (n=25). The intervention group received TCQ training consisting of two 60-minute sessions each week for 2 months. The control group was advised to maintain their usual activities. Sleep quality was measured by the Chinese Pittsburgh Sleep Quality Index. Quality of life was measured by Short-form 12, cognitive functions measured by mini-mental state examination, and subjective memory deficits measured by the memory inventory for Chinese.	Data were collected at baseline, 2 months, and 6 months. Significant results were noted at 6 months in the Chinese Pittsburgh Sleep Quality Index global score (P=0.004), sleep duration (P=0.003), habitual sleep efficiency (P=0.002), and the Short-form 12 mental health component (P<0.001). The TCQ participants reported better sleep quality and a better (quality of life) mental health component than the control group.	TCQ can be considered a useful nonpharmacological approach for improving sleep quality in older adults with cognitive impairment.	CUHK_CCT00448 (https://www2.ccrb.cuhk.edu.hk/registry/public/287).	
27695706	The goal of this study was to examine links between concerns about community violence and objective and subjective sleep parameters in an adolescent sample. Sex was considered as a moderator of effects.The study used a cross-sectional design.	The community-based sample included 252 adolescents (53% girls) with an average age of 15.79 years (SD = 0.81) from the Southeastern United States. The sample included 34% African American and 66% European American adolescents from a wide range of socioeconomic backgrounds.	Adolescent-reported community violence concerns were assessed using a composite of 3 separate subscales that measured perceived community safety and threats of community and school violence. Sleep duration and quality were assessed using actigraphy, and subjective sleep problems and daytime sleepiness were measured with subscales of the School Sleep Habits Survey.	Community violence predicted lower sleep efficiency, more long-wake episodes, and more sleep/wake problems and sleepiness. Sex-related moderation effects revealed that girls in the sample were more vulnerable to the effects of violence concerns on their objective sleep quality.	Findings highlight the role of community violence concerns on adolescents' sleep, revealing that greater community violence concerns are linked with lower levels of actigraphy-based and subjective reports of sleep quality, particularly for adolescent girls. Consideration of the mechanisms by which violence concerns may affect sleep is discussed.	
27693261	Maintenance dialysis patients experience a high burden of physical and emotional symptoms that directly affect their quality of life and health care utilization. In this review, we specifically highlight common troublesome symptoms affecting dialysis patients: insomnia, restless legs syndrome, and uremic pruritus. Epidemiology, pathophysiology, and evidence-based current treatment are reviewed with the goal of providing a guide for diagnosis and treatment. Finally, we identify multiple additional areas of further study needed to improve symptom management in dialysis patients.
27692277	Caregivers describe significant sleep disturbances in the vast majority of children and adolescents, which is diagnosed as fetal alcohol spectrum disorders (FASD), but objective data on sleep disorders in this population are almost completely lacking. Animal models suggest that intrauterine alcohol exposure may disrupt sleep wake patterns, cause sleep fragmentation, and specifically affect the suprachiasmatic nucleus, thus disrupting melatonin secretion. The objective of this pioneering study was to evaluate sleep and melatonin abnormalities in children with FASD using objective, gold-standard measures.Children and adolescents (N = 36, 6-18 years) with FASD participated in clinical assessments by sleep specialists, overnight polysomnography (PSG), and a dim light melatonin onset (DLMO) test in a pediatric sleep laboratory. PSG was analyzed according to standardized scoring guidelines and sleep architecture was compared with normative data. DLMOs were determined and melatonin secretion curves were evaluated qualitatively to classify melatonin profiles. Sleep disorders were evaluated according to international diagnostic criteria.	There was a high prevalence (58%) of sleep disorders. The most common sleep problems were parasomnias (27.9%) and insomnia (16.8%). The sleep studies showed lower than normal sleep efficiency and high rates of sleep fragmentation. Most participants (79%) had an abnormal melatonin profile.	This study led to the recognition that both sleep and melatonin secretion abnormalities are present in children with FASD. Therefore, to be effective in managing the sleep problems in children with FASD, one needs to consider both the sleep per se and a possible malfunction of the circadian regulation.	
27692059	Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared EEG and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD).Male Cntnap2 knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, EMG, body temperature and locomotor activity. Animals were subjected to a test battery for ASD-related behaviors, followed by 24-h EEG recordings which were analyzed for sleep/wake parameters and subjected to spectral analysis.	Cntnap2 KO rats exhibited severe motor seizures, hyperactivity, and increased consolidation of wakefulness and REM sleep. By contrast, Cntnap2 KO mice demonstrated absence seizure-like events, hypoactivity, and wake fragmentation. Although seizures observed in Cntnap2 KO rats were more similar to those in CDFE patients than in KO mice, neither model fully recapitulated the full spectrum of disease symptoms. However, KOs in both species had reduced spectral power in the alpha (9-12 Hz) range during wake, suggesting a conserved EEG biomarker.	Deletion of Cntnap2 impacts similar behaviors and EEG measures in rats and mice, but with profound differences in nature and phenotypic severity. These observations highlight the importance of cross-species comparisons to understand conserved gene functions and the limitations of single-species models to provide translational insights relevant to human diseases.	
27692050	To examine the prevalence of circadian misalignment in clinically diagnosed DSPD, and compare mood and daytime functioning in those with and without a circadian basis for the disorder.182 DSPD patients aged 16 to 64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime, or non-circadian DSPD, defined as DLMO occurring before desired bedtime.	103 patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 h later in circadian DSPD compared to non-circadian DSPD (p<0.001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p<0.05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64, p<0.01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD.	Almost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the desired bedtime, suggesting that the reported difficulties initiating sleep at the desired bedtime are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.	
27689899	Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30p.m.-7a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5h after awakening (vs. normal sleep, p<0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p<0.05). Moreover, plasma 2AG was elevated 15min post-exercise (+44%, p<0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration.

27686225	Prevention of lower extremity fluid pooling (LEFP) is associated with improved sleep quality. Physical activity and compression stockings are non-invasive methods used to manage LEFP, but both are associated with low adherence. Calf muscle pump (CMP) stimulation is an alternative and more convenient approach. Convenience sampling was used to recruit 11 participants between ages 45 and 65 with poor sleep quality. A within-person single-group pre-test-post-test design was used to evaluate changes in sleep quality, daytime sleepiness, and functional outcomes sensitive to impaired sleep as measured by the Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale after 4 weeks of CMP stimulation. Statistical analysis included effect size (ES) calculations. After daily use of CMP stimulation, participants demonstrated improvement in overall sleep quality (ES = -.97) and a large reduction in daily disturbance from poor sleep (ES = -1.25). Moderate improvements were observed in daytime sleepiness (ES = -.53) and functional outcomes sensitive to sleepiness (ES = .49). Although causality could not be determined with this study design, these results support further research to determine whether CMP stimulation can improve sleep quality. © 2016 Wiley Periodicals, Inc.
27679429	The causes of severe obesity are multifactorial and include metabolic, dietary, physical, and psychological aspects. Additionally, the impact of severe obesity affects more than one's physical health. This article attempts to explore the psychological impact of severe obesity specifically in the areas of mood, eating disorders, sleep disturbance, chronic pain, and quality of life. Additionally, obesity treatment options of lifestyle modification and bariatric surgery that include psychological assessment and/or cognitive behavioral intervention are discussed.
27678347	We aim to review the literature and provide guidance on preventive health measures in inflammatory bowel disease (IBD). Structured searches were performed in PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library from January 1976 to June 2016 using the following keywords: (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (health maintenance OR preventive health OR health promotion). Abstracts of the articles selected from each of these multiple searches were reviewed, and those meeting the inclusion criteria (that is, providing data regarding preventive health or health maintenance in IBD patients) were recorded. Reference lists from the selected articles were manually reviewed to identify further relevant studies. Patients with IBD are at increased risk of developing adverse events related to the disease course, therapeutic interventions, or non-adherence to medication. Recent studies have suggested that IBD patients do not receive preventive services with the same thoroughness as patients with other chronic diseases. Preventive health measures can avert morbidity and improve the quality of life of patients with IBD. Gastroenterologists and primary care physicians (PCPs) should have an up to date working knowledge of preventive health measures for IBD patients. A holistic approach and better communication between gastroenterologists and PCPs with explicit clarification of roles will prevent duplication of services and streamline care. 
27677675	Sleep-wake disturbances are frequently reported following traumatic brain injury (TBI), but they remain poorly documented in the acute stage of injury. Little is known about their origin and evolution.This study presents the case of a patient in the acute phase of a severe TBI. The patient was injured at work when falling 12 m into a mine and was hospitalized in the regular wards of a level I trauma centre. From days 31 to 45 post-injury, once he had reached a level of medical stability and continuous analgosedation had been ceased, his sleep-wake cycle was monitored using actigraphy. Results showed significant sleep-wake disturbances and severe sleep deprivation. Indeed, the patient had an average nighttime sleep efficiency of 32.7 ± 15.4 %, and only an average of 4.8 ± 1.3 h of sleep per 24-h period. After hospital discharge to the rehabilitation centre, where he remained for 5 days, the patient was readmitted to the same neurological unit for paranoid delusions. During his second hospital stay, actigraphy recordings resumed from days 69 to 75 post-injury. A major improvement in his sleep-wake cycle was observed during this second stay, with an average nighttime sleep efficiency of 96.3 ± 0.9 % and an average of 14.1 ± 0.9 h of sleep per 24-h period.	This study is the first to extensively document sleep-wake disturbances in both the acute and subacute phases of severe TBI. Results show that prolonged sleep deprivation can be observed after TBI, and suggest that the hospital environment only partially contributes to sleep-wake disturbances. Continuous actigraphic monitoring may prove to be a useful clinical tool in the monitoring of patients hospitalized after severe TBI in order to detect severe sleep deprivation requiring intervention. The direct impact of sleep-wake disturbances on physiological and cognitive recovery is not well understood within this population, but is worth investigating and improving.	
27669996	Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD.We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs").	Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders.	BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes.	
27669671	WHAT IS KNOWN ON THE SUBJECT?: Paediatric sleep problems are clinical conditions that often coexist with other mental health problems and meet criteria that warrant the implementation of screening procedures, including high prevalence, and significant clinical impact. Researchers have designed the BEARS, a user-friendly paediatric sleep screening tool that seems to increase the amount of sleep information recorded, as well as the likelihood of identifying sleep problems during routine health encounters. Nonetheless, there are no studies using the BEARS in Spanish-speaking samples. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Using a sample of children with mental health problems, this study provides support for the use of the Spanish version of the BEARS to identify the most common sleep problems seen in paediatric populations. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Considering how frequent sleep problems are, it is especially important for health professionals working with children in general, and with children with mental health problems in particular, to be aware of and be encouraged to use simple brief screening tools for paediatric sleep problems.Objective Research studies describe a high prevalence of sleep problems in children with mental health problems, up to 50%, and its role as a risk factor in the development of psychopathology. These often go unnoticed and are not evaluated in the clinical field. Our objective was to assess the concurrent validity of the BEARS, a brief paediatric sleep screening instrument, using the Children Sleep Habits Questionnaire (CSHQ) as the comparison instrument. Methods In this cross-sectional descriptive study, the BEARS was applied by a registered nurse to a sample of parents of children aged 2-16 years (n = 60, 71.7% male) who attended a mental healthcare facility (located in Murcia, Spain) for the first time to receive a group psychoeducational intervention. The association between the information collected with the BEARS and scores on the related subscales of the CSHQ was assessed by Mann-Whitney U tests. Results Children who, according to the BEARS, had a sleep problem obtained scores on the CSHQ-related subscales significantly higher than children who did not have a sleep problem (all Ps  < 0.05). Conclusion Our results support the concurrent validity of the Spanish translation of the BEARS to detect sleep problems in paediatric nursing assessments. Further studies, with bigger and more heterogeneous samples, are warranted.	
27665614	The degree to which different sinonasal symptoms contribute to the overall quality of life (QOL) detriment in chronic rhinosinusitis (CRS) patients remains unknown. In this study we sought to characterize the effect of different CRS symptoms on the general health-related QOL in patients.We performed a prospective cross-sectional study of 131 adult patients with CRS. Sinonasal symptoms were evaluated using the 22-item Sinonasal Outcomes Test (SNOT-22) and general health-related QOL was evaluated using the EuroQol 5-Dimensional general health-related QOL survey (EQ5D) and visual analog scale (EQ5D-VAS). Health utility values (HUV) were determined using responses to the EQ5D. SNOT-22 scores were broken down into subdomain scores for sleep, nasal, otologic/facial pain and emotional function symptoms.	The otologic/facial pain subdomain score consistently had the largest impact on EQ5D-VAS and HUV. After otologic/facial pain, the sleep subdomain score had the second largest effect while the nasal subdomain score had the least impact on general health-related QOL.	Different types of CRS symptoms - most prominently otologic/facial pain and sleep-related symptoms - and their underlying pathophysiologic mechanisms may differentially affect the general health-related QOL detriment associated with CRS. These findings raise the possibility that treatment of the various symptoms associated with CRS may lead to differential improvement in general-health related QOL.	
27662349	This study examined whether subjective measurements of in-flight sleep could be a reliable alternative to actigraphic measurements for monitoring pilot fatigue in a large-scale survey.Pilots (3-pilot crews) completed a 1-page survey on outbound and inbound long-haul flights crossing 1-7 time zones (N = 586 surveys) between 53 city pairs with 1-d layovers. Across each flight, pilots documented flight start and end times, break times, and in-flight sleep duration and quality if they attempted sleep. They also rated their fatigue (Samn-Perelli Crew Status Check) and sleepiness (Karolinska Sleepiness Scale) at top of descent (TOD). Mixed model ANCOVA was used to identify independent factors associated with sleep duration, quality, and TOD measures. Domicile time was used as a surrogate measure of circadian phase.	Sleep duration increased by 10.2 min for every 1-h increase in flight duration. Sleep duration and quality varied by break start time, with significantly more sleep obtained during breaks starting between (domicile) 22:00-01:59 and 02:00-05:59 compared to earlier breaks. Pilots were more fatigued and sleepy at TOD on flights arriving between 02:00-05:59 and 06:00-09:59 domicile time compared to other flights. With every 1-h increase in sleep duration, sleepiness ratings at TOD decreased by 0.6 points and fatigue ratings decreased by 0.4 points.	The present findings are consistent with previous actigraphic studies, suggesting that self-reported sleep duration is a reliable alternative to actigraphic sleep in this type of study, with use of validated measures, sufficiently large sample sizes, and where fatigue risk is expected to be low. van den Berg MJ, Wu LJ, Gander PH. Subjective measurements of in-flight sleep, circadian variation, and their relationship with fatigue. Aerosp Med Hum Perform. 2016; 87(10):869-875.	
27661417	Sleep and circadian abnormalities have been mostly demonstrated in bipolar patients. However, it is not clear whether these alterations are present in population at high risk for bipolar disorder (BD), indicating a possible risk factor for this condition.This systematic review aims to define current evidence about sleep and rhythm alterations in people at risk for BD and to evaluate sleep and circadian disorders as risk factor for BD.	The systematic review included all articles about the topic until February 2016. Two researchers performed an electronic search of PubMed and Cochrane Library. Keywords used were 'sleep' or 'rhythm' or 'circadian' AND 'bipolar disorder' or 'mania' or 'bipolar depression' AND 'high-risk' or 'risk'.	Thirty articles were analyzed (7451 participants at risk for BD). Sleep disturbances are frequent in studies using both subjective measures and actigraphy. High-risk individuals reported irregularity of sleep/wake times, poor sleep and circadian rhythm disruption. Poor sleep quality, nighttime awakenings, and inadequate sleep are possible predictive factors for BD. A unique study suggested that irregular rhythms increase risk of conversion. People at risk for BD showed high cortisol levels in different times of day. Studies about anatomopathology, melatonin levels, inflammatory cytokines and oxidative stress were not identified. The most important limitations were differences in sleep and rhythm measures, heterogeneity of study designs, and lack of consistency in the definition of population at risk.	Sleep and circadian disturbances are common in people at risk for BD. However, the pathophysiology of these alterations and the impact on BD onset are still unclear.	
27660995	This study examined whether sleep disturbance predicted or moderated responses to psychotherapy in participants who participated in STEP-BD, a national, multisite study that examined the effectiveness of different treatment combinations for bipolar disorder. Participants received either a brief psychosocial intervention called collaborative care (CC; n = 130) or intensive psychotherapy (IP; n = 163), with study-based pharmacotherapy. Participants (N = 243) were defined as current (past week) short sleepers (<6 hours/night), normal sleepers (6.5-8.5 hours/night), and long sleepers (≥9 hours/night), according to reported average nightly sleep duration the week before randomization. Sleep disturbances did not predict the likelihood of recovery nor time until recovery from a depressive episode. There was no difference in recovery rates between IP versus CC for normal sleepers, and medium effect sizes were observed for differences in short and long sleepers. In this study, sleep did not play a major role in predicting or moderating response to psychotherapy in bipolar disorder.
27660894	Polymorphisms in human circadian genes are potential genetic markers that affect diurnal preference in several populations. In this study, we evaluated whether four polymorphisms in circadian genes CLOCK, ARNTL, PER2, and GNB3 were associated with diurnal preference in a Korean population. In all, 499 healthy subjects were genotyped for four functional polymorphisms in CLOCK, ARNTL, PER2, and GNB3. Composite scale of morningness (CSM) was applied to measure phenotype patterns of human diurnal preference. In addition, three subscale scores, i.e. "morningness," "activity planning," and "morning alertness," were extracted from the CSM. No significant associations were observed between CSM scores and CLOCK (rs1801260) genotype or T allele carrier status, CSM scores and ARNTL (rs2278749) C allele carrier status, and CSM scores and GNB3 (rs5443) genotype or C allele carrier status. However, total CSM scores and scores of its subscales were significantly associated with PER2 (rs934945) genotype (p = 0.010, p = 0.018, and p = 0.005 for total, morningness, and activity planning, respectively) and G allele carrier status (p = 0.003, p = 0.005, and p = 0.002 for total, morningness, and activity planning, respectively). The best model result obtained by performing multifactor dimensionality reduction analysis ([Formula: see text]2 = 11.2798, p = 0.0008) indicated that interaction among C/T single nucleotide polymorphism (SNP) in ARNTL, C/T SNP in GNB3, and G/A SNP in PER2 synergistically affected the risk associated with diurnal preference toward eveningness. These results suggest that circadian gene PER2 is associated with diurnal preference in healthy Korean population. Although polymorphisms in ARNTL and GNB3 were not significantly associated with diurnal preference, their interactions with the polymorphism in PER2 may synergistically increase the risk of diurnal preference toward eveningness.
27660609	Sleep and wakefulness are characterized by distinct states of thalamocortical network oscillations. The complex interplay of ionic conductances within the thalamo-reticular-cortical network give rise to these multiple modes of activity and a rapid transition exists between these modes. To better understand this transition, we constructed a simplified computational model based on physiological recordings and physiologically realistic parameters of a three-neuron network containing a thalamocortical cell, a thalamic reticular neuron, and a corticothalamic cell. The network can assume multiple states of oscillatory activity, resembling sleep, wakefulness, and the transition between these two. We found that during the transition period, but not during other states, thalamic and cortical neurons displayed chaotic dynamics, based on the presence of strange attractors, estimation of positive Lyapunov exponents and the presence of a fractal dimension in the spike trains. These dynamics were quantitatively dependent on certain features of the network, such as the presence of corticothalamic feedback and the strength of inhibition between the thalamic reticular nucleus and thalamocortical neurons. These data suggest that chaotic dynamics facilitate a rapid transition between sleep and wakefulness and produce a series of experimentally testable predictions to further investigate the events occurring during the sleep-wake transition period. 
27658573	Fatigue is highly prevalent in patients with epilepsy and has a major impact on quality of life, but little data is available on its effects and management in epilepsy. To identify the incidence and risk factors of fatigue in patients with epilepsy, 105 epilepsy patients (45 women and 60 men) were enrolled in our study. Demographic and clinical data were collected and psychological variables including fatigue, sleep quality, excess daytime sleepiness, anxiety, and depression were measured by Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale, respectively. Of 105 patients, 29.5% exhibited fatigue (FSS score ⩾4). We found no correlation between the occurrence of fatigue and any of our demographic or clinical variables. Fatigue is correlated with low sleep quality, anxiety, and depression, but not with excess daytime sleepiness. Thus, we concluded that fatigue is highly prevalent in patients with epilepsy, and that low sleep quality, anxiety, and depression are significantly correlated with fatigue in epileptics, while excess daytime sleepiness not.
27656266	Unlike other organs that operate continuously, such as the heart and kidneys, many of the operations of the nervous system shut down during sleep. The evolutionarily conserved unconscious state of sleep that puts animals at risk from predators indicates that it is an indispensable integral part of systems operation. A reasonable expectation is that any hypothesis for the mechanism of the nervous system functions should be able to provide an explanation for sleep. In this regard, the semblance hypothesis is examined. Postsynaptic membranes are continuously being depolarized by the quantally-released neurotransmitter molecules arriving from their presynaptic terminals. In this context, an incidental lateral activation of the postsynaptic membrane is expected to induce a semblance (cellular hallucination of arrival of activity from its presynaptic terminal, which forms a unit for internal sensation) of the arrival of activity from its presynaptic terminal as a systems property. This restricts induction of semblance to a context of a very high ratio of the duration of the default state of neurotransmitter-induced postsynaptic depolarization to the total duration of incidental lateral activations of the postsynaptic membrane. This requirement spans within a time-bin of a few sleep-wake cycles. Since the duration of quantal release remains maximized, the above requirement can be achieved only by ceiling the total duration of incidental lateral activations of the postsynaptic membrane, which necessitates a state of sleep. 
27656022	Serotonin (5-HT) is a crucial neuromodulator linked to many psychiatric disorders. However, after more than 60 years of study, its role in behavior remains poorly understood, in part because of a lack of methods to target 5-HT synthesis specifically in the adult brain. Here, we have developed a genetic approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system by stereotaxic injection of an adeno-associated virus expressing Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele. We investigated the behavioral effects of deficient brain 5-HT synthesis and discovered a unique composite phenotype. Surprisingly, adult 5-HT deficiency did not affect anxiety-like behavior, but resulted in a robust hyperactivity phenotype in novel and home cage environments. Moreover, loss of 5-HT led to an altered pattern of circadian behavior characterized by an advance in the onset and a delay in the offset of daily activity, thus revealing a requirement for adult 5-HT in the control of daily activity patterns. Notably, after normalizing for hyperactivity, we found that the normal prolonged break in nocturnal activity (siesta), a period of rapid eye movement (REM) and non-REM sleep, was absent in all animals in which 5-HT deficiency was verified. Our findings identify adult 5-HT as a requirement for siestas, implicate adult 5-HT in sleep-wake homeostasis, and highlight the importance of our adult-specific 5-HT-synthesis-targeting approach in understanding 5-HT's role in controlling behavior.Serotonin (5-HT) is a crucial neuromodulator, yet its role in behavior remains poorly understood, in part because of a lack of methods to target specifically adult brain 5-HT synthesis. We developed an approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system. Using this technique, we discovered that adult 5-HT deficiency led to a novel compound phenotype consisting of hyperactivity, disrupted circadian behavior patterns, and elimination of siestas, a period of increased sleep during the active phase. These findings highlight the importance of our approach in understanding 5-HT's role in behavior, especially in controlling activity levels, circadian behavior, and sleep-wake homeostasis, behaviors that are disrupted in many psychiatric disorders such as attention deficit hyperactivity disorder.	
27655465	This questionnaire-based cross-sectional study was conducted (1) to estimate the prevalence of sleep-related problems, and (2) to explore factors associated with lower physical/mental quality of life (QOL), particularly addressing sleep-related problems among Japanese visually impaired people.This nationwide questionnaire-based survey was administered to visually impaired individuals through the Japan Federation of the Blind. Visually impaired individuals without light perception (LP) (n = 311), those with LP (n = 287), and age-matched and gender-matched controls (n = 615) were eligible for this study. Study questionnaires elicited demographic information, and information about visual impairment status, sleep-related problems, and health-related quality of life.	Visually impaired individuals with and without LP showed higher prevalence rates of irregular sleep-wake patterns and difficulty maintaining sleep than controls (34.7% and 29.4% vs. 15.8%, 60.1% and 46.7% vs. 26.8%, respectively; p < 0.001). These sleep-related problems were observed more frequently in visually impaired individuals without LP than in those with LP. Non-restorative sleep or excessive daytime sleepiness was associated with lower mental/physical QOL in visually impaired individuals with LP and in control subjects. However, visually impaired individuals without LP showed irregular sleep-wake pattern or difficulty waking up at the desired time, which was associated with lower mental/physical QOL.	Sleep-related problems were observed more frequently in visually impaired individuals than in controls. Moreover, the rates of difficulties were higher among subjects without LP. Sleep-related problems, especially circadian rhythm-related ones, can be associated with lower mental/physical QOL in visually impaired individuals without LP.	
27655452	To revise and enhance the current Behavioral Risk Factor Surveillance System (BRFSS) sleep questions for detection of sleep/wake disorders that contribute to health burden.A descriptive qualitative design was used to guide the investigation. The three methods were (1) a review of the current evidence on sleep related screening questions (including the results from the parent study validating the current BRFSS questions), (2) interviews with sleep experts about the questions they use in their clinical practice to screen for sleep problems, and (3) interviews with lay people to discuss contextual meanings, feelings, and beliefs about sufficient and restful sleep and not feeling rested.	Recommendations for revisions of the current BRFSS questions.	The current BRFSS questions should be refined to better screen for sleep disorders.	
27653891	Pain is a bothersome non-motor symptom in patients with Parkinson's disease (PD), but the relationships between PD, presence of pain, different pain characteristics, and other non-motor symptoms such as mood and sleep disturbances are unclear.To investigate the relationship between PD and pain as well as specific subtypes of pain with anxiety, depression and sleep quality.	This cross-sectional case-control study included two groups of PD patients; one with (n=37) and one without pain (n=37). Healthy controls with (n=37) and without pain (n=37) were recruited and matched to the PD groups for age and gender. All participants completed questionnaires regarding pain, mood and sleep.	PD patients with pain showed significantly higher anxiety severity and poorer sleep quality than PD patients without pain. Compared to controls with pain, PD patients with pain had more anxiety, depression and worsened sleep quality. PD patients with pain were more likely to report akathisic, tension and sharp pain compared to controls with pain, but these three pain characteristics did not correlate with each other. There were no differences in depression, anxiety, or sleep between PD patients with akathisic, tension and sharp pain and those without.	Pain in PD seems to be linked with specific pain characteristics (akathisic, tension and sharp pain) as well as heightened anxiety and worsened sleep quality. Integrative approach treatments which address pain in PD may also improve anxiety and sleep quality.	
27651236	The nucleus of the solitary tract (NTS) plays a determinant role in the antiepileptic effects of vagus nerve stimulation (VNS). One mechanism underlying the efficacy of VNS is the induction of cortical changes, detected by electroencephalogram (EEG), which can be mediated by the NTS through its projections to the cerebral nuclei responsible for modulating cortical activity. The effect of the electrical stimulation of the nucleus of the solitary tract (ENTS) on EEG activity and sleep states in freely moving animals is unknown.This study aims to analyze the effects of ENTS on the EEG spectral power and sleep-wake cycle in freely moving cats.	EEG was performed on the left amygdala and both pre-frontal cortices for 23 hours under baseline conditions and with ENTS in freely moving cats. The changes induced by ENTS on the EEG spectral power and the architecture of the sleep-wake cycle were analyzed.	ENTS increased the theta and beta band power for 12 hours. Furthermore, an increase in wakefulness occurred in the first six hours, followed by an increase in the total time of rapid eye movement (REM) sleep.	ENTS produces a long-lasting increase in the theta and beta band power, which favors wakefulness and REM sleep in freely moving cats.	
27651114	Several neuropsychiatric and neurological disorders have recently been characterized as dysfunctions arising from a 'final common pathway' of imbalanced excitation to inhibition within cortical networks. How the regulation of a cortical E/I ratio is affected by sleep and the circadian rhythm however, remains to be established. Here we addressed this issue through the analyses of TMS-evoked responses recorded over a 29 h sleep deprivation protocol conducted in young and healthy volunteers. Spectral analyses of TMS-evoked responses in frontal cortex revealed non-linear changes in gamma band evoked oscillations, compatible with an influence of circadian timing on inhibitory interneuron activity. In silico inferences of cell-to-cell excitatory and inhibitory connectivity and GABA/Glutamate receptor time constant based on neural mass modeling within the Dynamic causal modeling framework, further suggested excitation/inhibition balance was under a strong circadian influence. These results indicate that circadian changes in EEG spectral properties, in measure of excitatory/inhibitory connectivity and in GABA/glutamate receptor function could support the maintenance of cognitive performance during a normal waking day, but also during overnight wakefulness. More generally, these findings demonstrate a slow daily regulation of cortical excitation/inhibition balance, which depends on circadian-timing and prior sleep-wake history. 
27646310	The zebrafish is an ideal vertebrate model for neurobehavioral studies with translational relevance to humans. Many aspects of sleep have been studied, but we still do not understand how and why sleep deprivation alters behavioral and physiological processes. A number of hypotheses suggest its role in memory consolidation. In this respect, the aim of this study was to analyze the effects of sleep deprivation on memory in zebrafish (Danio rerio), using an object discrimination paradigm. Four treatments were tested: control, partial sleep deprivation, total sleep deprivation by light pulses, and total sleep deprivation by extended light. The control group explored the new object more than the known object, indicating clear discrimination. The partially sleep-deprived group explored the new object more than the other object in the discrimination phase, suggesting a certain degree of discriminative performance. By contrast, both total sleep deprivation groups equally explored all objects, regardless of their novelty. It seems that only one night of sleep deprivation is enough to affect discriminative response in zebrafish, indicating its negative impact on cognitive processes. We suggest that this study could be a useful screening tool for cognitive dysfunction and a better understanding of the effect of sleep-wake cycles on cognition.
27645286	Etiology of stuttering remains unknown and no pharmacologic intervention has been approved for treatment. We aimed to evaluate EEG parameters and the effect of adrenocorticotropic hormone (ACTH) therapy in stuttering.In this retrospective study, 25 patients with attention deficit and hyperactivity (ADHD) or autism spectrum disorder (ASD), and comorbid stuttering were followed and treated with ACTH for electrical status epilepticus in sleep (ESES). Sleep EEGs were recorded at referral and follow-up visits and short courses of ACTH were administered when spike-wave index (SWI) was ⩾15%. The assessment of treatment effectiveness was based on reduction in SWI, and the clinician-reported improvement in stuttering, and ADHD or ASD. Statistical analyses were conducted in order to investigate the relationship between the clinical and EEG parameters.	Following treatment with ACTH, a reduction in SWI in all the patients was accompanied by a 72% improvement in ADHD or ASD, and 83.8% improvement in stuttering. Twelve of the 25 patients with stuttering showed complete treatment response. Linear regressions established that SWI at final visit significantly predicted improvement in ADHD or ASD, and in stuttering. If symptoms had recurred, improvement was once again achieved with repeated ACTH therapies. Stuttering always improved prior to, and recurred following ADHD or ASD.	The underlying etiology leading to ESES may play a significant role in the pathophysiology of stuttering and connect stuttering to other developmental disorders. ACTH therapy has beneficial effects on stuttering and improves EEG parameters.	
27642784	The basal forebrain (BF) plays key roles in multiple brain functions, including sleep-wake regulation, attention, and learning/memory, but the long-range connections mediating these functions remain poorly characterized. Here we performed whole-brain mapping of both inputs and outputs of four BF cell types - cholinergic, glutamatergic, and parvalbumin-positive (PV+) and somatostatin-positive (SOM+) GABAergic neurons - in the mouse brain. Using rabies virus -mediated monosynaptic retrograde tracing to label the inputs and adeno-associated virus to trace axonal projections, we identified numerous brain areas connected to the BF. The inputs to different cell types were qualitatively similar, but the output projections showed marked differences. The connections to glutamatergic and SOM+ neurons were strongly reciprocal, while those to cholinergic and PV+ neurons were more unidirectional. These results reveal the long-range wiring diagram of the BF circuit with highly convergent inputs and divergent outputs and point to both functional commonality and specialization of different BF cell types. 
27636023	Daytime workers tend to have shorter sleep duration and earlier sleep onset during work days than on days off. Large individual differences in sleep onset and sleep duration may be observed on work days, but work usually synchronizes sleep offset to a similar time. The present study describes individual differences in sleep behaviour of 48 daytime workers (25 men, aged 20-58 years) from an iron ore mine in Northern Sweden. The aim of the study was to determine whether differences in sleep patterns during work days were associated with the outcomes of sleepiness and sleep complaints. Cluster analysis was used to group workers into two categories of sleep onset and sleep duration. The "Late Sleep Onset" cluster comprised workers who slept 1.30 h later than the "Early Sleep Onset" cluster (p < 0.0001 for all weekdays). The "Long Sleep Duration" cluster slept 1.10 h longer than the "Short Sleep Duration" cluster (p < 0.0002 for work nights). The "Late Sleep Onset" cluster reported less refreshing sleep (p < 0.01) and had lower sufficient sleep scores (p < 0.01) than the "Early Sleep Onset" cluster. The "Short Sleep Duration" cluster also reported lower scores for sufficient sleep (p < 0.04) than the "Long Sleep Duration" cluster. For combined characteristics (phase and duration), workers with a late phase and short sleep duration reported greater sleep debt and sleepiness than workers with an early phase and short sleep duration (p < 0.02). Work schedule and commuting time modulate both sleep phase and sleep duration independently. Workers, classified as having an intermediate sleep phase preference, can organize their sleep time in order to minimize sleep debt and sleepiness symptoms. Individual differences in sleep phase and duration should be considered when promoting well-being at work even among groups with similar sleep needs. In order to minimize sleep debt and sleepiness symptoms, successful sleep behaviour could be promoted involving extend use of flexitime arrangement (i.e. later starting times) and reduce use of alarm clocks.
27635614	Цель исследования. Оценка уровня знаний о гигиене сна в российской популяции. Материал и методы. 398 жителей Чувашии, 173 мужчины и 225 женщин в возрасте от 18 до 82 лет (средний - 36,3±13,2 года). При опросе использовалась анкета представлений о гигиене сна. Оценка ответов проводилась с учетом социально-демографических показателей (пол, возраст, место жительства, уровень образования), особенности сна и его нарушения. Результаты и заключение. Установлена низкая осведомленность населения о правилах гигиены сна. Среднее значение правильных ответов на 20 вопросов анкеты составило 8,1±3,6. Лучшие показатели осведомленности отмечались у женщин, людей с более высоким уровнем образования, худшие - у курящих и злоупотребляющих алкоголем респондентов. Выявлена связь между наличием нарушений сна и лучшей осведомленностью о гигиене сна.To estimate public awareness on sleep hygiene in general Russian population.	A sample consisted of 398 people (173 men, 225 women), aged from 18 to 82 years (mean age - 36.3±13.2 years), who were interviewed with the Sleep Beliefs Scale (SBS). Sociodemographic variables (gender, age, residence, education), sleep habits and disorders were recorded as well.	The low public awareness on sleep hygiene rules was demonstrated. Mean number of correct answers out of 20 in SBS was 8.1±3.6. Most informed were women and more educated persons, worst results were demonstrated in smoking and habitual alcohol consuming respondents. The connection between disordered sleep and awareness on sleep hygiene rules was revealed.	
27634809	To determine whether interdependence in couples' sleep (sleep-wake concordance i.e., whether couples are awake or asleep at the same time throughout the night) is associated with two markers of CVD risk, ambulatory blood pressure (BP) and systemic inflammation.Cross-sectional analysis.	Community-based study.	Forty-six adult couples without known sleep disorders, ages 18-45 years.	Percent sleep-wake concordance, the independent variable, was calculated for each individual using actigraphy. Ambulatory BP monitors measured BP across 48 hours. Dependent variables included mean sleep systolic BP (SBP) and diastolic BP (DBP), mean wake SBP and DBP, sleep-wake SBP and DBP ratios, and C-reactive protein (CRP). Mixed models were used and were adjusted for age, sex, education, race, and body mass index. Higher sleep-wake concordance was associated with lower sleep SBP (b = -.35, SE = .01) and DBP (b = -.22, SE = .10) and lower wake SBP (b = -.26, SE = .12; all p's < .05). Results were moderated by sex; for women, high concordance was associated with lower BP. Men and women with higher sleep-wake concordance also had lower CRP values (b = -.15, SE = .03, p < .05). Sleep-wake concordance was not associated with wake DBP or sleep/wake BP ratios. Significant findings remained after controlling for individual sleep quality, duration, and wake after sleep onset.	Sleep-wake concordance was associated with sleep BP, and this association was stronger for women. Higher sleep-wake concordance was associated with lower systemic inflammation for men and women. Sleep-wake concordance may be a novel mechanism by which marital relationships are associated with long-term CVD outcomes.	
27634801	Computational tools that predict the effects of daily sleep/wake amounts on neurobehavioral performance are critical components of fatigue management systems, allowing for the identification of periods during which individuals are at increased risk for performance errors. However, none of the existing computational tools is publicly available, and the commercially available tools do not account for the beneficial effects of caffeine on performance, limiting their practical utility. Here, we introduce 2B-Alert Web, an open-access tool for predicting neurobehavioral performance, which accounts for the effects of sleep/wake schedules, time of day, and caffeine consumption, while incorporating the latest scientific findings in sleep restriction, sleep extension, and recovery sleep.We combined our validated Unified Model of Performance and our validated caffeine model to form a single, integrated modeling framework instantiated as a Web-enabled tool. 2B-Alert Web allows users to input daily sleep/wake schedules and caffeine consumption (dosage and time) to obtain group-average predictions of neurobehavioral performance based on psychomotor vigilance tasks. 2B-Alert Web is accessible at: https://2b-alert-web.bhsai.org.	The 2B-Alert Web tool allows users to obtain predictions for mean response time, mean reciprocal response time, and number of lapses. The graphing tool allows for simultaneous display of up to seven different sleep/wake and caffeine schedules. The schedules and corresponding predicted outputs can be saved as a Microsoft Excel file; the corresponding plots can be saved as an image file. The schedules and predictions are erased when the user logs off, thereby maintaining privacy and confidentiality.	The publicly accessible 2B-Alert Web tool is available for operators, schedulers, and neurobehavioral scientists as well as the general public to determine the impact of any given sleep/wake schedule, caffeine consumption, and time of day on performance of a group of individuals. This evidence-based tool can be used as a decision aid to design effective work schedules, guide the design of future sleep restriction and caffeine studies, and increase public awareness of the effects of sleep amounts, time of day, and caffeine on alertness.	
27634789	To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration.Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases) aged 33 years on average, and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1).	Levels of β-amyloid were lower in patients with type 1 narcolepsy (375.4 ±143.5 pg/ml) and type 2 narcolepsy (455.9 ± 65.0 pg/ml) compared with controls (697.9 ± 167.3 pg/ml, p < 0.05). Furthermore, in patients with type 1 narcolepsy, levels of T-tau (79.0 ± 27.5 pg/ml), and P-tau181 (19.1 ± 4.3 pg/ml) were lower than in controls (162.2 ± 49.9 pg/ml and 33.8 ± 9.2 pg/ml, p < 0.05). Levels of α-synuclein, NF-L, and CHI3L1 in CSF from narcolepsy patients were similar to those of healthy individuals.	Six CSF biomarkers of neurodegeneration were decreased or normal in narcolepsy indicating that taupathy, synucleinopathy, and immunopathy are not prevalent in narcolepsy patients with a disease duration of 2-29 years. Lower CSF levels of β-amyloid, T-tau protein, and P-tau181 in narcolepsy may indicate that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in CNS.	
27634702	Sleep and fatigue management is one of the main challenges in airline operations scheduling. Our aim was to compare the differences regarding fatigue, sleep, and labor specificities between the two most common types of flight, short/medium haul (SM-H) and long haul (L-H), in a large sample of airline pilots.A self-report questionnaire was developed, composed of socio-economic and labor questions, and psychological assessment scales for fatigue and sleep. Associations of these variables and type of flight were tested.	Of the total sample of Portuguese airline pilots (N = 435), 313 (72%) were from SM-H and 122 (28%) were from L-H. For SM-H, the values obtained for sleep complaints were 34.2%, daytime sleepiness 61.6%, and fatigue 93.0%. For L-H, 36.9%, 53.3%, and 84.4%, respectively. Looking at labor variables, the differences between the two types of flights were evident, with SM-H pilots' having statistically significant higher mean values of duty and flight hours, numbers of sectors, and early mornings. Only the mean number of night periods was higher in L-H pilots. All values were reported for 28 consecutive scheduling days.	Night periods and time-zone crossing may explain higher prevalence levels of sleep disturbances in L-H pilots. However, the values for daytime sleepiness were higher in SM-H pilots, which may be attributed to diminished sleep caused by a combination of frequent early starts and long duty periods. Taking into account the large differences between the two types of flights, different regulatory limits should be considered by aviation authorities. Reis C, Mestre C, Canhão H, Gradwell D, Paiva T. Sleep and fatigue differences in the two most common types of commercial flight operations. Aerosp Med Hum Perform. 2016; 87(9):811-815.	
27633892	The aim of this study was to evaluate the results of sleep-wake cycle monitoring using amplitude-integrated EEG (aEEG) and neuroimaging in newborn infants with a possible perinatal hypoxic insult, investigate the correlation between the findings, and determine the relevance of the findings to reasonably predict neurological outcome.aEEG was recorded among newborn infants suspected of perinatal asphyxia between November, 2014 and June, 2015 in one neonatal intensive care unit facility. Brain imaging with serial ultrasonography and MRI when available were performed, and the infants were divided into two groups according to findings and potential neurological outcome: Group I (favorable findings) and Group II (severe findings such as high grade intraventricular hemorrhage, cerebral infarction or white matter injury). Established sleep-wake cycle times after birth was compared between the two groups.	Among 107 newborn infants, 85 subjects were classified as Group I and the remaining 22 subjects as Group II. The total number of aEEG sessions was 207 and recording time was 2,796 h with a mean of 14.43 ± 13.40 h per study. Estimated times of cyclicity were earlier in Group I (113.34 h, 95 % CI 82.31-144.37) as compared to Group II (504.39 h, 95 % CI 319.91-688.88; p < 0.001).	Delayed cyclicity on aEEG has a strong correlation with unfavorable brain neuroimages in newborns with possible perinatal asphyxia. If sleep-wake cycles do not appear during initial period after birth, follow-up aEEG studies are recommended.	Retrospectively registered Registration number: BD 2015-148 Name of registry: amplitude integrated EEG in neonate Date of registration: September 9, 2015.	
27624504	Sleep disturbance and decreased health-related quality of life (HRQOL) are significant complaints in patients with liver cirrhosis. Although the etiology of these complications is unclear, we propose that glucose intolerance may be a predisposing factor. Therefore, our aim was to investigate the relationship between glucose intolerance and these complications.We assessed continuous glucose monitoring in 43 patients with chronic liver disease. Among these patients, 36 completed the Pittsburgh Sleep Quality Index (PSQI), the 36-Item Short-form Health Survey (SF-36), and the Neuropsychological Test (NPT). We also assessed the change in glucose fluctuations between preoperative periods and 1 year after liver transplantation in 13 patients.	Standard deviation (SD) of blood glucose was 24.15 ± 13.52. SD values correlated to glucose metabolism measures, including HbA1c and glycoalbumin. SD values also correlated to markers of liver fibrosis, including type IV collagen. Twenty-one patients (58.3 %) were classified as "poor" sleepers, with a global PSQI score ≥6. Glucose fluctuations correlated with the global PSQI score (r = 0.456, p = 0.008) and the SF-36 score (r = 0.434, p = 0.013). Multivariate regression analysis identified SD values as an independent risk factor for sleep disturbance (r = 0.12, p = 0.039) and decreased HRQOL (r = -0.32, p = 0.024). SD values did not correlate with the NPT. SD values were also improved in 11 (84.6 %) patients 1 year after liver transplantation.	Abnormal glucose fluctuations are a risk factor for sleep disturbance and decrease of HRQOL in patients with cirrhosis.	
27621470	This study quantifies sex differences in the diurnal and circadian variation of sleep and waking while controlling for menstrual cycle phase and hormonal contraceptive use. We compared the diurnal and circadian variation of sleep and alertness of 8 women studied during two phases of the menstrual cycle and 3 women studied during their midfollicular phase with that of 15 men. Participants underwent an ultradian sleep-wake cycle (USW) procedure consisting of 36 cycles of 60-min wake episodes alternating with 60-min nap opportunities. Core body temperature (CBT), salivary melatonin, subjective alertness, and polysomnographically recorded sleep were measured throughout this procedure. All analyzed measures showed a significant diurnal and circadian variation throughout the USW procedure. Compared with men, women demonstrated a significant phase advance of the CBT but not melatonin rhythms, as well as an advance in the diurnal and circadian variation of sleep measures and subjective alertness. Furthermore, women experienced an increased amplitude of the diurnal and circadian variation of alertness, mainly due to a larger decline in the nocturnal nadir. Our results indicate that women are likely initiating sleep at a later circadian phase than men, which may be one factor contributing to the increased susceptibility to sleep disturbances reported in women. Lower nighttime alertness is also observed, suggesting a physiological basis for a greater susceptibility to maladaptation to night shift work in women. 
27614960	In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for darkness) from pineal. Nitric Oxide (NO) acts as an important neurotransmitter in generating the phase shifts of circadian rhythms and participates in sleep-wake processes, maintenance of vascular tone as well as signalling and regulating inflammatory processes. Aging is associated with disruption of circadian timing system and decline in endogenous melatonin leading to several physiological disorders. Here we report the effect of aging on NO daily rhythms in various peripheral clocks such as kidney, intestine, liver, heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12 and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in alteration of NO levels as well as phase of NO in both 12 and 24 months groups. Correlation analysis demonstrated loss of stoichiometric interaction between the various peripheral clocks with aging. Age induced alterations in NO daily rhythms were found to be most significant in liver and, interestingly least in lungs. Neurohormone melatonin, an endogenous synchroniser and an antiaging agent decreases with aging. We report further differential restoration with exogenous melatonin administration of age induced alterations in NO daily rhythms and mean levels in kidney, intestine and liver and the stoichiometric interactions between the various peripheral clocks.
27614441	Physical activity (PA) and sleep are important to health; thus, it is important for researchers to have valid tools to measure them. Accelerometers have been proven valid for measuring PA and sleep, but only one device does this simultaneously: the ActiGraph Link (ActiGraph, LLC); however, the sleep-monitoring function has not been validated. This study aimed to evaluate the predictive power of ActiGraph Link sleep parameters against a validated accelerometer (Actiwatch 2, Phillips Respironics Mini-Mitter).A total of 49 Hong Kong adults aged 18-64 provided valid data on both accelerometers on their non-dominant wrist for seven consecutive days. Epochs from both accelerometers were classified as either sleep or awake using seven established algorithms (Cole-Kripke, Sadeh, Sazonov, high sensitivity threshold, medium sensitivity threshold, low sensitivity threshold, and neural network model), and these data were transformed to total sleeping period, wake after sleep onset, and sleep efficiency.	The non-zero count data for both accelerometers (331,103 observations) were strongly correlated with a Spearman correlation of 0.83 (p < 0.001). The total sleeping period was highly correlated (Spearman correlation ranged from 0.74 to 0.90) regardless of the algorithms used. All algorithms yielded insignificant difference in total sleep time measured by the two accelerometers (p > 0.05) with a negligible effect size of d < 0.2. The agreement of sleep/wake status was high for all algorithms, with accuracy ranging from 93.05 % (Sadeh's algorithm) to 96.13 % (Cole-Kripke's algorithm).	Results showed that the sleep function of the ActiGraph Link performs similar to a validated accelerometer (Actiwatch 2) and provides an opportunity to measure both sleep and PA simultaneously.	
27611843	Although there have been described alterations of circadian rhythmicity both in patients with substance use disorder (SUD) and patients with major depressive disorder (MDD), the circadian characteristics of SUD patients with comorbid MDD (SUD-MDD) are unknown. Likewise, the possible influence of the different modalities of treatments (ambulatory or therapeutic community) upon the circadian rhythmicity of SUD patients has not been characterized. Therefore, this study analyzes the circadian rhythmic profiles of SUD and SUD-MDD patients under ambulatory and therapeutic community treatment. The sample was composed of 40 SUD and 40 SUD-MDD men, aged 22-55 yrs, under treatment and with abstinence for at least three months (including each group 20 ambulatory and 20 from therapeutic community). Patients completed a sociodemographic, clinical and sleep-wake schedules interview, the Composite Scale of Morningness, and wore on the wrist an ambulatory device known as iButton® Thermochron DS1921H, which registered their distal skin temperature every two minutes for 48 hours. All the groups showed a tendency to morningness without differences among them in concordance with their sleep-wake schedules. With regard to distal skin temperature circadian rhythm, SUD patients showed higher values than SUD-MDD in amplitude, relative amplitude, percentage rhythm, and first harmonic power, and lower minimum temperature in 10 consecutive hours (p < .043, in all cases). Therapeutic community group values were lower in minimum temperature and higher in amplitude, relative amplitude, and 12 harmonic accumulated power (p < .028, in all cases) as compared to ambulatory ones. Moreover, all groups showed higher Rayleigh vector and rhythm stability as compared to normative population (p < .043, in both cases). The circadian rhythmic differences observed for diagnosis and type of treatment are indicative of a higher circadian rhythmicity robustness in SUD and therapeutic community patients as compared to SUD-MDD and ambulatory ones, respectively. Although drug consumption exerts a negative effect on the circadian rhythmicity, our results (high amplitude and rhythm stability) are indicative of an adequate circadian functioning as well as of an adjustment to the light-dark cycle in both diagnosis and type of treatment which may constitute a marker of the adherence to treatment and recovery status.
27611743	The efficacy of bright light and/or melatonin treatment for Delayed Sleep Wake Phase Disorder (DSWPD) is contingent upon an accurate clinical assessment of the circadian phase. However, the process of determining this circadian phase can be costly and is not yet readily available in the clinical setting. The present study investigated whether more cost-effective and convenient estimates of the circadian phase, such as self-reported sleep timing, can be used to predict the circadian phase and guide the timing of light and/or melatonin treatment (i.e. dim-light melatonin onset, core body temperature minimum and melatonin secretion mid-point) in a sample of individuals with DSWPD.Twenty-four individuals (male = 17; mean age = 21.96, SD = 5.11) with DSWPD were selected on the basis of ICSD-3 criteria from a community-based sample. The first 24-hours of a longer 80-hour constant laboratory ultradian routine were used to determine core body temperature minimum (cBTmin), dim-light melatonin onset (DLMO) and the midpoint of the melatonin secretion period (DLMmid = [DLM°ff-DLMO]/2). Prior to the laboratory session subjective sleep timing was assessed using a 7-day sleep/wake diary, the Pittsburgh Sleep Quality Index (PSQI), and the Delayed Sleep Phase Disorder Sleep Timing Questionnaire (DSPD-STQ).	Significant moderate to strong positive correlations were observed between self-reported sleep timing variables and DLMO, cBTmin and DLMmid. Regression equations revealed that the circadian phase (DLMO, cBTmin and DLMmid) was estimated within ±1.5 hours of the measured circadian phase most accurately by the combination of sleep timing measures (88% of the sample) followed by sleep diary reported midsleep (83% of the sample) and sleep onset time (79% of the sample).	These findings suggest that self-reported sleep timing may be useful clinically to predict a therapeutically relevant circadian phase in DSWPD.	
27608683	The quality of life in patients receiving chronic hemodialysis is compromised despite of the substantial achievements in treatments. Quality of life in hemodialysis patients have been shown to be associated with decreased survival and increased hospitalization. Therefore, it is necessary to incorporate the managements of symptoms and patient self-perceived well-being as measurements of effective treatments for these patients.A survey of symptom distress, quality of sleep and quality of life was performed in 301 maintenance hemodialysis patients using Dialysis Symptom Index, Short Form-36, and Pittsburgh Quality of Sleep Index table. Patients were recruited from five hospitals in Guangdong area of China by convenience sampling.	The prevalence of various symptoms in maintenance hemodialysis patients was between 23.3 and 80.4 %. These patients had compromised sleep and poor quality of life. Moreover, poor quality of sleep and impaired quality of life were associated with high symptom burden of these patients.	The patients receiving chronic hemodialysis generally have heavy symptom distress, which could contribute to the disturbed sleep and impaired quality of life of these patients. Measurements of clinical outcomes for hemodialysis patients should include the management of symptoms and morbidity. The ultimate goal of treatments is to improve patient self-perceived quality of life.	
27607152	The review addresses the development of a new solid-state lighting system for the International Space Station (ISS) that is intended to enhance the illumination of the working and living environment of astronauts and to improve sleep, circadian entrainment, and daytime alertness.Spaceflight missions often expose astronauts and mission support ground crews to atypical sleep-wake cycles and work schedules. A recent, extensive study describes the sleep characteristics and use of sleep-promoting pharmaceuticals in astronauts before, during, and after spaceflight. The acceptability, feasibility, and efficacy of the new ISS solid-state lighting systems are currently being tested in ground-based, analog studies. Installation of this lighting system on the ISS is scheduled to begin later this year. In-flight testing of this lighting system is planned to take place during ISS spaceflight expeditions.	If the new ISS lighting system is capable of improving circadian entrainment and sleep during spaceflight, it should enhance astronaut health, performance, well-being, and safety. Such an advance would open the door to future lighting applications for humans living on Earth.	
27603791	The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. 
27599087	This multi-method study, including actigraphy, sleep diaries, and questionnaires, indicated significant sleep disturbances in young children with type 1 diabetes (age 3-5) and insufficient sleep duration in children and their parents. Results provide initial support for sleep as a potential target to improve both diabetes outcomes and parental distress. 
27596361	Deficiency of gamma-amino-butyrate aminotransferase (ABAT) is a rare inherited disorder. A six-month-old girl presented with hyper-somnolence, hyperkinetic movements of distal extremities during wakefulness, hypotonia, bi-pyramidal signs, and impaired response to sound and visual stimuli. Brain MRI at five months showed restricted diffusion along the internal capsule and genu of corpus callosum. A follow up MRI at 18months, showed hyperintensities in brainstem, external and internal capsule, 'trilaminated' appearance of posterior limb of internal capsule and dysmyelination of sub-cortical white matter. MRS showed a peak between 2.2ppm and 2.4ppm, corresponding to glutamine, glutamate and GABA. EEG was normal at six months but showed multifocal epileptiform discharges at 18months. Targeted exome sequencing revealed compound heterozygous missense variations in ABAT resulting in its reduced function. We report the novel association of hypersomnolence and hyperkinetic movement disorder with ABAT variations thus expanding the clinical spectrum of this uncommon neuro-metabolic disorder and discuss the emerging role of GABA in pathways regulating sleep-wake cycle and movement disorders.
27595887	Currently available evidence indicates that neurons containing melanin-concentrating hormone (MCH) in the lateral hypothalamus are critical modulators of sleep-wakefulness, but their precise role in this function is not clear. Studies employing optogenetic stimulation of MCH neurons have yielded inconsistent results, presumably due to differences in the optogenetic stimulation protocols, which do not approximate normal patterns of cell firing. In order to resolve this discrepancy, we (1) selectively activated the MCH neurons using a chemogenetic approach (Cre-dependent hM3Dq expression) and (2) selectively destroyed MCH neurons using a genetically targeted diphtheria toxin deletion method, and studied the changes in sleep-wake in mice. Our results indicate that selective activation of MCH neurons causes specific increases in rapid eye movement (REM) sleep without altering wake or non-REM (NREM) sleep. On the other hand, selective deletions of MCH neurons altered the diurnal rhythm of wake and REM sleep without altering their total amounts. These results indicate that activation of MCH neurons primarily drives REM sleep and their presence may be necessary for normal expression of diurnal variation of REM sleep and wake.
27595385	Dopaminergic ventral tegmental area (VTA) neurons are critically involved in a variety of behaviors that rely on heightened arousal, but whether they directly and causally control the generation and maintenance of wakefulness is unknown. We recorded calcium activity using fiber photometry in freely behaving mice and found arousal-state-dependent alterations in VTA dopaminergic neurons. We used chemogenetic and optogenetic manipulations together with polysomnographic recordings to demonstrate that VTA dopaminergic neurons are necessary for arousal and that their inhibition suppresses wakefulness, even in the face of ethologically relevant salient stimuli. Nevertheless, before inducing sleep, inhibition of VTA dopaminergic neurons promoted goal-directed and sleep-related nesting behavior. Optogenetic stimulation, in contrast, initiated and maintained wakefulness and suppressed sleep and sleep-related nesting behavior. We further found that different projections of VTA dopaminergic neurons differentially modulate arousal. Collectively, our findings uncover a fundamental role for VTA dopaminergic circuitry in the maintenance of the awake state and ethologically relevant sleep-related behaviors. 
27594405	Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4-10 years) from nine countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C).Parents from 454 C children and 700 A and/or AR children followed up in allergy reference clinics completed the Children's Sleep Habits Questionnaire (CSHQ) which is a retrospective one-week questionnaire composed of 33 questions composed of seven subscales (bedtime resistance, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing and daytime sleepiness). The total scale of CSHQ and the subscales were compared between groups C and A+AR, A (n=285) vs. AR (n=390), and between controlled A (CA, n=103) vs. partially controlled/uncontrolled A (UA, n=182).	The comparison between C and A+AR showed no significant differences in age (6.7 years vs. 7.0 years, respectively), mean Body Mass Index and total scale of CSHQ (53.3 vs. 63.2, respectively) and the subscales were significantly higher in the A+AR group. Comparison between groups A and AR, except for sleep anxiety, showed significantly higher values for CSHQ total scale (66.9 vs. 61.0, respectively) and subscales for group A. The UA group showed significantly higher values for total CSHQ scale and subscales in comparison to CA (71.1 vs. 59.4, respectively).	Latin-American children with asthma and/or allergic rhinitis showed sleep disorders identified by the CSHQ when compared to normal controls. Despite being treated, asthma causes sleep impairment, especially when uncontrolled.	
27594319	Preclinical Research Insomnia is one of the most common sleep disorders that is characterized by difficulty in sleep initiation, sleep maintenance, and/or poor sleep quality. Treatment for insomnia includes both pharmacological and non-pharmacological interventions. Recently, the development of pharmacological treatment for insomnia has been prompted by the understanding of the molecular neurobiology of sleep-wake regulation. For pharmacological treatment, benzodiazepines that target GABAergic system are the most widely used hypnotics. Besides GABA, the hypocretin/orexin system, and the hypothalamic-pituitary-adrenal (HPA) axis are involved in sleep-wake regulation and may also play important role in the pathogenesis of insomnia. Genetic studies have revealed the critical role of several important genes related to the above-mentioned systems in the regulation and function of sleep, suggesting the genetic/epigenetic factors could also contribute to the development and regulation of insomnia. Non-pharmacological interventions include cognitive behavioral therapy for insomnia (CBT-I) that is an effective insomnia treatment with less risk and side effects of drug therapy. Here the current treatments for insomnia based on the molecular mechanisms underlying sleep-wake regulation, were reviewed and some newer targets that may be beneficial in the development of new treatments for insomnia were discussed. Drug Dev Res 77 : 427-436, 2016. © 2016 Wiley Periodicals, Inc.
27591416	Long-haul truck drivers in the United States suffer disproportionately high injury rates. Sleep is a critical factor in these outcomes, contributing to fatigue and degrading multiple aspects of safety-relevant performance. Both sleep duration and sleep quality are often compromised among truck drivers; however, much of the efforts to combat fatigue focus on sleep duration rather than sleep quality. Thus, the current study has two objectives: (1) to determine the degree to which sleep impacts safety-relevant performance among long-haul truck drivers; and (2) to evaluate workday and non-workday sleep quality and duration as predictors of drivers' safety-relevant performance.A non-experimental, descriptive, cross-sectional design was employed to collect survey and biometric data from 260 long-haul truck drivers. The Trucker Sleep Disorders Survey was developed to assess sleep duration and quality, the impact of sleep on job performance and accident risk, and other relevant work organization characteristics. Descriptive statistics assessed work organization variables, sleep duration and quality, and frequency of engaging in safety-relevant performance while sleepy. Linear regression analyses were conducted to evaluate relationships between sleep duration, sleep quality, and work organization variables with safety composite variables.	Drivers reported long work hours, with over 70% of drivers working more than 11h daily. Drivers also reported a large number of miles driven per week, with an average of 2,812.61 miles per week, and frequent violations of hours-of-service rules, with 43.8% of drivers "sometimes to always" violating the "14-h rule." Sleep duration was longer, and sleep quality was better, on non-workdays compared on workdays. Drivers frequently operated motor vehicles while sleepy, and sleepiness impacted several aspects of safety-relevant performance. Sleep quality was better associated with driving while sleepy and with job performance and concentration than sleep duration. Sleep duration was better associated with accidents and accident risk than sleep quality.	Sleep quality appears to be better associated with safety-relevant performance among long-haul truck drivers than sleep duration. Comprehensive and multilevel efforts are needed to meaningfully address sleep quality among drivers.	
27590286	To examine frequent snoring, sleepiness, and sleep duration with baseline and longitudinal performance on neuropsychological (NP) battery.The analysis consists of 711 participants of the Northern Manhattan Study (NOMAS) with sleep data and NP assessment (age 63 ± 8 years, 62% women, 18% white, 17% black, 67% Hispanic) and 687 with repeat NP testing (at a mean of 6 ± 2 years). The main exposures were snoring, sleepiness, and sleep duration obtained during annual follow-up. Using factor analysis-derived domain-specific Z scores for episodic memory, language, executive function, and processing speed, we constructed multivariable regression models to evaluate sleep symptoms with baseline NP performance and change in performance in each NP domain.	In the cross-sectional analysis, adjusting for demographics and the NOMAS vascular risk score, participants with frequent snoring had worse executive function (β = -12; p = 0.04) and processing speed (β = -13; p = 0.02), but no difference in with episodic memory or language. Those with severe daytime sleepiness (β = -26; p = 0.009) had worse executive function, but no changes in the other NP domains. There was no cross-sectional association between sleep duration and NP performance. Frequent snoring (β = -29; p = 0.0007), severe daytime sleepiness (β = -29; p = 0.05), and long sleep duration (β = -29; p = 0.04) predicted decline in executive function, adjusting for demographic characteristics and NOMAS vascular risk score. Sleep symptoms did not explain change in episodic memory, language, or processing speed.	In this race-ethnically diverse community-based cohort, sleep symptoms led to worse cognitive performance and predicted decline in executive function.	
27587429	The architectural design of the pediatric intensive care unit may play a major role in optimizing the environment to promote patients' sleep while improving stress levels and the work experience of critical care nurses.To examine changes in nurses' perceptions of the environment of a pediatric critical care unit for promotion of patients' sleep and the nurses' work experience after a transition from multipatient rooms to single-patient rooms.	A cross-sectional survey of nurses was conducted before and after the move to a new hospital building in which all rooms in the pediatric critical care unit were single-patient rooms.	Nurses reported that compared with multipatient rooms, single-patient private rooms were more conducive to patients sleeping well at night and promoted a more normal sleep-wake cycle (P < .001). Monitors/alarms and staff conversations were the biggest factors that adversely influenced the environment for sleep promotion in both settings. Nurses were less annoyed by noise in single-patient rooms (33%) than in multipatient rooms (79%; P < .001) and reported improved exposure to sunlight.	Use of single-patient rooms rather than multipatient rooms improved nurses' perceptions of the pediatric intensive care unit environment for promoting patients' sleep and the nurses' own work experience.	
27586066	To collect objective and subjective sleep data on 6- to 8-year-old children across the week and to identify factors within the family environment associated with sleep differences.Data were collected (n = 52) using actigraphy and diaries for 7 consecutive days and nights and a questionnaire incorporating the Children's Sleep Habits Questionnaire was completed by parents.	Children's actigraphic sleep periods averaged 10 h on school nights and 9.5 h on non-school nights and parents over-estimated children's sleep compared with actigraphy. One third (37%) of children had potential sleep problems. Children who shared a bedroom (31%) had shorter sleep onset latencies and those who consumed caffeinated drinks (33%) went to sleep and awoke later. Increased screen time was associated with later bedtimes on school nights and children with screens in bedrooms (12%) went to bed later and slept less on school nights, and had higher Children's Sleep Habits Questionnaire scores. Children living with a shift-working adult (27%) slept longer on non-school nights and had shorter sleep onset latencies on school nights.	It is important to consider children's sleep within the wider family context and to be aware that parents may over-estimate their children's sleep. Simple strategies to promote sleep health in clinical settings or education programmes include regular weekend bedtimes that align with those on school nights, removing technology from bedrooms and minimising caffeine consumption. An awareness of potential sleep differences associated with shift-working adults may ensure children are supported to have consistent sleep routines that promote adequate sleep.	
27585541	Circadian rhythm is an internal biological clock which initiates and monitors various physiological processes with a fixed time-related schedule. The master circadian pacemaker is located in the suprachiasmatic nucleus in the hypothalamus. The circadian clock undergoes significant changes throughout the life span, at both the physiological and molecular levels. This cyclical physiological process, which is very complex and multifactorial, may be associated with metabolic alterations, atherosclerosis, impaired cognition, mood disturbances and even development of cancer. Sex differences do exist, and the well-known sleep disturbances associated with menopause are a good example. Circadian rhythm was detected in the daily pattern of hot flushes, with a peak in the afternoons. Endogenous secretion of melatonin decreases with aging across genders, and, among women, menopause is associated with a significant reduction of melatonin levels, affecting sleep. Although it might seem that hot flushes and melatonin secretion are likely related, there are not enough data to support such a hypothesis.
27582722	This study examined in real time the role of sleep and daydreaming as potentiating states for subsequent dissociation in depersonalization/derealization disorder (DDD). Research and theory suggests that dissociation may be exacerbated and maintained by a labile sleep-wake cycle in which "dream-like" mentation intrudes into waking life and fuels dissociative symptoms. We explore and extend this idea by examining the state of daydreaming in dissociation. Daydreaming is a state of consciousness between dreaming and waking cognition that involves stimulus-independent and task-unrelated mentation. We report the results of a unique intensive N = 1 study with an individual meeting diagnostic criteria for DDD. Using experience-sampling methodology, the participant rated (six times daily for 40 days) current daydreaming, mood, and dissociative symptoms. At the start of each day sleep quality and duration was also rated. Daydreaming was reported on 45% of occasions and significantly predicted greater dissociation, in particular when daydreams were repetitive and negative (but not fanciful) in content. These relationships were mediated by feelings of depression and anxiety. Sleep quality but not duration was a negative predictor of daily dissociation and also negatively predicted depression but not anxiety. Findings offer initial evidence that the occurrence and content of daydreams may act as potentiating states for heightened, in the moment, dissociation. The treatment implications of targeting sleep and daydreaming for dissociative disorders are discussed. 
27582452	Medical residency programs are traditionally known for long working hours, which can be associated with a poor quality of sleep and daytime sleepiness. However, few studies have focused on this theme. Our objective was to investigate sleep quality, daytime sleepiness, and their relation with anxiety, social phobia, and depressive symptoms.This cross-sectional observational study involved 59 psychiatry residents. The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) were used to measure the quality of sleep and excessive daytime sleepiness ([EDS] and ESS > 10), respectively.	Among the 59 psychiatry residents, 59.3% had poor sleep quality (PSQI > 5) and 28.8% had EDS. Poor sleep quality was associated with higher EDS (P = 0.03) and the year of residency program (P = 0.03). Only 20% of residents with poor sleep had consulted at least once for sleep problems; 54.2% had used medications for sleep; and 16.9% were using medications at the time of interview. Only 30% obtained medication during medical consultations. Poor sleep was associated with irregular sleep hours (P = 0.001) and long periods lying down without sleep (P = 0.03). Poor sleep quality was also associated with high scores of anxiety symptoms (P < 0.001) and social phobia symptoms (P = 0.02).	Psychiatry residents frequently have poor sleep quality and EDS. Considering that sleep disorders can affect quality of life, predispose to metabolic syndrome, and be associated with worse performance at work, attention to this clinical problem is needed.	
27582156	Sleep is one of the essential biorhythms of the body that helps in optimum restoration of many body functions. The sleep-wake cycle is determined by the circadian centre and is responsible for the anabolic functions in the body. Infants require about 14 to 18 hours of sleep per day, which reduces gradually to about 8 hours in adults. Urbanization and evolutionary changes have altered the sleep hygiene and shortened the sleep duration. This lead to various sleep disorders like sleep disordered breathing, insomnia and narcolepsy. Sleep disorders lead to adverse cardio-metabolic consequences, including insulin resistance and hyperglycaemia. Pregnancy poses an enormous burden on the homeostasis of the women with alteration in many physiological functions. The sleep disorders during pregnancy lead to adverse foeto-maternal outcomes with long term cardiovascular implications. In this article, I review the pathophysiology of sleep disorders during pregnancy and their glycaemic implications. 

27578033	Sleep problems are associated with problems of cognitive functioning, learning, attention and school performance. It has been found that sleep problems are highly prevalent in children with Autistic spectrum disorders (ASD), with rates ranging from 40% to 80%. We aimed to identify the prevalence of sleep problems on children with ASD in Indonesia and Japan.A cross-sectional study was conducted in Surabaya, Indonesia and Kobe, Japan. Children aged 4 -10 years old were enrolled using stratified cluster sampling. Children's Sleep Habits Questionnaire-Abbreviated (CSHQ-A) was used in this research to assess the sleep problems, consisted of 22 questions (NICHD SECCYD-Wisconsin). Data were analyzed with Mann-Whitney U test to compare the CSHQ-A scores between Indonesian and Japanese children, while the proportion of sleep problems was evaluated by chi-square test with 95% confidence interval.	Fifty children with ASD were included in this study, 25 children from Kobe, Japan and 25 children from Surabaya, Indonesia. The prevalence of sleep problems on children with ASD was 60% (15 children) in Indonesia and 16% (4 children) in Japan respectively. There were significant differences in total waking during the night and in morning wake for the CSHQ-A between children from Indonesia and Japan (p<0.005).	The prevalence of sleep problems on children with ASD was higher in children from Indonesia than from Japan.	
27575618	To describe changes in sleep quality in family caregivers of ICU survivors from the patients' ICU admission until two months post-ICU discharge.Descriptive repeated measure design.	Academic hospital medical ICU.	Subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and objective sleep/wake variables (SenseWear Armband™) were measured in family caregivers at patients' ICU admission, within two weeks post-ICU discharge and two months post-ICU discharge.	In 28 family caregivers of ICU survivors, most caregivers reported poor sleep quality (i.e. PSQI >5) across the three time points (64.3% during patients' ICU admission, 53.6% at each post-ICU time point). Worse trends in sleep quality and objective sleep/wake pattern were observed in caregivers who were employed, and a non-spouse. There were trends of worsening sleep quality in caregivers of patients unable to return home within two months post-ICU discharge compared to patients able to return home.	Poor sleep quality was highly prevalent and persisted in family caregivers of ICU survivors for two months post-ICU discharge. Our data support the need for a larger longitudinal study to examine risk factors associated with sleep quality in family caregivers of ICU survivors to develop targeted interventions.	
27575508	Excessive daytime sleepiness (EDS) affects 5% to 20% of the population and is involved in a large number of traffic accidents. EDS is a major symptom in sleep disorders, especially obstructive sleep apnea syndrome (OSA). The daytime sleepiness is evaluated subjectively using scales and questionnaires based on perception. This study is aimed to build a new questionnaire more suited to our lifestyle and then to compare it to the Epworth sleepiness scales (ESS).We administered to 91 adult's patients (76 men and 15 women) consulting for sleep disturbance the ESS and a single subjective question tendency to drowsiness during the Friday prayer. Patients were listed in four groups according to their response to the question «During the past month, have you ever doze or fall asleep during the sermon of the Friday prayer? » By G1 never dozes, G2 low chance of falling asleep, G3 average chance of dozing, G4 high chance of falling asleep.	Only 63 patients (58 men and 5 women) responded to both questionnaires. Group 1 included 14 patients with a ESS of 5.5 +/- 1.8, Group 2 included 18 patients with a ESS of 7.3 +/- 1.9, Group 3 included 18 patients with a ESS of 11.05 +/- 2 and Group 4 included 13 patients with a ESS of 14.69 +/- 2.3. The Rho correlation coefficient was high (0.86) and shows a strong correlation between the Results of the two questionnaires.	the answer to the question " During the past month, have you ever doze or fall asleep during the sermon of the Friday prayer? » seems to be an appropriate Sleepiness Scale among Muslim patients.	
27573669	α-Pinene is a major monoterpene of the pine tree essential oils. It has been reported that α-pinene shows anxiolytic and hypnotic effects upon inhaled administration. However, hypnotic effect by oral supplementation and the molecular mechanism of α-pinene have not been determined yet. By combining in vivo sleep behavior, ex vivo electrophysiological recording from brain slices, and in silico molecular modeling, we demonstrate that (-)-α-pinene shows sleep enhancing property through a direct binding to GABAA-benzodiazepine (BZD) receptors by acting as a partial modulator at the BZD binding site. The effect of (-)-α-pinene on sleep-wake profiles was evaluated by recording electroencephalogram and electromyogram. The molecular mechanism of (-)-α-pinene was investigated by electrophysiology and molecular docking study. (-)-α-pinene significantly increased the duration of non-rapid eye movement sleep (NREMS) and reduced the sleep latency by oral administration without affecting duration of rapid eye movement sleep and delta activity. (-)-α-pinene potentiated the GABAA receptor-mediated synaptic response by increasing the decay time constant of sIPSCs in hippocampal CA1 pyramidal neurons. These effects of (-)-α-pinene on sleep and inhibitory synaptic response were mimicked by zolpidem, acting as a modulator for GABAA-BZD receptors, and fully antagonized by flumazenil, an antagonist for GABAA-BZD receptor. (-)-α-pinene was found to bind to aromatic residues of α1- and -γ2 subunits of GABAA-BZD receptors in the molecular model. We conclude that (-)-α-pinene enhances the quantity of NREMS without affecting the intensity of NREMS by prolonging GABAergic synaptic transmission, acting as a partial modulator of GABAA-BZD receptors and directly binding to the BZD binding site of GABAA receptor.
27569701	Recent advances in electrophysiological [e.g., surface high-density electroencephalographic (hd-EEG) and intracranial recordings], video-polysomnography (video-PSG), transcranial stimulation and neuroimaging techniques allow more in-depth and more accurate investigation of the neural correlates of dreaming in healthy individuals and in patients with brain-damage, neurodegenerative diseases, sleep disorders or parasomnias. Convergent evidence provided by studies using these techniques in healthy subjects has led to a reformulation of several unresolved issues of dream generation and recall [such as the inter- and intra-individual differences in dream recall and the predictivity of specific EEG rhythms, such as theta in rapid eye movement (REM) sleep, for dream recall] within more comprehensive models of human consciousness and its variations across sleep/wake states than the traditional models, which were largely based on the neurophysiology of REM sleep in animals. These studies are casting new light on the neural bases (in particular, the activity of dorsal medial prefrontal cortex regions and hippocampus and amygdala areas) of the inter- and intra-individual differences in dream recall, the temporal location of specific contents or properties (e.g., lucidity) of dream experience and the processing of memories accessed during sleep and incorporated into dream content. Hd-EEG techniques, used on their own or in combination with neuroimaging, appear able to provide further important insights into how the brain generates not only dreaming during sleep but also some dreamlike experiences in waking.
27569407	Wind is considered one of the most advantageous alternatives to fossil energy because of its low operating cost and extensive availability. However, alleged health-related effects of exposure to wind turbine (WT) noise have attracted much public attention and various symptoms, such as sleep disturbance, have been reported by residents living close to wind developments. Prospective cohort study with synchronous measurement of noise and sleep physiologic signals was conducted to explore the possibility of sleep disturbance in people hosting new industrial WTs in Ontario, Canada, using a pre and post-exposure design. Objective and subjective sleep data were collected through polysomnography (PSG), the gold standard diagnostic test, and sleep diary. Sixteen participants were studied before and after WT installation during two consecutive nights in their own bedrooms. Both audible and infrasound noises were also concurrently measured inside the bedroom of each participant. Different noise exposure parameters were calculated (LAeq, LZeq) and analyzed in relation to whole-night sleep parameters. Results obtained from PSG show that sleep parameters were not significantly changed after exposure. However, reported sleep qualities were significantly (P = 0.008) worsened after exposure. Average noise levels during the exposure period were low to moderate and the mean of inside noise levels did not significantly change after exposure. The result of this study based on advanced sleep recording methodology together with extensive noise measurements in an ecologically valid setting cautiously suggests that there are no major changes in the sleep of participants who host new industrial WTs in their community. Further studies with a larger sample size and including comprehensive single-event analyses are warranted. 
27569054	This study first aimed to establish the prevalence and predictors of subclinical seizures in patients with epilepsy undergoing video electroencephalographic monitoring, then to evaluate the relationship of sleep/wake and circadian pattern with subclinical seizures.We retrospectively reviewed the charts of 742 consecutive patients admitted to our epilepsy center between July 2012 and October 2014. Demographic, electro-clinical data and neuroimage were collected.	A total of 148 subclinical seizures were detected in 39 patients (5.3%) during video electroencephalographic monitoring. The mean duration of subclinical seizures was 47.18 s (range, 5-311). Pharmacoresistant epilepsy, abnormal MRI and the presence of interictal epileptiform discharges were independently associated with subclinical seizures in multivariate logistic regression analysis. Subclinical seizures helped localizing the presumed epileptogenic zone in 24 (61.5%) patients, and suggested multifocal epilepsy in five (12.8%). In addition, subclinical seizures occurred more frequently in sleep and night than wakefulness and daytime, respectively, and they were more likely seen between 21:00-03:00 h, and less likely seen between 09:00-12:00 h. Thirty patients (76.9%) had their first subclinical seizures within the first 24 h of monitoring while only 7.7% of patients had their first subclinical seizures detected within 20 min.	Subclinical seizures are not uncommon in patients with epilepsy, particularly in those with pharmacoresistant epilepsy, abnormal MRI or interictal epileptiform discharges. Subclinical seizures occur in specific circadian patterns and in specific sleep/wake distributions. A 20-min VEEG monitoring might not be long enough to allow for their detection.	

27568806	Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and spontaneous snack intake in patients with narcolepsy type 1 (n = 24) compared with healthy matched controls (n = 19). In additional analyses, we also included patients with idiopathic hypersomnia (n = 14) to assess sleepiness-related influences.Participants were first trained on a choice task to earn salty and sweet snacks. Next, one of the snack outcomes was devalued by having participants consume it until satiation (i.e., sensory-specific satiety). We then measured the selective reduction in choices for the devalued snack outcome. Finally, we assessed the number of calories that participants consumed spontaneously from ad libitum available snacks afterwards.	After satiety, all participants reported reduced hunger and less wanting for the devalued snack. However, while controls and idiopathic hypersomnia patients chose the devalued snack less often in the choice task, patients with narcolepsy still chose the devalued snack as often as before satiety. Subsequently, narcolepsy patients spontaneously consumed almost 4 times more calories during ad libitum snack intake.	We show that the manipulation of food-specific satiety has reduced effects on food choices and caloric intake in narcolepsy type 1 patients. These mechanisms may contribute to their obesity, and suggest an important functional role for orexin in human eating behavior.	Study registered at Netherlands Trial Register. URL: www.trialregister.nl. Trial ID: NTR4508.	
27568803	Previous laboratory studies in narcolepsy patients showed altered core body and skin temperatures, which are hypothesised to be related to a disturbed sleep wake regulation. In this ambulatory study we assessed temperature profiles in normal daily life, and whether sleep attacks are heralded by changes in skin temperature. Furthermore, the effects of three months of treatment with sodium oxybate (SXB) were investigated.Twenty-five narcolepsy patients and 15 healthy controls were included. Core body, proximal and distal skin temperatures, and sleep-wake state were measured simultaneously for 24 hours in ambulatory patients. This procedure was repeated in 16 narcolepsy patients after at least 3 months of stable treatment with SXB.	Increases in distal skin temperature and distal-to-proximal temperature gradient (DPG) strongly predicted daytime sleep attacks (P < 0.001). As compared to controls, patients had a higher proximal and distal skin temperature in the morning, and a lower distal skin temperature during the night (all P < 0.05). Furthermore, they had a higher core body temperature during the first part of the night (P < 0.05), which SXB decreased (F = 4.99, df = 1, P = 0.03) to a level similar to controls. SXB did not affect skin temperature.	This ambulatory study demonstrates that daytime sleep attacks were preceded by clear changes in distal skin temperature and DPG. Furthermore, changes in core body and skin temperature in narcolepsy, previously only studied in laboratory settings, were partially confirmed. Treatment with SXB resulted in a normalisation of the core body temperature profile. Future studies should explore whether predictive temperature changes can be used to signal or even prevent sleep attacks.	
27568798	Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia.EEG/EMG recording electrodes were implanted in mice. After a 24 h baseline recording, limb ischemia was induced by tightening an elastic band around the left quadriceps for 10 minutes followed by 10 minutes of release for two cycles. Two days following remote preconditioning, a second 24 h EEG/EMG recording was completed and was immediately followed by a 60-minute suture occlusion of the middle cerebral artery (modeled ischemic stroke). This experiment was then repeated in a model of circadian and sleep abnormalities (Bmal1 knockout [KO] mice sleep 2 h more than wild-type littermates). Brain infarction was determined by vital dye staining, and sleep was assessed by trained identification of EEG/EMG recordings.	Two days after limb ischemia, wild-type mice slept an additional 2.4 h. This additional sleep was primarily comprised of non-rapid eye movement (NREM) sleep during the middle of the light-phase (i.e., naps). Repeating the experiment but preventing increases in sleep after limb ischemia abolished tolerance to ischemic stroke. In Bmal1 knockout mice, remote preconditioning did not increase daily sleep nor provide tolerance to subsequent focal ischemia.	These results suggest that sleep induced by remote preconditioning is both sufficient and necessary for its neuroprotective effects on stroke outcome.	
27567629	Poor sleep quality (SQ) is increasingly recognized as giving rise to decreased quality of life, and raising pain perception. Our aim is to evaluate the SQ in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy. This was a prospective observational and open-label study of RA patients. A total of 35 patients with RA were enrolled in this study. Of the 35 patients, 22 had high disease activity (DA), and 13 were in remission. High DA group was initiated an anti TNF-α therapy. Clinical and objective parameters of SQ were assessed by using the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG). The total PSQI score and the frequency of poor SQ were high in 60 % of the RA patients. The median PSQI score was significantly higher in the high DA group than in the remission group (P = 0.026). Following an anti-TNF-α therapy initiation, significant improvements were observed in the high DA group by PSQI test (P = 0.012). However, no statistically significant difference was found by PSG (P > 0.05). Although an improvement in DA with anti-TNF-alpha therapy did not provide an amelioration in laboratory parameters, we found a significant improvement in SQ by subjective PSQI test. These findings may support that sleep disorders in RA are likely to be associated with a complex pathophysiology.
27566502	Patients are commonly provided tools in the hospital to overcome poor sleep. Whether education on use of sleep tools can impact health outcomes from a patient perspective is not known.We recruited 120 adults admitted to a nonintensive care unit cardiac-monitored floor. All patients received a set of sleep-enhancing tools (eye mask, ear plugs, and a white noise machine) and were randomized to receive direct education on use of and benefit of these sleep-enhancing tools (intervention), or an equal amount of time was spent discussing general benefits of sleep (control). Measurement of several symptom domains was assessed daily by health outcome survey responses, and change from baseline was assessed for differences between groups. Inpatient opioid use and length of stay were also measured.	Participants randomized to receive the education intervention had a significantly greater decrease in fatigue scores over the 3 days, compared with controls (5.30 ± 6.93 vs 1.81 ± 6.96, t = 2.32, P = .028). There was a trend toward improvements in multiple other sleep-related domains, including sleep disturbance, sleep-related impairment, physical functioning, pain severity, or pain interference (all P >.140). There was no difference in length of stay between intervention and control groups (7.40 ± 7.29 vs 7.71 ± 6.06 days, P = .996). The change in number of opioid equivalents taken did not differ use between the groups (P = .688).	In a randomized trial of education in the use of sleep-enhancing tools while hospitalized, patient fatigue was significantly improved, whereas several other patient-reported outcomes showed a trend toward improvements. Implementation of this very low-cost approach to improving sleep and well-being could substantially improve the patient care experience.	
27565806	Several studies in patients with schizophrenia reported a marked reduction in sleep spindle activity. To investigate whether the reduction may be linked to genetic risk of the illness, we analysed sleep spindle activity in healthy volunteers, patients with schizophrenia and first-degree relatives, who share an enriched set of schizophrenia susceptibility genes. We further investigated the correlation of spindle activity with cognitive function in first-degree relatives and whether spindle abnormalities affect both fast (12-15 Hz) and slow (9-12 Hz) sleep spindles. We investigated fast and slow sleep spindle activity during non-rapid eye movement sleep in a total of 47 subjects comprising 17 patients with schizophrenia, 13 healthy first-degree relatives and 17 healthy volunteers. Groups were balanced for age, gender, years of education and estimated verbal IQ. A subsample of relatives received additional testing for memory performance. Compared to healthy volunteers, fast spindle density was reduced in patients with schizophrenia and healthy first-degree relatives following a pattern consistent with an assumed genetic load for schizophrenia. The deficit in spindle density was specific to fast spindles and was associated with decreased memory performance. Our findings indicate familial occurrence of this phenotype and thus support the hypothesis that deficient spindle activity relates to genetic liability for schizophrenia. Furthermore, spindle reductions predict impaired cognitive function and are specific to fast spindles. This physiological marker should be further investigated as an intermediate phenotype of schizophrenia. It could also constitute a target for drug development, especially with regard to cognitive dysfunction.
27563323	Premature infants are subjected to many painful procedures during care and treatment. The aim of this study was to assess the effect of music therapy on physiological and behavioral pain responses of premature infants during and after blood sampling.This study was a cross-over clinical trial conducted on 20 infants in a hospital affiliated to Tehran University of Medical Sciences for a 5-month period in 2011. In the experimental group, Transitions music was played from 5 min before until 10 min after blood sampling. The infants' facial expressions and physiological measures were recorded from 10 min before until 10 min after sampling. All steps and measurements, except music therapy, were the same for the control group. Data were analyzed using SAS and SPSS software through analysis of variance (ANOVA) and Chi-square tests.	There were significant differences between the experimental and control groups (P = 0.022) in terms of heart rate during needle extraction and at the first 5 min after sampling (P = 0.005). Considering the infant's sleep-wake state in the second 5 min before sampling, the statistical difference was significant (P = 0.044). Difference was significant (P = 0.045) during injection of the needle, in the first 5 min after sampling (P = 0.002), and in the second 5 min after sampling (P = 0.005). There were significant difference in infants' facial expressions of pain in the first 5 min after sampling (P = 0.001).	Music therapy reduces the physiological and behavioral responses of pain during and after blood sampling.	
27562056	Shiftworkers run an increased risk of developing metabolic disorders, presumably as a result of disturbed circadian physiology. Eating at a time-of-day that is normally dedicated to resting and fasting, may contribute to this association. The hypothalamus is the key brain area that integrates different inputs, including environmental time information from the central biological clock in the suprachiasmatic nuclei, with peripheral information on energy status to maintain energy homeostasis. The orexin system within the lateral hypothalamus is an important output of the suprachiasmatic nuclei involved in the control of sleep/wake behavior and glucose homeostasis, among other functions. In this study, we tested the hypothesis that feeding during the rest period disturbs the orexin system as a possible underlying contributor to metabolic health problems. Male Wistar rats were exposed to an 8-week protocol in which food was available ad libitum for 24-h, for 12-h during the light phase (i.e., unnatural feeding time) or for 12-h during the dark phase (i.e., restricted feeding, but at the natural time-of-day). Animals forced to eat at an unnatural time, i.e., during the light period, showed no changes in orexin and orexin-receptor gene expression in the hypothalamus, but the rhythmic expression of clock genes in the lateral hypothalamus was absent in these animals. Light fed animals did show adverse changes in whole-body physiology and internal desynchronization of muscle and liver clock and metabolic gene expression. Eating at the 'wrong' time-of-day thus causes internal desynchronization at different levels, which in the long run may disrupt body physiology.
27558667	Drosophila melanogaster is a powerful model organism for dissecting the molecular mechanisms that regulate sleep, and numerous studies in the fly have identified genes that impact sleep-wake cycles. Conditional genetic analysis is essential to distinguish the mechanisms by which these genes impact sleep: some genes might exert their effects developmentally, for instance by directing the assembly of neuronal circuits that regulate sleep; other genes may regulate sleep in adulthood; and yet other genes might influence sleep by both developmental and adult mechanisms. Here we have assessed two ligand-inducible expression systems, Geneswitch and the Q-system, for conditional and neuronally restricted manipulations of sleep in Drosophila While adult-specific induction of a neuronally expressed Geneswitch transgene (elav-GS) is compatible with studies of sleep as shown previously, developmental induction of elav-GS strongly and nonspecifically perturbs sleep in adults. The alterations of sleep in elav-GS animals occur at low doses of Geneswitch agonist and in the presence of transgenes unrelated to sleep, such as UAS-CD8-GFP Furthermore, developmental elav-GS induction is toxic and reduces brood size, indicating multiple adverse effects of neuronal Geneswitch activation. In contrast, the transgenes and ligand of the Q-system do not significantly impact sleep-wake cycles when used for constitutive, developmental, or adult-specific neuronal induction. The nonspecific effects of developmental elav-GS activation on sleep indicate that such manipulations require cautious interpretation, and suggest that the Q-system or other strategies may be more suitable for conditional genetic analysis of sleep and other behaviors in Drosophila.
27558205	To study the effect of hemispherotomy on electrical status epilepticus in sleep (ESES) and language development.Children with a confirmed diagnosis of ESES prior to surgery and a minimum of 24 months of developmental follow-up data were compared with age-matched controls without ESES. Language quotients (LQs) were calculated before and after surgery.	Eleven patients (five females, six males) and 21 controls (11 females, 10 males) were included. Before surgery a significantly higher number of children in the study group (n=9) demonstrated severe developmental delay compared with children in the control group (n=13; p=0.015). In the study group ESES remitted immediately after surgery in 10 children, and a significant catch-up in LQs was observed in this group (preoperative mean 40.0 [standard deviation (SD) 22.2, interquartile range (IQR) 30.0-62.0]; postoperative mean 73.0 [SD 33.5, IQR 41.0-97.0]; p=0.037). There was no significant difference compared with controls at last follow-up after surgery (study group: five with severe impairment; control group: eight with severe impairment [p=0.971]). Overall, a favourable developmental outcome was associated with freedom from seizures (seizure-free group: median preoperative LQ 61.5, median postoperative LQ 78.0 [p=0.017]; seizure group: median preoperative LQ 35.5, median postoperative LQ 56.5 [p=0.273]) and antiepileptic drug withdrawal (off medication: median preoperative LQ 49.5, median postoperative LQ 78.0 [p=0.011]; on medication: median preoperative LQ 78.0, median postoperative LQ 83.5 [p=0.889]).	Children with ESES showed significantly lower preoperative language abilities than children without ESES. In cases with remission of ESES after surgery, marked improvement in LQs was noticed. This improvement cannot be fully explained by seizure-freedom alone as seizure-free children without preoperative ESES showed less improvement.	
27556115	To collect data on treatment of behavioural sleep disorders in children and adolescents.A literature review based on the PUBMED database.	Based on the analysed materials three basic complementary procedures were identified - implementation of sleep hygiene, behavioural interventions and pharmacological treatment. The rules of sleep hygiene proven to be effective include: regular sleep schedule, adequately prepared place to sleep (a dark, quiet bedroom without multimedia), bedtime routine, avoiding caffeinated beverages. The following issues require further studies to confirm their effectiveness: falling asleep independently without parent's assistance, bedtime reading, physical activity, reducing daytime multimedia use, tryptophan rich breakfasts. Behavioural interventions and pharmacological treatment may in some cases be temporarily implemented to complement the sleep hygiene.	The implementation of sleep hygiene is a primary, fully acceptable to the child and parents, way to improve the baby sleep. In case of ineffectiveness of the proposed rules, those can be complemented with behavioural methods that are highly effective but some parents do not accept them or make mistakes in their introduction. Pharmacotherapy can be used as a temporary support for families with severe behavioural problems as an aid in the implementation of sleep hygiene and behavioural methods.	
27555754	Old age is a stage of life featured with many physiological and mental changes. The Iranian population is aging, and one of the problems that the elderly are faced with is sleep disorders. The present study is an attempt to examine the effectiveness of an exercise program on the sleep quality of the elderly.A semi-experimental study was carried out on the elderly males referred to the Shahid Yari Elderly Center, Kermanshah, Iran. The sample group comprised of 46 participants: 23 in the experimental group and 23 in the control group. The study was carried out for a period of 2 months and follow-up was conducted every week. To improve the quality of sleep of the participants, a four-stage exercise program was implemented and the collected data were analyzed by SPSS version 20.	The results of a Mann-Whitney test showed that the quality of sleep of the majority in the experimental group improved compared with that of the control group (P<0.05). In addition, a Wilcoxon test showed improvement of the Petersburg's sleep quality index based on subelements and the results of a total score of sleep in the experimental group after the intervention.	The study showed effectiveness of scheduled exercising on the quality of sleep of the elderly. It is recommended, therefore, to add an exercise program to the daily program of the elderly.	
27554656	What are the synaptic drives controlling the sleep-wake circuitry in the mammalian brain? In a new study it was found that GABAergic cells in posterior lateral hypothalamus inhibit sleep-promoting anterior hypothalamic cells to cause waking, whereas their inhibition augments sleep. 
27552026	Background In pediatric neuromuscular disorders (NMD), respiratory muscle weakness parallels respiratory failure. The objectives of this study are (1) to evaluate respiratory muscle capacity in neuromuscular children and (2) to assess the relationship between vital capacity, respiratory muscle performance, and alveolar ventilation during sleep and wakefulness. Methods Inspiratory vital capacity (IVC), peak inspiratory pressure (PIP), mouth occlusion pressure (P0.1), and noninvasive tension-time index of the respiratory muscles (TTImus) were studied in 80 NMD subjects (12.1 ± 3.3 years) and 80 healthy children (11.1 ± 2.2 years). Subjects' results were compared with arterial blood gases and polysomnography. Results In 15 NMD subjects with normal ventilation IVC and PIP were reduced to 70% predicted but TTImus was normal. In 50 NMD subjects with nocturnal hypoventilation IVC and PIP were lower than 50% predicted, TTImus was doubled compared with the control group. In 15 NMD subjects with diurnal and nocturnal hypoventilation IVC and PIP were below 30% predicted, TTImus was increased fourfold, and thus the main determinant of respiratory failure. Conclusions In NMD children, reduced IVC and PIP result in increased respiratory muscle load and disturbed ventilation. TTImus is an important noninvasive determinant of disturbed ventilation in children with NMD.
27551934	Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep-wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans. 
27551178	Saat genlerini anlamamıza olan katkısından dolayı bir Türk bilim adamı Nobel ödülünü aldıktan sonra, bu genlerle yakın ilişkili olan melatoninin önemi arttı. Melatonin, pineal bezden gece salınan bir hormondur, uyku/uyanıklık döngüsünde, pubertal gelişimde ve mevsimsel adaptasyonda rol alır. Melatoninin antinosiseptif, antidepresan, anksiyolitik, antineofobik, locomotor aktiviteyi düzenleyici, nöroprotektif, antiinflamatuvar, ağrı düzenleyici, kan basıncını düşürücü, retinal, vasküler, tümör baskılayıcı ve antioksidan etkileri vardır. Hafıza, over fizyolojisi ve osteoblast diferansiasyonuyla ilişkilidir. Melatonin seviyelerinde artış veya azalışla seyreden patolojiler derlemede özetlenmiştir. Melatonin 4 mekanizmayla etkir: 1) Plazma membranında melatonin reseptörlerine bağlanma, 2) Kalmodulin gibi hücre içi reseptörlere bağlanma, 3) Yetim nükleer reseptörlere bağlanma, 4) Antioksidan etkiler. Melatoninle ilişkili reseptörler şunlardır: 1) Melatonin reseptör tip1a: MT1 (hücre zarında), 2) Melatonin reseptör tip1b: MT2 (hücre zarında), 3) Melatonin reseptör tip1c (balık, amfibiler ve kuşlarda bulunur), 4) Kuinon redüktaz-2 enzimi (MT3 reseptörü, bir detoksifikasyon enzimi), 5) RZR/RORα: Retinoid-ilişkili Yetim çekirdek hormon reseptörü (bu reseptörle melatonin çekirdekte transkripsiyon faktörlerine bağlanır), 6) GPR50: X-geçişli Melatonin-ilişkili yetim reseptör (melatoninin MT1’e bağlanmasında etkilidir). Ramelteon, agomelatin, sirkadin, TIK-301 and tasimelteon gibi Melatonin agonistleri tanıtılacak ve yan etkileri karşılaştırılacaktır. Sonuçta, melatonin ve ilişkili ilaçlar tıpta yeni ve umut vaat eden bir alandır. Melatonin reseptörleri ve ilaçları gelecekte de artan oranda ilgi çekmeye devam edecektir.After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. 	
27549768	Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms. We recommend that medications and guidelines in NT2 should be the same as for NT1 (except for cataplexy), but the benefit risk ratio should be reassessed regularly. The main symptom in both diseases is a disabling excessive daytime sleepiness (EDS). First-line medications should be stimulants such as modafinil, armodafinil, or sodium oxybate, second-line methylphenidate and pitolisant, where available, and amphetamines as third-line therapy. Sodium oxybate has the advantage to be also effective to manage the fragmented nocturnal sleep, another common symptom in NT1. We advise to wait a few weeks with a stimulant drug before starting an anticataplectic treatment in NT1, except for severe cataplexy. Furthermore, cataplexy treatment should not be systematic. First-line strategy is the use of sodium oxybate, the only drug approved for cataplexy and EDS in adults. However, antidepressant agents such as venlafaxine are also commonly used, with few adverse effects and a good efficacy, although based on expert consensus only. A clinically relevant tool is required to quantify the severity of narcolepsy, subjective symptoms, and their consequences, to monitor the treatment efficacy, and to finally optimize narcolepsy management. In the future, Hcrt replacement or Hcrt agonists will certainly be options to treat NT1, but for now the different peptides do not cross easily the blood brain barrier. Immune-based therapies are other possibilities in NT1, at disease onset, with already some successful attempts to slow down or stop the autoimmune process.
27546185	Adolescents are vulnerable to inadequate sleep due to a unique constellation of risk factors. In particular, the puberty-related phase delay in the timing of the circadian system postpones the onset of sleep. Resultantly, disordered sleep is common among teenagers and young adults, with the most common sleep problem being delayed sleep wake-phase disorder (DSWPD). Although current treatments for DSWPD show promise, novel ways to improve our youth's sleep are needed. The purpose of this review is to critically evaluate the evidence for the role of exercise as a method to shift and/or regulate circadian timing, and thus improve sleep, in adolescents and young adults. A growing body of evidence suggests that nocturnal exercise can delay circadian timing. However, exercise administered at different times of the 24-h day may result in phase advances, particularly when the timing of exercise is gradually advanced in small daily increments. The implications of these results for young people's sleep health are discussed and suggestions are provided for ways that exercise could be used clinically, to improve the treatment of DSWPD.
27545669	This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression. 
27544998	Hericium erinaceus (HE), an edible mushroom, has been used as a herbal medicine in several Asian countries since ancient times. HE has potential as a medicine for the treatment and prevention of dementia, a disorder closely linked with circadian rhythm. This study investigated the effects of the intake of HE extracts on behavioral rhythm, photosensitivity of the circadian clock, and clock gene mRNA expression in the suprachiasmatic nucleus (SCN), a central clock, in mice. Although the HE ethanol extract only affected the offset time of activity, the HE water extract advanced the sleep-wake cycle without affecting the free-running period, photosensitivity, or the clock gene mRNA expression in SCN. In addition, both extracts decreased wakefulness around end of active phase. The findings of the present study suggest that HE may serve as a functional food in the prevention and treatment of Alzheimer's disease and delayed sleep phase syndrome. 
27542884	Delayed sleep-wake phase disorder (DSWPD) is commonly defined as an inability to fall asleep and wake at societal times resulting in excessive daytime sleepiness. Although the cause is multifaceted, delays in sleep time are largely driven by misalignment between the circadian pacemaker and the desired sleep-wake timing schedule. Current treatment approaches focus on correcting the circadian delay; however, there is a lack of data investigating combined therapies for treatment of DSWPD. 
27542877	Obstructive sleep apnea (OSA) is associated with numerous comorbid medical conditions. Symptoms of OSA may mimic those of comorbid conditions. The presence of OSA may worsen outcomes from the primary condition. Conversely, OSA treatment may benefit both sleep symptomatology and comorbid illness. Because of potential significant benefit, it is important to screen for sleep apnea symptoms, to have a low threshold to perform diagnostic testing, to treat OSA if present, and to closely monitor symptoms. OSA management does not necessarily replace, but rather, should be performed in conjunction with primary therapy for comorbid conditions. 
27540540	Impaired sleep is associated with negative effects on quality of life and daytime functioning. Higher rates of sleep disturbance are reported in children with various developmental disorders. However, little is known about sleep in children with developmental coordination disorder (DCD), a condition characterized by everyday movement difficulties. Previously, in a preliminary study, we found higher rates of parent-reported sleep disturbance in children with DCD compared to controls.To examine sleep in DCD using objective measures and to examine links with daytime fatigue and sleepiness.	Two groups (primary and secondary school-aged) of 15 children with DCD, plus matched controls, participated. Parent-reported child sleep was assessed using the Children's Sleep Habits Questionnaire and actigraphy provided an objective measure of sleep-wake patterns over 1 week (including weekdays and weekend). Pediatric restless legs syndrome (RLS) semi-structured diagnostic interview was conducted with each child and parent to capture symptoms of RLS. Aspects of self-rated child functioning were assessed with questionnaires (Pre-sleep Arousal Scale, Pediatric Daytime Sleepiness Scale, PedsQL Multidimensional Fatigue Scale) and mothers' reported thoughts about child sleep with the Maternal Cognitions about Infant Sleep Questionnaire.	The DCD groups had greater parent-reported sleep disturbance. Actigraphy results suggested that for secondary aged children with DCD their sleep quality was impaired and there were differences in the timing of sleep compared to controls (including some differences in the variation between weekday and weekend sleep times). The actigraphy of the primary age group with DCD was unremarkable compared to controls. No child in the study met the criteria for RLS. Exploratory analyses suggested that daytime fatigue, aspects of pre-sleep arousal, and daytime sleepiness were reported as greater in the DCD groups and were particularly related to objective sleep parameters in the DCD groups. Maternal thoughts about sleep did not differ between the DCD and control groups.	The nature and underlying cause of sleep disturbance and how it might be linked with aspects of daytime functioning in adolescents with DCD requires further research. Meanwhile, clinical awareness of the risk of atypical sleep patterns/sleep problems in DCD is important to ensure early identification and implementation of appropriate support.	
27539857	Hypothalamic neurons expressing histamine and orexin/hypocretin (hcrt) are necessary for normal regulation of wakefulness. In Parkinson's disease, the loss of dopaminergic neurons is associated with elevated histamine levels and disrupted sleep/wake cycles, but the mechanism is not understood. To characterize the role of dopamine in the development of histamine neurons, we inhibited the translation of the two non-allelic forms of tyrosine hydroxylase (th1 and th2) in zebrafish larvae. We found that dopamine levels were reduced in both th1 and th2 knockdown, but the serotonin level and number of serotonin neurons remained unchanged. Further, we demonstrated that th2 knockdown increased histamine neuron number and histamine levels, whereas increased dopaminergic signaling using the dopamine precursor l-DOPA (l-3,4-dihydroxyphenylalanine) or dopamine receptor agonists reduced the number of histaminergic neurons. Increases in the number of histaminergic neurons were paralleled by matching increases in the numbers of hcrt neurons, supporting observations that histamine regulates hcrt neuron development. Finally, we show that histaminergic neurons surround th2-expressing neurons in the hypothalamus, and we suggest that dopamine regulates the terminal differentiation of histamine neurons via paracrine actions or direct synaptic neurotransmission. These results reveal a role for dopaminergic signaling in the regulation of neurotransmitter identity and a potential mechanism contributing to sleep disturbances in Parkinson's disease.
27538100	Our current 24-h society and the weekday-weekend switch of our social clocks may affect young children's sleep and circadian rhythms. However, such evidence is scarce. We conducted a nationwide epidemiological study of sleep and health in preschool children aged 3-5 years attending kindergarten or childcare centers in Japan, using stratified one-stage cluster sampling. The target population was 2 969 627 individuals (as of 1 April 2013). The Children's ChronoType Questionnaire was used to measure chronotypes (morning (M)-type, neither (N)-type and evening (E)-type), and weekday and weekend sleep-wake parameters. Randomly sampled population estimates were obtained via respondents with a person-level weight, which accounted for survey responses and poststratification. Standard errors and 95% confidence intervals were adjusted for the complex survey design using jackknife estimation. A linear regression model of the correlation between chronotype and sleep-wake parameters and a multivariate logistic regression model for the links between chronotype and putative associated factors were used for statistical analyses. The estimated prevalence of M-, N- and E-types were 31.6%, 55.9% and 10.0%, respectively. The corresponding numbers of children were 937 910, 1 659 574 and 296 083. The remaining 2.5% was not specified. The proportions of children who woke up by themselves during the weekdays were 55.1%, 43.0% and 1.9% for M-, N- and E-types, respectively. Overall, bedtime, sleep onset time, wake-up time and get-up time during the weekdays were 21:04, 21:26, 6:55 and 6:59, respectively. Nocturnal sleep period, time in bed (TIB) and 24 h TIB (TIB and nap) during the weekdays were 9.49, 9.93 and 10.55 h, respectively. Sleep-wake timings were significantly and linearly delayed from M-, N-, to E-types (p < 0.001). The weekday 24 h TIB (10.47-10.66 h) and weekend nocturnal sleep period (9.58-9.76 h) did not differ significantly among chronotypes. For E-types, socially advanced weekdays rising times (approximately 1 h) caused nocturnal sleep deficit (0.57 h). Children's socially scheduled times (e.g. start and finish times, mealtimes and daytime nap) and their parents' diurnal preferences had significant adjusted odds ratios among E-types, while the significant unadjusted odds ratios for morning sunlight and multimedia exposure disappeared. These results suggest the importance of chronobiologically planned sleep discipline at home as well as assessment of socially scheduled times in children.
27537980	A delayed sleep-wake and circadian rhythm often occurs during puberty. While some individuals only develop a delayed sleep phase (DSP), others will fulfill the criteria for the diagnosis of delayed sleep phase disorder (DSPD). All previous studies have however not separated DSP from DSPD, and, as a result, the prevalence and associated factors are largely unknown for the two conditions individually. We estimated the prevalence of DSP and DSPD in a Swedish cohort of adolescents and young adults. We also investigated associated factors in the two conditions relative to each other and individuals with no DSP. A questionnaire regarding sleep patterns, demographics, substance use/abuse and symptoms of depression, anxiety, worry and rumination was sent to 1000 randomly selected participants (16-26 years of age) in Uppsala, Sweden (response rate = 68%). DSP was defined as a late sleep onset and a preferred late wake-up time. The DSPD diagnosis was further operationalized according to the Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM-5) criteria including insomnia or excessive sleepiness, distress or dysfunction caused by the DSP and that the sleep problem had been evident for 3 months. DSP occurred at a frequency of 4.6% and DSPD at a frequency of 4% in the investigated cohort. DSP was more common in males and was associated with not attending educational activity or work, having shift work, nicotine and alcohol use and less rumination. DSPD was equally common in males and females and was associated with not attending educational activity or work and with elevated levels of anxiety. Both DSP and DSPD appear to be common in adolescents and young adults in this Swedish cohort. No educational activity or work was associated with both DSP and DSPD. However, there were also apparent differences between the two groups in shift work, substance use and mental health, relative to persons with no DSP. Thus, it seems reasonable to assess DSP and DSPD as distinct entities in future studies.
27535380	The temporal organization of activity/rest or sleep/wake rhythms for mammals is regulated by the interaction of light/dark cycle and circadian clocks. The neural and molecular mechanisms that confine the active phase to either day or night period for the diurnal and the nocturnal mammals are unclear. Here we report that prokineticin 2, previously shown as a circadian clock output molecule, is expressed in the intrinsically photosensitive retinal ganglion cells, and the expression of prokineticin 2 in the intrinsically photosensitive retinal ganglion cells is oscillatory in a clock-dependent manner. We further show that the prokineticin 2 signaling is required for the activity and arousal suppression by light in the mouse. Between the nocturnal mouse and the diurnal monkey, a signaling receptor for prokineticin 2 is differentially expressed in the retinorecipient suprachiasmatic nucleus and the superior colliculus, brain projection targets of the intrinsically photosensitive retinal ganglion cells. Blockade with a selective antagonist reveals the respectively inhibitory and stimulatory effect of prokineticin 2 signaling on the arousal levels for the nocturnal mouse and the diurnal monkey. Thus, the mammalian diurnality or nocturnality is likely determined by the differential signaling of prokineticin 2 from the intrinsically photosensitive retinal ganglion cells onto their retinorecipient brain targets. 

27530500	Both repeated practice and sleep improve long-term retention of information. The assumed common mechanism underlying these effects is memory reactivation, either on-line and effortful or off-line and effortless. In the study reported here, we investigated whether sleep-dependent memory consolidation could help to save practice time during relearning. During two sessions occurring 12 hr apart, 40 participants practiced foreign vocabulary until they reached a perfect level of performance. Half of them learned in the morning and relearned in the evening of a single day. The other half learned in the evening of one day, slept, and then relearned in the morning of the next day. Their retention was assessed 1 week later and 6 months later. We found that interleaving sleep between learning sessions not only reduced the amount of practice needed by half but also ensured much better long-term retention. Sleeping after learning is definitely a good strategy, but sleeping between two learning sessions is a better strategy.
27529127	Familial Advanced Sleep Phase (FASP) is a heritable human sleep phenotype characterized by very early sleep and wake times. We identified a missense mutation in the human Cryptochrome 2 (CRY2) gene that co-segregates with FASP in one family. The mutation leads to replacement of an alanine residue at position 260 with a threonine (A260T). In mice, the CRY2 mutation causes a shortened circadian period and reduced phase-shift to early-night light pulse associated with phase-advanced behavioral rhythms in the light-dark cycle. The A260T mutation is located in the phosphate loop of the flavin adenine dinucleotide (FAD) binding domain of CRY2. The mutation alters the conformation of CRY2, increasing its accessibility and affinity for FBXL3 (an E3 ubiquitin ligase), thus promoting its degradation. These results demonstrate that CRY2 stability controlled by FBXL3 plays a key role in the regulation of human sleep wake behavior. 
27524212	The military is a unique occupational group and, because of this, military personnel face different kinds of stress than civilian populations. Sleep problems are an example. The purpose of this study was to investigate the relationship between sleep problems, depression level and coping strategies among military personnel.In this cross-sectional study, military personnel completed the Beck Depression Inventory, the Pittsburgh Sleep Quality Index and the Jalowiec Coping Scale.	An evaluation of the test scores showed that officers had better sleep quality and fewer depressive symptoms than enlisted personnel. Military personnel with higher educational levels and less physical illness also had fewer depressive symptoms. Officers and noncommissioned officers preferred problem-focused strategies. Those with higher Beck Depression Inventory and Pittsburgh Sleep Quality Index scores and those who drank alcohol frequently preferred affective-focused strategies.	Our results revealed that sleep quality, physical illness and alcohol consumption were associated with the mental health of military personnel. Treating these factors may improve the mental health of military personnel and enhance effective coping strategies.	
27524211	This study was conducted to investigate whether there is a direct association between subjective sleep quality and esophageal acid reflux in patients with gastroesophageal reflux disease.We enrolled patients with classic reflux symptoms for endoscopy and ambulatory pH monitoring. The severity of esophageal mucosal injury was assessed by upper endoscopy. Distal esophageal acid exposure was determined by ambulatory 24-hour pH monitoring. Sleep disturbance was assessed by using the Pittsburgh Sleep Quality Index. In total, 103 patients (53 patients without sleep dysfunction and 50 patients with sleep dysfunction) were studied.	Erosive esophagitis was found more in patients with sleep disturbance than in those without sleep disturbance (45% versus 31%, P = 0.04). Abnormal esophageal pH was found more in patients with dysfunction (22%) than in patients without sleep dysfunction (5.7%, P = 0.03). Recumbent acid contact time (%) was greater in patients with sleep disturbance than in those without sleep disturbance (3.7 ± 2.4 versus 1.9 ± 0.9, P = 0.04). Sleep quality score positively correlated with acid contact time (r = 0.32, P = 0.02), prolonged reflux events (r = 0.45, P = 0.008) and longer reflux event (r = 0.28, P = 0.03) during recumbent period.	Patients with gastroesophageal reflux disease along with sleep dysfunction are characterized with greater nocturnal acid reflux and more erosive esophagitis. Our study suggests that increased nocturnal acid reflux may play a role in inducing sleep disturbance in patients with gastroesophageal reflux disease.	
27518472	Sleep-wake disturbances are common in patients with cirrhosis and have a considerable effect on health-related quality of life; however, the underlying mechanism behind the phenomenon is unclear. Cytokines are involved in the mediation of signalling pathways regulating fibrogenesis, leading to cirrhosis. In addition, increased cytokines could contribute to sleep disturbances.To determine the relationship between pro-inflammatory cytokines and sleep disturbance in cirrhotic patients.	Ninety-eight nonalcoholic cirrhotic patients without overt hepatic encephalopathy were enrolled in this cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Psychometric Hepatic Encephalopathy Score (PHES) was used to examine cognitive performance and define minimal hepatic encephalopathy (MHE). The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the mood status of the patients. Pro-inflammatory cytokines that include interleukin 6 (IL-6) and tumour necrosis factor-α, as well as HBV-DNA or HCV-RNA levels were determined in patients.	A total of 56 (57%) cirrhotic patients were identified as 'poor' sleepers (PSQI > 5). After multivariate analysis, IL-6 (P = 0.001) and HADS scores (P = 0.002) were found to be independent predictive factors of poor sleep quality. No significant relationships were observed between the sleep indices and the presence of MHE. HCV-RNA, but not HBV-DNA, viraemia was associated with sleep disturbance in cirrhotic patients.	Sleep disturbance is found commonly in cirrhotic patients and a high serum IL-6 level is predictive of poor sleep quality. Minimal hepatic encephalopathy by itself may not contribute to sleep dysfunction in cirrhotic patients.	
27515515	Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer.Adult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission.	The outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer.	
27514301	Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep.

27510570	Sleep-wake patterns are often significantly disturbed in critically ill patients. This disturbance is closely linked to secondary brain dysfunctions in these patients. Sedation not only impairs sleep quality in ICU patients but also has detrimental effects on short- and long-term outcome. In other contexts, light therapy has been proven to be effective in maintaining and resynchronizing circadian rhythmicity in humans. The objective of this systematic review was to analyse studies that investigated the effect of exposure to light or darkness on physiological measures and clinical outcomes of adult ICU patients. Studies were systematically identified by searching electronic bibliographic databases (The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2002) and MEDLINE via PubMed). The search algorithm identified a total of 156 articles, 10 of which were taken into final review. These 10 selected articles included 3 were monocentric RCTs, five prospective cohort studies, one retrospective cohort study, and one manuscript that included a partial systematic review of the literature. Included trials were published between 2007 and 2015. Five of these studies used multiple intervention approaches while four trials used a single intervention approach. Among all studies, 1,278 patients were analysed (489 prospectively). There was a high heterogeneity among the studies in terms of applied intervention and outcome measures. The most frequent methodological limitations were a lack of precise definitions regarding the illuminance and the light spectrum utilised. The analyses indicate that further studies including clearly defined interventions with objective outcome measures, as these are currently lacking, would add significant knowledge to this new field of research. 
27509339	Sleep disturbances are common in the elderly. Endogen regulation mechanisms are often unstable. Light treatment and melatonin are proved chronobiological interventions. Cataract surgery is effective to enhance the sleep-wake-rhythm.Mandibular advancement devices are a reliable alternative to continuous positive air pressure (CPAP) in obstructive sleep apnea syndrome (OSAS). 

27503746	Few studies have investigated the predictors of the specific and non-specific effects of acupuncture. The aim of this secondary analysis was to determine patient characteristics that may predict a better treatment response to acupuncture for insomnia.We pooled the data of three randomised, double-blind, placebo-controlled trials of acupuncture for insomnia to examine sociodemographic variables, clinical characteristics, baseline sleep-wake variables, and treatment expectancy in relation to acupuncture response. Subjects with an improvement in insomnia severity index (ISI) scores of ≥8 points from baseline to 1 week post-treatment were classified as responders. Factors were compared between responders and non-responders, and also by univariate and multivariate logistic regression analysis.	A total of 116 subjects who received traditional needle acupuncture were included, of which 37 (31.9%) were classified as responders. Acupuncture responders had a higher educational level (p<0.01) and higher baseline ISI score (p<0.05), compared to non-responders. In the multivariate logistic regression analysis, only the number of years spent in full-time education remained significant as a predictor of treatment response (OR 1.21, 95% CI 1.06 to 1.38, p<0.01).	Consistent with previous studies, our data suggest that the response to acupuncture is difficult to predict. Although the predictive power of educational level is weak overall, our findings provide potentially valuable information that could be built upon in further research (including a larger sample size), and may help to inform patient selection for the treatment of chronic insomnia with acupuncture in the future.	
27503044	Flight attendants (FAs) may experience circadian disruption due to travel during normal sleep hours and through multiple time zones. This study investigated whether FAs are at higher risk for sleep disturbance compared to teachers, as assessed by questionnaire, diary, and activity monitors.Sleep/wake cycles of 45 FAs and 25 teachers were studied. For one menstrual cycle, participants wore an activity monitor and kept a daily diary. Sleep metrics included total sleep in the main sleep period (MSP), sleep efficiency (proportion of MSP spent sleeping), and nocturnal sleep fraction (proportion of sleep between 10 p.m. to 8 a.m. home time). Relationships between sleep metrics and occupation were analyzed with mixed and generalized linear models.	Both actigraph and diary data suggest that FAs sleep longer than teachers. However, several actigraph indices of sleep disturbance indicated that FAs incurred significant impairment of sleep compared to teachers. FAs were more likely than teachers to have poor sleep efficiency [adjusted odds ratio (OR) for lowest quartile of sleep efficiency = 1.9, 95% Confidence Interval (CI) 1.2 - 3.0] and to have a smaller proportion of their sleep between 10 p.m. and 8 a.m. home time (adjusted OR for lowest quartile of nocturnal sleep fraction = 3.1, CI 1.1 -9.0).	Study FAs experienced increased sleep disturbance compared to teachers, which may indicate circadian disruption. Grajewski B, Whelan EA, Nguyen MM, Kwan L, Cole RJ. Sleep disturbance in female flight attendants and teachers. Aerosp Med Hum Perform. 2016; 87(7)638-645.	
27502815	The aim of this study is to examine the effectiveness of foot reflexology and back massage on optimizing the sleep quality and reducing the fatigue of hemodialysis patients.The study includes 105 volunteer patients who were registered at a private dialysis clinic and were receiving hemodialysis treatment. Foot reflexology and back massage were administered to the patients two times a week for four weeks. The Visual Analogue Scale for Fatigue and the Pittsburg Sleep Quality Index were used to collect data.	The differences between the pretest and posttest score averages of the patients on the Visual Analogue Scale for Fatigue and the Pittsburg Sleep Quality Index were statistically significant (p < 0.001).	Foot reflexology and back massage were shown to improve the sleep quality and reduce the fatigue of hemodialysis patients. Compared to back massage, foot reflexology was determined to be more effective.	
27502810	Fibromyalgia Syndrome (FMS) is characterized by musculoskeletal pain, muscle tenderness leading to disability, impaired quality of life (QoL), fatigue and it is accompanied by sleep disorders and psychological distress. Mind body therapies (MBT), such as Tai Ji Quan (TJQ), use different techniques to facilitate the ability of the mind to influence disease characteristics and symptoms. Some studies showed that TJQ, in patients with rheumatic diseases, particularly FMS, improved QoL, disability and psychological distress.To evaluate the efficacy of TJQ on disability, QoL, fatigue, sleep and psychological distress in an Italian cohort of FMS patients.	We enrolled 44 FMS patients: 22 patients (Experimental Group) participated to a course of Tai Ji Quan style of (2/week for 16 weeks); 22 patients (Control Group) participated to an educational course about FMS (2/week for 16 weeks). At baseline (T0) and at the end of treatment (T1), patients were assessed for disability [Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ)], Quality of Life [Short-Form 36 (SF36)], fatigue [Functional Assessment of Chronic Illness-Fatigue (FACIT-F)], pain [Widespread Pain Index (WPI)], tenderness [Tender Points (TP)], Sleep Quality [Pittsburgh Sleep Quality Index (PSQI)] and mood disorders [Hospital Anxiety and Depression Scale (HADS)].	At T1 versus T0, patients of the Experimental Group showed a significant improvement in FIQ, FACIT, SF36 (Summary Physical Index, Physical activity, physical role, bodily pain, general health, vitality, emotional role limitations), in WPI, TP, PSQI (total, sleep duration, and sleep disturbance) and HADS (total score and anxiety subscale), while Patients in the Control Group did not improve in any parameter.	In FMS patients TJQ, if performed by an expert physiotherapist, should be regarded as an effective rehabilitation method.	
27502301	Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with β-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis. 
27500879	Цель исследования. Изучение неврологических и электрофизиологических проявлений депривации сна (ДС) у пациентов с локально обусловленными симптоматическими формами эпилепсии и у здоровых, а также исследование нейроморфологических паттернов ДС в экспериментальных условиях. Материал и методы. Комплексное клиническое и электроэнцефалографическое (видео-ЭЭГ мониторинг с обязательной записью сна) исследования выполнены до и после ДС в течение 48 ч у 178 пациентов с локально обусловленной эпилепсией (ЛОЭ) и у 45 здоровых контрольной группы. Проведены нейрогистологическое и электронно-микроскопическое исследования головного мозга крыс после 48-часовой ДС. Результаты и обсуждение. ДС приводит к усилению эпилептиформной активности у больных ЛОЭ (увеличивается частота эпилептических приступов) и появлению ее у здоровых. Обнаруженные в ЦНС крыс после ДС такие морфологические изменения, как плейокония митохондрий, повреждение элементов гематоэнцефалического барьера, признаки истощения астроцитов, изменение ядер глиоцитов и некоторых нейронов по типу апоптоза и кариорексиса, а также деструкция синапсов свидетельствуют о нарушении механизмов нейропластичности после ДС. Полученные результаты позволяют рассматривать ДС у пациентов как повреждающий ЦНС фактор, провоцирующий развитие эпилептических приступов и эпилепсии. ДС у экспериментальных животных может быть использована в качестве модели для дальнейшего изучения механизмов нейропластичности.Learning cycle «sleep-wake» is of great theoretical and practical importance because it allows to understand the general patterns of adaptive mechanisms of human interaction with the environment (neuroplasticity), violations of which are the basis of many diseases of the CNS, including epilepsy.	Complex clinical and electroencephalographic (video-EEG monitoring with mandatory recording of sleep) study was carried out before and after prolonged sleep deprivation (for at least 1 day) of 178 patients with locally due to epilepsy (LEi). 45 healthy volunteers were examined in the control group as well as the patients with epilepsy. The work was carried out to compare the results of clinical and neurological and electrophysiological studies during sleep deprivation (SD) in patients with LEi and in healthy individuals with neurohistological and electron microscopic patterns of changes in the brain of rats in an experiment with 48-hour SD.	Discovered in the CNS of rats after SD morphological changes such as pleyokoniya of mitochondria, damage in the blood-brain barrier, signs of exhaustion astrocytes, glial cells and the change of the nuclei of gliocytes and some neurons of the type of apoptosis and karyorrhexis and destruction of synapses reveal a violation of the fundamental mechanisms of neuroplasticity. The results allow us to consider the SD patients as a damaging factor for the central nervous system, provoking the development of epileptic seizures and epilepsy, and the SD in laboratory animals can be used as a model for further study of the mechanisms of neuroplasticity. In addition the findings greatly complement current understanding of the mechanisms of neuroplasticity and pathogenesis of epilepsy, and justify the need for the study of therapeutic efficacy of modulators of neuroplasticity (transcranial magnetic stimulation, ipidacrin etc.) in the complexe treatment of patients with the this specified profile.	
27500861	Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non-24-hour sleep-wake disorder (or non-24). However, three additional commercially available melatonin receptor agonists-agomelatine, prolonged-release melatonin, and ramelteon-have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs. 
27496645	Aging causes considerable decline in both physiological and mental functions, particularly cognitive function. The hippocampal theta rhythm (4-12Hz) is related to both cognition and locomotion. Aging-related findings of the frequency and amplitude of hippocampal theta oscillations are inconsistent and occasionally contradictory. This inconsistency may be due to the effects of the sleep/wake state and different frequency subbands being overlooked. We assumed that aged rats have lower responses of the hippocampal theta rhythm during running, which is mainly due to the dominant modulation of theta frequency subbands related to cognition. By simultaneously recording electroencephalography, physical activity (PA), and the heart rate (HR), this experiment explored the theta oscillations before, during, and after treadmill running at a constant speed in 8-week-old (adult) and 60-week-old (middle-aged) rats. Compared with adult rats, the middle-aged rats exhibited lower theta activity in all frequency ranges before running. Running increased the theta frequency (Frq, 4-12Hz), total activity of the whole theta band (total power, TP), activity of the middle theta frequency (MT, 6.5-9.5Hz), and PA in both age groups. However, the middle-aged rats still showed fewer changes in these parameters during the whole running process. After the waking baseline values were substracted, middle-aged rats showed significantly fewer differences in ΔFrq, ΔTP, and ΔMT but significantly more differences in low-frequency theta activity (4.0-6.5Hz) and HR than the adult rats did. Therefore, the decreasing activity and response of the whole theta band in the middle-aged rats resulted in dominant modulation of the middle to lower frequency (4.0-9.5Hz) theta rhythm. The different alterations in the theta rhythm during treadmill running in the two groups may reflect that learning decline with age. 
27488802	Sleep has been shown to impact glucose regulation, and may be altered in persons with type 1 diabetes (T1D).To assess sleep characteristics in T1D patients and the possible association between sleep disturbances and diabetes-related variables.	In a cross-sectional study in 154 young patients with T1D and 154 age-range-matched nondiabetic controls subjective sleep characteristics were assessed using validated questionnaires: Sleep Disturbance Scale for Children (SDSC), Adolescent Sleep-Wake Scale (ASWS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS). Clinical and disease-related variables were obtained from medical charts.	Sleep disorders were frequent in all age groups, with no significant difference in prevalence or total scores of the SDSC, ASWS, PSQI, or ESS between the patients and the controls. In T1D children, SDSC score was significantly higher in those using continuous glucose monitoring (CGM) vs glucose meters (P = .042). The score of disorders related to "initiating and maintaining sleep" was significantly higher in those treated with pumps vs patients treated with injections (P = .014), in those using CGM vs glucose meters (P = .02), and in those with nocturnal hypoglycemia vs those without (P = .023). The percentage of children with excessive daytime sleepiness was significantly lower in patients vs controls (P = .035). No significant differences were found in the other two age groups.	The prevalence of sleep disorders among most of the young T1D patients was no higher than in the nondiabetic population. Studies using objective sleep measures are warranted to further assess sleep quality in T1D patients.	
27488603	Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) are highly prevalent in stroke patients. Recent studies suggest that they represent both a risk factor and a consequence of stroke and affect stroke recovery, outcome, and recurrence.Review of literature.	Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in TIA and stroke patients are recommended in view of the very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of obstructive SDB with continuous positive airway pressure is recommended given the strength of the increasing evidence in support of a positive effect on outcome (Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB. Recently, both reduced and increased sleep duration, as well as hypersomnia, insomnia, and restless legs syndrome (RLS), were also suggested to increase stroke risk. Mainly experimental studies found that SWD may in addition impair neuroplasticity processes and functional stroke recovery. Treatment of SWD with hypnotics and sedative antidepressants (insomnia), activating antidepressants or stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias) are based on single case observations and should be used with caution.	SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome. Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units.	
27487592	High blood pressure is a major cause of morbidity and mortality in Sub-Saharan Africa and firemen (firefighters) may be especially predisposed to it or even exacerbate pre-existing hypertension as a result of the nature of their job. This study was to determine the prevalence of hypertension among firemen in Rivers state, South-South Nigeria.Following ethical clearance, 125 consenting firemen of the Rivers State Fire Service were recruited in this descriptive cross sectional study. They responded to a pre-tested, structured, closed-ended self-administered questionnaire which probed their socio-demographics, knowledge, attitude and practice towards hypertension. Also, their blood pressures heights and weights were measured from where Body Mass Index (BMI) was calculated. A WalkThrough Survey for immediate work place situation and safety was carried out. Data collected were later analyzed using descriptive and analytical statistical tools.	There was a 9.6% prevalence of hypertension among this group of workers in Rivers State. The workforce was essentially young with a modal age group of between 31-36 years. The attendant associated risk factors included altered sleep patterns, over weight and smoking which were all statistically significant P < 0.05. Whilst knowledge of hypertension was high (96%), the behaviour of respondents towards prevention and control of hypertension was poor.	There is hypertension among firemen of the Rivers State Fire Service occasioned by modifiable risk factors despite adequate knowledge. It is recommended that intensive health education, early detection and treatment be instituted among this group of workers.	
27487378	A search for papers was made in the databases Bireme, Scielo and Pubmed with the following keywords: post polio syndrome, cardiorespiratory and rehabilitation in English, French and Spanish languages. Although we targeted only seek current studies on the topic in question, only the relevant (double-blind, randomized-controlled and consensus articles) were considered.Certain features of PPS such as generalized fatigue, generalized and specific muscle weakness, joint and/or muscle pain may result in physical inactivity deconditioning obesity and dyslipidemia. Respiratory difficulties are common and may result in hypoxemia.	Only when evaluated and treated promptly, somE patients can obtain the full benefits of the use of respiratory muscles aids as far as quality of life is concerned.	
27487216	Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep. In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex. Artificial activation of these cells induces sleep, whereas reductions in excitability cause insomnia. dFB neurons in sleep-deprived flies tend to be electrically active, with high input resistances and long membrane time constants, while neurons in rested flies tend to be electrically silent. Correlative evidence thus supports the simple view that homeostatic sleep control works by switching sleep-promoting neurons between active and quiescent states. Here we demonstrate state switching by dFB neurons, identify dopamine as a neuromodulator that operates the switch, and delineate the switching mechanism. Arousing dopamine caused transient hyperpolarization of dFB neurons within tens of milliseconds and lasting excitability suppression within minutes. Both effects were transduced by Dop1R2 receptors and mediated by potassium conductances. The switch to electrical silence involved the downregulation of voltage-gated A-type currents carried by Shaker and Shab, and the upregulation of voltage-independent leak currents through a two-pore-domain potassium channel that we term Sandman. Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in response to dopamine. dFB-restricted interference with the expression of Shaker or Sandman decreased or increased sleep, respectively, by slowing the repetitive discharge of dFB neurons in the ON state or blocking their entry into the OFF state. Biophysical changes in a small population of neurons are thus linked to the control of sleep-wake state.
27486325	This review summarizes the empirical and clinical literature on sleep paralysis most relevant to practitioners. During episodes of sleep paralysis, the sufferer awakens to rapid eye movement sleep-based atonia combined with conscious awareness. This is usually a frightening event often accompanied by vivid, waking dreams (ie, hallucinations). When sleep paralysis occurs independently of narcolepsy and other medical conditions, it is termed "isolated" sleep paralysis. Although the more specific diagnostic syndrome of "recurrent isolated sleep paralysis" is a recognized sleep-wake disorder, it is not widely known to nonsleep specialists. This is likely due to the unusual nature of the condition, patient reluctance to disclose episodes for fear of embarrassment, and a lack of training during medical residencies and graduate education. In fact, a growing literature base has accrued on the prevalence, risk factors, and clinical impact of this condition, and a number of assessment instruments are currently available in both self-report and interview formats. After discussing these and providing suggestions for accurate diagnosis, differential diagnosis, and patient selection, the available treatment options are discussed. These consist of both pharmacological and psychotherapeutic interventions which, although promising, require more empirical support and larger, well-controlled trials. 
27481936	Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.
27480652	To investigate sleep architecture and blood pressure dynamic change in patients with Sleep apnea syndrome by electrocardiogram-based cardiopulmonary coupling analysis system.Seventy-nine sleep disorder participants (PSQI≥8) were enrolled. Electrocardiogram-based cardiopulmonary coupling analysis device and ambulatory blood pressure monitoring were synchronously used to evaluate sleep architecture and blood pressure circadian rhythm. The patients were divided into SAS group (47 participants) and non-SAS group (32 participants) according to the Apnea Hypopnea Index (AHI) that calculated by CPC device. The data of sleep architecture and blood pressure variability were compared between two groups.	Compared with non-SAS group, SAS group have less proportion of deep sleep, more proportion of light sleep, higher mean blood pressure in 24 hours and daytime, lower nocturnal blood pressure dipping, faster mean heart rate in night time (P<0.05). AHI has moderate inverse correlation with deep sleep time, wake/dream time (-0.6≤r<-0.3), moderate positive correlation with light sleep time (0.3<r≤0.6), high inverse correlation with nocturnal blood pressure dipping (r=-0.785, P=0.000), moderate positive correlation with mean diastolic blood pressure (r=0.425, P=0.019).	Our study shows that less proportion of deep sleep, more proportion of light sleep, 24 hours mean blood pressure and nocturnal blood pressure increase in the patients with Sleep Apnea Syndrome. The severity of Sleep Apnea Syndrome has a positive correlation with the severity of abnormal sleep architecture and the degree of blood pressure elevation.	
27479324	Little is known about the ability of Drosophila circadian neurons to promote sleep. Here we show, using optogenetic manipulation and video recording, that a subset of dorsal clock neurons (DN1s) are potent sleep-promoting cells that release glutamate to directly inhibit key pacemaker neurons. The pacemakers promote morning arousal by activating these DN1s, implying that a late-day feedback circuit drives midday siesta and night-time sleep. To investigate more plastic aspects of the sleep program, we used a calcium assay to monitor and compare the real-time activity of DN1 neurons in freely behaving males and females. Our results revealed that DN1 neurons were more active in males than in females, consistent with the finding that male flies sleep more during the day. DN1 activity is also enhanced by elevated temperature, consistent with the ability of higher temperatures to increase sleep. These new approaches indicate that DN1s have a major effect on the fly sleep-wake profile and integrate environmental information with the circadian molecular program.
27478137	Lithium has been used for the treatment of bipolar disorder (BD). However, the mechanisms how lithium exerts its mood stabilizing effects remain to be studied. The disorder in circadian pacemaking has been suggested as an underlying mechanism of the characteristic mood instability of the BD. Lithium is also known to lengthen the circadian periods. We recently proposed that chronic methamphetamine treatment induced circadian oscillation as a complex oscillator including multiple dopaminergic brain areas, and the complex oscillator regulates behavior rhythm independent from the central circadian oscillator in the suprachiasmatic nucleus (SCN). Sleep-wake pattern of rapid cycling BD exhibits similar rhythm disorganization to methamphetamine treated animals. Therefore, we hypothesized that the dysregulated circadian rhythm in BD patients is caused by desynchronization of sleep-wake rhythms from the central clock in the SCN, and that mood stabilizing effect of lithium is achieved through their resynchronization. In the present experiment, we examined how lithium affects the circadian rhythms of brain areas involved in the complex oscillator as well as the SCN. Here we report that lithium lengthens the circadian periods in the SCN, olfactory bulb, median eminence and substantia nigra with dose and area specific manner. The effective lithium dose was much higher than the plasma levels that are required for lengthening the circadian behavior rhythms as well for therapeutic use. Low dose of lithium did not lengthen the period but enhanced the amplitude of circadian rhythms, which may exert therapeutic effects on BD. 
27477578	Movement and behavior disorders developing during sleep or in the transitional state from sleep to wakefulness are mostly unfamiliar to Japanese neurologists, primarily because these disorders are objects of basic research. In addition, the patients with sleep related movement and behavior disorders (SRMBD) show no signs and symptoms in our consulting rooms, and cannot be identified without polysomnography (PSG) attended by trained sleep technologists. Although attended PSG is not widely available in Japan, some kinds of SRMBD ought to be clinical targets for neurologists, and they are the scope of this review. 
27474266	What is the topic of this review? This review highlights temporal partitioning of cardiac metabolism by the cardiomyocyte circadian clock. What advances does it highlight? Advances include: 1) cardiac glucose utilization peaks during the active period to meet increased energetic demands at this time; 2) synthesis of glycogen and triglyceride peak in the heart during the latter half of the active period, likely in anticipation of the upcoming sleep/fasting period; and 3) protein turnover increases in the heart at the beginning of the sleep phase, probably to promote growth and repair at this time. Cell-autonomous circadian clocks have emerged as crucial mediators of 24 h rhythms in cellular processes. In doing so, these molecular timekeepers confer the selective advantage of anticipation, allowing cells and organs to prepare for stimuli and stresses before their onset. The heart is subjected to dramatic fluctuations in energetic demand and nutrient supply in association with sleep-wake and fasting-feeding cycles. Recent studies suggest that the cardiomyocyte circadian clock orchestrates daily rhythms in both oxidative and non-oxidative glucose and fatty acid metabolism, as well as protein turnover. Here, I review this evidence and discuss whether disruption of these rhythms can contribute to cardiovascular disease.
27473327	Many adults are insufficiently physically active, have prolonged sedentary behaviour and report poor sleep. These behaviours can be improved by interventions that include education, goal setting, self-monitoring, and feedback strategies. Few interventions have explicitly targeted these behaviours simultaneously or examined the relative efficacy of different self-monitoring methods.This study aims to compare the efficacy of two self-monitoring methods in an app-based multi-behaviour intervention to improve objectively measured physical activity, sedentary, and sleep behaviours, in a 9 week 2-arm randomised trial. Participants will be adults (n = 64) who report being physically inactive, sitting >8 h/day and frequent insufficient sleep (≥14 days out of last 30). The "Balanced" intervention is delivered via a smartphone 'app', and includes education materials (guidelines, strategies to promote change in behaviour), goal setting, self-monitoring and feedback support. Participants will be randomly allocated to either a device-entered or user-entered self-monitoring method. The device-entered group will be provided with a activity tracker to self-monitor behaviours. The user-entered group will recall and manually record behaviours. Assessments will be conducted at 0, 3, 6, and 9 weeks. Physical activity, sedentary behaviour and sleep-wake behaviours will be measured using the wrist worn Geneactiv accelerometer. Linear mixed models will be used to examine differences between groups and over time using an alpha of 0.01.	This study will evaluate an app-based multi-behavioural intervention to improve physical activity, sedentary behaviour and sleep; and the relative efficacy of two different approaches to self-monitoring these behaviours. Outcomes will provide information to inform future interventions and self-monitoring targeting these behaviours.	ACTRN12615000182594 (Australian New Zealand Clinical Trials Registry. Registry URL: www.anzctr.org.au ; registered prospectively on 25 February 2015).	
27471489	Humans spend more than one-fourth of their life sleeping, and sleep quality has been significantly linked to health. However, the objective examination of ambulatory sleep quality remains a challenge, since sleep is a state of unconsciousness, which limits the reliability of self-reports. Therefore, a non-invasive, continuous, and objective method for the recording and analysis of naturalistic sleep is required.Portable sleep recording devices provide a suitable solution for the ambulatory analysis of sleep quality. In this study, the performance of two activity-based sleep monitors (Actiwatch and MTN-210) and a single-channel electroencephalography (EEG)-based sleep monitor (SleepScope) were compared in order to examine their reliability for the assessment of sleep quality.	Twenty healthy adults were recruited for this study. First, data from daily activity recorded by Actiwatch and MTN-210 were compared to determine whether MTN-210, a more affordable device, could yield data similar to Actiwatch, the de facto standard. In addition, sleep detection ability was examined using data obtained by polysomnography as reference. One simple analysis included comparing the sleep/wake detection ability of Actiwatch, MTN-210, and SleepScope. Furthermore, the fidelity of sleep stage determination was examined using SleepScope in finer time resolution.	The results indicate that MTN-210 demonstrates an activity pattern comparable to that of Actiwatch, although their sensitivity preferences were not identical. Moreover, MTN-210 provides assessment of sleep duration comparable to that of the wrist-worn Actiwatch when MTN-210 was attached to the body. SleepScope featured superior overall sleep detection performance among the three methods tested. Furthermore, SleepScope was able to provide information regarding sleep architecture, although systemic bias was found.	The present results suggest that single-channel EEG-based sleep monitors are the superior option for the examination of naturalistic sleep. The current results pave a possible future use for reliable portable sleep assessment methods in an ambulatory rather than a laboratory setting.	
27469144	It has been known that RA, one of major constituents of Perilla frutescens which has been used as a traditional folk remedy for sedation in oriental countries, shows the anxiolytic-like and sedative effects. This study was performed to know whether RA may enhance pentobarbital-induced sleep through γ-aminobutyric acid (GABA)A-ergic systems in rodents. RA (0.5, 1.0 and 2.0 mg/ kg, p.o.) reduced the locomotor activity in mice. RA decreased sleep latency and increased the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleeping mice. RA also increased sleeping time and number of falling sleep mice after treatment with sub-hypnotic pentobarbital (28 mg/kg, i.p.). In electroencephalogram (EEG) recording, RA (2.0 mg/kg) not only decreased the counts of sleep/wake cycles and REM sleep, but also increased the total and NREM sleep in rats. The power density of NREM sleep showed the increase in δ-waves and the decrease in α-waves. On the other hand, RA (0.1, 1.0 and 10 μg/ml) increased intracellular Cl- influx in the primary cultured hypothalamic cells of rats. RA (p.o.) increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAA receptors subunits except β1 subunit. In conclusion, RA augmented pentobarbital-induced sleeping behaviors through GABAA-ergic transmission. Thus, it is suggested that RA may be useful for the treatment of insomnia.
27466289	Poor breast cancer-related quality of life is associated with flattened cortisol rhythms and inflammation in breast cancer survivors and women with advanced disease. We explored the associations of cancer-specific distress (Impact of Events Scale), mood (Profile of Mood States), activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient) and cortisol (diurnal slope) circadian rhythms, and inflammation (interleukin-6) with quality of life (Functional Assessment of Cancer Therapy-Breast) among patients awaiting breast cancer surgery ( N = 57). Models were adjusted for differences in age and cancer stage. Distress and mood disturbance were significantly correlated with lower quality of life. Ethnic differences in the relationship between distress and mood disturbance with global quality of life and subscales of quality of life were observed. Actigraphic measures showed that in comparison with non-Hispanic patients, African Americans had significantly poorer activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient). Circadian disruption and inflammation were not associated with quality of life. Physiological dysregulation and associated comorbidities may take time to develop over the course of disease and treatment.
27465732	In humans, numbers of circulating T cells show a circadian rhythm with peak counts during the night and a steep decline in the morning. Sleep per se appears to counter this rhythm by acutely reducing the total number of T cells. The T-cell population, however, is rather heterogeneous, comprising various subpopulations with different features and functions and also different circadian rhythms. Therefore, we examined here whether sleep likewise differentially affects these subsets. We measured eight different T-cell subsets (naïve, central memory, effector memory, and effector CD4+ and CD8+ T cells) over a 24-h period under conditions of sustained wakefulness compared with a regular sleep-wake cycle in 14 healthy young men. Sleep reduced the number of all T-cell subsets during nighttime with this effect reaching the P < 0.05 level of significance in all but one subpopulation, i.e., effector CD4+ T cells, where it only approached significance. Furthermore, sleep was associated with an increase in growth hormone, prolactin, and aldosterone levels, whereas concentrations of catecholamines tended to be lower than during nocturnal wakefulness. The effect of sleep uniformly decreasing the different T-cell subsets is surprising considering their differential function and circadian rhythms, and even more so, since the sleep-induced decreases in these subsets are probably conveyed by different hormonal mediators. Although the reductions in cell numbers are rather small, they are comparable to changes seen, for example, after vaccination and are, therefore, likely to be of physiological relevance.
27464768	Ankylosing spondylitis (AS) is a chronic inflammatory disease that is associated with poor sleep quality.The present study aimed to investigate the relationship between disease activity and sleep quality in patients with AS and to evaluate the potential effect of anti-tumor necrosis factor (TNF) treatment on sleep quality and pattern.	Fifty-nine patients with AS were consecutively included in the study. Twenty-eight patients (47.5%) were receiving anti-TNF, and 31 (52.5%) patients were receiving only nonsteroidal anti-inflammatory drugs (NSAIDs). Demographic and treatment characteristics, spinal mobility measurements, disease activity measurements, and sleep questionnaire results of each patient were recorded. Each patient underwent a polysomnography examination for the evaluation of sleep patterns.	When compared with the patients on NSAID treatment, patients receiving anti-TNF treatment had significantly greater total sleep time and sleep efficiency (P = 0.003 and P < 0.001, respectively). They had a significantly lower (better) Pittsburgh Sleep Quality Index, sleep onset latency, number of awakenings, and arousal index (P < 0.001, for all). Moreover, they had a significantly shorter superficial sleep period (stage 1) and a significantly longer rapid eye movement sleep period (P < 0.001 and P = 0.02, respectively). Higher indexes of disease activity (Bath AS Disease Activity Index, Bath AS Functional Index, and visual analog scale) were reflecting poorer sleep quality.	Sleep quality and pattern was markedly better in patients with AS on anti-TNF compared with the patients on NSAID treatments. Increased disease activity can impair the quality of sleep in AS. Improved sleep quality and pattern in patients on anti-TNF treatment may be related to improved disease activity.	
27463411	The circadian time structure of an organism can be desynchronized in a large number of instances, including the intake of specific drugs. We have previously found that propofol, which is a general anesthetic, induces a desynchronization of the circadian time structure in rats, with a 60-80 min significant phase advance of body temperature circadian rhythm. We thus deemed it worthwhile to examine whether this phase shift of body temperature was related to a modification of the circadian period Tau. Propofol was administered at three different Zeitgeber Times (ZTs): ZT6 (middle of the rest period), ZT10 (2 h prior to the beginning of activity period), ZT16 (4 h after the beginning of the activity period), with ZT0 being the beginning of the rest period (light onset) and ZT12 being the beginning of the activity period (light offset). Control rats (n = 20) were injected at the same ZTs with 10% intralipid, which is a control lipidic solution. Whereas no modification of the circadian period of body temperature was observed in the control rats, propofol administration resulted in a significant shortening of the period by 96 and 180 min at ZT6 and ZT10, respectively. By contrast, the period was significantly lengthened by 90 min at ZT16. We also found differences in the time it took for the rats to readjust their body temperature to the original 24-h rhythm. At ZT16, the speed of readjustment was more rapid than at the two other ZTs that we investigated. This study hence shows (i) the disruptive effects of the anesthetic propofol on the body temperature circadian rhythm, and it points out that (ii) the period Tau for body temperature responds to this anesthetic drug according to a Tau-response curve. By sustaining postoperative sleep-wake disorders, the disruptive effects of propofol on circadian time structure might have important implications for the use of this drug in humans.
27461837	To determine the prevalence of sleep disorders in children with attention-deficit/hyperactivity disorder (ADHD) and in a control population. To examine the relationship between sleep disorders and symptoms of inattention, hyperactivity/impulsiveness and executive dysfunction.We studied 126 children with ADHD and 1036 control children aged between 5 and 18 years old. Caregivers completed the Pediatric Sleep Questionnaire and the ADHD Rating Scale (ADHD-RS). Children with ADHD were subsequently assessed for executive function with the Conner's Continuous Performance Test (CPT) or with AULA Nesplora.	Children with ADHD slept less at night and were more likely to display sleep-related rhythmic movements. Children in the ADHD group who were under 12 years old and who had total ADHD-RS scores over the 90th percentile had more difficulty falling asleep than other children; there was also a relationship between total ADHD-RS scores over the 90th percentile and certain parasomnias in the control population. There was a correlation between shorter duration of night-time sleep and omission errors in children who were 12 or older and who were under pharmacological treatment for ADHD. Bedtime resistance and difficulty falling sleep were more frequent in children with ADHD whose symptoms were not treated pharmacologically, than in children receiving treatment.	Symptoms of inattention and hyperactivity are correlated with impaired sleep duration and quality; specifically, there is an association between ADHD symptoms and problems falling asleep and parasomnias, however, the current study does not address the nature and direction of causality. Children with ADHD and receiving methylphenidate had fewer sleep disorders, suggesting that, at least in some children, stimulant treatment is associated with improvement of some aspects of sleep. Shorter sleep duration in adolescents under pharmacological treatment for ADHD tended to result in more errors of omission, suggesting that it is important to promote good sleep habits in this population.	
27458683	To provide an evidence-based practice overview on the clinical use of bromocriptine-quick release (QR) across the natural history of type 2 diabetes mellitus (T2DM).Articles for inclusion were selected after a comprehensive literature search of English-language PubMed articles and identification of other relevant references through other sources. Inclusion criteria were animal studies examining the mechanism of action and efficacy of bromocriptine, and clinical studies examining the safety and efficacy of bromocriptine-QR in patients with T2DM, without a time limitation.	The brain plays a key role in total body metabolism, in particular ensuring that sufficient levels of glucose are available for proper neural functioning. The hypothalamic suprachiasmatic nucleus (SCN), the body's biological clock, plays a key role in the regulation of seasonal and diurnal variations of insulin sensitivity. A daily surge of dopaminergic activity in the SCN upon waking enables insulin sensitivity throughout the day. When this is disrupted (e.g. by a high fat/sugar diet, stress, altered [diminished] exercise, altered sleep/wake cycle, diabetes), insulin resistance persists throughout the day and overnight. Improving the morning surge in dopaminergic activity with the short-acting dopamine D2 receptor agonist bromocriptine-QR can safely and effectively improve glycemic control, while improving cardiovascular disease risk factors and related adverse events, and reducing sympathetic tone, as demonstrated by 5 reports of the Cycloset Safety Trial and 3 additional clinical studies of bromocriptine-QR.	In patients with T2DM, the dopamine D2 receptor agonist bromocriptine-QR has been shown to be well tolerated, efficacious, and a logical treatment option.	
27458335	In this paper, we show that neuronal assemblies plated on Micro Electrode Arrays present synchronized, low frequency firing patterns similar to in vivo slow wave oscillations, which are a key parameter of sleep-like state. Although neuronal cultures lack the characteristic high-frequency waves of wakefulness, it is possible to modulate their spontaneous firing pattern through the administration of specific neurotransmitters such as acetylcholine. We thus stimulated the cortical cultures with an agonist of acetylcholine receptor, Carbachol, which caused a desynchronization of the spontaneous firing of the cultures. We recorded and monitored the cultures for a period of over 31 h. We analyzed the electrophysiological signals by exploiting novel methodological approaches, taking into account the different temporal scales of the recorded signals, and considering both spikes and local field potentials. Supporting the electrophysiological analysis results, gene expressions of targeted genes showed the activation of specific markers involved in sleep-wake rhythms. Our results demonstrate that the Carbachol treatment induces desynchronization of neuronal activity, altering sleep-like properties in an in vitro model. 
27456718	Цель исследования. Оценка эффективности препарата нооклерин в профилактической терапии головной боли напряжения (ГБН) у детей и подростков. Материал и методы. Проведено слепое рандомизированное плацебо-контролируемое исследование эффективности нооклерина (деанола ацеглумат), назначавшегося в течение 2 мес с целью профилактической терапии ГБН. Лечили 40 пациентов, 15 мужского и 25 женского пола в возрасте 9-16 лет, распределенных на две группы по 20 человек (препарат и плацебо). Результаты и заключение. Применение нооклерина привело к существенному уменьшению частоты, продолжительности и интенсивности ГБН, положительной динамике в повседневной активности пациентов, регрессу проявлений астении и нормализации цикла сон-бодрствование.To study clinical characteristics mechanisms and pathogenesis of the tension-type headache (TTH) in children and adolescents treated with nooclerin.	The blind randomized placebo-controlled study of the efficacy of nooclerin (deanol aceglumate) indicated during 2 months as a preventive treatment of TTH was performed. Forty patients (15 male and 25 female), aged 9-16 years, were randomized into two equal groups to receive either nooclerin or placebo.	Nooclerin significantly reduced the frequency, duration and intensity of TTH. The treatment resulted in positive dynamics in daily activities, regression of fatigue symptoms and normalization of the sleep-wake cycle.	
27456383	The number of older adults with cancer is increasing. Given the limited amount of research and the inconsistent findings regarding age differences in common physical symptoms associated with cancer and its treatments, the purposes of this study, in a sample of oncology outpatients receiving chemotherapy (CTX), were to evaluate for age differences in demographic and clinical characteristics, as well as in occurrence rates of and severity ratings for fatigue, decrements in energy, and sleep disturbance. In addition, using regression analysis techniques, within and across age groups, demographic and clinical characteristics associated with the severity of each symptom were evaluated.Patients (n = 1343) were dichotomized into younger (<65 years) and older (≥65 years) age groups. Patients completed self-report questionnaires prior to their next dose of CTX.	Overall, our findings suggest that compared to younger patients, older adults experience a lower or similar level of fatigue, decrements in energy, and sleep disturbance. However, it should be noted that both age groups experienced high occurrence rates and moderate to severe levels of all three symptoms.	Clinicians need to assess all oncology patients receiving CTX for these three symptoms. Future research needs to determine the biopsychosocial reasons that underlie these age-related differences in fatigue, decrements in energy, and sleep disturbance.	
27456222	Serotonergic neurons in the dorsal raphe nucleus (DRN) are involved in the control of sleep-wake states. Our previous studies have indicated that calcium (Ca(2+)) modulation in the DRN plays an important role in rapid-eye-movement sleep (REMS) and non-REMS (NREMS) regulation during pentobarbital hypnosis. The present study investigated the effects of Ca(2+) in the DRN on sleep-wake regulation and the related neuronal mechanism in freely moving rats. Our results showed that microinjection of CaCl2 (25 or 50 nmol) in the DRN promoted wakefulness and suppressed NREMS including slow wave sleep and REMS in freely moving rats. Application of CaCl2 (25 or 50 nmol) in the DRN significantly increased serotonin in the DRN and hypothalamus, and noradrenaline in the locus coeruleus and hypothalamus. Immunohistochemistry study indicated that application of CaCl2 (25 or 50 nmol) in the DRN significantly increased c-Fos expression ratio in wake-promoting neurons including serotonergic neurons in the DRN, noradrenergic neurons in the locus coeruleus, and orxinergic neurons in the perifornical nucleus, but decreased c-Fos expression ratio of GABAergic sleep-promoting neurons in the ventrolateral preoptic nucleus. These results suggest that Ca(2+) in the DRN exert arousal effects via up-regulating serotonergic functions in the endogenous sleep-wake regulating pathways. 
27455241	Psoriasis is an inflammatory disease frequently associated with psychiatric disturbances and sleep disorders. The aim of the study was to assess the prevalence of depression, interaction anxiety, audience anxiety, and sleep quality in psoriatic patients. One hundred and two psoriatic patients were enrolled and underwent the following questionnaires: Zung Self-Rating Depression Scale (SDS), Interaction Anxiousness Scale (IAS), Audience Anxiousness Scale (AAS), Pittsburgh Sleep Quality Index (PSQI). The severity of skin lesions was assessed by Psoriasis Area Severity Index (PASI). The presence of a link between clinical variables and with demographic data has been investigated. Psoriasis was linked to depression, interaction and audience anxiety, as well as to poor sleep quality; 37.5% of patients were depressed, 46.1% scored above 37 at the IAS, 47.1% scored above 33 at the AAS. Thirty-nine subjects (38.2%) presented a PSQI ≥ 5. An association between interaction anxiety and lower limbs psoriasis-related erythema as well as between PSQI and head psoriasis-related erythema was found, particularly among male patients. Hence, psoriatic patients should be assessed from a holistic point of view, in order to identify associated disorders that could benefit from targeted treatments. 
27454077	This article reports the development of a treatment protocol, based on cognitive behavioral therapy (CBT) principles, for delayed sleep-wake phase disorder (DSWPD). The protocol consists of psycho-education, presenting a CBT model for DSWPD, case formulation, motivational interviewing, registering sleep in a diary, strategies to improve the rhythm of sleep and wakefulness, relaxation training, cognitive restructuring, strategies to cope with daytime symptoms, constructing an individualized CBT program, and learning how to deal with relapses. Qualitative data, focusing on how the patients perceived the protocol, were collected within the realm of a trial exploring the efficacy of the protocol. These findings highlighted several advantages but also disadvantages of the therapy. It is our hope that this paper might act as a platform for further clinical work and future research efforts in patients with DSWPD. 
27453206	In this study, we investigated the effects of chronic administration of the selective serotonin reuptake inhibitor (SSRI) citalopram on sleep/wake cycles and masseter (jaw-closing) muscle electromyogram (EMG) activity over a 24-h period. From the dark to the light period, the times of wakefulness decreased, while those of non-rapid eye movement (NREM) and REM sleep increased. Citalopram did not induce major alterations in the temporal changes of sleep-wake distributions, except for leading to a decrease in the time of NREM sleep during the light period and an increase in the durations of REM sleep episodes. Moreover, citalopram did not modify mean masseter EMG activity during any of the vigilance states and did not affect the temporal changes related to the shifts between dark/light periods. However, citalopram increased the time engaged in masseter EMG activation during NREM sleep in the second and the first halves of the dark and light periods, respectively. These results suggest that chronic citalopram treatment does not affect the temporal changes of sleep-wake distributions, but has a limited facilitatory influence that fails to increase the number of epochs of high levels of masseter muscle activation.
27449472	Extracellular field potentials (ECFs) generated in the cerebral cortex span a vast range of spatiotemporal scales. The process(es) leading to this large dynamic range remain debatable. Here we propose a novel statistical description of the amplitude spectrum of the human electrocorticogram (ECoG).Spectral analysis was performed on long-term recordings from epilepsy patients undergoing pre-surgical evaluation with intracranial electrodes. Amplitude spectra were fit with a multi-component Gaussian model on semi-logarithmic axes.	The Gaussian formulation provided excellent fits to the data. It also suggested how the changes accompanying the sleep-wake cycle and certain epileptiform transitions could be understood by variation in the parameters of the model.	The proposed continuum model synthesizes several previous observations regarding the statistical structure of the resting human ECoG. It offers a conceptual platform for understanding the EEG changes accompanying the sleep-wake cycle and pathologically hypersynchronous behaviour.	Statistical characterisation of the spectral distribution of field potentials yield insight into the cortico-cortical interactions that underlie the summated cortical ECFs comprising the ECoG. Such insight is relevant for a synoptic understanding of major state changes in the brain that are diagnosed in clinical practice by visual inspection of the ECoG.	
27449011	This study investigated the relative contribution of psychiatric symptoms and psychotropic medications on the sleep-wake cycle. Actigraphy and clinical assessments (Brief Psychiatric Rating Scale) were conducted in 146 youths with anxiety, depression or bipolar disorders. Independently of medications, mania symptoms were predictive of lower circadian amplitude and rhythmicity. Independently of diagnosis and symptoms severity: i) antipsychotics were related to longer sleep period and duration, ii) serotonin-norepinephrine reuptake inhibitors to longer sleep period, and iii) agomelatine to earlier sleep onset. Manic symptoms and different subclasses of medications may have independent influences on the sleep-wake cycle of young people with mental disorders. 
27448323	Although infant sleep-wake behavior presents several developmental changes during the first six months, literature lacks on reference values and few studies have explored the role of individual change and stability on infant sleep-wake behavior during the first six months. This study aimed (1) to describe infant sleep-wake behaviors during the 24-h period, day and night, at two weeks, three, and six months, (2) and to explore developmental changes and the role of individual change and stability on infant sleep-wake behaviors from two weeks to six months. Ninety-four primiparous mothers completed measures on infant sleep-wake behaviors at two weeks, three and six months. Significant developmental changes were found on infant sleep-wake behaviors from two weeks to six months. Two-week-old infants sleep 13.3h, spend 8.7h awake, awake 6.1 times, have 0.4h of latency to sleep, and 3.2h of longest sleep period. Three-month-old infants sleep 13.0h, spend 9.2h awake, awake 5.5 times, have 0.4h of latency to sleep, and 5.2h of longest sleep period. Six-month-old infants sleep 12.2h, spend 10.0h awake, awake 5.2 times, have 0.4h of latency to sleep, and 5.6h of longest sleep period. Significant individual change and stability were also found on infant sleep-wake behaviors from two weeks to six months. Despite significant developmental and individual changes, individual stability explains a significant amount of the variance on infant sleep-wake behaviors over the first six months of life. 
27445538	Excessive daytime sleepiness (EDS) is a common problem that is important to recognize and address. Initial steps in management are generally straightforward and only the most advanced cases would require referral to a subspecialist. Of particular concern is that of driving safety. There is a broad differential diagnosis for conditions contributing to EDS but a few common conditions account for the majority of clinical presentations. Subjective self-reporting will often lead to identification of potential problems, but this is often unreliable. Traditional neurophysiologic tests can help in objectively quantifying symptoms but current tests are not always practical clinically and may have little validation in real world situations. There are many treatment options that should generally be able to sufficiently manage most patients presenting with hypersomnolence. This review provides a practical clinical approach to the problem based on current guidelines. 
27445242	Sleep disorders are common in neurology practice, but are often undiagnosed and untreated. Specific patient cohorts, such as older adults, patients residing in nursing homes, and patients with underlying chronic neurologic and psychiatric disorders, are at particular risk. If these sleep problems are not properly evaluated and managed the patient may experience exacerbation of the underlying neurologic disorder. This article highlights some of the key sleep disorders relevant to practicing neurologists, emphasizing hypersomnolence, insomnia, and sleep-related movement disorders in the setting of neurologic disorders to enhance the tools available for evaluation, and discusses management strategies. 
27443156	Fatigue is one of the most frequent symptoms of multiple sclerosis (MS) and one of the main reasons for underemployment and early retirement. The mechanisms of MS-related fatigue are unknown but comorbid disorders play a major role. Anemia, diabetes, side effects of medication and depression should be ruled out. Moreover, excessive daytime sleepiness (EDS) should be differentiated from fatigue. No approved medicinal therapy of MS fatigue is currently available.Presentation of current treatment strategies with a particular focus on secondary fatigue due to sleep disorders.	A review of the literature was carried out.	All MS patients suffering from fatigue should be questioned with respect to EDS and if necessary sleep medical investigations should be carried out; however, pure fatigue without accompanying EDS can also be caused by a sleep disorder. Medications, particularly freely available antihistamines, can also increase fatigue. Furthermore, anemia, iron deficits, diabetes and hypothyroidism should be excluded. Self-assessment questionnaires show an overlap between depression and fatigue. Several studies have shown that cognitive behavioral therapy and various psychotherapeutic measures, such as vertigo training, progressive exercise training and individualized physiotherapy as well as fatigue management interventions can lead to a significant improvement of MS-related fatigue. There is currently no medication which is suitable for treatment of fatigue, with the exception of fampridine for the treatment of motor functions and motor fatigue.	
27442503	Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients. 
27440914	The mammalian circadian clock plays a central role in the temporal coordination of physiology across the 24-h light-dark cycle. A major function of the clock is to maintain energy constancy in anticipation of alternating periods of fasting and feeding that correspond with sleep and wakefulness. While it has long been recognized that humans exhibit robust variation in glucose tolerance and insulin sensitivity across the sleep-wake cycle, experimental genetic analysis has now revealed that the clock transcription cycle plays an essential role in insulin secretion and metabolic function within pancreatic beta cells. This review addresses how studies of the beta cell clock may elucidate the etiology of subtypes of diabetes associated with circadian and sleep cycle disruption, in addition to more general forms of the disease. 
27436545	Sleep and feeding behaviors closely interact to maintain energy homeostasis. While it is known that sleep disorders can lead to various metabolic issues such as insulin resistance, the mechanism for this effect is poorly understood. We thus investigated whether different feeding rhythms during the active period affect sleep-wake regulation.For 2weeks, mice were randomly assigned to 1 of 3 feeding schedules as follows: free access to lab chow during the active period (ZT12-24, Ad-lib group), free access to lab chow during the first half of the active period (ZT12-18; Morning group), or free access to lab chow during the second half of the active period (ZT18-24, Evening group). Food intake, body weight, body temperature, locomotor activity, and sleep were evaluated. The hypothalamus and cerebral cortex were examined post-mortem.	No alterations in food intake or body weight were observed among the 3 groups. The Evening group showed lower slow-wave activity (SWA) than the other 2 groups, in addition to higher expression of orexin mRNA in the hypothalamus and higher concentrations of dopamine and its metabolites in the cerebral cortex. AMPK phosphorylation was increased in the hypothalamus of mice in the Evening group; however, AMPK inhibition had no effect on SWA.	We concluded that late feeding reduces SWA in NREM sleep via a mechanism that involves orexin-mediated arousal in the hypothalamus and elevated monoamines in the cerebral cortex. These data have important implications for the relationship between sleep-wake disturbances and metabolic disorders.	
27432116	An improvement to our current quantitative model of arousal state dynamics is presented that more accurately predicts sleep propensity as measured with sleep dynamics depending on circadian phase and prior wakefulness. A nonlinear relationship between the circadian variables within the dynamic circadian oscillator model is introduced to account for the skewed shape of the circadian rhythm of alertness that peaks just prior to the onset of the biological night (the "wake maintenance zone") and has a minimum toward the end of the biological night. The revised circadian drive thus provides a strong inhibitory input to the sleep-active neuronal population in the evening, counteracting the excitatory effects of the increased homeostatic sleep drive as originally proposed in the opponent process model of sleep-wake regulation. The revised model successfully predicts the sleep propensity profile as reflected in the dynamics of the total sleep time, sleep onset latency, wake/sleep ratio, and sleep efficiency during a wide range of experimental protocols. Specifically, all of these sleep measures are predicted for forced desynchrony schedules with day lengths ranging from 1.5 to 42.85 h and scheduled time in bed from 0.5 to 14.27 h. The revised model is expected to facilitate more accurate predictions of sleep under normal conditions as well as during circadian misalignment, for example, during shiftwork and jetlag. 
27428201	New-type drugs are popular with adolescents and could lead to psychiatry disorders, but no medications have been proven to be effective for these disorders of new-type drug dependence. We aimed to evaluate the efficacy of tryptophan on sleeping disorders and mental symptoms in detoxified individuals with new-type drug dependence.This randomized, placebo-controlled trial included 80 detoxified individuals with new-type drug dependence, recruited successively from a Compulsory Residential Drug Abstinence Institution in Wuhan, China, from April 2012 to November 2012. Eligible participants were randomly allocated to be treated with tryptophan (1000 mg/d, n = 40) or placebo (n = 40) for 2 weeks. The sleeping disorders and mental symptoms were assessed using Athens Insomnia Scale and Symptom Check-List-90 at baseline and 2 weeks. Results were analyzed according to the "intention-to-treat" approach.	Forty-five participants completed the 2-week study, 24 in the tryptophan group and 21 in the placebo group. There were no statistically significant differences in baseline characteristics between groups and the treatment adherence was similar between groups. The reduction in the Athens Insomnia Scale score in the tryptophan group was significantly greater than that in the placebo group (P = 0.017). However, no significant differences were found in Symptom Check-List-90 scores (either by individual dimension or the overall score) between groups (all P > 0.05). The frequency of adverse events was similar and no serious adverse events were reported during the study.	Tryptophan was unlikely to be effective for mental symptoms, but could alleviate sleep disorders in short term among detoxified individuals with new-type drug dependence. Future large-scale trials are required to confirm findings from this study.	
27426511	The largest synaptic input to the sleep-promoting ventrolateral preoptic area (VLPO) [1] arises from the lateral hypothalamus [2], a brain area associated with arousal [3-5]. However, the neurochemical identity of the majority of these VLPO-projecting neurons within the lateral hypothalamus (LH), as well as their function in the arousal network, remains unknown. Herein we describe a population of VLPO-projecting neurons in the LH that express the vesicular GABA transporter (VGAT; a marker for GABA-releasing neurons). In addition to the VLPO, these neurons also project to several other established sleep and arousal nodes, including the tuberomammillary nucleus, ventral periaqueductal gray, and locus coeruleus. Selective and acute chemogenetic activation of LH VGAT(+) neurons was profoundly wake promoting, whereas acute inhibition increased sleep. Because of its direct and massive inputs to the VLPO, this population may play a particularly important role in sleep-wake switching. 
27426067	Burn patients are facing not only their physical recovery but also some complex problems caused by the injury, including pruritus, sleep disorders, pain, and psychological disorders. These problems may bring about challenges for survivors and burn treatment team members who work with them. The purpose of this paper is to improve the understanding and knowledge of these occult problems for clinicians in this field. 
27424986	To conduct monitoring analysis of lesion degree and long-term prognosis using ambulatory electroencephalography (aEEG) in newborns with hypoxic-ischemic encephalopathy (HIE).48 cases of newborns with HIE (aged 37 to 41 weeks) as the observation group and another 50 cases of full-term infants with non-traumatic brain illness as the control group were chosen from March 2012 to March 2013. The aEEG were observed, and the continuity and sleep-wake cycle (SWC) between the two groups were compared. The relevance of aEEG monitoring results and HIE, as well as the long-term prognosis, were analyzed.	33.33% (16/48) of EEG results appeared to be continuous and 20.83% (10/48) of the SWC results were mature for observation group. These EEG and SWC results are conspicuously lower than the control group 100% (50/50) and differences were statistically significant (p<0.05). The maximum voltage of observation group was 56.54±19.33 LV, notably higher than the control group (37.77±2.79 LV). The minimum voltage of the observation group was 4.26±1.25 LV, markedly lower than the control group (7.75±0.67 LV) and these differences were statistically significant (p<0.05). Correlational analysis based on the Spearman approach showed that the monitoring results are positively correlated with clinical classification of HIE. After six months of follow-up, 11 of the 48 cases (22.92%) were found to be disabled (including mental retardation and cerebral palsy).	aEEG enjoys easy operation, effective diagnosis, supports continuous monitoring and reflects the lesion degree as well as long-term prognosis of newborns with HIE and is, thus, highly recommended in clinical practices.	
27423356	Sleep-wake disturbances, such as sleep irregularity, are common in bipolar disorder. Early studies suggest that sleep irregularity is associated with mood symptoms in bipolar disorder, but little research has been conducted to identify other correlates of sleep irregularity. We investigated the relationship between sleep irregularity and sleep quality, social rhythms, eveningness, sleep-related cognitions and behaviors, and past and future mood episodes in 84 patients with inter-episode bipolar I or II disorder.This is a retrospective and prospective, naturalistic follow-up study. The Expanded Consensus Sleep Diary, Pittsburgh Sleep Quality Index (PSQI), Social Rhythm Metric (SRM-II-5), Composite Scale of Morningness (CSM), Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS-16), and Sleep Hygiene Practice Scale (SHPS) were administered. The Square Successive Difference (SSD), derived from a week-long sleep diary, was used as an index of sleep irregularity. Multilevel modeling analysis, which adjusts for biases in parameter estimates, was used to minimize the impact of missing data. Bonferroni correction was performed to account for multiple testing.	Higher SSD scores of sleep diary variables were significantly associated with higher PSQI, SRM-II-5, DBAS-16, and SHPS scores. Irregularity in total sleep time was related to more depressive episodes in the past 5years (p=.002), while irregularity in wake after sleep onset predicted the onset of depressive episodes over the next 2years (p=.002).	Sleep irregularity was associated with poor sleep quality, irregular social rhythms, dysfunctional sleep-related cognitions and behaviors, and greater number of depressive episodes in bipolar disorder.	
27420105	Circadian rhythms refer to oscillations in biological processes with a period of approximately 24 h. In addition to the sleep/wake cycle, there are circadian rhythms in metabolism, body temperature, hormone output, organ function and gene expression. There is also evidence of circadian rhythms in synaptic plasticity, in some cases driven by a master central clock and in other cases by peripheral clocks. In this article, I review the evidence for circadian influences on synaptic plasticity. I also discuss ways to disentangle the effects of brain state and rhythms on synaptic plasticity. 
27418862	Bipolar disorder is a serious mental illness characterized by alternating periods of elevated and depressed mood. Sleep disturbances in bipolar disorder are present during all stages of the condition and exert a negative impact on overall course, quality of life, and treatment outcomes. We examine the partnership between circadian system (process C) functioning and sleep-wake homeostasis (process S) on optimal sleep functioning and explore the role of disruptions in both systems on sleep disturbances in bipolar disorder. A convergence of evidence suggests that sleep problems in bipolar disorder result from dysregulation across both process C and process S systems. Biomarkers of depressive episodes include heightened fragmentation of rapid eye movement (REM) sleep, reduced REM latency, increased REM density, and a greater percentage of awakenings, while biomarkers of manic episodes include reduced REM latency, greater percentage of stage I sleep, increased REM density, discontinuous sleep patterns, shortened total sleep time, and a greater time awake in bed. These findings highlight the importance of targeting novel treatments for sleep disturbance in bipolar disorder. 
27415404	To date, studies on sleep disturbances in type 1 diabetes (T1D) have been limited to youth and/or small samples. We therefore assessed the prevalence of subjective sleep disturbances and their associations with glycemia and estimated insulin sensitivity in individuals with long-standing T1D.We conducted a cross-sectional study including 222 participants of the Epidemiology of Diabetes Complications study of childhood-onset T1D attending the 25-year examination (mean age=52years, diabetes duration=43years). The Berlin Questionnaire (risk of obstructive sleep apnea, OSA), the Epworth Sleepiness Scale (daytime sleepiness), and the Pittsburgh Sleep Quality Index (sleep quality, bad dreams presence, and sleep duration) were completed. Associations between sleep disturbances and poor glycemic control (HbA1c⩾7.5%/58mmol/mol), log-transformed HbA1c, and estimated insulin sensitivity (estimated glucose disposal rate, eGDR, squared) were assessed in multivariable regression.	The prevalences of high OSA risk, excessive daytime sleepiness, poor sleep quality, and bad dreams were 23%, 13%, 41%, and 26%, respectively, with more women (51%) reporting poor sleep quality than men (30%, p=0.004). Participants under poor glycemic control were twice as likely to report bad dreams (p=0.03), but not independently (p=0.07) of depressive symptomatology. Sleep duration was directly associated with HbA1c among individuals with poor glycemic control, but inversely in their counterparts (interaction p=0.002), and inversely associated with eGDR (p=0.002).	These findings suggest important interrelationships between sleep, gender, depressive symptomatology, and glycemic control, which may have important clinical implications. Further research is warranted to examine the mechanism of the interaction between sleep duration and glycemic control.	
27413344	Community pharmacists are in a suitable position to give advice and provide appropriate services related to sleep disorders to individuals who are unable to easily access sleep clinics. An intervention with proper objective measure can be used by the pharmacist to assist in consultation.The study objectives are to evaluate: (1) The effectiveness of a community pharmacy-based intervention in managing sleep disorders and (2) the role of actigraph as an objective measure to monitor and follow-up individuals with sleeping disorders.	The intervention care group (ICG) completed questionnaires to assess sleep scale scores (Epworth Sleepiness Scale [ESS] and Insomnia Severity Index [ISI]), wore a wrist actigraph, and completed a sleep diary. Sleep parameters (sleep efficiency in percentage [SE%], total sleep time, sleep onset latency, and number of nocturnal awakenings) from actigraphy sleep report were used for consultation and to validate sleep diary. The usual care group (UCG) completed similar questionnaires but received standard care.	Pre- and post-mean scores for sleep scales and sleep parameters were compared between and within groups. A significant difference was observed when comparing pre- and post-mean scores for ISI in the ICG, but not for ESS. For SE%, an increase was found in the number of subjects rated as "good sleepers" at post-assessment in the ICG.	ISI scores offer insights into the development of a community pharmacy-based intervention for sleeping disorders, particularly in those with symptoms of insomnia. It also demonstrates that actigraph could provide objective sleep/wake data to assist community pharmacists during the consultation.	
27413249	Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis. 
27395462	Dementia, including Alzheimer's disease, is often associated with various sleep disorders such as insomnia, hypersomnia, circadian rhythm sleep disorders, sleep-disordered breathing and sleep debt due to organic damages of sleep/wake-promoting nucleus and circadian center (suprachiasmatic nucleus). These sleep disorders reduce the quality of life of individuals with dementia, and increase the care burden, which are major social issues. Recent studies have revealed that sleep deterioration is not only a comorbid symptom but also a prodrome and a risk factor for the development of dementia. 
27395437	Inadequate sleep and heavy alcohol use have been associated with negative outcomes among college students; however, few studies have examined the interactive effects of sleep and drinking quantity in predicting alcohol-related consequences. This study aimed to determine if adequate sleep moderates the prospective association between weekly drinking quantity and consequences.College students (N=568) who were mandated to an alcohol prevention intervention reported drinks consumed per week, typical sleep quantity (calculated from sleep/wake times), and perceptions of sleep adequacy as part of a larger research trial. Assessments were completed at baseline and one-, three-, and five-month follow-ups.	Higher baseline quantities of weekly drinking and inadequate sleep predicted alcohol-related consequences at baseline and one-month follow-up. Significant interactions emerged between baseline weekly drinking quantity and adequate sleep in the prediction of alcohol-related consequences at baseline, one-, three-, and five-month assessments. Simple slopes analyses revealed that weekly drinking quantity was positively associated with alcohol-related consequences for those reporting both adequate and inadequate sleep, but this association was consistently stronger among those who reported inadequate sleep.	Subjective evaluation of sleep adequacy moderates both the concurrent and prospective associations between weekly drinking quantity and consequences, such that heavy-drinking college students reporting inadequate sleep experience more consequences as a result of drinking. Research needs to examine the mechanism(s) by which inadequate sleep affects alcohol risk among young adults.	
27394056	This study aimed to (1) compare sleep problems between children and adolescents with epilepsy and non-epileptic controls, and (2) examine whether there is an association between sleep problems and quality of life, Attention-Deficit Hyperactivity Disorder (ADHD) and mothers' emotional symptoms.Fifty-three patients from a cohort of epilepsy (aged 7-18 years) and 28 controls with minor medical problems (aged 7-18 years) were included. Parents completed Children's Sleep Habits Questionnaire (CSHQ) and Kinder Lebensqualitätsfragebogen: Children's Quality of Life Questionnaire-revised (KINDL-R) for patients and controls. Turgay DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S) parent and teacher forms were used to assess ADHD symptoms for patients. Mothers of the patients completed Beck Depression Inventory and State-Trait Anxiety Inventory (STAI). Neurology clinic charts were reviewed for the epilepsy-related variables.	Children with epilepsy had a higher CSHQ Total score than the control group. Those with a CSHQ score >56 (which indicates moderate to severe sleep problems) had lower scores on KINDL-R. Parent-rated T-DSM-IV-S Total and Hyperactivity-Impulsivity scores, STAI trait and Beck scores were found to be higher in those with a CSHQ score >56. Significant positive correlations were found between CSHQ Total score and T-DSM-IV-S, STAI trait and Beck scores. Binary logistic regression analysis revealed that T-DSM-IV-S Total, Inattention and Hyperactivity-Impulsivity scores were significantly associated with a higher CSHQ Total score. None of the epilepsy-related variables were found to be related with the CSHQ Total score.	Among children with epilepsy, sleep problems lead to a poor quality of life. The link between sleep problems and psychiatric symptoms must be conceptualized as a bilateral relationship. ADHD appears to be the strongest predictor of sleep problems.	
27385272	Subjective insufficient sleep and delayed sleep-wake patterns have been reported as the primary causes for daytime sleepiness, a reasonably significant and prevalent problem for adolescents worldwide. Systematic reviews have indicated that the success of sleep education programs has thus far been inconsistent, due to the lack of a tailored approach that allows for evaluation of individual differences in behavior patterns. One way to resolve this problem is to assess the individual sleep behaviors of adolescents by using a checklist containing the recommended behaviors for promoting sleep health. Such self-help education programs have already been implemented for elementary school children, school nurses and the elderly. The present study aimed to verify the effects of a sleep education program with supplementary self-help treatment, based on a checklist of sleep-promoting behaviors, in addition to evaluation of changes in sleeping patterns, sleep-promoting behaviors and daytime sleepiness in adolescents. A cluster randomized controlled trial involving 5 Japanese junior high schools was conducted, and 243 students (sleep education: n = 122; waiting list: n = 121; 50.6% female; 7th grade) were included in the final analysis. The sleep education group was provided with information on proper sleep health and sleep-promoting behaviors. The students in this group were asked to practice one sleep-promoting behavior as a goal for 2 weeks and to monitor their practice using sleep diaries. Both pre- and post-treatment questionnaires were administered to students in order to assess knowledge of sleep-promoting behaviors, sleeping patterns and daytime functioning. Students in the sleep education group showed significant improvement in their knowledge of sleep health (F1,121 = 648.05, p < 0.001) and in their sleep-promoting behaviors (F1,121 = 55.66, p < 0.001). Bedtime on both school nights (F1,121 = 50.86, p < 0.001) and weekends (F1,121 = 15.03, p < 0.001), sleep-onset latency (F1,121 = 10.26, p = 0.002), total sleep time on school nights (F1,121 = 12.45, p = 0.001), subjective experience of insufficient sleep (McNemar χ(2)(1) = 4.03, p = 0.045) and daytime sleepiness (McNemar χ(2)(1) = 4.23, p = 0.040) were also improved in the sleep education group. In contrast, no significant improvement in these variables was observed for students in the waiting-list group. In conclusion, the sleep education program with self-help treatment was effective not only in increasing sleep knowledge but also in improving sleep-promoting behavior and sleeping patterns/reducing daytime sleepiness for students in the sleep education group, in comparison with the waiting-list group. 
27385076	To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX).Of 36 patients (28-joint Disease Activity Score, DAS28CRP≥3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16.	BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6±8.8 vs. 49.4±16.6; mean disease duration (months): 19.6±46.3 vs. 81.2±79.2; and DAS28CRP: 4.4±0.9 vs. 4.4±1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p≤0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group.	Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters.	

27383495	To evaluate the safety and efficacy of Linkus, Aminophylline with Diphenhydramine group and Acefyllin Piperazine with Diphenhydramine cough syrup on children having cough and sleep difficulty associated with cough. To determine the effects of Linkus polyherbal syrup (group A) and compared with other parallel allopathic groups (Group B and C) for cough on children and associated sleep quality and improvement. 360 children having cough inducted in 3 different groups randomly selected. Three parallel groups were the part of the study. The first study group was the herbal syrup Linkus, second group of children were taking a syrup of multinational pharmaceutical industry having Aminophylline plus Diphenhydramine however the third group received another famous brand having Acefyllin Piperazine with Diphenhydramine. Informed assent and informed consent have taken from the study subjects and their parents. Subjects with acute cough were included in the study however the subjects with chronic cough considered to be excluded. Every group of individual in the study was informed about the investigational drugs provided. Ethnic groups, frequency of cough and diseases illness (<0.05) were determine on every group on the investigational syrup. Cough impact on child and its sleep of three different syrups (every group) were assessed on day1 and day 14(p<0.001) via a likert scale. For the evaluation of pain assessment Wong baker face scale were used and level of significance in each group (p<0.001). Significant results were observed in the Linkus Group as compared to the other parallel groups including Aminophylline plus Diphenhydramine and Acefyllin Piperazine with Diphenhydramine on day 14 (p<0.001). Side effects on group B and group C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine) were almost similar in number however Linkus syrup has minimum side effects on study duration. Polyherbal syrup Linkus shows better results in treatment of cough including side effects as compare to the other parallel groups B and C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine). For nocturnal sleep Linkus providing better results in cough and associated problems. Pain were significantly reduce on day 14 with the herbal Linkus syrup group A (<0.001). Group B and C found less effective with more side effects as compared to Linkus syrup. Poly herbal Linkus syrup could substantially improve the clinical effect and relieves coughs and benefit lung functions and better sleep facilitation. 
27383113	Previous epidemiological studies have suggested an association between nighttime light levels and the prevalence of obesity, although evidence is limited to cross-sectional studies.To evaluate the longitudinal association between ambient light exposure and the subsequent changes in obesity parameters.	Data from 1110 elderly participants at baseline (mean age, 71.9 years) and data from 766 at follow-up (median, 21 months) were included in this prospective population-based study.	Time-dependent ambient light exposure based on objective measurements and changes in the waist-to-height ratio (WHtR) and body mass index (BMI) were measured.	Multivariable mixed-effect linear regression models showed a significant association between light exposure and the %WHtR gain; this was independent of potential confounders (eg, caloric intake, physical activity, and sleep/wake parameters). Nighttime or evening exposure to higher light intensity was significantly associated with subsequent %WHtR gain. Morning exposure to a longer time ≥500 lux or nighttime exposure to a longer time <3 lux was significantly associated with subsequent %WHtR loss. These association trends were nearly consistent when the BMI was used as an obesity parameter. Increased nighttime light exposure (mean ≥3 vs <3 lux) was estimated to correspond to a 10.2% WHtR gain and a 10.0% increase in BMI over 10 years.	Ambient light exposure, such as increased nighttime or evening light exposure and decreased morning light exposure, was independently associated with subsequent increases in obesity parameters. Further interventional studies are warranted to establish an optimal controlled lighting environment as a preventive option against obesity.	
27382667	Every 40 seconds a person dies of cardiovascular disease.Individuals do not recognize the warning signs--prodromalsymptoms--of an imminent myocardial ischemic event. TheProdromal Symptoms-Screening Scale (PS-SS) is a nine-itemmeasure designed to evaluate PS in individuals with coronaryartery disease.This article reports onfour studies (systematic review,focusgroup study, content validity testing and factor analysis) that contributed to the development and psychometric examination ofthe PS-SS.	PS experienced included: unusual fatigue, sleep disturbance, chest pain, anxiety, gastrointestinal symptoms andshortness of breath. The CVI derived was 0.85. The PS-SS presented a two-factor structure pertaining to Specific ProdromalSymptoms and Non-Specific Prodromal Symptoms. Internal consistency reliability was 0.61.	The PS-SS reflects current prodromal literature,clinical practice and ACS patients' experiences of PS. Furtheritem generation, clarity of symptom description and psychometricevaluation needs to occur prior to use in clinical practice.Keywords: prodromal symptoms, acute coronarysyndrome, psychometric testing, tool development	
27382345	Good sleep quality and quantity are fundamental to the maintenance of normal physiological processes. Changes in sleep patterns are commonly observed among young adults and are shown to impact neurocognitive, academic, and psychological well-being. Given the scarcity of sleep information about Lebanon and acknowledging the sex differences in various sleep dimensions, we conducted a study that aimed at assessing sex differences in sleep habits among university students in Lebanon in relation to psychoacademic status. A total of 540 students (50.6% females) completed a questionnaire that inquired about sociodemographics and evaluated sleep quality and depression using the Pittsburg Sleep Quality Index (PSQI) and Center for Epidemiological Studies Depression Scale (CES-D), respectively. The mean PSQI global score (6.57±3.49) indicated poor sleep, with no significant differences between men and women. The sleep/wake rhythm was delayed on weekends for both sexes. Females exhibited earlier bedtimes and rise times and longer sleep durations on both weekdays and weekends. However, unlike males females showed a greater phase delay in wake times than bedtimes on weekends (149 minutes vs 74 minutes, respectively). In all, 70.9% of females suffered from depressive symptoms, which was a significantly higher proportion compared with 58.5% of males (P<0.01). Based on the mean cumulative self-reported grade point average (GPA), the academic performance of females was significantly better than that of males (2.8±0.61 vs 2.65±0.61, P<0.05, respectively). Depression, as scored by CES-D, in females was significantly negatively correlated with the cumulative GPA (r=-0.278, P<0.01), earlier wake time (r=-0.168, P<0.05), and average sleep duration (r=-0.221, P<0.01) on weekdays. GPA of males was significantly correlated with bedtime on weekends (r=-0.159, P<0.05). We conclude that sex differences in sleep timing, such as bedtime/rise time and nocturnal sleep duration, rather than sleep quality exist among Lebanese university students. Sex-specific sleep patterns have differential impact on psychological and academic well-being. 
27381332	People with bipolar disorder (BD) have a mortality gap of up to 20 years compared to the general population. Physical conditions, such as cardiovascular disease (CVD) and cancer, cause the majority of excess deaths in psychiatric populations and are the leading causes of mortality in people with BD. However, comparatively little attention has been paid to reducing the risk of physical conditions in psychiatric populations. Unhealthy lifestyle behaviors are among the potentially modifiable risk factors for a range of commonly comorbid chronic medical conditions, including CVD, diabetes, and obesity. This systematic review will identify and evaluate the available evidence for effective interventions to reduce risk and promote healthy lifestyle behaviors in BD.We will search MEDLINE, Embase, PsychINFO, Cochrane Database of Systematic Reviews, and CINAHL for published research studies (with at least an abstract published in English) that evaluate behavioral or psychosocial interventions to address the following lifestyle factors in people with BD: tobacco use, physical inactivity, unhealthy diet, overweight or obesity, sleep-wake disturbance, and alcohol/other drug use. Primary outcomes for the review will be changes in tobacco use, level of physical activity, diet quality, sleep quality, alcohol use, and illicit drug use. Data on each primary outcome will be synthesized across available studies in that lifestyle area (e.g., tobacco abstinence, cigarettes smoked per day), and panel of research and clinical experts in each of the target lifestyle behaviors and those experienced with clinical and research with individuals with BD will determine how best to represent data related to that primary outcome. Seven members of the systematic review team will extract data, synthesize the evidence, and rate it for quality. Evidence will be synthesized via a narrative description of the behavioral interventions and their effectiveness in improving the healthy lifestyle behaviors in people with BD.	The planned review will synthesize and evaluate the available evidence regarding the behavioral or psychosocial treatment of lifestyle-related behaviors in people with BD. From this review, we will identify gaps in our existing knowledge and research evidence about the management of unhealthy lifestyle behaviors in people with BD. We will also identify potential opportunities to address lifestyle behaviors in BD, with a view to reducing the burden of physical ill-health in this population.	PROSPERO CRD42015019993.	
27378192	To explore sleep quality in patients with chronic illness in primary care.Many people suffer from chronic illness with the numbers increasing. One common issue arises from problems that people have with their quality of sleep: a largely under-researched topic. This study exploring poor quality sleep allowed patients to describe their daily struggles with poor sleep in their own lives. This allowed the development of a deeper understanding of what it means to sleep poorly and find out how participants cope with not sleeping well.	A qualitative approach enabling a deep exploration of patient's experiences of sleep quality was used. Interviews were conducted with a purposive sample of nine participants from a primary care clinic. Analysis utilised an interpretative approach.	Data analysed produced four recurrent themes that were grouped into two categories. First, themes that identified the recognition by participants that 'something was wrong' were abrupt beginning and impact on their life. Second, themes that identified that the participants considered there was 'nothing wrong' were I am fine and I just carry on.	Data revealed that poor quality sleep can have a profound effect on quality of life. Participants lived without good quality sleep for years. They had come to accept two seemingly irreconcilable ideas that not being able to sleep is an enduring problem with a distinct starting point, and paradoxically, this is not a problem that deserves much professional attention.	Important original data were generated on the impact of poor quality sleep indicating that chronically disturbed sleep can increase the disease burden on patients with chronic illness. The results of this study suggest healthcare professionals need to understand how sleep quality issues impact on patient's experience of chronic illness. Data from this study will help nurses and other health professionals to deepen their understanding of the profound impact of poor quality sleep on patients with chronic illness. A programme of education highlighting the important role of sleep quality in chronic illness is suggested by the issues raised in this study. Nurses are ideally placed to assess sleep quality in patients and tailor intervention to positively affect the quality of life for this group.	
27372436	Poor sleep quality contributes to the inferior quality of life of patients with Parkinson's disease (PD) despite appropriate treatment of motor symptoms. The literature about the impact of sleep quality on quality of life of patients with PD is as yet sparse.One hundred patients of PD diagnosed as per UK Brain Bank criteria were assessed for severity and stage of PD using UPDRS and modified Hoehn &Yahr scales. The quality of sleep was assessed by Pittsburgh Sleep Quality Index and excessive daytime somnolence (EDS) was evaluated using Epworth Sleepiness Scale. Parkinson's Disease Questionnaire -39 (PDQ-39) was used to determine quality of life of the patients. Comorbid depression and anxiety were assessed using Inventory of Depressive Symptoms-Self Rated and Hamilton Anxiety Rating Scale. Pearson's correlation and multiple linear regressions were used to analyze relation of sleep quality with quality of life of patients.	Fifty patients had poor sleep quality. EDS was present in only 9 patients. Co-morbid depression and anxiety were present in 52 and 34 patients respectively. While the motor severity assessed by UPDRS-III was observed to adversely affect quality of life, it did not negatively impact quality of sleep. Higher score on UPDRS-total and UPDRS IV suggesting advanced disease correlated with poor sleep quality. Depression and anxiety were significantly more frequent in patients with poor sleep quality (p<0.01). Patients with poor sleep quality had worse quality of life (r=0.338, p<0.05). Depression and anxiety were also observed to have significant negative impact on quality of life of PD patients (p<0.01). Poor sleep quality was not found to be an independent predictor of quality of life using multiple linear regression analysis.	Poor sleep quality along with comorbid depression, anxiety and advanced stage of disease is associated with poor quality of life.	
27372108	Collectively, cross-sectional and longitudinal studies on self-reported sleep duration and obesity do not show a clear pattern of association with some showing a negative linear relationship, some showing a U-shaped relationship, and some showing no relationship. Associations between sleep duration and obesity seem stronger in younger adults. Cross-sectional studies using objectively measured sleep duration (actigraphy or polysomnography (PSG)) also show this mixed pattern whereas all longitudinal studies to date using actigraphy or PSG have failed to show a relationship with obesity/weight gain. It is still too early and a too easy solution to suggest that changing the sleep duration will cure the obesity epidemic. Given novel results on emotional stress and poor sleep as mediating factors in the relationship between sleep duration and obesity, detection and management of these should become the target of future clinical efforts as well as future research. 
27368060	The purpose of the present study was to determine the efficacy of the multi-component training distress scale (MTDS), in monitoring swimmers prior to national competition. Twenty-one national-level adolescent swimmers completed eight weeks of testing. Once a week participants completed an 8 × 50 m sprint test, vertical jump test, sit-and-reach test, the MTDS and the Recovery-Stress Questionnaire for Athletes (REST-Q). All testing was incorporated into the swimmers' normal training programme. The REST-Q accounted for the following variances in performance: flexibility (14.6%, p = 0.009), power output (17.7%, p = 0.003), swimming speed (15.5%, p = 0.006) and swimming endurance (17.5%, p = 0.002). In comparison, the MTDS accounted for the following variances in performance: flexibility (12.1%, p = 0.095), power output (16.4%, p = 0.023), swimming speed (20.5%, p = 0.003) and swimming speed endurance (23.8%, p = 0.001). The findings of the current study suggest that both the REST-Q Sport and the MTDS have the capacity to predict performance on a range of fitness components associated with swimming. 
27364793	Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by recurrent episodes of hypersomnia. Polysomnographic (PSG) researches of KLS have been reported only in few publications in the past decades. This study aimed to investigate the characteristics of PSG of KLS.This study, which was conducted from March 2010 to July 2014, included seven patients diagnosed with KLS in the Sleep and Wake Disorder Center of Huashan Hospital, Fudan University (Shanghai, China). PSG and multiple sleep latency tests (MSLT) were performed during their episodes and the results were evaluated.	Five of the seven patients were males. The mean age at KLS onset was 15.6 ± 3.6 years. The number of episodes ranged from 2 to 7. The duration of episodes lasted from 4 to 11 days. The sleep architecture and proportion were normal in most of the patients. The average value of mean sleep latency was 6.9 ± 4.1 min. No sleep-onset rapid eye movement (SOREM) was detected in three of the patients, whereas one patient experienced one period of SOREM, and such episodes occurred twice in other two patients.	We found that sleep architecture and proportion were normal in most KLS patients. However, the results of PSG and MSLT had no specificity for KLS patients.	
27364774	Male erectile dysfunction (ED) may cause anxiety and depression, while mental disorders and sleep disturbances may also be closely related to ED. However, the exact nature of their relationship remains unclear, and whether personal basic background data affect erectile function is unknown. We conducted a cross-sectional study among Chinese outpatients with ED from January 2012 to December 2014. All the men answered a questionnaire collecting information about mental health status, sleep disturbances and personal data, underwent a physical examination and had a blood sample drawn. Sleep disturbances were assessed on the basis of a 19-item version of the Pittsburgh Sleep Quality Index, which includes questions on sleep patterns during the past month. Among the 462 patients, 128 patients with alcohol abuse, diabetes, hypertension, hyperlipidaemia, psychiatric drugs, neurologic injury or abnormal hormones were excluded from the study; 86.27% and 68.66% of the patients suffered from anxiety and depression respectively. Sleep quality and anxiety symptoms significantly affected erectile function, whereas personal income and education level had no significant effects. Our study suggested that it is necessary to pay attention to the psychological status of patients with ED, especially anxiety disorder. Sleep quality may be an important factor affecting erectile function according to the personal data.
27362512	Sleep disturbance is common among patients with heart failure (HF) who also experience symptom burden and poor functional performance.We evaluated the extent to which sleep-related, daytime symptoms (fatigue, excessive daytime sleepiness, and depressive symptoms) mediate the relationship between sleep disturbance and functional performance among patients with stable HF.	We recruited patients with stable HF for this secondary analysis of data from a cross-sectional, observational study. Participants completed unattended ambulatory polysomnography from which the Respiratory Disturbance Index was calculated, along with a Six-Minute Walk Test, questionnaires to elicit sleep disturbance (Pittsburgh Sleep Quality Index, Insomnia Symptoms from the Sleep Habits Questionnaire), daytime symptoms (Center for Epidemiologic Studies Depression Scale, Global Fatigue Index, Epworth Sleepiness Scale), and self-reported functional performance (Medical Outcomes Study SF36 V2 Physical Function Scale). We used structural equation modeling with latent variables for the key analysis. Follow-up, exploratory regression analysis with bootstrapped samples was used to examine the extent to which individual daytime symptoms mediated effects of sleep disturbance on functional performance after controlling for clinical and demographic covariates.	The sample included 173 New York Heart Association Class I-IV HF patients (n = 60/34.7% women; M = 60.7, SD = 16.07 years of age). Daytime symptoms mediated the relationship between sleep disturbance and functional performance. Fatigue and depression mediated the relationship between insomnia symptoms and self-reported functional performance, whereas fatigue and sleepiness mediated the relationship between sleep quality and functional performance. Sleepiness mediated the relationship between the respiratory index and self-reported functional performance only in people who did not report insomnia.	Daytime symptoms explain the relationships between sleep disturbance and functional performance in stable HF.	
27357996	The purpose of this study was to determine the levels of sleep problems, anxiety, depression and fatigue in family members of intensive care patients in Turkey and factors affecting these complaints. This cross-sectional study was carried out with 350 first-degree relatives of intensive care patients at a university and state hospital. Data were collected between 5 January and 30 May 2014 using a personal information form, the Visual Analogue Scale for Fatigue, the Hospital Anxiety and Depression Scale and the modified Post Sleep Inventory. Of the 350 family members, 76% reported moderate or more serious problems. Anxiety was reported by 81.4% of the family members, and depression by 94.2%. Family members in the study had fatigue, with average scores of 79.42. There were significant correlations between the Visual Analogue Scale for Fatigue and anxiety, depression and scores on the Modified Post-Sleep Inventory (P < 0.05). Family members of intensive care patients experienced symptoms of fatigue, anxiety, depression and sleep problems. The prevalence of symptoms of sleep problems, anxiety and depression and complaints of fatigue was significantly higher in the family members of intensive care patients in Turkey than reported in the literature.
27355229	To estimate prevalence and identify predictors and outcomes of reporting sleep problems in M&#257;ori and non-M&#257;ori of advanced age.Participants were 251 M&#257;ori, and 398 non-M&#257;ori adults (79-90 years) from Te Pu&#257;waitanga o Ng&#257; Tapuwae Kia Ora Tonu. Life and Living in Advanced Age: A Cohort Study in New Zealand. Multiple logistic regression identified predictors of reporting a current sleep problem and investigated relationships between current sleep problems and physical and mental health.	26.3% of M&#257;ori and 31.7% of non-M&#257;ori reported a current sleep problem. Reporting a current sleep problem was associated with ethnicity (non-M&#257;ori, adjusted OR=0.52, 95% CI=0.30-0.90), and reporting a past sleep problem (adjusted OR=2.67, 95% CI=1.25-5.72). Sleep problems were related to poorer physical and mental health, and falling.	Sleep problems are commonly reported and associated with poorer health. Early recognition and management of sleep problems could improve physical and mental health.	
27354979	Poor quality of sleep is a distressing and worrying condition that can disturb academic performance of medical students. Sleep hygiene practices are one of the important variables that affect sleep quality. The objective of this study was to assess association between sleep hygiene practices and sleep quality of medical students in Qazvin University of Medical Sciences.In this descriptive-correlational study, a total of 285 medical students completed a self-administered questionnaire. Demographic data, sleep-wake schedule in weekday and weekend, and sleep duration were collected. Students' sleep quality was assessed by Pittsburg Sleep Quality Index (PSQI). Data were analyzed by SPSS Ver 13.	Overall, 164 (57.5) of students had poor sleep quality. Mean global PSQI score and average score of four subscales were significantly higher in male than female. Regression analysis showed that male students (β=-0.85, P<0.05), students at senior level (β=-0.81, P<0.05), married students (β=-0.45, P<0.05), and those with improper sleep hygiene practices slept worse.	The findings of this study showed that the prevalence of poor sleep quality in medical students is high. Improper sleep hygiene behaviors might be a reason for poor quality of sleep in medical students.	
27353709	This study aims to assess the status of successful aging (SA) in longevity areas in China and explore multiple factors associated with SA among the young-old and oldest-old.A total of 2296 elderly people aged 65 and older were interviewed in the longevity areas sub-sample of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2012. Baseline assessments included a researcher-administered questionnaire, physical examination, and laboratory testing. A logistic regression model was used to identify factors associated with SA.	The prevalence of SA was 38.81% in the CLHLS in 2012. There were significant differences between ages groups, with SA compromising 56.85% among ⋝65 years group and 20.31% among ⋝100 years group (χ2trend=126.73, P<0.01). The prevalence of SA among females was 33.59%, which was significantly lower than that among males (45.58%) (χ2gender=33.65, P<0.05). In the regression analysis, having anemia (OR=0.744, 95% CI: 0.609-0.910), poor lifestyle (OR=0.697, 95% CI: 0.568-0.854), poor sleep quality (OR=0.558, 95% CI: 0.456-0.682), and central obesity (OR=0.684, 95% CI: 0.556-0.841) were the main factors associated with SA. The promoting SA rate decreased as age increased, and the group of 65-79 years had higher odds than the other age group.	Preventing central obesity, improving sleep quality and promoting healthy lifestyle may contribute to achieve SA among the elderly.	
27351568	To observe the development of neonatal sleep among healthy infants of different conceptional age (CA) by analyzing the amplitude-integrated electroencephalography (aEEG) of their sleep-wake cycles (SWC).Bedside aEEG monitoring was carried out for healthy newborns from 32 to 46 weeks CA between September 1, 2011 and August 30, 2012. For each aEEG tracing, mean duration of every complete SWC, number of SWC repetition within 12 hours, mean duration of each narrow and broadband of SWC, mean voltage of the upper edge and lower edge of SWC, mean bandwidth of SWC were counted and calculated. Analysis of the correlations between voltages or bandwidth of SWC and CA was performed to assess the developmental changes of central nervous system of newborns with different CA.	The SWC of different CA on aEEG showed clearly identifiable trend after 32 weeks of CA. The occurrence of SWC gradually increases from preterm to post-term infants; term infants had longer SWC duration. The voltage of upper edge of the broadband decreased at 39 weeks, while the lower edge voltage increases and the bandwidth of broadband declined along with the growing CA. The upper edge of the narrowband dropped while the lower edge rised gradually, especially in preterm stage. The width of the narrowband narrowed down while CA increased.	The SWC on aEEG of 32-46 weeks infants showed a continuous, dynamic and developmental progress. The appearance of SWC and the narrowing bandwidth of narrowband is the main indicator to identify the CA-dependent SWC from the preterm to the late preterm period. The lower edge of the broadband identifies the term to post-term period.	
27351343	Cigarette smoking during adolescence is linked to a number of sleep disturbances and has been consistently linked to sleep onset latency among adults. However, little research has examined factors that may influence the relation between cigarette smoking level and sleep onset latency among adolescents. One factor that may be particularly important in this regard is anxiety sensitivity (AS). The current study examined whether cigarette smoking level interacted with AS in its association with sleep onset latency among 94 adolescent (Mage = 15.72) cigarette smokers. As hypothesized, AS interacted with smoking level to relate to sleep onset latency, even after controlling for age and gender. This relation was specific to sleep onset latency as opposed to other types of sleep disturbances, and that adolescents who smoked at higher levels tended to go to sleep later and wake up later than adolescents who smoked at relatively lower levels.
27348620	In this study, we explore the sleep disorders and its associated factors in patients with Guillain-Barré syndrome (GBS), so as to work out appropriate interventions to promote early recovery of the patients. This study subjects included 49 patients with GBS who had been admitted to the Department of Neurology at The Affiliated Hospital of Hebei University, fulfilling National Institute of Neurological and Communicative Diseases and Stroke (NINCDS) criteria for GBS; 37 cases were male and 12 female (age: 27-68 years). Patients were evaluated once daily for two consecutive weeks. By using Wong and Baker Face Scale (WBFS) to evaluate the numbness and pain in patients, 0 points representing completely no pain and 10 points represents the most severity of the pain reactions; the same applies for numbness. The GBS Disability Scale (GBS DS) is used to evaluate the severity of GBS. The Hospital Anxiety and Depression Scale (HADS) is used to evaluate the anxiety and depression the patient is experiencing. All patients take routine EMG and sleep EEG. The sleep quality of the subjects was evaluated by the Pittsburgh Sleep Quality Index Scale (PSQI) and Richard Campbell Sleep Rating Scale. This study found that the application of ventilators, numbness, anxiety and severe limb movement disorders are the main factors causing sleep disorders. Cerebrospinal fluid (CSF) protein concentration is also associated with sleep disorders. But, no obvious abnormalities were found in sleep EEG. The application of the ventilator, numbness, anxiety and severe limb movement disorder are main factors causing sleep disorders. CSF protein concentration is also associated with sleep disorders. 
27339435	Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).	We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies	Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.	Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.	We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.	Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.	
27338977	Gender differences in the epidemiology, pathophysiology, clinical manifestations and outcomes of cardiovascular disease are well established but there is still a lack of awareness of this both in the general population and among healthcare providers. In addition to the traditionally recognized cardiovascular risk factors, more recently psychosocial risk factors such as stress, mood disorders, low socioeconomic status and sleep disorders have been linked to cardiovascular diseases and hypertension. Psychosocial factors may have different cardiovascular consequences in men and women; thus further efforts are required to explore pathophysiological mechanisms, to obtain gender-specific data from clinical trials and to translate this knowledge into everyday clinical practice.
27334057	Almost all living organisms, including humans, exhibit diurnal rhythms of physiology and behavior, which are driven by the circadian clock. Many studies have found that chronic misalignment between circadian and environmental/social rhythms carries a significant risk of various disorders, including sleep disorders, metabolic syndrome, cardiovascular diseases and cancer. However, irregular sleep-wake cycles and circadian maladjustment often cause 'social jet lag', which is minor but chronic jet-lag in our daily lives. Establishment of objective and convenient circadian-phase estimation methods in the clinical setting would therefore greatly contribute not only to resolving this global health problem but also to developing chronomedicine, a clinical approach for optimizing the time of day of treatments. Traditional melatonin-based methods have limitations with respect to circadian-phase evaluation; however, estimation methods based on clock gene expression may be able to compensate for these limitations. As a representative application of circadian-phase estimation based on clock gene expression, our method of using hair follicle cells may aid in the rapid clinical detection of circadian-related sleep problems, especially circadian rhythm sleep disorders that are masked because of forced adaptation to social time schedules. 
27332066	Retrospective review of medical records from patients with multiple sclerosis to collect data on severity of fatigue, disability, daytime sleepiness, and depression. From 912 medical records reviewed, 122 reported daytime sleepiness: 67% had relapsing remitting, 12% had primary progressive, and 21% had secondary progressive.In 95% of the patients with relapsing remitting who complained of daytime sleepiness and fatigue, association was found between these symptoms and neurological disability. Patients with relapsing remitting who complained of daytime sleepiness and fatigue also experienced depression (p = 0.001). No association between fatigue, excessive daytime sleepiness, depression, and disability was found in patients with progressive disease.	In relapsing remitting, there is correlation between functional disability, excessive daytime sleepiness and fatigue, a finding not confirmed in primary progressive and secondary progressive form.	

27330163	The aim was to investigate the importance of aspects of health for patients with axial SpA (axSpA) and to explore differences across different subgroups.A Best Worst Scaling exercise was conducted in patients with axSpA from 20 countries (10 patients per country) worldwide. Using the 17 items of the Assessment of SpondyloArthritis international Society Health Index, a set of 17 choice tasks was generated. Patients had to indicate in each choice task the most and least important out of four varying items. The hierarchical Bayes method was used to estimate the relative importance score for each item (summing to 100). Subgroup comparisons were performed for relevant demographic (gender, age, work status, geographical area and education) and disease characteristics (SpA phenotype, disease duration and disease activity) using one-way analysis of variance or the Mann-Whitney U-test.	The experiment was completed by 199 patients with axSpA [117 (58.8%) men, mean (sd) age 42.3 (13.6) years, mean (sd) disease duration 11.1 (11.2) years, 130 (65.3%) AS]. The highest relative importance was assigned to pain (14.2; 95% CI: 13.8, 14.6), sleep (10.3; 95% CI: 9.6, 11.0), being exhausted (9.6; 95% CI: 9.0, 10.3), standing (9.25; 95% CI: 8.5, 10.0) and motivation to do anything that requires physical effort (8.7; 95% CI: 8.1, 9.3). The lowest relative importance was assigned to sexual relationships, toileting, contact with people, driving and washing hair. Differences between subgroups were small or in aspects with lower importance.	A clear gradient was seen in the importance of the different aspects of health that impact functioning of patients with axSpA. Differences between subgroups were small or non-existent. These findings help to align clinical care to patients' needs.	
27329002	To study the phenomenology and motor sub-types of delirium in patients admitted in a Coronary Care Unit (CCU).Three hundred and nine consecutive patients were screened for delirium, and those found positive for the same were evaluated by a psychiatrist on DSM-IVTR criteria to confirm the diagnosis. Those with a diagnosis of delirium were evaluated on the DRS-R-98 to study the phenomenology and on the amended Delirium Motor Symptom Scale (DMSS) to study the motor sub-types.	Eighty-one patients were found to have delirium. Commonly seen symptoms of delirium included: disturbances in sleep-wake cycle, lability of affect, thought abnormality, disturbance in attention, disorientation, short-term memory, and long-term memory. Very few patients had delusions. More than half of the participants were categorized as having hyperactive (n = 46; 56.8%) followed by hypoactive sub-type (n = 21; 26%) and mixed sub-type (n = 9; 11.1%) of delirium. There were minor differences in the frequency and severity of symptoms of delirium between incidence and prevalence cases of delirium and those with different motoric sub-types.	Delirium in CCU set-up is characterized by the symptoms of disturbances in sleep-wake cycle, lability of affect, thought abnormality, disturbance in attention, disorientation, short-term memory, and long-term memory. Hyperactive delirium is more common than hypoactive delirium.	
27327537	We explored the effects of acupressure training on older adults' sleep quality and cognitive function. Ninety older adults with impaired sleep quality were selected from screened volunteers and randomly divided into equal control and experimental groups; 82 completed the 1-year follow-up. Participants in the control group were given instructions on sleep health, while those in the experimental group received sleep health instructions plus individual and small group acupressure training sessions and support to practice the intervention on their own each day. All participants were assessed by trained assistants blind to study group allocation using Chinese versions of the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Mini-Mental State Examination, and four subscales from the revised Chinese version of the Wechsler Memory Scale, at baseline and at 3, 6, and 12 months. Repeated measures analysis of variance showed that acupressure training improved older adults' sleep quality and cognitive function, but the mediating effect of sleep on the relationship between acupressure training and cognitive function was not supported. Given the ease, simplicity, and safety of acupressure training observed with community-dwelling older adults in China, attempts should be made to replicate these preliminary positive findings with larger samples. © 2016 Wiley Periodicals, Inc. 
27320125	Disruption of sleep/wake activity in Alzheimer's disease (AD) patients significantly affects their quality of life and that of their caretakers and is a major contributing factor for institutionalization. Levels of amyloid-β (Aβ) have been shown to be regulated by neuronal activity and to correlate with the sleep/wake cycle. Whether consolidated sleep can be disrupted by Aβ alone is not well understood. We hypothesize that Aβ42 can increase wakefulness and disrupt consolidated sleep. Here we report that flies expressing the human Aβ42 transgene in neurons have significantly reduced consolidated sleep compared with control flies. Fatty acid binding proteins (Fabp) are small hydrophobic ligand carriers that have been clinically implicated in AD. Aβ42 flies that carry a transgene of either the Drosophila Fabp or the mammalian brain-type Fabp show a significant increase in nighttime sleep and long consolidated sleep bouts, rescuing the Aβ42-induced sleep disruption. These studies suggest that alterations in Fabp levels and/or activity may be associated with sleep disturbances in AD. Future work to determine the molecular mechanisms that contribute to Fabp-mediated rescue of Aβ42-induced sleep loss will be important for the development of therapeutics in the treatment of AD. © 2016 Wiley Periodicals, Inc.
27319613	To explore factors related to sleep disturbance in patients with rheumatoid arthritis (RA).Cross-sectional data from 986 patients in the Oslo RA Register (ORAR) collected in 2009 were included. Sleep problems were assessed by four measures: the Medical Outcomes Study (MOS) sleep disturbance scale, and the sleep components of the Rheumatoid Arthritis Impact of Disease (RAID) score, the Multi-Dimensional Health Assessment Questionnaire (MDHAQ), and the 15-dimensional quality of life questionnaire (15D). Patient-reported outcomes (PROs) were recorded using standard questionnaires for physical and mental function [the HAQ and the MOS 36-item Short-Form Health Survey (SF-36), disease activity (the RA Disease Activity Index, RADAI), utility (SF-6D), and visual analogue scales (VAS) for pain, fatigue, and disease activity]. Demographics including comorbidity were collected. Information on use of medication for RA and sleep disturbance was obtained using checklists. Multivariate analyses were used to identify factors independently associated with sleep problems by four different measures.	The mean (standard deviation, SD) age of the patients was 59.4 (12.5) years, 76.9% were females, and the mean (SD) disease duration was 13.7 (10.7) years. The correlation between the various sleep measures was high (r2 = 0.71-0.78). Sleep disturbance was moderately correlated to pain (r2 = 0.41-0.61), fatigue (r2 = 0.44-0.58), physical function (r2 = 0.33-0.48), RADAI (r2 = 0.42-0.55), and utility (r2 = 0.49-0.61). RAID sleep demonstrated the highest correlation with other PROs. RADAI, fatigue, the mental component score of SF-36, physical function, body mass index (BMI), and use of Z-drugs/benzodiazepines were independently associated with two or more measures of sleep problems (all p < 0.001).	Sleep disturbance measured by four different measures was independently related to other PROs including fatigue, pain, and disease activity in RA patients.	
27319572	Most actigraphy devices use different analysis methods and a non-standardized threshold value to estimate sleep/wake status and identify rest intervals. To address limitations of these approaches, a new algorithm was developed that makes no assumptions about sleep/wake status, objectively selects an optimal threshold for different populations, and provides mathematical endpoints to more fully describe the activity patterns of subjects. The optimal threshold (cts min(-1)) is defined as the value that maximizes the duration of the rest period while minimizing the inclusion of epochs from the active period. This value is identified as the beginning of a plateau region of a rest duration versus threshold value graph. Application of this new algorithm to data from 56 healthy adults, 6 healthy children, and 14 children with autism spectrum disorder (ASD) showed that the three groups had different optimal threshold values (35, 40, and 45 cts min(-1) for adults, children and ASD respectively). The rest periods of healthy children was longer than that of adults (8.5  ±  0.5 versus 6.3  ±  0.9 h, p  <  0.001). Healthy children also had less activity during the rest periods than adults (10.5  ±  1.8 versus 15.1  ±  11.8 cts min(-1)) and ASD children (12.0  ±  2.2 cts min(-1)) but these differences were not statistically significant. However, the distributions of their activity values during rest periods as measured by skewness and kurtosis were significantly greater than that of healthy adults (skewness: 7.3  ±  0.9 versus 6.2  ±  0.9, p  <  0.01, kurtosis: 83.3  ±  16.5 versus 52.8  ±  14.4, p  <  0.001) and of ASD children (skewness: 6.4  ±  0.6. p  <  0.05, kurtosis: 57.7  ±  12.8, p  <  0.001). These findings are consistent with more restful sleep patterns which would have mostly low levels of activity with few large values. The new analysis tool may be helpful in standardizing actigraphy data analyses while providing new insights into activity patterns.
27319034	The use of CBCT technology in the dental office is increasing rapidly. These scans provide information on anatomy not previously evaluated with traditional 2D films. One structure often mentioned in a CBCT radiology report is the pineal gland. The pineal gland will show evidence of calcification, but this calcification is often dismissed as a normal aging process. This review of the function and influence of the pineal gland may influence the doctor to complete further evaluation of the patient.
27318227	Circadian rhythm sleep-wake disorders (CRSWDs) often manifest during the adolescent years. Measurement of circadian phase such as the dim light melatonin onset (DLMO) improves diagnosis and treatment of these disorders, but financial and time costs limit the use of DLMO phase assessments in clinic. The current analysis aims to inform a cost-effective and efficient protocol to measure the DLMO in older adolescents by reducing the number of samples and total sampling duration.A total of 66 healthy adolescents (26 males) aged 14.8-17.8 years participated in a study; they were required to sleep on a fixed baseline schedule for a week before which they visited the laboratory for saliva collection in dim light (<20 lux). Two partial 6-h salivary melatonin profiles were derived for each participant. Both profiles began 5 h before bedtime and ended 1 h after bedtime, but one profile was derived from samples taken every 30 min (13 samples) and the other from samples taken every 60 min (seven samples). Three standard thresholds (first three melatonin values mean + 2 SDs, 3 pg/mL, and 4 pg/mL) were used to compute the DLMO. An agreement between DLMOs derived from 30-min and 60-min sampling rates was determined using Bland-Altman analysis; agreement between the sampling rate DLMOs was defined as ± 1 h.	Within a 6-h sampling window, 60-min sampling provided DLMO estimates within ± 1 h of DLMO from 30-min sampling, but only when an absolute threshold (3 or 4 pg/mL) was used to compute the DLMO. Future analyses should be extended to include adolescents with CRSWDs.	
27318095	Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy. 
27317942	Serotonin (5-hydroxytryptamine, 5-HT) contributes in multifarious ways to the regulation of brain function, spanning key aspects such as the sleep-wake cycle, appetite, mood and mental health. The 5-HT receptors comprise seven receptor families (5-HT1-7) that are further subdivided into 14 receptor subtypes. The role of the 5-HT receptor in the modulation of neuronal excitability has been well documented. Recently, however, it has become apparent that the 5-HT4 receptor may contribute significantly to cognition and regulates less ostensible aspects of brain function: it engages in metaplastic regulation of synaptic responsiveness in key brain structures such as the hippocampus, thereby specifically promoting persistent forms of synaptic plasticity, and influences the direction of change in synaptic strength in selected hippocampal subfields. This highly specific neuromodulatory control by the 5-HT4 receptor may in turn explain the reported role for this receptor in hippocampus-dependent cognition. In this review article, we describe the role of the 5-HT4 receptor in hippocampal function, and describe how this receptor plays a unique and highly specialised role in synaptic information storage and cognition.
27315795	Sleep problems are common in adolescents and can have a negative impact on daily functioning and quality of life; therefore recognition of sleep problems is important. The PROMIS (Patient-Reported Outcomes Information System) Sleep Disturbance (SD) and Sleep Related Impairment (SRI) items banks are internationally used, well-validated instruments developed for and tested in adults. This study evaluates the content validity of the self- and proxy versions of the PROMIS-SD and the PROMIS-SRI in adolescents.Experts (n = 6), adolescents (n = 24, 12-18 years) and their parents (n = 7) commented on the relevance and comprehensibility of the item banks.	Experts considered all items relevant, only a few items were found irrelevant by adolescents and parents. The majority of items were comprehensible. The ability of parents to report on their adolescent's sleep was limited.	The PROMIS-SD and PROMIS-SRI have adequate content validity in adolescents. Considering their psychometric robustness and the possibility of Computerized Adaptive Testing, which is efficient as well as patient-friendly, these item banks could prove very useful in the evaluation of adolescent sleep. The validity of the proxy scales, however, is limited considering the difficulties reported by the parents. Further psychometric evaluation of these scales in adolescents is required.	
27313610	The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1-3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined. 
27312978	Fibromyalgia is characterized by chronic widespread pain, fatigue and nonrestorative sleep. Polysomnography showed reduced short-wave sleep and abnormal alpha rhythms during nonrapid eye movement sleep in patients with fibromyalgia. However, sleep dysfunction might be pathogenic in fibromyalgia since myalgia and fatigue could be induced in healthy individuals by disrupting sleep. Poor sleep quality was a major risk factor for the subsequent development of chronic widespread pain in healthy pain-free individuals. Sleep disruption leads to impairment of the descending pain inhibition pathways. Aside from good sleep, hygiene, exercise can promote sleep. Among currently available pharmacological treatments, evidence suggests amitriptyline and pregabalin can improve sleep in fibromyalgia. 
27312974	Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h "days" in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD (p = 0.007, p = 0.06) and control participants (p < 0.001, p = 0.02, respectively). Between 12% and 19% of the variance in DSWPD patients' sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients' persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD disorders. 
27308960	Biological processes are organized in time as innate rhythms defined by the period (τ), phase (peak [Φ] and trough time), amplitude (A, peak-trough difference) and mean level. The human time structure in its entirety is comprised of ultradian (τ < 20 h), circadian (20 h > τ < 28 h) and infradian (τ > 28 h) bioperiodicities. The circadian time structure (CTS) of human beings, which is more complicated than in lower animals, is orchestrated and staged by a brain central multioscillator system that includes a prominent pacemaker - the suprachiasmatic nuclei of the hypothalamus. Additional pacemaker activities are provided by the pineal hormone melatonin, which circulates during the nighttime, and the left and right cerebral cortices. Under ordinary circumstances this system coordinates the τ and Φ of rhythms driven by subservient peripheral cell, tissue and organ clock networks. Cyclic environmental, feeding and social time cues synchronize the endogenous 24 h clocks and rhythms. Accordingly, processes and functions of the internal environment are integrated in time for maximum biological efficiency, and they are also organized and synchronized in time to the external environment to ensure optimal performance and response to challenge. Artificial light at night (ALAN) exposure can alter the CTS as can night work, which, like rapid transmeridian displacement by air travel, necessitates realignment of the Φ of the multitude of 24 h rhythms. In 2001, Stevens and Rea coined the phrase "circadian disruption" (CD) to label the CTS misalignment induced by ALAN and shift work (SW) as a potential pathologic mechanism of the increased risk for cancer and other medical conditions. Current concerns relating to the effects of ALAN exposure on the CTS motivated us to renew our long-standing interest in the possible role of CD in the etiopathology of common human diseases and patient care. A surprisingly large number of medical conditions involve CD: adrenal insufficiency; nocturia; sleep-time non-dipping and rising blood pressure 24 h patterns (nocturnal hypertension); delayed sleep phase syndrome, non-24 h sleep/wake disorder; recurrent hypersomnia; SW intolerance; delirium; peptic ulcer disease; kidney failure; depression; mania; bipolar disorder; Parkinson's disease; Smith-Magenis syndrome; fatal familial insomnia syndrome; autism spectrum disorder; asthma; byssinosis; cancers; hand, foot and mouth disease; post-operative state; and ICU outcome. Poorly conceived medical interventions, for example nighttime dosing of synthetic corticosteroids and certain β-antagonists and cyclic nocturnal enteral or parenteral nutrition, plus lifestyle habits, including atypical eating times and chronic alcohol consumption, also can be causal of CD. Just as surprisingly are the many proven chronotherapeutic strategies available today to manage the CD of several of these medical conditions. In clinical medicine, CD seems to be a common, yet mostly unrecognized, pathologic mechanism of human disease as are the many effective chronotherapeutic interventions to remedy it. 
27306267	The rise in obesity has been paralleled by a decline in sleep duration in epidemiological studies. However, the potential mechanisms linking energy balance and the sleep/wake cycle are not well understood. We aimed to examine the effects of manipulating energy balance on the sleep/wake cycle.Twelve healthy normal weight men were housed in a clinical research facility and studied at three time points: baseline, after energy balance was disrupted by 2 days of caloric restriction to 10% of energy requirements, and after energy balance was restored by 2 days of ad libitum/free feeding. Sleep architecture, duration of sleep stages, and sleep-associated respiratory parameters were measured by polysomnography.	Two days of caloric restriction significantly increased the duration of deep (stage 4) sleep (16.8% to 21.7% of total sleep time; P = 0.03); an effect which was entirely reversed upon free feeding (P = 0.01). Although the apnea-hypopnea index stayed within the reference range (< 5 events per hour), it decreased significantly from caloric restriction to free feeding (P = 0.03). Caloric restriction was associated with a marked fall in leptin (P < 0.001) and insulin levels (P = 0.002). The fall in orexin levels from baseline to caloric restriction correlated positively with duration of stage 4 sleep (Spearman rho = 0.83, P = 0.01) and negatively with the number of awakenings in caloric restriction (Spearman rho = -0.79, P = 0.01).	We demonstrate that changes in energy homeostasis directly and reversibly impact on the sleep/wake cycle. These findings provide a mechanistic framework for investigating the association between sleep duration and obesity risk.	
27306266	Intermittent short sleep (ISS) is pervasive among students and workers in modern societies, yet the lasting consequences of repeated short sleep on behavior and brain health are largely unexplored. Wake-activated neurons may be at increased risk of metabolic injury across sustained wakefulness.To examine the effects of ISS on wake-activated neurons and wake behavior, wild-type mice were randomized to ISS (a repeated pattern of short sleep on 3 consecutive days followed by 4 days of recovery sleep for 4 weeks) or rested control conditions. Subsets of both groups were allowed a recovery period consisting of 4-week unperturbed activity in home cages with littermates. Mice were examined for immediate and delayed (following recovery) effects of ISS on wake neuron cell metabolics, cell counts, and sleep/wake patterns.	ISS resulted in sustained disruption of sleep/wake activity, with increased wakefulness during the lights-on period and reduced wake bout duration and wake time during the lights-off period. Noradrenergic locus coeruleus (LC) and orexinergic neurons showed persistent alterations in morphology, and reductions in both neuronal stereological cell counts and fronto-cortical projections. Surviving wake-activated neurons evidenced persistent reductions in sirtuins 1 and 3 and increased lipofuscin. In contrast, ISS resulted in no lasting injury to the sleep-activated melanin concentrating hormone neurons.	Collectively these findings demonstrate for the first time that ISS imparts significant lasting disturbances in sleep/wake activity, degeneration of wake-activated LC and orexinergic neurons, and lasting metabolic changes in remaining neurons most consistent with premature senescence.	
27305623	Factors contributing to sleep timing and sleep restriction in daily life include chronotype and less flexibility in times available for sleep on scheduled days versus free days. There is some evidence that these two factors interact, with morning types and evening types reporting similar sleep need, but evening types being more likely to accumulate a sleep debt during the week and to have greater sleep extension on weekend nights. The aim of the present study was to evaluate the independent contributions of circadian phase and weekend-to-weekday variability to sleep timing in daily life. The study included 14 morning types and 14 evening types recruited from a community-based sample of New Zealand adults (mean age 41.1 ± 4.7 years). On days 1-15, the participants followed their usual routines in their own homes and daily sleep start, midpoint and end times were determined by actigraphy and sleep diaries. Days 16-17 involved a 17 h modified constant routine protocol in the laboratory (17:00 to 10:00, <20 lux) with half-hourly saliva samples assayed for melatonin. Mixed model ANCOVAs for repeated measures were used to investigate the independent relationships between sleep start and end times (separate models) and age (30-39 years versus 40-49 years), circadian phase [time of the dim light melatonin onset (DLMO)] and weekday/weekend schedules (Sunday-Thursday nights versus Friday-Saturday nights). As expected on weekdays, evening types had later sleep start times (mean = 23:47 versus 22:37, p < .0001) and end times (mean = 07:14 versus 05:56, p < .0001) than morning types. Similarly on weekend days, evening types had later sleep start times (mean = 00:14 versus 23:07, p = .0032) and end times (mean = 08:56 versus 07:04, p < .0001) than morning types. Evening types also had later DLMO (22:06 versus 20:46, p = .0002) than morning types (mean difference = 80.4 min, SE = 18.6 min). The ANCOVA models found that later sleep start times were associated with later DLMO (p = .0172) and weekend-to-weekday sleep timing variability (p < .0001), after controlling for age, while later sleep end times were associated with later DLMO (p = .0038), younger age (p = .0190) and weekend days (p < .0001). Sleep end times showed stronger association with DLMO (for every 30 min delay in DLMO, estimated mean sleep end time occurred 14.0 min later versus 10.19 min later for sleep start times). Sleep end times also showed greater delays on weekends versus weekdays (estimated mean delay for sleep end time = 84 min, for sleep start time = 28 min). Comparing morning types and evening types, the estimated contributions of the DLMO to the mean observed differences in sleep timing were on weekdays, 39% for sleep start times and 49% for sleep end times; and on weekends, 41% for sleep start times and 34% of sleep end times. We conclude that differences in sleep timing between morning types and evening types were much greater than would be predicted on the basis of the independent contribution of the difference in DLMO on both weekdays and weekend days. The timing of sleep in daily life involves complex interactions between physiological and psychosocial factors, which may be moderated by age in adults aged 30-49 years. 

27304755	To assess the prevalence of common mental disorders (CMD) and the association of CMD with sociodemographic characteristics in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort.We analyzed data from the cross-sectional baseline assessment of the ELSA-Brasil, a cohort study of 15,105 civil servants from six Brazilian cities. The Clinical Interview Schedule-Revised (CIS-R) was used to investigate the presence of CMD, with a score ≥ 12 indicating a current CMD (last week). Specific diagnostic algorithms for each disorder were based on the ICD-10 diagnostic criteria. Prevalence ratios (PR) of the association between CMD and sociodemographic characteristics were estimated by Poisson regression.	CMD (CIS-R score ≥ 12) was found in 26.8% (95% confidence intervals [95%CI] 26.1-27.5). The highest burden occurred among women (PR 1.9; 95%CI 1.8-2.0), the youngest (PR 1.7; 95%CI 1.5-1.9), non-white individuals, and those without a university degree. The most frequent diagnostic category was anxiety disorders (16.2%), followed by depressive episodes (4.2%).	The burden of CMD was high, particularly among the more socially vulnerable groups. These findings highlight the need to strengthen public policies aimed to address health inequities related to mental disorders.	
27302606	The hypothalamus is among the most phylogenetically conserved regions in the vertebrate brain, reflecting its critical role in maintaining physiological and behavioural homeostasis. By integrating signals arising from both the brain and periphery, it governs a litany of behaviourally important functions essential for survival. In particular, the lateral hypothalamic area (LHA) is central to the orchestration of sleep-wake states, feeding, energy balance and motivated behaviour. Underlying these diverse functions is a heterogeneous assembly of cell populations typically defined by neurochemical markers, such as the well-described neuropeptides hypocretin/orexin and melanin-concentrating hormone. However, anatomical and functional evidence suggests a rich diversity of other cell populations with complex neurochemical profiles that include neuropeptides, receptors and components of fast neurotransmission. Collectively, the LHA acts as a hub for the integration of diverse central and peripheral signals and, through complex local and long-range output circuits, coordinates adaptive behavioural responses to the environment. Despite tremendous progress in our understanding of the LHA, defining the identity of functionally discrete LHA cell types, and their roles in driving complex behaviour, remain significant challenges in the field. In this review, we discuss advances in our understanding of the neurochemical and cellular heterogeneity of LHA neurons and the recent application of powerful new techniques, such as opto- and chemogenetics, in defining the role of LHA circuits in feeding, reward, arousal and stress. From pioneering work to recent developments, we review how the interrogation of LHA cells and circuits is contributing to a mechanistic understanding of how the LHA coordinates complex behaviour.
27301498	Objective Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances; however, the detailed differences in the characteristics of sleep disturbances between GERD and non-GERD patients are unknown. The aim of the present study was to analyze the clinical characteristics as well as health-related quality of life in GERD and non-GERD patients with sleep disturbances. Methods Three hundred and fifty patients, including 124 patients with GERD and 226 patients without GERD, completed a self-administered questionnaire that evaluated clinical information. The Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and 8-item Short-Form Health Survey (SF-8) were also used. Sleep disturbance was considered to be present if the PSQI was >5.5. Results The prevalence of sleep disturbances was significantly higher in the GERD patients (66/124, 53.9%) than in the non-GERD patients (89/226, 39.3%). Depression and anxiety were significantly more common in the subjects with sleep disturbances than in those without sleep disturbances, although there were no differences between the GERD and non-GERD patients. Among the subjects with sleep disturbances, daytime sleepiness was more common in the GERD patients than in the non-GERD patients. The subjects with sleep disturbances had a poorer health-related quality of life. The physical components of quality of life were impaired, particularly in the GERD patients with sleep disturbances. Conclusion GERD patients with sleep disturbances commonly experience daytime sleepiness and an impaired health-related quality of life, especially in terms of physical components. 
27294991	To describe sleeping behaviors and trends over time among an ethnically diverse group of community-living older adults.A descriptive secondary data analysis of a subsample (n = 217) from the Lifestyle Redesign randomized controlled trial was done to explore baseline napping and sleeping patterns as well as 6-mo changes in these outcomes.	At baseline, the average time sleeping was 8.2 hr daily (standard deviation = 1.7). Among all participants, 29% reported daytime napping at baseline, of which 36% no longer napped at follow-up. Among participants who stopped napping, those who received an occupation-based intervention (n = 98) replaced napping time with nighttime sleep, and those not receiving an intervention (n = 119) experienced a net loss of total sleep (p < .05).	Among participants who stopped napping, the occupation-based intervention may be related to enhanced sleep. More research examining the role of occupation-based interventions in improving sleep is warranted.	
27294196	Though overlapping in distribution through the hypothalamus, orexin (Orx) and melanin-concentrating hormone (MCH) neurons play opposite roles in the regulation of sleep-wake states. Orx neurons discharge during waking, whereas MCH neurons discharge during sleep. In the present study, we examined in mice whether GABAA and GABAB receptors (Rs) are present on Orx and MCH neurons and might undergo differential changes as a function of their different activities following sleep deprivation (SD) and sleep recovery (SR). Applying quantitative stereological image analysis to dual-immunofluorescent stained sections, we determined that the proportion of Orx neurons positively immunostained for GABAARs was significantly higher following SD (∼48%) compared with sleep control (SC; ∼24%) and SR (∼27%), and that the luminance of the GABAARs was significantly greater. In contrast, the average proportion of the MCH neurons immunostained for GABAARs was insignificantly lower following SD (∼43%) compared with SC (∼54%) and SR (56%), and the luminance of the GABAARs was significantly less. Although, GABABRs were observed in all Orx and MCH neurons (100%), the luminance of these receptors was differentially altered following SD. The intensity of GABABRs in the Orx neurons was significantly greater after SD than after SC and SR, whereas that in the MCH neurons was significantly less. The present results indicate that GABA receptors undergo dynamic and differential changes in the wake-active Orx neurons and the sleep-active MCH neurons as a function of and homeostatic adjustment to their preceding activity and sleep-wake state. 
27294030	For many studies, participants' sleep-wake patterns are monitored and recorded prior to, during and following an experimental or clinical intervention using actigraphy, i.e. the recording of data generated by movements. Often, these data are merely inspected visually without computation of descriptive parameters, in part due to the lack of user-friendly software. To address this deficit, we developed a package for R Core Team [6], that allows computing several non-parametric measures from actigraphy data. Specifically, it computes the interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of activity and gives the start times and average activity values of M10 (i.e. the ten hours with maximal activity) and L5 (i.e. the five hours with least activity). Two functions compute these 'classical' parameters and handle either single or multiple files. Two other functions additionally allow computing an L-value (i.e. the least activity value) for a user-defined time span termed 'Lflex' value. A plotting option is included in all functions. The package can be downloaded from the Comprehensive R Archives Network (CRAN). •The package 'nparACT' for R serves the non-parametric analysis of actigraphy data.•Computed parameters include interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) as well as start times and average activity during the 10 h with maximal and the 5 h with minimal activity (i.e. M10 and L5). 
27292003	Pruritus in elderly patients can have a significant impact on the quality of life but may be underestimated and poorly addressed by healthcare professionals.From March to May 2010, a structured interview questionnaire including the Dermatology Life Quality Index (DLQI) was administered to all patients admitted to the geriatric ward in Changi General Hospital, Singapore, except for those with cognitive impairment.	A total of 194 patients were enrolled in the study; 94 patients (48.5%) were experiencing itch at the point of the interview; mean DLQI score for patients with itch was 6.7; 35.1% of patients experienced sleep disruption whilst 30.9% reported impairment of concentration levels as a consequence of their itch. Of the patients who had informed their doctor about the problem, 73.7% felt that doctors had not adequately addressed the cause of the itch. Among patients who reported itch, the DLQI score correlates with the severity of pruritus with a regression coefficient of 0.2737 (P <0.001); 9.6% of patients with itch were independent with their activities of daily living compared to 21% of patients who did not experience itch.	Almost half of the subjects in our study experienced itch and a third of them reported impairment of quality of life. Patients who were independent of their activities of daily living were also less likely to experience itch. This study highlights the importance of increasing awareness of pruritus among physicians as pruritus can have adverse consequences on patients' quality of life when left unaddressed.	
27291459	Consciousness is thought to scale with brain complexity, and it may be diminished in anesthesia. Lempel-Ziv complexity (LZC) of field potentials has been shown to be a promising measure of the level of consciousness in anesthetized human subjects, neurological patients, and across the sleep-wake states in rats. Whether this relationship holds for intrinsic networks obtained by functional brain imaging has not been tested. To fill this gap of knowledge, we estimated LZC from large-scale dynamic analysis of functional magnetic resonance images (fMRI) in conscious sedated and unconscious anesthetized rats. Blood oxygen dependent (BOLD) signals were obtained from 30-min whole-brain resting-state scans while the anesthetic propofol was infused intravenously at constant infusion rates of 20mg/kg/h (conscious sedated) and 40mg/kg/h (unconscious). Dynamic brain networks were defined at voxel level by sliding window analysis of regional homogeneity (ReHo) of the BOLD signal. From scans performed at low to high propofol dose, the LZC was significantly reduced by 110%. The results suggest that the difference in LZC between conscious sedated and anesthetized unconscious subjects is conserved in rats and this effect is detectable in large-scale brain network obtained from fMRI. 
27287886	Depression is a heterogeneous disorder characterized by alterations at psychological, behavioural, physiological, neurophysiological, and neurochemical levels. Social stress is a prevalent stress in man, and the repeated social defeat stress model in rats has been proposed as being the rodent equivalent to loss of control, which in subordinate animals produces alterations that resemble several of the cardinal symptoms found in depressed patients. Here, rats followed a resident-intruder protocol for 4 consecutive days during which behavioural, physiological, and electroencephalographic (EEG) parameters were simultaneously monitored in subordinate rats. On day 5, prefrontal dopamine (DA) and hippocampal serotonin (5-HT) as well as corticosterone were measured in submissive rats that had visual, acoustic, and olfactory (but no physical) contact with a dominant, resident conspecific rat. Socially defeated rats demonstrated increases in ultrasonic vocalizations (20-25 KHz), freezing, submissive defensive behaviour, inactivity, and haemodynamic response, while decreases were found in repetitive grooming behaviour and body weight. Additionally, alterations in the sleep-wake architecture were associated with reduced active waking, enhanced light sleep, and increased frequency of transitions from light sleep to quiet wakefulness, indicating sleep instability. Moreover, the attenuation of EEG power over the frequency range of 4.2-30 Hz, associated with a sharp transient increase in delta oscillations, appeared to reflect increased brain activity and metabolism in subordinate animals. These EEG changes were synchronous with a marked increase in body temperature and a decrease in locomotor activity. Furthermore, psychosocial stress consistently increased 5-HT, DA, and corticosterone levels. The increased levels of cortical DA and hippocampal 5-HT during social threat may reflect a coping mechanism to promote alertness and psychological adaptation to provocative and threatening stimuli. These neurophysiological changes are hypothesized to be the consequence of dynamics in monoamine systems, which could be useful markers for disease progression in the aetiology of depression. 
27287840	Each year, the number of hospice services and terminally ill patients increase while the number of hospice workers is falling. The intensification of the physical and mental burdens of the latter can lead to burnout and the fluctuation of the workers.The aim of the authors was to survey the physical and mental state of hospice workers, as well as the risk of burnout and coping strategies.	A questionnaire survey in hospice experts and volunteers (n ≈ 1500) based on the Hungarostudy survey was performed.	Those who filled in the questionnaire (n = 195) had on average 1.86 workplaces and 45.8% of them reported working 12 or more hours a day. Most often, they suffered from lack of energy (65.1%), disturbing physical pain (46.9%), sleeping (56.9%) and digestion (35%), they considered themselves overweight (56.9%) and they were occupied with work problems even at bedtime (72.8%).	Hospice workers are overloaded, they have physical and mental symptoms and they are characterized by compassion fatigue. At the same time, they are also characterized by compassion satisfaction as an ability to accept appreciation for the caretaking.	
27287793	This study aimed to evaluate the current sleep disorder status of nurses in general hospitals and analyze its influencing factors.A total of 2,033 nurses who have worked for 6 months in 3 general hospitals, namely, The First Affiliated Hospital of Harbin Medical University, The Second Affiliated Hospital of Harbin Medical University, and The Third Affiliated Hospital of Harbin Medical University, were selected by random sampling from April 2015 to November 2015 and investigated. The Effort-Reward Imbalance Questionnaire (ERI) and Job Content Questionnaire (JCQ) were applied to evaluate occupational stress. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep disorder status of the research subjects. Logistic regression analysis was adopted to determine the influencing factors of nurses' sleep disorders.	The average PSQI score of 2,003 research subjects is 7.26±3.56, including 860 subjects with PSQI ≥8, accounting for 42.9%. The female research subjects in the department of gynecology and obstetrics, emergency department, and ICU show high risks of sleep disorders (i.e., many years of working; job title: registered nurse; many times of night shift per month; no frequent exercise; many efforts and few rewards; high decision-making autonomy). Educational background and marital status did not exhibit statistical relevance with sleep disorders.	The sleep disorder status of nurses in general hospitals is closely related to occupational stress. As such, nurse managers should focus more attention to the influencing factors of nurses' sleep disorders and relieve their occupational stress to reduce the occurrence rate of sleep disorders.	
27287030	Non-rapid eye movement (NREM) sleep increases interictal epileptiform discharges and frequency of seizures, whereas REM sleep suppresses them. The pedunculopontine nucleus (PPN), one of the REM sleep-modulating structures, is postulated to have a potent antiepileptogenic role. We asked if patients with sleep-predominant seizures (SPS) show volume changes in the region of the PPN compared to those with seizures occurring during awake state only (nSPS). The volume of the PPN region was assessed in patients with SPS, those with nSPS, and healthy volunteers, through voxel-based morphometry and automated, nonbiased region of interest (ROI) analysis of T1 magnetic resonance (MR) images. The volume of PPN region was statistically smaller in patients with SPS (n = 33) than in those with nSPS (n = 40) and healthy controls (n = 30) after controlling for covariates. These results suggest that a structural change in the PPN may be associated with sleep-predominant timing of seizure occurrence. Our findings might help understand the intervening pathomechanism that lies between the human sleep-wake cycle and epilepsy. 
27286798	Sleep-wake disturbances are defined as perceived or actual alterations in sleep that result in impaired daytime functioning. Unlike other cancers, there is limited information about sleep-wake disturbances in adults with primary brain tumors throughout the illness trajectory. Sleep-wake disturbance is among the most severe and common symptoms reported by primary brain-tumor patients, particularly those undergoing radiation therapy. As with other cancers and neurologic illness, sleep-wake disturbance may also be clustered or related to other symptoms such as fatigue, depression, and cognitive impairment. There is increasing evidence for a genetic basis of normal sleep and sleep regulation in healthy adults. Specific mutations and single nucleotide variants have been reported to be associated with both fatigue and sleep-wake disorders, and both inflammation and alterations in circadian rhythms have been postulated to have a potential role. Guidelines for assessment and interventions have been developed, with cognitive behavioral therapy, exercise, and sleep hygiene demonstrating benefit in patients with other solid tumors. Further research is needed to identify risk and appropriate treatment in the brain-tumor patient population.

27283446	Many cardiac rehabilitation (CR) guidelines and position statements recommend screening for psychosocial risk factors, although there is wide variation in the recommended factors and recommended screening tools. Little is known about screening in CR in Australia.Cardiac rehabilitation coordinators at the 314 CR programs operating across Australia, drawn from the 2014 Australian Directory of Cardiac Rehabilitation Services were invited to participate in an online survey.	Of 165 complete responses, 157 (95%) CR coordinators indicated that they screened at entry with 132 (80%) screening on exit. At CR entry, programs screened for - depression (83%), anxiety (75%), stress (75%), and sleep disturbance (57%). The use of standardised instruments by those screening at entry varied from 89% for depression to only 9% for sleep disturbance. Organisational, resource and personal barriers inhibited the routine screening for many psychosocial factors.	Surveys such as this are useful for monitoring the rate of adoption of guideline recommendations and identifying barriers to implementation. Findings can also inform discussions about what should be included in minimum data sets for CR programs, and the identification of brief screening tools that have been validated not just in the general population but in cardiac patients.	
27282669	Research into the effects of touch in disabled adults in residential care remains largely unexplored in the current literature. Evidence suggests however, that massage therapy may improve mood state, including anxiety and stress, reduce pain and improve sleep/wake behavior and fatigue. These benefits are of importance as they have substantial impact on quality of life.This pilot study evaluated the effect of therapeutic massage on the quality of life of adults with complex care needs living in residential care.	Participants were recruited from three residential homes (Queensland, Australia) for 18-65 year olds with severe disability. 25 participants were recruited and received a massage program consisting of five weeks of twice weekly massages. Structured interviews were conducted pre-post intervention. Additionally, mood was ascertained preceding and following each massage session.	Mood of participants improved markedly immediately following massage session (p < 0.05) and pre-massage mood was observed to increase over the study period. However, pre- and post-intervention measures indicated massage did not improve pain, sleepiness, depression or stress levels or sustain positive mood three days post-intervention. Participants' satisfaction with their current health significantly improved (Z = -2.51, p = 0.012), as did their satisfaction with their current happiness (Z = -2.06, p = 0.04), suggesting that massage therapy offered some improvement in quality of life.	The results of this pilot indicates that massage may be of benefit to people living with high care needs and represents a practical innovation providing tactile stimulation that may be integrated into care.	
27282092	Various sleep-related symptoms occur in Parkinson's disease (PD). Their occurrence with health-related quality of life (HRQL), comorbid sleep disorders, and other comorbidities was studied.Altogether, 1447 randomly selected patients with Parkinson's disease, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, sleep disorders, and comorbidities were included.	The response rate was 59.0%, and of these, 80% had answered to all questions that were used in the analyses (N=684). Occurrence of long sleep was found in 26.2% of the subjects, short sleep in 32.5%, poor sleep in 21.2%, sleep deprivation in 33.8%, disrupted sleep in 47.4%, and difficulties to fall asleep in 12.2%, respectively. Poor self-rated health and poor quality of life occurred in 44.4% and in 43.3% of all participants. In the logistic regression, age and gender differentially predicted long sleep and sleep deprivation, such that older age and being male were positively associated with long sleep but negatively associated with the report of sleep deprivation. Depression, subjective negative stress, and fatigue occurred with long sleep. On the other hand, poor sleep and excessive daytime sleepiness occurred with short sleep and sleep deprivation.	The sleep difficulties in PD are frequent. The long sleeping patients have depression, stress, and fatigue.	
27276867	Non-auditory effects of noise on humans have been intensively studied in the last four decades. The International Commission on Biological Effects of Noise has been following scientific advances in this field by organizing international congresses from the first one in 1968 in Washington, DC, to the 11th congress in Nara, Japan, in 2014. There is already a large scientific body of evidence on the effects of noise on annoyance, communication, performance and behavior, mental health, sleep, and cardiovascular functions including relationship with hypertension and ischemic heart disease. In the last five years new issues in this field have been tackled. Large epidemiological studies on community noise have reported its relationship with breast cancer, stroke, type 2 diabetes, and obesity. It seems that noise-induced sleep disturbance may be one of the mediating factors in these effects. Given a large public health importance of the above-mentioned diseases, future studies should more thoroughly address the mechanisms underlying the reported association with community noise exposure. Keywords: noise; cancer; stroke; diabetes mellitus type 2; obesity
27276768	The aim of the study was to show the role of tools in the evaluation of chronic pain (CP) in general practitioner (GP) everyday clinical practice. The study was done by analyzing electronic database of the first visits of 1090 CP patients referred to the Pain Clinic of the Karlovac General Hospital, Karlovac, Croatia, by their GPs. All patient records were analyzed according to the cause of CP, strongest pain a week before the examination, quality of sleep, and the Patients' Global Impression of Change scale. All statistical analyses were done using the IBM SPSS Statistics version 19.0.0.1 (www.spss.com). CP predominantly occurs in older age group. Patients with musculoskeletal pain accounted for the highest percentage (n = 316; 29%), followed by those with neuropathic pain (n = 253; 23.20%) and those with low back pain (n = 225; 20.60%). The mean pain intensity rating scale score was 8.3 ± 1.8 a week before the examination and the mean quality of sleep score was 6.8 ± 1.9. Moderate and severe sleep quality disorder was significantly present in patients over 65 years of age (p = 0.007), patients with musculoskeletal and neuropathic pain, back pain, and those having rated Patients' Global Impression of Change scale as worsening (p = 0.001). The severity of pain and poor quality of sleep are the leading causes of deterioration of the Patients' Global Impression of Change scale in patients suffering from musculoskeletal and neuropathic pain. In order to treat CP comprehensively, it is important for GPs to evaluate the outcomes of clinical treatment using tools for CP assessment.
27269389	Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use.A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies.	Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.	

27264958	Orexins are hypothalamic neuropeptides involved in the central regulation of feeding behavior, sleep-wake cycle and other physiological functions. Orexin-A can regulate energy metabolism and increase glucose uptake, suggesting a role in glucose metabolism. In this study, we investigated the effects of orexin-A on GLUT4 mRNA and protein levels and the intracellular signaling mechanisms mediating orexin-A activity in the hepatocytes of grouper. Our results demonstrate that intraperitoneal injection of orexin-A increased the expression of GLUT4 in the liver, and this effect was significantly enhanced by co-injection of glucose. Treatment of primary cultured hepatocytes with either orexin-A or glucose alone had no effect on the expression of GLUT4, while co-treatment with orexin-A and glucose significantly increased the expression of GLUT4. This stimulatory effect was partially blocked by inhibitors to ERK1/2, JNK or p38 MAPK and was further blocked by an orexin receptor antagonist, which indicates that orexin-A could stimulate the expression of GLUT4 in a glucose dependent manner in primary hepatocytes via ERK1/2, JNK and p38 signaling. Our results suggest that orexin-A could play a pivotal role in stimulating glucose utilization in grouper, for a long-term goal, which might be useful in reducing costs in the aquaculture industry. 
27264543	The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology. 
27262147	In recent years progress has been made in the detection and evaluation of nonmotor symptoms in Parkinson's disease. The pathophysiology is better understood and new treatment is available, which will be discussed in this review.The most intriguing recent finding is the fact that Parkinson's disease may be a spreading disease. From the environment a toxin, bacteria, or virus may start in genetically susceptible patients a cascade of α-synuclein aggregation which reaches via the olfactory and the enteric system of the gut the brain where further spreading causes symptoms, such as sleep disturbances, motor impairment, and neuropsychiatric symptoms. New treatment should address the abnormal α-synuclein folding. If this would be achieved premotor signs, such as hyposmia, rapid eye movement-sleep behavior disorder, constipation, or depression may be a kind of biomarkers which allow together with other diagnostic tools, such as parenchymal sonography, iodobenzamide-scintigraphy and dopamine transporter scans the prediction whether somebody might be under way to develop the full-blown Parkinson's disease syndrome.	Parkinson's disease seems to be a spreading disease which causes not only a dopaminergic deficit as major cause for the movement disorder but also impairs function of many other brain centers which leads to a multitransmitter malfunction.	
27261553	Biological rhythms in infants are described as evolving from an ultradian to a circadian pattern along the first months of life. Recently, the use of actigraphy and thermistors with memory has contributed to the understanding of temporal relations of different variables along development. The aim of this study was to describe and compare the development of the rhythmic pattern of wrist temperature, activity/rest cycle, sleep/wake and feeding behavior in term and preterm newborns maintained in a neonatal intensive care unit (NICU).Nineteen healthy preterm and seven fullterm newborns had the following variables monitored continuously while they were in the NICU: activity recorded by actigraphy, wrist temperature recorded with a thermistor and observed sleep and feeding behavior recorded by the NICU staff with diaries. Subjects were divided in 3 groups according to their gestational age at birth and rhythmic parameters were compared.	A dominant daily rhythm was observed for wrist temperature since the first two weeks of life and no age relation was demonstrated. Otherwise, a daily pattern in activity/rest cycle was observed for most preterm newborns since 35 weeks of postconceptional age and was more robust in term babies. Feeding and sleep/wake data showed an almost exclusive 3h rhythm, probably related to a masking effect of feeding schedules.	We found that wrist temperature develops a daily pattern as soon as previously reported for rectal temperature, and with acrophase profile similar to adults. Moreover, we were able to find a daily rhythm in activity/rest cycle earlier than previously reported in literature. We also suggest that sleep/wake rhythm and feeding behavior follow independent developmental courses, being more suitable to masking effects.	
27261547	Despite being the focus of widespread public health efforts, childhood obesity remains an epidemic worldwide. Given the now well-documented consequences of obesity for childhood health and psychosocial functioning, as well as associated morbidity in adulthood, identifying novel, modifiable behaviors that can be targeted to improve weight control is imperative. Enhancing children's sleep may show promise in assisting with weight regulation. The present paper describes the development of a brief behavioral sleep intervention for school-aged children, including preliminary findings of this work as well as areas for future study.
27259177	Ultimately, almost all patients who are appropriately treated for pituitary tumours enter a chronic phase with control or cure of hormonal excess, adequate treatment of pituitary insufficiency and relief of mass effects. This phase is associated with improvement of initial signs and symptoms, but also with the persistent consequences of the initial disease and associated treatments. Pituitary insufficiency is a common denominator in many of these patients, and is associated with a reduction in quality of life, despite adequate endocrine substitution. Hypothalamic dysfunction can be present in patients previously treated for visual impairments caused by large suprasellar adenomas, or craniopharyngiomas. In addition to hypopituitarism, these patients can have multisystem morbidities caused by altered hypothalamic function, including weight gain and disturbed regulation of sleep-wake cycles. Mortality can also be affected. Patients cured of Cushing disease or acromegaly have chronic multisystem morbidities (in the case of Cushing disease, also affecting mortality) caused by irreversible effects of the previous excesses of cortisol in Cushing disease and growth hormone and insulin-like growth factor 1 in acromegaly. In addition to early diagnosis and treatment of pituitary tumours, research should focus on the amenability of these chronic post-treatment syndromes to therapeutic intervention, to improve quality of life and clinical outcomes. 
27256922	Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism. 
27255692	Although pain is one of the main sources of suffering during the acute phase and rehabilitation in burn patients, it remains as a major challenge for burn care, and clinical management not always correlates with the experience felt by patients. The aim of this study was to understand the experience of pain from people who has suffered severe burns, to identify personal strategies used to cope with this challenging event. A qualitative phenomenological study with purposive sampling was carried out with severe burn patients admitted to a Burn Unit. Through individual in-depth interviews, verbatim transcription and content analysis, two main categories were isolated: a dynamic and changing experience of pain, from the onset to the hospital discharge, and diverse strategies developed by patients to cope with pain, being distraction the most frequently used. Pain experienced acquires its maximum intensity during wound care, and divergent patients' opinions about sedation are present. This study highlights how understanding subjective experiences is an invaluable aid to improve care in pain assessment and management. Furthermore, it points out the need to guarantee patient involvement in the organization and improvement of burn care, inasmuch as traditional professional centered approach is not ensuring an optimal management. 
27254266	Patients with pituitary diseases have decreased quality of life. Sleep disorders are prevalent among patients with pituitary diseases and contribute to decreased quality of life.Patients previously treated for compression of the optic chiasm by surgery, and in some cases postoperative radiotherapy, suffer from sleep disorders. These are characterized by decreased sleep quality, delayed onset of sleep, and daytime sleepiness. Circumstantial evidence suggests that this may be caused by hypothalamic dysfunction. A challenging speculation is that previous compression of the optic chiasm compromised the function of the retinohypothalamic tract. Through this tract the eyes convey information on day-night cycles to the hypothalamic nuclei. Patients with acromegaly, even despite biochemical control, suffer frequently from obstructive sleep apnea. Patients with Cushing's disease suffer from fragmented sleep, sleep apnea, and snoring. Prolactinomas do not seem to affect sleep characteristics. The association between appropriately substituted pituitary insufficiency and sleep disorders is less clear. The effects of recombinant human growth hormone on sleep characteristics in adults are inconsistent.	Pituitary disorders are associated with different sleep disorders. Different studies point to irreversible changes in sleep-wake rhythmicity in patients treated previously for pituitary tumors with chiasm compression. VIDEO ABSTRACT.	
27254262	Sensorimotor abilities are crucial for performance in athletic, military, and other occupational activities, and there is great interest in understanding learning in these skills. Here, behavioral performance was measured over three days as twenty-seven participants practiced multiple sessions on the Nike SPARQ Sensory Station (Nike, Inc., Beaverton, Oregon), a computerized visual and motor assessment battery. Wrist-worn actigraphy was recorded to monitor sleep-wake cycles. Significant learning was observed in tasks with high visuomotor control demands but not in tasks of visual sensitivity. Learning was primarily linear, with up to 60% improvement, but did not relate to sleep quality in this normal-sleeping population. These results demonstrate differences in the rate and capacity for learning across perceptual and motor domains, indicating potential targets for sensorimotor training interventions. 
27253971	Age-associated changes in different bandwidths of the human electroencephalographic (EEG) spectrum are well documented, but their functional significance is poorly understood. This spectrum seems to represent summation of simultaneous influences of several sleep-wake regulatory processes. Scoring of its orthogonal (uncorrelated) principal components can help in separation of the brain signatures of these processes. In particular, the opposite age-associated changes were documented for scores on the two largest (1st and 2nd) principal components of the sleep EEG spectrum. A decrease of the first score and an increase of the second score can reflect, respectively, the weakening of the sleep drive and disinhibition of the opposing wake drive with age. In order to support the suggestion of age-associated disinhibition of the wake drive from the antagonistic influence of the sleep drive, we analyzed principal component scores of the resting EEG spectra obtained in sleep deprivation experiments with 81 healthy young adults aged between 19 and 26 and 40 healthy older adults aged between 45 and 66 years. At the second day of the sleep deprivation experiments, frontal scores on the 1st principal component of the EEG spectrum demonstrated an age-associated reduction of response to eyes closed relaxation. Scores on the 2nd principal component were either initially increased during wakefulness or less responsive to such sleep-provoking conditions (frontal and occipital scores, respectively). These results are in line with the suggestion of disinhibition of the wake drive with age. They provide an explanation of why older adults are less vulnerable to sleep deprivation than young adults. 
27253676	On trips with multiple transmeridian flights, pilots experience successive non-24 h day/night cycles with circadian and sleep disruption. One study across a 9-day sequence of transpacific flights (no in-flight sleep, 1-day layovers between flights) reported an average period in the core body temperature rhythm of 24.6 h (circadian drift). Consequently, pilots were sometimes flying through the circadian performance nadir and had to readapt to home base time at the end of the trip. The present study examined circadian drift in trip patterns with longer flights and in-flight sleep. Thirty-nine B747-400 pilots (19 captains, 20 first officers, mean age = 55.5 years) were monitored on 9- to 13-day trips with multiple return flights between East Coast USA and Japan (in 4-pilot crews) and between Japan and Hawaii (in 3-pilot crews), with 1-day layovers between each flight. Measures included total in-flight sleep (actigraphy, log books) and top of descent (TOD) measures of sleepiness (Karolinska Sleepiness Scale), fatigue (Samn-Perelli Crew Status Check) and psychomotor vigilance task (PVT) performance. Circadian rhythms of individual pilots were not monitored. To detect circadian drift, mixed-model analysis of variance examined whether for a given flight, total in-flight sleep and TOD measures varied according to when the flight occurred in the trip sequence. In addition, sleep propensity curves for pre-trip and post-trip days were examined (Chi-square periodogram analyses). Limited data suggest that total in-flight sleep of relief crew at landing may have decreased across successive East Coast USA-Japan (flights 1, 3, 5 or 7; median arrival 03:45 Eastern Daylight Time (EDT)). However, PVT response speed at TOD was faster on East Coast USA-Japan flights later in the trip. On these flights, circadian drift would result in flights later in the trip landing closer to the evening wake maintenance zone, when sleep is difficult and PVT response speeds are fastest. On Japan-East Coast USA flights (flights 2, 4, 6 or 8; median arrival time 14:52 EDT), PVT response speeds were slower on flight 8 than on flight 2. Circadian drift would move these arrivals progressively earlier in the SCN pacemaker cycle, where PVT response speeds are slower. Across the five post-trip days, 12 pilots (Group A) immediately resumed their pre-trip sleep pattern of a single nocturnal sleep episode; 9 pilots (Group B) had a daytime nap on most days that moved progressively earlier until it merged with nocturnal sleep and 17 pilots (Group C) had nocturnal sleep and intermittent naps. Chi-square periodogram analyses of the sleep propensity curves for each group across baseline and post-trip days suggest full adaptation to EDT from post-trip day 1 (dominant period = 24 h). However, in Groups B and C, the patterns of split sleep post-trip compared to pre-trip suggest that this may be misleading. We conclude that the trends in total in-flight sleep and significant changes in PVT performance speed at TOD provide preliminary evidence for circadian drift, as do persistent patterns of split sleep post-trip. However, new measures to track circadian rhythms in individual pilots are needed to confirm these findings. 
27251337	This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms.To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults.	We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors.	We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults.	We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.	We included a total of four studies with 296 participants.Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety).Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low quality evidence). There was no statistically significant difference between quetiapine and placebo in the proportion of participants withdrawing due to adverse events (tolerability) (very low quality evidence), in the frequency of serious adverse events (safety) (very low quality evidence) and in the proportion of participants reporting dizziness and somnolence as an adverse event (very low quality evidence). In more participants in the quetiapine group a substantial weight gain was noted (RD 0.08, 95% CI 0.02 to 0.15; number needed to treat for an additional harm (NNTH) 12, 95% CI 6 to 50) (very low quality evidence). We downgraded the quality of evidence by three levels to a very low quality rating because of limitations of study design, indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed).One parallel design study with 90 participants compared quetiapine (50 to 300 mg/day flexible at bedtime) to amitriptyline (10 to 75 mg/day flexible at bedtime). The study had three major risks of bias and we judged it to be at moderate risk of bias overall. We downgraded the quality of evidence by two levels to a low quality rating because of indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). Third tier evidence indicated no statistically significant differences between the two drugs. Both drugs did not statistically significantly differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life and in the proportion of participants reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared to amitriptyline, more participants left the study due to adverse events (low quality evidence). No serious adverse events were reported (low quality evidence).We found no relevant study with other antipsychotics than quetiapine in fibromyalgia.	Very low quality evidence suggests that quetiapine may be considered for a time-limited trial (4 to 12 weeks) to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits in shared decision making with the patient.	
27250816	Perception of sleep-wake times may differ from objective measures, although the mechanisms remain elusive. Quantifying the misperception phenotype involves two operational challenges: defining objective sleep latency and treating sleep latency and total sleep time as independent factors. We evaluated a novel approach to address these challenges and test the hypothesis that sleep fragmentation underlies misperception.We performed a retrospective analysis on patients with or without obstructive sleep apnea during overnight diagnostic polysomnography in our laboratory (n = 391; n = 252). We compared subjective and objective sleep-wake durations to characterize misperception. We introduce a new metric, sleep during subjective latency (SDSL), which captures latency misperception without defining objective sleep latency and allows correction for latency misperception when assessing total sleep time (TST) misperception.	The stage content of SDSL is related to latency misperception, but in the opposite manner as our hypothesis: those with > 20 minutes of SDSL had less N1%, more N3%, and lower transition frequency. After adjusting for misperceived sleep during subjective sleep latency, TST misperception was greater in those with longer bouts of REM and N2 stages (OSA patients) as well as N3 (non-OSA patients), which also did not support our hypothesis.	Despite the advantages of SDSL as a phenotyping tool to overcome operational issues with quantifying misperception, our results argue against the hypothesis that light or fragmented sleep underlies misperception. Further investigation of sleep physiology utilizing alternative methods than that captured by conventional stages may yield additional mechanistic insights into misperception.	A commentary on this article appears in this issue on page 1211.	
27250813	For centuries the scope of sleep disorders in medical writings was limited to those disturbances which were either perceived by the sleeper him- or herself as troublesome, such as insomnia, or which were recognized by an observer as strange behavioral acts during sleep, such as sleepwalking or sleep terrors. Awareness of other sleep disorders, which are caused by malfunction of a physiological system during sleep, such as sleep-related respiratory disorders, were widely unknown or ignored before sleep monitoring techniques became available, mainly in the second half of the 20(th) century. Finally, circadian sleep-wake disorders were recognized as a group of disturbances by its own only when chronobiology and sleep research began to interact extensively in the last two decades of the 20(th) century. Sleep medicine as a medical specialty with its own diagnostic procedures and therapeutic strategies could be established only when key findings in neurophysiology and basic sleep research allowed a breakthrough in the understanding of the sleeping brain, mainly since the second half of the last century.
27247803	It is well established that local field potentials (LFP) in the rodent olfactory bulb (OB) follow respiration. This respiration-related rhythm (RR) in OB depends on nasal air flow, indicating that it is conveyed by sensory inputs from the nasal epithelium. Recently RR was found outside the olfactory system, suggesting that it plays a role in organizing distributed network activity. It is therefore important to measure RR and to delineate it from endogenous electrical rhythms like theta which cover similar frequency bands in small rodents. In order to validate such measurements in freely behaving mice, we compared rhythmic LFP in the OB with two respiration-related biophysical parameters: whole-body plethysmography (PG) and nasal temperature (thermocouple; TC). During waking, all three signals reflected respiration with similar reliability. Peak power of RR in OB decreased with increasing respiration rate whereas power of PG increased. During NREM sleep, respiration-related TC signals disappeared and large amplitude slow waves frequently concealed RR in OB. In this situation, PG provided a reliable signal while breathing-related rhythms in TC and OB returned only during microarousals. In summary, local field potentials in the olfactory bulb do reliably reflect respiratory rhythm during wakefulness and REM sleep but not during NREM sleep. 
27245317	Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson's disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson's Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients. 
27242171	Mood disorders are characterized by disabling symptoms and cognitive difficulties which may vary in intensity throughout the course of the illness. Sleep-wake cycles and circadian rhythms influence emotional regulation and cognitive functions. However, the relationships between the sleep-wake disturbances experienced commonly by people with mood disorders and the longitudinal changes in their clinical and cognitive profile are not well characterized. This study investigated associations between initial sleep-wake patterns and longitudinal changes in mood symptoms and cognitive functions in 50 young people (aged 13-33 years) with depression or bipolar disorder. Data were based on actigraphy monitoring conducted over approximately 2 weeks and clinical and neuropsychological assessment. As part of a longitudinal cohort study, these assessments were repeated after a mean follow-up interval of 18.9 months. No significant differences in longitudinal clinical changes were found between the participants with depression and those with bipolar disorder. Lower sleep efficiency was predictive of longitudinal worsening in manic symptoms (P = 0.007). Shorter total sleep time (P = 0.043) and poorer circadian rhythmicity (P = 0.045) were predictive of worsening in verbal memory. These findings suggest that some sleep-wake and circadian disturbances in young people with mood disorders may be associated with less favourable longitudinal outcomes, notably for subsequent manic symptoms and memory difficulties.
27238836	The role of serotonin (5-HT) in sleep-wake regulation has been a subject of intense debate and remains incompletely understood. In the ventrolateral preoptic nucleus (VLPO), the main structure that triggers non-rapid eye movement (NREM) sleep, putative sleep-promoting (PSP) neurons were shown ex vivo to be either inhibited (Type-1) or excited (Type-2) by 5-HT application. To determine the complex action of this neurotransmitter on PSP neurons, we recorded spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, sIPSCs, mEPSCs and mIPSCs) in response to bath application of 5-HT. We established in mouse acute VLPO slices that 5-HT reduces spontaneous and miniature EPSC and IPSC frequencies to Type-1 neurons, whereas 5-HT selectively increases sIPSC and mIPSC frequencies to Type-2 VLPO neurons. We further determined that Type-1 neurons display a lower action potential threshold and a smaller soma size than Type-2 neurons. Finally, single-cell RT-PCR designed to identify the 13 serotonergic receptor subtypes revealed the specific mRNA expression of the 5-HT1A,B,D,F receptors by Type-1 neurons. Furthermore, the 5-HT2A-C,4,7 receptors were found to be equivalently expressed by both neuronal types. Altogether, our results establish that the excitatory and inhibitory inputs to Type-1 and Type-2 VLPO PSP neurons are differentially regulated by 5-HT. Electrophysiological, morphological and molecular differences were also identified between these two neuronal types. Our results provide new insights regarding the orchestration of sleep regulation by 5-HT release, and strongly suggest that Type-2 neurons could play a permissive role, whereas Type-1 neurons could have an executive role in sleep induction and maintenance. 
27237578	In order to characterize sleep and the cognitive patterns in patients with acute minor thalamic infarction (AMTI), we enrolled 27 patients with AMTI and 12 matched healthy individuals. Questionnaires about sleep and cognition as well as polysomnography (PSG) were performed on days 14 and 90 post-stroke. Compared to healthy controls, in patients with AMTI, hyposomnia was more prevalent; sleep architecture was disrupted as indicated by decreased sleep efficiency, increased sleep latency, and decreased non-rapid eye movement sleep stages 2 and 3; more sleep-related breathing disorders occurred; and cognitive functions were worse, especially memory. While sleep apnea and long-delay memory recovered to a large extent in the patients, other sleep and cognitive function deficit often persisted. Patients with AMTI are at an increased risk for hyposomnia, sleep structure disturbance, sleep apnea, and memory deficits. Although these abnormalities improved over time, the slow and incomplete improvement suggest that early management should be considered in these patients. 
27234190	The Dark Triad (DT) describes a set of three closely related personality traits, Machiavellianism, narcissism, and psychopathy. The aim of this study was to examine the associations between DT traits, sleep disturbances, anxiety sensitivity and intolerance of uncertainty.A total of 341 adults (M=29years) completed a series of questionnaires related to the DT traits, sleep disturbances, anxiety sensitivity, and intolerance of uncertainty.	A higher DT total score was associated with increased sleep disturbances, and higher scores for anxiety sensitivity and intolerance of uncertainty. In regression analyses Machiavellianism and psychopathy were predictors of sleep disturbances, anxiety sensitivity, and intolerance of uncertainty.	Results indicate that specific DT traits, namely Machiavellianism and psychopathy, are associated with sleep disturbances, anxiety sensitivity and intolerance of uncertainty in young adults.	
27234180	Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders.Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels.	In CSF, melatonin levels were significantly decreased in bipolar (P<0.001), but not major depressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition.	This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations.	
27232103	The association between family economic hardship and adolescent adjustment outcomes, including sleep quality, is well-established. Few studies, however, have examined the mediating and moderating mechanisms underlying the relation between family economic hardship and adolescents' sleep quality. The aim of this study was to investigate the effect of family economic hardship on Chinese adolescents' sleep quality, as well as the role of perceived economic discrimination as a mediator and the role of coping strategy as a moderator. Survey data from a cross-sectional sample of 997 Chinese adolescents (45% male, mean age = 15.04 years) were analyzed using path analysis in Mplus 7.0. The results of this study indicated that family economic hardship was significantly associated with adolescents' sleep quality. This association was mediated by adolescents' perceived economic discrimination. In addition, adolescents' coping strategy significantly moderated the path from perceived economic discrimination to sleep quality, with the "shift" coping strategy as a protective factor. The present study contributes to our understanding of key mechanisms underlying the association between family economic hardship and adolescent sleep quality and highlights the importance of improving sleep quality for adolescents exposed to economic hardship.
27231745	In recent years, translational research (TR) has become a new approach for bridging basic research and clinical practice. This article examines studies in which the authors used TR to learn more about the underlying causes of selected symptoms, and to discuss these results in the context of cancer nursing and symptom management. A literature review was undertaken, plus critical analysis of the authors. TR conducted by cancer nursing scholars has been relatively limited in the past, but is becoming more common as nurses complete additional academic work in the basic sciences and develop research teams with colleagues of those areas of knowledge. The goal in these studies is to show how a set of variables explains differential interventional effects. The availability of TR provides new evidence for the management of symptoms experienced by individuals with cancer, which could lead to improvements in the care of cancer patients across the world. 
27228790	The current study evaluated the relationship between tic, sleep disorders and specific psychiatric symptoms (anxiety, depression, obsessive compulsive symptoms).Assessment of 36 consecutive children and adolescents with tic disorders included: the Yale Global Tic Severity Scale (YGTSS) to assess the severity of tic symptoms; the Self-administered scale for children and adolescents (SAFA) to evaluate the psychopathological profile; a specific sleep questionnaire consisting of 45 items to assess the presence of sleep disorders. An age and sex-matched control group was used for comparisons.	Sleep was significantly more disturbed in patients with tic disorders than in controls. Difficulties in initiating sleep and increased motor activity during sleep were the most frequent sleep disturbances found in our sample. Patients showed also symptoms of anxiety (SAFA A), depressed mood (SAFA D) and doubt-indecision (SAFA O). Additionally, difficulties in initiating sleep resulted associated with other SAFA subscales relative to obsessive-compulsive symptoms and depression symptoms. Furthermore, anxiety symptoms (SAFA A) resulted associated with increased motor activity during sleep.	Findings confirm literature studies reporting high frequency of sleep problems, anxiety and other psychopathological symptoms in patients with tic disorders, and support the hypothesis that intrusive thoughts and other emotional disturbances might disrupt the sleep onset of these patients. These results suggest the importance of a thorough assessment of sleep and psychiatric disturbances in patients with tic disorders.	
27227054	The advent of genetically engineered systems, including transgenic animals and recombinant viral vectors, has facilitated a more detailed understanding of the molecular and cellular substrates regulating brain function. In this review we highlight some of the most recent molecular biology and genetic technologies in the experimental "systems neurosciences," many of which are rapidly becoming a methodological standard, and focus in particular on those tools and techniques that permit the reversible and cell-type specific manipulation of neurons in behaving animals. These newer techniques encompass a wide range of approaches including conditional deletion of genes based on Cre/loxP technology, gene silencing using RNA interference, cell-type specific mapping or ablation and reversible manipulation (silencing and activation) of neurons in vivo. Combining these approaches with viral vector delivery systems, in particular adeno-associated viruses (AAV), has extended, in some instances greatly, the utility of these tools. For example, the spatially- and/or temporally-restricted transduction of specific neuronal cell populations is now routinely achieved using the combination of Cre-driver mice and stereotaxic-based delivery of AAV expressing Cre-dependent cassettes. We predict that the experimental application of these tools, including creative combinatorial approaches and the development of even newer reagents, will prove necessary for a complete understanding of the neuronal circuits subserving most neurobiological functions, including the regulation of sleep and wake. 
27227052	In the past, studies on stress responses and sleep/wake regulation were performed separately. The discovery of orexin (hypocretin) in 1998, however, dramatically changed the course of research and new findings regarding its role in these complex processes provided a better insight into their interactions and intricacies. Orexin-containing neuronal activity has been found to be minimal during sleep. It increases during the waking period and further increases during the active waking period, which includes stress responses and exploratory behaviors. Autonomic regulation of the body, which includes body temperature, blood flow, and ventilation, is also activated along with the change in vigilance states. Our recent findings suggest that orexin neurons act as a conductor of orchestration for vigilance states, behaviors, and autonomic functions. Body temperature regulation by orexin neurons seems to be mediated by one of its cotransmitters while cardiovascular and respiratory regulation are mediated by orexin itself. 

27221043	Sleep-wake disturbances are highly prevalent following traumatic brain injury (TBI), impeding rehabilitaion and quality of life. However, the mechanisms underlying these sleep disturnbances are unclear, and efficacious treatments are lacking. To investigate possible mechanisms underlying sleep disturbance in TBI, we examined characteristics of the circadian rhythm of melatonin, a hormone involved in sleep-wake regulation. We compared TBI patients reporting sleep disturbance with age- and gender-matched healthy volunteers.We conducted an overnight observational study with salivary melatonin samples collected hourly in 9 patients with severe TBI and 9 controls. Salivary dim light melatonin onset (DLMO) as well as melatonin synthesis onset (SynOn) and offset (SynOff) were used to determine circadian timing. Total overnight salivary melatonin production was calculated as the area under the curve from melatonin synthesis onset to offset.	Compared with healthy individuals, TBI patients showed 42% less melatonin production overnight (d = 0.87; P = .034). The timing of DLMO was delayed by approximately 1.5 hours in patients with TBI compared with controls (d = 1.23; P = .003).	In patients with TBI, melatonin production was attenuated overnight, and the timing of melatonin secretion was delayed. We suggest that disruption to the circadian regulation of melatonin synthesis is a feature of severe TBI, possibly contributing to the sleep difficulties that are commonly reported in this population.	
27216303	To determine if there was a difference in the inflammatory reaction after tonsil surgery with "traditional" techniques (tonsillectomy and adenoidectomy or TA) compared to partial intracapsular tonsillectomy and adenoidectomy (PITA).Randomized, double-blind study.	tertiary care academic hospital. Children under the age of 16 years with a diagnosis of obstructive sleep disordered breathing were randomly allocated into three study groups: TA with electrocautery (n = 34), PITA with CO2 laser (n = 30) and PITA with debrider (n = 28). All of the children underwent adenoidectomy with a current at the same surgical procedure.	c-reactive protein level (CRP) was the primary endpoint. In addition, the following were assessed: white blood cells (WBC), neutrophils (NEU), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Pre- and post-procedure measurements were compared between the groups. Parents filled out a questionnaire daily during the first postoperative week assessing pain, swallowing and snoring. CRP levels ascended higher in the PITA groups after surgery (p = 0.023), WBC and NEU showed the same pattern, IL-6 levels were higher in PITA group and there was no difference in TNF-alpha levels between the two types of procedures. Postoperative pain and postoperative hemorrhage were significantly lower in the PITA groups as compared to the TA group (p = 0.01 and 0.048). PITA in comparison to TA is associated with lower morbidity; however, the inflammatory response does not differ significantly in the first 24 h after surgery. Additional long-term studies assessing efficacy of PITA are warranted.	Level 1, prospective randomized controlled trial.	
27215830	Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence.We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders.	Of the one hundred and thirty-four studies selected, 7.6 % investigated social and economic participation, 2.1 % physical health, 15.3 % suicide and self-harm behaviours, 6.9 % alcohol and substance use, whereas the majority (68.1 %) focussed on clinical syndrome.	Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories.	
27215362	Intensive care units may place acutely ill patients with cancer at additional risk for sleep loss and associated negative effects. Research suggests that communication about sleep in patients with cancer is suboptimal and sleep problems are not regularly assessed or adequately treated throughout the cancer trajectory. However, many sleep problems and fatigue can be managed effectively. This article synthesizes the current literature regarding the prevalence, cause, and risk factors that contribute to sleep disturbance in the context of acute cancer care. It describes the consequences of poor sleep and discusses appropriate assessment and treatment options. 
27215355	Sleep disturbances are common in the intensive care unit setting. This article describes the causal factors associated with alterations in sleep in the intensive care setting, effects of sleep disturbances for patients, and strategies to mitigate sleep disturbances. A review of normal sleep architecture is provided, as is a discussion of the methods of measuring sleep in the critical care setting. 
27213144	Seasonality is noted in various aspects of human behavior and functioning which have led to an increasing interest in their seasonality in the recent years.We aimed to examine the seasonal variation in the incidence of rectal foreign bodies in the US using a large inpatient database.	We used the Nationwide Inpatient Sample database to identify patients aged ≥18 years admitted with a primary diagnosis of the rectal foreign body from 2009 to 2011. We used the Edward's recognition and estimation of cyclic trend method to study the seasonal variation of the incidence of rectal foreign body and Z-test to compare the seasonal incidences.	A total of 3359 hospitalizations with primary diagnosis of the rectal foreign body were reported from 2009 to 2011. The peak incidence of rectal foreign bodies was seen in October (peak/low ratio 1.20, 95% confidence interval [CI]: 1.10-1.32).	Data on seasonal variation of rectal foreign bodies are extremely limited. Further studies would be required to verify whether our findings of a higher incidence in the fall season are reflective of acute changes in the length of the days, climate, sleep-wake cycle, or decreased sexual intercourse at this time of the year. High suspicion at this time of the year may help promptly diagnose and avoid unnecessary investigations.	
27212090	Providers of obstetric and gynecologic care are often the most commonly seen medical providers for adult women, providing primary and reproductive care. Even where psychiatric care is readily available, obstetricians/gynecologists are frequently the front line for recognition, education, and initial management of many mental health problems. In settings where psychiatric treatment is a more scarce resource, obstetricians/gynecologists often are responsible for ongoing treatment of these disorders. This review focuses on the impact of the female reproductive life cycle on the presentation and management of some of the most common behavioral health problems in women: major depression, bipolar disorder, anxiety disorders, and primary sleep disorders. 
27211063	The metabotropic glutamate receptor type 7 (mGluR7), a most abundant presynaptic G protein-coupled receptor in the brain provides an attractive mechanism to fast fine-tune abnormal excitatory neurotransmission and synaptic plasticity associated with emotional and cognitive impairments in neuropsychiatric and neurodegenerative disorders. Preclinical studies using AMN082, the mGluR7 allosteric agonist, produced conflicting results, so that results of further in-vivo studies are needed. Here, we investigated effects of subcutaneous administration at the lights onset of AMN082 on sleep-wake architecture and spectral contents in rats. In an attempt to solve the reported mixed results, we estimated the specific functional effects in mGluR7 (-/-) mice and their wild type (WT) littermates. In rats, AMN082 (2.5mg/kg) elicited a primary waking effect over the first 2h post-administration by consistent increases in the number of waking bouts and transitions from sleep states towards wakefulness. In mice, baseline recordings over 72h showed comparable spontaneous sleep-wake cycle in mGluR7 (-/-) mice and their WT littermates, suggesting that mGluR7 is not involved in the regulation of vigilance states. Remarkably, cortical arousal properties of AMN082 were confirmed in WT mice, and occurred concomitantly with a marked decrease in body temperature, likely dissociated from locomotor activity. Surprisingly, the wake arousal and hypothermia effects of AMN082 were also observed in mGluR7 (-/-) mice. AMN082 significantly attenuated the slow wave activity during sleep and had no effect on waking EEG power in the 4-50Hz range. The present findings in rats do not lend support to proposed somnogenic effects of AMN082, while comparable responses in WT and mGluR7 (-/-) mice provide further evidence of an off-target action of AMN082 that contributes to its waking properties. 


27208716	Chronic pain is associated with symptoms that may impair a patient's quality of life, including emotional distress, fatigue, and sleep disturbance. There is a high prevalence of concomitant pain and sleep disturbance. Studies support the hypothesis that sleep and pain have a bidirectional and reciprocal relationship. Clinicians who manage patients with chronic pain often focus on interventions that relieve pain, and assessing and treating sleep disturbance are secondary or not addressed. This article reviews the literature on pain and co-occurring sleep disturbance, describes the assessment of sleep disturbance, and outlines nonpharmacologic and pharmacologic treatment strategies to improve sleep in patients with chronic pain. 
27207257	Functional somatic syndromes are mostly associated with pain and emotional distress. As one marker for the autonomic stress response, the distal skin temperature decreases during psychological stress. In patients with functional somatic syndromes, the distal skin temperature under baseline conditions (without stress induction) is usually lower than in healthy subjects, which could be due to the sustained presence of pain-related stress in such patients. The aim of our study was to investigate whether patients with functional somatic syndromes show altered skin temperatures also under everyday life conditions. 14 patients with functional somatic syndromes and 14 matched healthy control subjects were investigated under ambulatory conditions over six consecutive days. During this time, distal and proximal skin temperatures were continuously recorded and sleep-wake cycles were monitored by actimetry and sleep-wake diaries. Unexpectedly, the patients showed higher distal skin temperatures than control subjects in the afternoon. The objective temperature data did not match the patients' subjective experience: ratings of thermal comfort did not vary between the two groups. Moreover, similar levels of daytime activity were recorded in the two samples, even though patients reported more tiredness and more body tension than controls. We interpret the observed dissociation between objective skin temperature measurements and subjective ratings of the bodily thermal comfort as support for the notion of an alexisomia account (reduced bodily awareness) for functional somatic syndromes. Moreover, findings indicate that subjective complaints of tiredness and tension do not necessarily result in physical avoidance behaviour.
27206906	Postural tachycardia syndrome (POTS) is an autonomic disturbance characterized by an excessive increase in heart rate when an individual moves from a sitting to an upright position. POTS patients often complain of fatigue, daytime sleepiness and insomnia, but there is limited evidence to elucidate the mechanism or the prevalence of sleep-related symptoms in POTS, as well as the effect on patient quality of life. Here, we investigated the prevalence of sleep disturbances in POTS patients, as well as the use of medication and effects on daily life.A survey was administered to 30 patients with POTS. The survey contained 22 questions on various characteristics of sleep disturbances in POTS. Answers were recorded on a five-point Likert rating scale.	The majority of the patients reported fatigue (96.7%) and low energy (93.3%) during the day. Most (83.3%) patients reported that they do not feel well rested when waking up in the morning. More than half of the patients reported trouble falling asleep at night (63.3%) and maintaining sleep through the night (62.1%). Despite the frequent complaint of sleep disturbance, a very low percentage of POTS patient actually report seeking treatment.	In this study, we explored the prevalence of sleep disturbance in patients with POTS. Almost all POTS patients reported trouble with sleep and fatigue; however, there is major discrepancy between the high percentage of symptoms and small percentage of patients seeking medical assistance for better sleep quality.	
27206295	Sleep-wake disturbances are experienced by as many as 75% of patients with cancer and are associated with poor symptom management, lower functionality, and decreased quality of life. Although promising sleep interventions exist, they require extensive resources and time.The objectives of this study were to develop a brief, self-administered sleep intervention and to evaluate the feasibility and potential efficacy of its implementation with adult patients with cancer who were about to receive, were receiving, or had received radiation therapy in an ambulatory cancer care setting.	Pre- and postintervention surveys and qualitative interviews were conducted with patients with cancer experiencing insomnia (N = 28) and receiving radiation treatment within the past six months. Patients received instruction on breathing, visualization, and intonation. Adherence and sleep quality were primary study outcomes. Analyses included descriptive statistics and repeated measure regression analysis. Thematic analysis was conducted on qualitative data.	Adherence to the sleep intervention was high (75%), and significant improvement was found in global sleep quality (p < 0.0001) regardless of level of adherence. Sleep onset latency (p = 0.0005), sleep duration (p = 0.0016), and sleep quality (p < 0.0001) were significantly improved. Age was significantly correlated with sleep quality (p = 0.0094), with older participants reporting greater benefit from the intervention. Participants reported that the intervention was easy to learn and implement and that it "calmed the mind."	
27199064	Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy. 
27198952	The study aimed to determine if an automated algorithm, capable of batch scoring, could extract naps and other 24-h sleep-wake variables from actigraphy without the need for parental sleep diaries, which rely heavily on parental awareness of child sleep.A cross-sectional design was used for the study.	The study examined healthy infants/children in their home setting.	A total of 160 infants/children in five age groups (6 months, and 1, 2, 3½ and 5 years) participated in the study.	Participants wore actigraphs for 5-7 days, and parents completed sleep diaries over 2 consecutive days. Three criteria were applied to find the minimum sleep time (20, 30 and 40 min) yielding the best nap agreement between diaries and actigraphy for nap/no-nap identification. Best agreements were 72.1% (20 min minimum), 78.4% (20 min), 91.0% (30 min) and 93.3% (30 min) for ages 6 months, 1, 2 and 3½ years, respectively. Kappa statistics classified nap-nap agreement as 'slight' for 6-month data but 'moderate' or 'almost perfect' for older age groups. The number of daytime naps extracted at each age group yielded no significant discrepancies between the methods. Diaries generally returned significantly earlier sleep onset, later sleep offset, longer sleep duration and fewer night wakings at 6 months and 1 and 2 years, but this was not significant at 3½ or 5 years of age.	Minimum age-specific sleep time thresholds are recommended to improve nap identification in actigraphy across infant and toddler age groups. The findings strengthen our confidence in the ability to collect actigraphy data in the absence of parental diaries, in 3½- and 5-year-olds, at least.	
27198945	This epidemiological study evaluated the impact of school time on sleep parameters of children and adolescents.This cross-sectional study involved 639 elementary and high school students (mean age 13.03 years, range 8-18, 58.5% female) from the south of Brazil. Participants answered the Morningness-Eveningness Questionnaire (MEQ), and were asked about their sleeping habits on weekdays and weekends. Sleep deficit was defined as the difference between sleep duration on weekdays and weekends.	The morning-school-time students presented significantly higher age, bedtime and wake up differences, sleep deficits, and social jetlag. The sleep deficit presented by girls was greater than that observed in boys of the same age. The difference between weekday and weekend waking times was also significantly greater in girls than in boys aged 13-18 years. Sleep deficit was significantly positively correlated with age and differences in wake up times, and significantly negatively correlated with MEQ scores, social jetlag, difference between weekday and weekend bedtimes, midpoint of sleep on weekends, and midpoint of sleep on weekends corrected for sleep deficit. A step-by-step multivariate logistic regression identified social jetlag, the difference between waking times on weekdays and weekends, and the midpoint of sleep on weekends as significant predictors of sleep deficit (Adjusted R(2) = 0.95; F = 1606.87; p <0.001).	The results showed that school time influences the sleep parameters. The association of school schedules and physiological factors influence the sleep/wake cycle.	
27195315	Nocturia is a prevalent condition of waking to void during the night. The concept of nocturia has evolved from being a symptomatic aspect of disease associated with the prostate or bladder to a form of lower urinary tract disorder. However, recent advances in circadian biology and sleep science suggest that it might be important to consider nocturia as a form of circadian dysfunction. In the current review, nocturia is reexamined with an introduction to sleep disorders and recent findings in circadian biology in an attempt to highlight the importance of rediscovering nocturia as a problem of chronobiology. 
27191770	To present the first case of induced next-day somnolence in a patient taking suvorexant concomitantly with diltiazem.The patient was an 88-year-old female who had suffered from insomnia and anorexia, for which a psychiatric clinic had prescribed 1.5 mg/day aripiprazole and 15 mg/day suvorexant (both once daily at bedtime), which cured her insomnia. Subsequently, a different hospital prescribed diltiazem hydrochloride (100 mg, sustained-release, daily after breakfast) for treatment of hypertension. After starting diltiazem, the patient was unable to wake up in the morning and overslept by ~ 3 hours. On the third day of taking diltiazem, the patient, on the basis of her own judgment, took only half a tablet of suvorexant, and found that she was able to sleep, and there was no somnolence the following morning. As halving suvorexant tablets is an off-label usage, and lower-dose tablets are not available, her prescription was switched to 1-mg rilmazafone hydrochloride. Since then, her sleep disorder has not recurred.	Because suvorexant is metabolized by CYP3A4, next-day somnolence could have occurred as a result of increased plasma suvorexant concentration due to CYP3A4 inhibition by diltiazem.	Elderly patients may suffer next-day somnolence if they concomitantly take suvorexant and sustained-release diltiazem hydrochloride, even if the diltiazem dose is low and there is a significant interval between the administration times of the two drugs. In order to avoid drug interaction, it may be desirable to switch from suvorexant to a different soporific that is not metabolized by CYP3A4.	
27189909	Caloric sweeteners such as sugar and honey are replaced in thousands of food products by noncaloric artificial sweeteners (NASs). The aim of the present study was to determine the effects of chronic NAS intake on circadian sleep regulation.Circadian rhythms of sleep and locomotor activity were evaluated in mice after consumption of drinking water containing 0.1% (w/v) saccharin for 2 wk.	The intake of saccharin ad libitum significantly reduced wakefulness and increased non-rapid eye movement sleep during the first half of the active (dark) phase, whereas wakefulness was significantly increased at the start of the sleep phase. Saccharin consumption obviously reduced spontaneous activity during the first half of the dark period.	The findings suggest that NASs disturb the circadian sleep-wake cycle and cause behavioral inactivity in mice.	
27189470	The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. 
27186939	Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention to treat poorly controlled motor symptoms in Parkinson's disease (PD). Both surgical targets (the subthalamic nucleus and globus pallidus) have proven equally efficacious in treating motor symptoms but unique differences may exist in effects on nonmotor symptoms. Sleep dysfunction, a common disabling symptom in PD, has only been examined directly in the subthalamic target, demonstrating some beneficial changes in sleep quality. We aimed to explore sleep changes after pallidal stimulation; hypothesizing similar benefits would be seen.We performed a prospective nonblinded clinical trial evaluating sleep in five PD patients already slated for pallidal DBS pre and six months postimplantation using validated sleep surveys and polysomnograms (PSGs). Surveys included the Epworth sleepiness scale, PD sleep scale, Insomnia severity index (ISI), and RLS severity scale.	Most patients had notable improvements in sleep quality as measured by PSG metrics such as sleep efficiency and latency to sleep but they did not reach statistical significance. Most surveys reflected an improvement as well with the ISI scale showing the most promising trend post pallidal DBS (14.4 ± 7.02 vs. 9.0 ± 2.55; p = 0.07).	In this small pilot trial, pallidal DBS failed to demonstrate statistically significant improvements in sleep metrics postimplantation but did reveal improving trends in several PSG measures including sleep efficiency and latency to sleep onset as well as sleep survey scores. A larger, blinded clinical trial is needed to more definitively determine whether pallidal DBS may benefit sleep.	
27186147	Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson's disease who experience abnormalities in sleep electroencephalographic frequencies, sleep-wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism. 
27184329	In this cross-sectional study associations were examined between eight shift schedule characteristics with shift-specific sleep complaints and need for recovery and generic health and performance measures. It was hypothesized that shift schedule characteristics meeting ergonomic recommendations are associated with better sleep, need for recovery, health and performance. Questionnaire data were collected from 491 shift workers of 18 companies with 9 regular (semi)-continuous shift schedules. The shift schedule characteristics were analyzed separately and combined using multilevel linear regression models. The hypothesis was largely not confirmed. Relatively few associations were found, of which the majority was in the direction as expected. In particular early starts of morning shifts and many consecutive shifts seem to be avoided. The healthy worker effect, limited variation between included schedules and the cross-sectional design might explain the paucity of significant results. 
27183564	Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses.
27183274	The primary objective was to determine if poor sleep predicts postconcussion symptoms in the subacute period after mild traumatic brain injury (TBI). The impact of poor sleep pre- and post-injury was examined. The research design was cross-sectional. After screening to detect response invalidity, 61 individuals with a self-reported history of mild TBI 1-to-6 months prior answered an online fixed order battery of standardized questionnaires assessing their sleep (current and preinjury) and persistent postconcussion symptoms (Neurobehavioral Symptom Inventory, minus sleep, and fatigue items). The sleep measures were the Insomnia Severity Index, Epworth Sleepiness Scale, a single Likert-scale pre-injury sleep quality rating, and two PROMIS™ measures (sleep-related impairment and sleep disturbance). After controlling for the effects of preinjury sleep quality and demographics, the combination of the sleep measures made a significant contribution to the outcome (F[8,58] = 4.013, p = .001, [Formula: see text]). Only current sleep-related impairment (ß = .60, p < .05) made a significant and unique contribution to neurobehavioral symptoms. Preinjury sleep was not a predictor (ß = -.19, p > .05), although it contributed 3% of the variance in NSI scores after controlling for demographics. Sleep-related impairment is a modifiable factor. As a significant contributor to neurobehavioral symptoms, treatment for post-injury sleep-related impairment warrants further attention. 
27182013	This article provides an overview of current knowledge on the impact of caregiving on the psychological and physical health of family caregivers of intensive care unit (ICU) survivors and suggestions for future research.Review of selected papers published in English between January 2000 and October 2015 reporting psychological and physical health outcomes in family caregivers of ICU survivors.	In family caregivers of ICU survivors followed up to five years after patients' discharge from an ICU, psychological symptoms, manifested as depression, anxiety and post-traumatic stress disorder, were highly prevalent. Poor self-care, sleep disturbances and fatigue were identified as common physical health problems in family caregivers. Studies to date are mainly descriptive; few interventions have targeted family caregivers. Further, studies that elicit unique needs of families from diverse cultures are lacking.	Studies to date have described the impact of caregiving on the psychological and physical health in family caregivers of ICU survivors. Few studies have tested interventions to support unique needs in this population. Therefore, evidence for best strategies is lacking. Future research is needed to identify ICU caregivers at greatest risk for distress, time points to target interventions with maximal efficacy, needs of those from diverse cultures and test interventions to mitigate family caregivers' burden.	
27180356	Sleep disturbance is a risk factor for somatic, psycho-social and spiritual dysfunction. It is also arguably the most deleterious effect of traffic noise pollution. Quantification of its burden is an anchor element of environmental policy making but no data are currently available for Bulgaria where the preponderance of dangerous nighttime noise exposure is highest in Europe.The aim of this study was to quantify the socio-economic burden of severe sleep disturbance due to traffic noise (road, aircraft and railway) in Bulgaria.	The official World Health Organization methodology used in Europe was applied in order to estimate this annual loss expressed as disability-adjusted life-years (DALYs) and their corresponding monetary value (assuming € 12 000 per DALY).	Results showed that severe sleep disturbance due to all traffic sources was associated conservatively with 15 468 DALYs (8 839 - 22 097) and € 185 615 861 (€ 106 066 206 - € 265 165 516) lost in 2012, with road traffic being the single most important noise source.	In conclusion, severe sleep disturbance due to traffic noise bears a heavy environmental and socio-economic burden in Bulgaria which prompts vigorous political action and greater involvement in environmental research. In order to increase the accuracy of future burden of disease analyses other studies would need to establish exposure-response functions based on population-based socio-acoustic surveys in the country.	
27179365	The apnoea-hypopnoea index (AHI) is the primary measurement used to characterize the obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Despite its popularity, there are limiting factors to its application such as night-to-night variability.To evaluate the variability of AHI in the OSAHS.	A prospective study was designed in our university hospital's sleep unit. Adults with clinical suspicion of OSAHS underwent 2 consecutive nights of polysomnographic recording. The population was divided in two groups according to an AHI>or<10. Patients with psychiatric disorders or professions that might result in sleep deprivation or an altered sleep/wake cycle were excluded.	Twenty patients were enrolled. The mean age was 50.6±9.3 years. OSAHS was mild in 4 cases, moderate in 6 cases and severe in 8 cases. AHI was less than 5 in two cases. AHI values were not significantly altered throughout both recording nights (33.2 vs. 31.8 events/h). A significant positive correlation was found between AHI measured on the first and the second night. However, a significant individual variability was noted. Comparison between both patient's groups showed a correlation between AHI and the body mass index.	This study demonstrates that the AHI in OSAHS patients is well correlated between two consecutive nights. However, a significant individual variability should be taken into consideration, especially when AHI is used in the classification of OSAHS or as a criterion of therapeutic success.	
27178377	Sleep problems and disorders are prevalent in patients with traumatic brain injury (TBI) and are associated with negative outcomes. Incidence varies because of challenges including differences in assessment methods, particularly in the acute stages of recovery when patients are cognitively impaired and unable to complete traditional self-report methods. Actigraphy (ACG) recently has been validated in the acute TBI rehabilitation setting and may serve as a superior method of assessing sleep-wake patterns at this stage of recovery. Although a few studies with small sample sizes have described the use of ACG, none have described feasibility and implementation protocols.To describe the feasibility and implementation protocol of ACG to evaluate sleep-wake patterns and white-light exposure data in patients with acute TBI during inpatient rehabilitation. Sleep-wake patterns and light exposure data are presented to characterize the sample using these methods to inform future research.	Retrospective study.	Acute inpatient rehabilitation unit at a Veterans' Affairs Polytrauma Rehabilitation Center.	Veterans (age ≥18 years) admitted to inpatient rehabilitation and enrolled in the Traumatic Brain Injury Model Systems study who were admitted and discharged in the calendar year 2013.	Veterans underwent actigraph watch placement as soon as possible after admission. Records from the calendar year 2013 were reviewed to determine the number of admissions that met study criteria and what percentage of those patients had 3 days of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected for the study sample.	Percentage of patients who met study criteria and who had 72 hours of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected.	Of 22 eligible Traumatic Brain Injury Model Systems admissions, 3 consecutive nights of ACG data were successfully obtained for 86% (n = 19) of the sample. Barriers to data collection included patient access due to abbreviated lengths of stay, staff availability for ACG placement, and data collection protocols to prevent loss of data in Veterans' Affairs computing systems.	ACG is feasible for collecting data about sleep, wake, and light exposure in patients who are in acute TBI inpatient rehabilitation settings.	III.	

27173764	Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls.We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers.	Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001).	Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.	
27173360	Commercial motor vehicle (CMV) drivers in the US may start a new duty cycle after taking a 34-h restart break. A restart break provides an opportunity for sleep recuperation to help prevent the build-up of fatigue across duty cycles. However, the effectiveness of a restart break may depend on its timing, and on how many nighttime opportunities for sleep it contains. For daytime drivers, a 34-h restart break automatically includes two nighttime periods. For nighttime drivers, who are arguably at increased risk of fatigue, a 34-h restart break contains only one nighttime period. To what extent this is relevant for fatigue depends in part on whether nighttime drivers revert back to a nighttime-oriented sleep schedule during the restart break. We conducted a naturalistic field study with 106 CMV drivers working their normal schedules and performing their normal duties. These drivers were studied during two duty cycles and during the intervening restart break. They provided a total of 1260days of data and drove a total of 414,937 miles during the study. Their duty logs were used to identify the periods when they were on duty and when they were driving and to determine their duty cycles and restart breaks. Sleep/wake patterns were measured continuously by means of wrist actigraphy. Fatigue was assessed three times per day by means of a brief psychomotor vigilance test (PVT-B) and a subjective sleepiness scale. Data from a truck-based lane tracking and data acquisition system were used to compute lane deviation (variability in lateral lane position). Statistical analyses focused on 24-h patterns of duty, driving, sleep, PVT-B performance, subjective sleepiness, and lane deviation. Duty cycles preceded by a restart break containing only one nighttime period (defined as 01:00-05:00) were compared with duty cycles preceded by a restart break containing more than one nighttime period. During duty cycles preceded by a restart break with only one nighttime period, drivers showed more nighttime-oriented duty and driving patterns and more daytime-oriented sleep patterns than during duty cycles preceded by a restart break with more than one nighttime period. During duty cycles preceded by a restart break with only one nighttime period, drivers also experienced more lapses of attention on the PVT-B and increased lane deviation at night, and they reported greater subjective sleepiness. Importantly, drivers exhibited a predominantly nighttime-oriented sleep schedule during the restart break, regardless of whether the restart break contained only one or more than one nighttime period. Consistent with findings in laboratory-based studies of the restart break, the results of this naturalistic field study indicate that having at least two nighttime periods in the restart break provides greater opportunity for sleep recuperation and helps to mitigate fatigue. 
27172667	Penile erection (PE) is a physiological phenomenon involving complex mechanisms. PE may occur as reactive erections, psychogenic erections in the conscious state and spontaneous erections during the sleep. Sleep-related PE refers to the erections occurring spontaneously during the sleep with rapid eye movement. Studies have shown a correlation between sleep and PE as well as between sleep disorders and erectile dysfunction but not yet revealed the exact mechanisms. This paper updates the relationship between sleep and erectile function.
27167889	Knowledge of the physiology of sleep-wake regulation can contribute to an understanding of the pathophysiology and symptoms of neurological diseases and is helpful for initiating specific therapies for sleep-wake cycle stabilization. Based on historically important observations on the close relationship between sleep and neurological diseases, new insights and developments in selected neurological entities are presented in this review article. 
27167478	The prevalence of the insomnia syndrome and the effects of caffeine on sleep are in part genetically determined. Pharmacogenetic studies in humans demonstrate that functional polymorphisms of the genes encoding adenosine A2A receptors and dopamine transporters contribute to individual differences in impaired sleep quality by caffeine. The A2A receptor and dopamine transporter are preferentially expressed in the striatum. Together, these observations suggest that the striatum plays an important role in sleep-wake regulation. Individual caffeine sensitivity and A2A receptor genotype should be taken into account in the development of possible novel adenosine-based pharmacotherapies of sleep-wake disorders and neurodegenerative disorders such as Parkinson's disease. This may permit the prediction of individual drug effects and improve the reliability of clinical trials.
27166297	Sleep patterns of pediatric patients in unresponsive wakefulness syndrome (UWS) have been poorly investigated, and the prognostic potential of polysomnography (PSG) in these subjects is still uncertain. The goal of the study was to identify quantitative PSG indices to be applied as possible prognostic markers in pediatric UWS.We performed PSG in 27 children and adolescents with UWS due to acquired brain damage in the subacute phase. Patients underwent neurological examination and clinical assessment with standardized scales. Outcome was assessed after 36 mo. PSG tracks were scored for sleep stages and digitally filtered. The spectral difference between sleep and wake was computed, as the percent difference at specific spectral frequencies. We computed (1) the ratio between percent power in the delta and alpha frequency bands, (2) the ratio between alpha and theta frequency bands, and (3) the power ratio index, during wake and sleep, as proposed in previous literature. The predictive role of several clinical and PSG measures was tested by logistic regression.	Correlation was found between the differential measures of electroencephalographic activity during sleep and wake in several frequency bands and the clinical scales (Glasgow Outcome Score, Level of Cognitive Functioning Assessment Scale, and Disability Rating Scale) at follow-up; the Sleep Patterns for Pediatric Unresponsive Wakefulness Syndrome (SPPUWS) scores correlated with the differential measures, and allowed outcome prediction with 96.3% of accuracy.	The differential measure of electroencephalographic activity during sleep and wake in the beta band and, more incisively, SPPUWS can help in determining the capability to recover from pediatric UWS well before the confirmation provided by suitable clinical scales.	
27166238	To evaluate the efficacy and safety of oral JZP-110, a second-generation wake-promoting agent with dopaminergic and noradrenergic activity, for treatment of impaired wakefulness and excessive sleepiness in adults with narcolepsy.This was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 28 centers in the United States. Patients were adults with narcolepsy who had baseline scores ≥ 10 on the Epworth Sleepiness Scale (ESS) and baseline sleep latency ≤ 10 min on the Maintenance of Wakefulness Test (MWT). Patients received a daily placebo (n = 49) or JZP-110 (n = 44) 150 mg/day weeks 1-4 and 300 mg/day weeks 5-12. Primary efficacy endpoints were change from baseline in average MWT sleep latency, and the Clinical Global Impression-Change (CGI-C); secondary endpoints were change from baseline in ESS score and Patient Global Impression-Change.	Improvements were significantly greater with JZP-110 versus placebo on mean MWT sleep latency (4 w, 9.5 versus 1.4 min, P < 0.0001; 12 w, 12.8 versus 2.1 min, P < 0.0001), percentage of patients with CGI-C improvement (4 w, 80% versus 51%, P = 0.0066; 12 w, 86% versus 38%, P < 0.0001), and mean change in ESS (4 w, -5.6 versus -2.4, P = 0.0038; 12 w, -8.5 versus -2.5, P < 0.0001). Three JZP-110-treated patients (6.8%) discontinued due to adverse events (AEs). The most common AEs with JZP-110 versus placebo were insomnia (23% versus 8%), headache (16% versus 10%), nausea (14% versus 6%), diarrhea (11% versus 6%), decreased appetite (14% versus 0%), and anxiety (11% versus 0%).	At doses of 150-300 mg/day, JZP-110 was well tolerated and significantly improved the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy.	
27165820	The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic kidney disease has not been shown. We examined this in a prospective cohort study of 4238 participants from the Nurses' Health Study and analyzed the association of self-reported sleep duration with decline in renal function over an 11-year period (1989 to 2000). Individuals who reported shorter sleep duration were more likely to experience a rapid decline in estimated glomerular filtration rate (30% or more). Compared with sleeping 7 to 8 hours per night, the adjusted odds ratios for a rapid decline in renal function were a significant 1.79 (95% CI, 1.06-3.03) for 5 hours or less sleep per night, a significant 1.31 (95% CI, 1.01-1.71) for 6 hours sleep per night, but an insignificant 0.88 (95% CI, 0.50-1.57) for 9 or more hours sleep per night. Similarly, there was a significant trend in the adjusted annualized decline in estimated glomerular filtration rate of 1.2 ml/min/1.73 m(2)/year, 0.9 ml/min/1.73 m(2)/year, 0.8 ml/min/1.73 m(2)/year, and 0.8 ml/min/1.73 m(2)/year for individuals sleeping 5 hours or less per night, 6 hours per night, 7 to 8 hours per night, and 9 hours or more per night, respectively. Thus, shorter sleep duration is prospectively and independently associated with faster decline in renal function. 
27165217	This study aimed to determine sleep disorders and associated risk factors in leukemia patients undergoing chemotherapy in Imam Khomeini Hospital of Sari, Iran. This cross-sectional study was conducted in 2015 with 100 patients selected. Inclusion criteria included complete mental and psychological health and being over 18 years old, and exclusion criteria included suffering other cancers, other chronic diseases, concurrent radiotherapy, and chemotherapy. The Pittsburgh Sleep Quality standard questionnaire was used to collect data. The questionnaire consisted of mental sleep quality, sleep latency, sleep duration, sleep quality, sleep disturbances, use of sleeping drugs, and impaired daily functioning. Data were analyzed by software SPSS 18 and by using descriptive and inferential tests (Pearson, Spearman, T-test and chi-square). Totals of 47 men (47%) and 53 women (53%) with a mean age of 44.1±1.7, participated in the study. The mean overall score of sleep quality was 9.3±3.9, which represents the average sleep quality in most participants. T-test shows that males have better sleep quality than females (t=2.1; 95%CI:0.004-0.25; P<0.01). Also the sleep quality increased with age (r=0.22, P=0.03). Results show that the amount of sleep quality was only moderate in most patients, so it is necessary to take coping strategies to improve their quality of sleep.
27164924	In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain.To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters.	A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs.	All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant.	Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this multilevel explanation of the phenomena of bipolar disorder.	

27164676	This study is a prospective, controlled clinical and electrophysiologic trial examining the chronic course of posttraumatic sleep-wake disturbances (SWD).We screened 140 patients with acute, first-ever traumatic brain injury of any severity and included 60 patients for prospective follow-up examinations. Patients with prior brain trauma, other neurologic or systemic disease, drug abuse, or psychiatric comorbidities were excluded. Eighteen months after trauma, we performed detailed sleep assessment in 31 participants. As a control group, we enrolled healthy individuals without prior brain trauma matched for age, sex, and sleep satiation.	In the chronic state after traumatic brain injury, sleep need per 24 hours was persistently increased in trauma patients (8.1 ± 0.5 hours) as compared to healthy controls (7.1 ± 0.7 hours). The prevalence of chronic objective excessive daytime sleepiness was 67% in patients with brain trauma compared to 19% in controls. Patients significantly underestimated excessive daytime sleepiness and sleep need, emphasizing the unreliability of self-assessments on SWD in trauma patients.	This study provides prospective, controlled, and objective evidence for chronic persistence of posttraumatic SWD, which remain underestimated by patients. These results have clinical and medicolegal implications given that SWD can exacerbate other outcomes of traumatic brain injury, impair quality of life, and are associated with public safety hazards.	
27163762	End-stage renal disease (ESRD) is associated with high rates of morbidity and mortality, and increased health care use. Optimal management of patients with ESRD requires close collaboration among primary care physicians, nephrology subspecialists, and other subspecialists. Critical issues for the family physician include helping patients transition from chronic kidney disease to ESRD, recognizing and managing common issues in patients receiving dialysis or after kidney transplantation, and understanding palliative care for patients with ESRD. Dialysis typically is initiated for patients with a glomerular filtration rate less than 15 mL/min/1.73 m(2) if they are symptomatic due to uremia or if medical management of metabolic conditions is unsuccessful. Kidney transplantation is the optimal form of renal replacement therapy in suitable patients. The choice between hemodialysis and peritoneal dialysis often is based on patient preference and coexisting conditions. Meticulous monitoring of volume status is necessary to achieve and maintain control of blood pressure. Sleep disorders and pruritus are common and can be managed by optimization of metabolic parameters, adequacy of dialysis, and drugs. 
27157560	A study carried out in 2014 in a hospital focused on the sources of discomfort of patients in intensive care. Resulting in raised awareness across all disciplines, it has enabled the actions to be undertaken to improve professional practices to be prioritised, in a culture of compassionate care. 
27157399	Sleep disturbances, affective disorders, pain and fatigue are often present in individuals affected by fibromyalgia (FM). The pathophysiology of FM is not yet well understood and, to date, no treatment has been proven to be fully effective in alleviating all symptoms. Adopting a transdiagnostic perspective could thus be useful for clinicians: treatment would target a transdiagnostic process across a range of disturbances, not just a single disorder. The aim of this review is to revise the available literature about the potential role of sleep disturbances as a transdiagnostic process in FM symptomatology and mood or anxiety disorders comorbidity. We are proposing a model under which sleep disturbances can play a central role. Because conditions of sleep loss are related to the activation of the stress system, including the activation of the inflammation system, we propose this mechanism as a key one: it can be shared by mental, sleep disturbances and pain in FM and it may explain, in part, the high levels of comorbidity between them. In this frame-work sleep disturbances may play a key role and be the target of therapeutic strategies across FM symptomatology and mental disorders. 

27155860	Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated. 
27154736	This article provides an overview of the neurobiology of orofacial pain as well as the neural processes underlying sleep, with a particular focus on the mechanisms that underlie pain and sleep interactions including sleep disorders. Acute pain is part of a hypervigilance system that alerts the individual to injury or potential injury of tissues. It can also disturb sleep. Disrupted sleep is often associated with chronic pain states, including those that occur in the orofacial region. The article presents many insights that have been gained in the last few decades into the peripheral and central mechanisms involved in orofacial pain and its modulation, as well as the circuits and processes in the central nervous system that underlie sleep. Although it has become clear that sleep is essential to preserve and maintain health, it has also been found that pain, particularly chronic pain, is commonly associated with disturbed sleep. In the presence of chronic pain, a circular relationship may prevail, with mutual deleterious influences causing an increase in pain and a disruption of sleep. This article also reviews findings that indicate that reducing orofacial pain and improving sleep need to be targeted together in the management of acute to chronic orofacial pain states in order to improve an orofacial pain patient's quality of life, to prevent mood alterations or exacerbation of sleep disorder (e.g., insomnia, sleep-disordered breathing) that can negatively affect their pain, and to promote healing and optimize their health. 
27149919	Narcolepsy type 1 is a neurological disorder characterized by a unique syndrome, including the pathognomonic symptom of cataplexy. The diagnosis can be confirmed by objective measures, such as typical findings in the multiple sleep latency test, reduced or undetectable levels of orexin (hypocretin) in the cerebrospinal fluid, and linkage to a specific HLA haplotype. Nevertheless, the mean time that elapses from symptom onset to the correct diagnosis ranges between 10 and 20 years, and the causes and correlates of this delay are poorly understood. Diagnostic delay was assessed on 52 well-defined patients with narcolepsy type 1, evaluating clinical, electrophysiological and neurochemical parameters and the results of a 41-item questionnaire developed to obtain the patients' perspective on various aspects of the diagnostic process. The mean time gap between disease onset and first medical consultation was 3.2 ± 5.1 years; the mean diagnostic delay was 8.9 ± 11.0 years. Prior to correct diagnosis, patients received a wide variety of misdiagnoses. The self-ratings of the patients revealed that the undiagnosed symptoms caused high levels of anxiety and unjustified criticism by family, friends and employers. Multiple regression analysis identified higher cerebrospinal fluid orexin levels (β = 0.311, P = 0.01), and a longer interval between the onset of excessive daytime sleepiness and cataplexy (β = 0.368, P = 0.002) as independent associates of longer diagnostic delay. The diagnostic delay decreased over the last decades (β = -0.672, P < 0.001). In conclusion, delayed diagnosis of narcolepsy type 1 is very common, associated with many adverse consequences, and requires educational efforts to improve awareness on narcolepsy among healthcare providers and the general population.
27149248	Scientific knowledge about symptoms of common mental disorders among elite Gaelic athletes is lacking. Consequently, this study aimed to (i) determine the prevalence, comorbidity and 6-month incidence of symptoms of common mental disorders (distress, anxiety/depression, sleep disturbance, adverse alcohol use) among elite Gaelic athletes and (ii) evaluate their association with potential stressors (severe musculoskeletal injuries, surgeries, recent life events, career dissatisfaction).An observational prospective cohort study by means of questionnaires was conducted over six months among elite Gaelic athletes (N=204). Using validated questionnaires to assess symptoms of common mental disorders as well as several stressors, an electronic questionnaire was set up and distributed by the Gaelic Players' Association.	Prevalence ranged from 23% for adverse alcohol use to 48% for anxiety/depression. Around 24% of the participants reported at baseline two symptoms. Six-month incidence ranged from 11% for sleep disturbance to 21% for anxiety/depression. Severe musculoskeletal injury, surgery, recent life events and career dissatisfaction led to an increased risk for common mental disorders.	Our findings indicate that raising the self-awareness of all stakeholders in Gaelic sports about common mental disorders should be prioritized, as well as the evidence-based development and application of adequate preventive and supportive measures.	
27148829	Dopamine has been implicated in the regulation of sleep-wake states and the circadian rhythm. However, there is no consensus on the impact of two established dopaminergic gene variants: the catechol-O-methyltransferase Val158Met (COMT Val158Met; rs4680) and the dopamine D4 receptor Exon III variable-number-of-tandem-repeat polymorphism (DRD4 VNTR). Pursuing a multi-method approach, we examined their potential effects on circadian preferences, arousal regulation and sleep. Subjects underwent a 7-day actigraphy assessment (SenseWear Pro3), a 20-minute resting EEG (analyzed using VIGALL 2.0) and a body mass index (BMI) assessment. Further, they completed the Morningness-Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). The sample comprised 4625 subjects (19-82 years) genotyped for COMT Val158Met, and 689 elderly subjects (64-82 years) genotyped for DRD4 VNTR. The number of subjects varied across phenotypes. Power calculations revealed a minimum required phenotypic variance explained by genotype ranging between 0.5% and 1.5% for COMT Val158Met and between 3.3% and 6.0% for DRD4 VNTR. Analyses did not reveal significant genotype effects on MEQ, ESS, PSQI, BMI, actigraphy and EEG variables. Additionally, we found no compelling evidence in sex- and age-stratified subsamples. Few associations surpassed the threshold of nominal significance (p < .05), providing some indication for a link between DRD4 VNTR and daytime sleepiness. Taken together, in light of the statistical power obtained in the present study, our data particularly suggest no impact of the COMT Val158Met polymorphism on circadian preferences, arousal regulation and sleep. The suggestive link between DRD4 VNTR and daytime sleepiness, on the other hand, might be worth investigation in a sample enriched with younger adults. 
27148632	This study investigates health behaviors, health-related quality of life (HRQOL) and sleep among chronotypes in a community-based sample (n = 2,976). Analysis of covariance indicated evening types (E-types) had a significantly higher percentage of current smokers and more sleep-interfering behaviors compared to intermediate and morning types (M-type), and also lower physical activity and more sleep disturbance compared to M-types. E-types also had worse mental HRQOL compared to both chronotypes, and worse physical HRQOL compared to M-types. Exploratory analyses indicated E-types consumed more caffeinated beverages at night, smoked or ate heavy meals before bedtime, kept irregular sleep-wake schedules, and took more naps. Mediational analyses indicated that sleep-interfering behavior partially mediated the relationship between chronotype and sleep disturbance, and physical activity partially mediated the relationship between chronotype and mental HRQOL. E-types had more unhealthy behaviors, which may subsequently place them at higher risk for health problems.
27148626	Light-dark alternation has always been the strongest external circadian "zeitgeber" for humans. Due to its growing technological preference, our society is quickly transforming toward a progressive "eveningness" (E), with consequences on personal circadian preference (chronotype), depending on gender as well. The aim of this study was to review the available evidence of possible relationships between chronotype and gender, with relevance on disturbances that could negatively impact general health, including daily life aspects.Electronic searches of the published literature were performed in the databases MEDLINE and Web of Science, by using the Medical Subject Heading (MeSH), when available, or other specific keywords.	Results were grouped into four general areas, i.e. (a) "General and Cardiovascular Issues", (b) "Psychological and Psychopathological Issues", (c) "Sleep and Sleep-Related Issues" and (d) "School and School-Related Issues". (a) E is associated with unhealthy and dietary habits, smoking and alcohol drinking (in younger subjects) and, in adults, with diabetes and metabolic syndrome; (b) E is associated with impulsivity and anger, depression, anxiety disorders and nightmares (especially in women), risk taking behavior, use of alcohol, coffee and stimulants, psychopathology and personality traits; (c) E has been associated, especially in young subjects, with later bedtime and wake-up time, irregular sleep-wake schedule, subjective poor sleep, school performance and motivation, health-related quality of life; (d) E was associated with lowest mood and lower overall grade point average (especially for women).	Eveningness may impact general health, either physical or mental, sleep, school results and achievements, especially in younger age and in women. The role of family support is crucial, and parents should be deeply informed that abuse of technological devices during night hours may lead to the immature adjustment function of children's endogenous circadian pacemakers.	
27144559	Sleep disorders are very common, often under-recognized and therefore undertreated, are associated with a myriad of medical conditions and could lead to significant impairment of quality of life. This review provides an up-to-date synopsis of common sleep disorders encompassing insufficient sleep syndrome, insomnia, circadian rhythm disorders and obstructive sleep apnea with a brief overview of epidemiology, screening, diagnostic testing and treatment. We also emphasize the emerging area of the intersection of sleep disorders and dermatologic conditions and present compelling data regarding underlying mechanisms including sleep dysfunction in relation to disorders of skin inflammation, aging and skin cancer. 
27143601	Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep. 
27140951	Process C (internal clock) and Process S (sleep-wake homeostasis) are the basis of sleep-wake regulation. In the last trimester of pregnancy, foetal heart rate is synchronized with the maternal circadian rhythm. At birth, this interaction fails and an ultradian rhythm appears. Light exposure is a strong factor influencing the synchronization of sleep-wake processes. However, little is known about the effects of phototherapy on the sleep rhythm of premature babies. It was hypothesized that sleep in preterm infants would not differ during phototherapy, but that a maturation effect would be seen. Sleep states were studied in 38 infants born < 32 weeks gestational age and/or < 1 500 g birth weight. Videos of 3 h were taken over the first 5 days of life. Based on breathing and movement patterns, behavioural states were defined as: awake; active sleep; or quiet sleep. Videos with and without phototherapy were compared for amounts of quiet sleep and active states (awake + active sleep). No significant association between phototherapy and amount of quiet sleep was found (P = 0.083). Analysis of videos in infants not under phototherapy revealed an increase in time spent awake with increasing gestational age. The current data suggest that the ultradian rhythm of preterm infants seems to be independent of phototherapy, supporting the notion that sleep rhythm in this population is mainly driven by their internal clock.
27140809	Epilepsy is one of the most common chronic neurologic disorders. Daily periodicity of epileptic seizures has been known for over a century. The diurnal patterns of epileptic seizures have also been observed in studies.To investigate the sleep/wake cycle, day/night, and 24-h periodicity of various seizure subtypes and seizure onset localizations in children.	We analyzed the clinical seizures of 170 consecutive epilepsy patients who underwent video-electroencephalography (EEG) monitoring over the last 5 years. Semiology of the seizures was classified according to the semiological seizure classification. Origin of the seizures was defined by the onset of ictal activity on EEG. Seizures were evaluated in terms of occurrence during the day (06:00-18:00 h) or night (18:00-06:00 h), in wakefulness or in sleep, and within a 3-h time interval throughout 24 h.	A total of 909 seizures were analyzed. Auras, dialeptic, myoclonic, hypomotor, atonic seizures, and epileptic spasms occurred more frequently in wakefulness; tonic, clonic, and hypermotor seizures occurred more frequently in sleep. Auras, dialeptic, and atonic seizures and epileptic spasms occurred more often during daytime; hypermotor seizures occurred more often at night. Generalized seizures were seen most frequently in wakefulness (between 12:00 and 18:00 h); frontal lobe seizures were seen at night and in sleep (between 24:00 and 03:00 h); temporal lobe seizures were seen in wakefulness (between 06:00 and 09:00 h and between 12:00 and 15:00 h); occipital seizures were seen during daytime and in wakefulness (between 09:00 and 12:00 h and between 15:00 and 18:00 h, respectively); parietal seizures were seen mostly during daytime.	Seizures in children occur in specific circadian patterns and in specific sleep/wake distributions depending on seizure onset location and semiology.	
27136936	The aim of our study was to apply the electrical impedance tomography (EIT) technique to the study of ventilation during wake and NREM and REM sleep in patients with obstructive sleep apneas (OSA).This is a prospective, observational, monocentric, pilot study in a neurology department with a sleep disorder center. Inclusion criteria were age ≥18 years, both gender, and diagnosis of OSA. Exclusion criteria were the contraindications to the thoracic EIT. All patients underwent laboratory-based polysomnography (PSG) alongside thoracic EIT. Primary endpoint was to compare the global impedance (GI) among the conditions: "Wake" vs "Sleep," "NREM" vs "REM," and "OSA" vs "Non-OSA." Secondary endpoint was to measure the regional distribution of impedance in the four regions of interest (ROIs), in each condition.	Of the 17 consecutive patients enrolled, two were excluded because of poor-quality EIT tracings. Fifteen were analyzed, 10 men and 5 women, mean age 51.6 ± 14.4 years. GI was higher in Wake vs Sleep (Wake 13.24 ± 11.23; Sleep 12.56 ± 13.36; p < 0.01), in NREM vs REM (NREM 13.48 ± 13.43; REM 0.59 ± 0.01; p < 0.01), and in Non-OSA vs OSA (Non-OSA 10.50 ± 12.99; OSA 18.98 ± 10.06; p < 0.01). No significant differences were observed in the regional distribution of impedance between Wake and Sleep (χ 2 = 3.66; p = 0.299) and between Non-OSA and OSA (χ 2 = 1.00; p = 0.799); conversely, a significant difference was observed between NREM and REM sleep (χ 2 = 62.94; p < 0.001).	To our knowledge, this is the first study that addresses the issue of regional ventilation in OSA patients during sleep. Thoracic electrical impedance changes through the sleep-wake cycle and during obstructive events. The application of thoracic EIT can prove a valuable additional strategy for the evaluation of OSA patients.	
27134503	Restless legs syndrome (RLS) is a disease characterized by the urge to move the legs and sleep disturbances. Similarly, chronic spontaneous urticaria (CSU) is a dermatological disease characterized by pruritus and sleep disorders. In this study, we aimed to determine the prevalence and severity of RLS in patients with chronic spontaneous urticaria (CSU) and to compare the quality of sleep of patients with and without RLS in the CSU group using the Pittsburgh Sleep Quality Index. A total of 130 patients with CSU and 100 healthy controls were included in this study. The frequency of RLS, frequency of sleep disturbances, and average score of RLS in patients with CSU were statistically significantly higher than control groups (respectively P = 0.008, P = 0.009, P = 0.004). Subjective sleep quality, sleep latency and habitual sleep efficiency scores in patients with RLS were statistically significantly higher than patients without RLS (respectively P = 0.016, P = 0.007, P = 0.035). We claimed that pruritus of urticaria may decrease the quality of sleep in patients with RLS and it may trigger and worsen the restless legs syndrome. Furthermore, RLS and CSU may share a common etiology. 
27132952	Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made.This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations.	
27132701	Consumer-driven sleep-tracking technologies are becoming increasingly popular with patients with sleep disorders and the general population. As the list of sleep-tracking technologies continues to grow, clinicians and researchers are faced with new challenges and opportunities to incorporate these technologies into current practice. We review diagnostic tools used in sleep medicine clinical practice, discuss categories of consumer sleep-tracking technologies currently available, and explore the advantages and disadvantages of each. Potential uses of consumer sleep-tracking technologies to enhance sleep medicine patient care and research are also discussed. 
27132483	Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronic schizophrenia and from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα and DBP. In fibroblasts obtained from patients with chronic schizophrenia, we found a loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls. We also estimated the sleep quality in these patients and found that most of them suffered from poor sleep in comparison with the healthy controls. In another patient sample, we analyzed mononuclear blood cells from patients with schizophrenia experiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock in schizophrenia and have important implications in our understanding of the aberrant rhythms reported in this disease. 
27131794	Canada's wind energy capacity has grown from approximately 137MW (MW) in 2000 to over 9700MW in 2014, and this progressive development has made Canada the fifth-largest market in the world for the installation of new wind turbines (WTs). Although wind energy is now one of the fastest growing sources of power in Canada and many other countries, the growth in both number and size of WTs has raised questions regarding potential health impacts on individuals who live close to such turbines. This study is the first published research using a prospective cohort design, with noise and sleep measurements obtained before and after installation of WTs to investigate effect of such turbines on self-reported sleep disturbances of nearby residents. Subjective assessment of sleep disturbance was conducted in Ontario, Canada through standard sleep and sleepiness scales, including the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth daytime Sleepiness Scale (ESS). Both audible and infra-sound noises were also measured inside the bedroom. Descriptive and comparison analyses were performed to investigate the effect of WT exposure on sleep data. Results of the analysis show that participants reported poorer sleep quality if they had a negative attitude to WTs, if they had concerns related to property devaluation, and if they could see turbines from their properties. This study provides evidence for the role of individual differences and psychological factors in reports of sleep disturbance by people living in the vicinity of WTs. 
27131333	Esophageal infusion of capsaicin-containing red pepper sauce induced heartburn symptoms in patients with gastroesophageal reflux disease (GERD). We aimed to test the hypothesis whether sleep disturbance modulates esophageal sensitivity to capsaicin infusion in patients with GERD.We enrolled 40 patients with their sleep quality measured by the Pittsburg Sleep Quality Index with > 5 indicating sleep disturbance. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score by esophageal infusion of capsaicin-containing red pepper sauce. Objective sleep measures were assessed by ambulatory actigraphy.	We found 22 patients with sleep disturbance. The patients with sleep disturbance had shorter lag time to initial heartburn perception (P = 0.03) and greater sensory intensity rating (P = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance (P = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency (P = 0.04), longer average awakening time (P = 0.03), and greater total activity account (P = 0.04). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time (r = 0.43, P = 0.03).	We have shown that GERD patients with sleep disturbance have significantly enhanced heartburn perception to capsaicin infusion as compared with those with normal sleep. Our findings suggest that sleep disturbance is associated with esophageal hypersensitivity to capsaicin infusion in patients with GERD.	
27128899	The circadian biological clock is essentially based on the light/dark cycle. Some people working with shift schedules cannot adjust their sleep/wake cycle to the light/dark cycle, and this may result in alterations of the circadian biological clock. This study explored the circadian biological clock of shift and daytime nurses using non-invasive methods. Peripheral skin temperature, cortisol and melatonin levels in saliva, and Per2 expression in pubic hair follicle cells were investigated for 24 h after a day off. Significant differences were observed in peripheral skin temperature and cortisol levels between shift and daytime nurses. No differences in melatonin levels were obtained. Per2 maximum values were significantly different between the two groups. Shift nurses exhibited lower circadian variations compared to daytime nurses, and this may indicate an adjustment of the circadian biological clock to continuous shift schedules. Non-invasive procedures, such as peripheral skin temperature measurement, determination of cortisol and melatonin in saliva, and analysis of clock genes in hair follicle cells, may be effective approaches to extensively study the circadian clock in shift workers. 
27128479	To investigate the association between circulating Chlamydia pneumoniae (C pneumoniae) immunoglobulin G (IgG) antibody and migraine in Indian patients.A total of 300 migraine patients and 150 age-matched and sex-matched controls were recruited from the Department of Neurology at Yashoda Hospital in Hyderabad, India, during the study period between August 2011 and July 2013. All patients and controls were assessed for the presence of the C pneumoniae IgG antibody and also C-reactive protein (CRP) as well as for depression, which was assessed by the Hamilton Depression Rating Scale (HDRS).	Of the patients with migraine, 69% were female and the mean age ± standard deviation (SD) was 45.8 ± 4.8 years (range 18 to 62 years). The C pneumoniae IgG antibody was present in 151 of the patients (50.3%; P < .0001), CRP in 180 (60%; P < .0001), depression in 270 (90%; P < .0001), and history of sleep disturbances in 70 (23.3%; P < .0001); all measurements were significantly higher in migraine patients compared with controls. After adjustment for multiple logistic regression analyses, C pneumoniae IgG antibody positivity (odds ratio [OR] 2.6; 95% confidence interval [CI] = 1.3 to 3.7), CRP positivity (OR 6.2; 95% CI = 3.3 to 11.6), mild depression (OR 16.9; 95% CI = 6.5 to 39.4), and history of sleep disturbance (OR 2.1; 95% CI = 1.1 to 3.1) were independently associated with migraine.	This study showed that the presence of C pneumoniae IgG antibody was independently associated with migraine in Indian patients.	
27126038	Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K(+) concentration ([K(+)]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K(+)]e concomitant with decreases in [Ca(2+)]e, [Mg(2+)]e, [H(+)]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K(+)]e while increasing [Ca(2+)]e, [Mg(2+)]e, and [H(+)]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity. 

27125332	To investigate the lifetime prevalence, epidemiological characteristics and psychological factors of globus symptoms in Guangzhou (Guangzhou Province, China).A total of 3 360 individuals were randomly selected and participated in the study. Respondents completed questionnaires about their physical and psychological characteristics, globus symptomatology and the Glasgow-Edinburgh throat scale questionnaires and quality of sleep and life. Those who had experienced a globus sensation with no history of gastroesophageal reflux disease, dysphagia, odynophagia or alerting symptoms such as weight loss and hoarseness were diagnosed as having globus.	A total of 3 006 respondents completed the questionnaires, giving a response rate of 89.5%. The overall lifetime prevalence of globus was 21.5%, with a peak age at disease onset of 35-54 years. The prevalence of globus was higher in participants from the urban region than those from the rural areas (26.5% vs 16.4%, P = 0.001). No sex-related difference was observed (P = 0.082). Anxiety (39.8% vs 22.3%, P = 0.001), depression (31.2% vs 18.0%, P = 0.001) and sleep disorders (23.7% vs 13.6%, P = 0.001) were significantly more common in respondents with globus than in those without. Scores on all dimensions of the 36-item short-form health survey, except physical function, were lower in respondents with globus than in those without (all P < 0.05).	Globus symptoms are common and often accompanied by psychological and sleep disorders. The medical community should pay more attention to globus in clinical setting.	
27124542	Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise.
27124215	The coexistence of hypertension, abdominal obesity, and carbohydrate and lipid metabolism disturbances favors the acceleration of other disease entities - also apart from cardiovascular system disorders. This study was planned to estimate the relationship between the presence of metabolic syndrome and sleep disorders among a group of hypertensive patients.The study was conducted on unselected group of 261 patients from the Outpatient Hypertension Clinic. The standardized questionnaire was used to collect the data on medical history, prescribed drugs and lifestyle. Sleep disorders were diagnosed based on the Athens Insomnia Scale and STOP-Bang Questionnaire. According to the study protocol, anthropometric parameters (weight, height, waist and neck circumferences), blood pressure, serum lipids and fasting glucose laboratory measurements were performed. Metabolic syndrome was defined according to IDF criteria.	Sleep disorders were recognized in 183 participants of the study - significantly more frequently (P=0.03) among patients with diagnosed metabolic syndrome (120; 75%) in comparison with participants without this disturbance (63; 62.38%). Male gender, poor financial situation, tingling sensations before falling asleep and combination therapy of hypertension significantly increased the risk of sleep disorder occurrence in the group of patients with metabolic syndrome. Night food intake, aging, hypertension combination therapy and poor socioeconomic status were the factors increasing the risk of sleep problems among participants without metabolic syndrome.	Sleep disorders often coexist with metabolic syndrome in hypertensive patients. A number of factors increase the probability of occurrence of sleep disorders, but most of them are modifiable.	
27124208	Sleep disturbance may be the most often endorsed symptom of posttraumatic stress disorder (PTSD). Much of this research is based on subjective reports from trauma survivors; however, objective measures of sleep-related impairment have yielded findings inconsistent with self-report data. More studies investigating subjective and objective assessments concordantly are needed to understand sleep impairment in PTSD. The current study examined PTSD-related sleep disturbance in a female interpersonal violence cohort with full PTSD diagnoses (N=51) assessing subjective (global and daily diary measures) and objective (actigraphy) sleep measures concurrently. PTSD severity was positively associated with global, subjective reports of sleep impairment and insomnia. Subjective measures of sleep (including global sleep impairment, insomnia, and daily sleep diary reports of total sleep time, sleep efficiency, and sleep onset latency) were moderately to strongly correlated. However, no significant correlations between subjective and objective reports of sleep impairment were found in this cohort. Analyses demonstrated an overall elevation in subjectively reported sleep impairment when compared to objective measurement assessed concurrently. Findings demonstrate a lack of agreement between subjective and objective measurements of sleep in a PTSD-positive female cohort, suggesting objective and subjective sleep impairments are distinct sleep parameters that do not necessarily directly co-vary.
27124064	Migraine has been associated with sleep disturbances. Relationship between sleep quality and migraine frequency is yet to be determined. The present study aimed to investigate sleep disturbances among low-frequency, moderate-frequency, high-frequency, and chronic migraineurs, with and without auras, with well-controlled confounding variables.This cross-sectional controlled study included 357 subjects from an outpatient headache clinic in Taiwan. Standardized questionnaires were utilized to collect demographic, migraine, sleep, depression, anxiety, and restless leg syndrome characteristics in all participants. According to frequency of migraine attacks, patients were divided into 4 groups: with 1 to 4 migraine days per month, 5 to 8 migraine days in a month, 9 to 14 migraine days in a month, and >14 migraine days per month. The Pittsburgh Sleep Quality Index (PSQI) and subgroup items were used to evaluate sleep quality. The association between migraine frequency and sleep quality was investigated using multivariable linear regression and logistic regression.The PSQI total score was highest in patients with high frequent migraine (10.0 ± 3.4) and lowest in controls (7.0 ± 3.4) with a significant trend analysis (P for trend = 0.006). Migraine frequency had an independent effect on the items "Cannot get to sleep within 30 minutes" (P < 0.001), "Wake up in the middle of the night or early morning" (P < 0.001), "Bad dreams" (P = 0.001), "Pain" (P = 0.004), and "Quality of sleep" (P < 0.001). The result showed the effect of migraine frequency in both the aura-present (P for trend = 0.008) and the aura-absent subgroups (P for trend = 0.011).High migraine frequency correlates with poor sleep quality and a higher prevalence of poor sleepers. These associations occur in migraine with aura and without aura. 

27117836	To examine the association between autism spectrum disorder (ASD) symptoms and (a) social functioning, (b) mental health, (c) quality of life and (d) sleep in children with and without attention-deficit hyperactivity disorder (ADHD).Participants were 6-10-year-old children with ADHD (N=164) and without ADHD (N=198). ADHD was assessed via community-based screening (wave 1) and case confirmation using the Diagnostic Interview Schedule for Children IV (DISC-IV) (wave 2). ASD symptoms were identified using the Social Communication Questionnaire (SCQ). Outcome measures were social functioning (Strengths and Difficulties Questionnaire (SDQ)), mental health (DISC-IV, SDQ), quality of life (QoL, Pediatric Quality of Life Inventory 4.0) and sleep problem severity.	Greater ASD symptoms were associated with more parent and teacher-reported peer problems and emotional and conduct problems. For every SD increase in SCQ scores, internalising (OR 1.8, 95% CI 1.3 to 2.6, p=0.001) and externalising disorders (OR 1.5, 95% CI 1.1 to 2.1, p=0.02) increased, QoL decreased by 6.7 units (p<0.001), and moderate/severe sleep problems increased (OR 1.5, 95% CI 1.0 to 2.2, p=0.04). Most findings held in analyses adjusting for socio-demographic factors, ADHD symptom severity and comorbidities (when not the outcome), with the exception of externalising disorders and sleep problems.	ASD symptoms are associated with poorer functioning in children with ADHD. It is important to identify and potentially manage ASD symptoms in children with ADHD given that they exacerbate functional impairments in this already vulnerable group.	
27117064	Sleep abnormalities are associated with acute and chronic use of addictive substances. Although sleep complaints associated with use and abstinence from addictive substances are widely recognized, familiarity with the underlying sleep abnormalities is often lacking, despite evidence that these sleep abnormalities may be recalcitrant and impede good outcomes. Substantial research has now characterized the abnormalities associated with acute and chronic use of alcohol, cannabis, cocaine, and opiates. This review summarizes this research and discusses the clinical implications of sleep abnormalities in the treatment of substance use disorders. 
27112685	A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic. 
27112318	Little is known about the effects of noninvasive ventilation (NIV) on sleep quality in amyotrophic lateral sclerosis (ALS). We aim to evaluate the long-term effects of NIV on sleep quality and quality of life in patients with ALS.In this prospective observational study, 13 ALS patients were followed for one year after initiating NIV. We evaluated sleep quality, quality of life and functional status with several questionnaires: Epworth sleepiness Scale (ESS), Pittsburg sleep quality index (PSQI), Short Form 36 Health Questionnaire (SF-36), McGill Quality of Life questionnaire (McGillQoL) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores (ALSFRS-R).	Median and interquartile range (IQR) at the start of NIV was 59 (53-65) years. The ALSFRS-R at start was 30 (24-37) (median, IQR), with three patients having severe bulbar impairment (ALSFRS-R-bulbar ≤ 9). The PaCO2 at start of NIV treatment was 48 (43-52) mmHg (median, IQR). During the one-year follow-up period, a significant decrease in the ALSFRS-R was observed. The impact of NIV in a short term (1 month) revealed a statistically significant decrease in ESS, decrease in total PSQI and of four PSQI subscales and improvement of almost all subscales of the McGill questionnaire. Long-term analyses (9 months to 1 year) revealed that amelioration in ESS and total PSQI was sustained.	We conclude that accurately titrated NIV in ALS patients can stabilize sleep quality and quality of life for at least one year, despite significant disease progression.	

27108448	Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease. 
27107522	Kidney failure affects different aspects of normal life. Among different manifestations, sleep problem can be considered as a common complaint of ESRD (End Stage Renal Disease) patients. In this study, we aimed to investigate the interrelationship between sleep disorders in ESRD patients and their characteristics. Through a cross-sectional study (2010-2011), 88 ESRD patients undergoing maintenance hemodialysis thrice weekly were recruited to enter the study. We used a self-administered questionnaire into which the data were reflected. The patients selected their specific sleep disorders using a nine-item scale while the Epworth Sleepiness Scale (ESS) determined both the presence and severity of sleep disorders. The data was finally analyzed with their baseline characteristics, dialysis characteristics, medication/stimulants use, and clinical and biochemical parameters. Over 95% of the patients had, at least, one specific sleep disorder while the ESS revealed 36.36% of patients as normal, 59.09% as having mild sleep disorders, and 4.54% as having moderate to severe sleep disorders. Sleep disorders were significantly correlated with older ages (P=0.035), dialysis dose (P=0.001), blood creatinine levels (P=0.037), upper airways obstruction (P=0.035), hepatomegaly (P=0.006), hepatic failure (P=0.001), higher blood TSH levels (P=0.039), history of hypothyroidism (P=0.005), and the use of levodopa (P=0.004), anti-hypertensive medications (P=0.006), benzodiazepines (P=0.006), Eprex (Erythropoietin) (P=0.001), Venofer (Iron Sucrose Injection) (P=0.013), and phosphate-binders agents (P=0.018). Sleep disorders are common findings among ESRD patients and seem to be a more complicated issue than a simple accumulation of the wastes products in the body. Whatever the causes of sleep disorders are, disorder-specific treatments should be considered. 
27103935	Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210-2340 h, (2) treadmill exercise alone from 2210-2340 h, or (3) bright light (2210-2340 h) followed by exercise from 0410-0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect. 
27103523	Recent studies in mouse models of Alzheimer's disease (AD) and in humans suggest that sleep disruption and amyloid-beta (Aβ) accumulation are interrelated, and may, thus, exacerbate each other. We investigated the association between self-reported sleep variables and neuroimaging data in 51 healthy older adults. Participants completed a questionnaire assessing sleep quality and quantity and underwent positron emission tomography scans using [18F]florbetapir and [18F]fluorodeoxyglucose and an magnetic resonance imaging scan to measure Aβ burden, hypometabolism, and atrophy, respectively. Longer sleep latency was associated with greater Aβ burden in prefrontal areas. Moreover, the number of nocturnal awakenings was negatively correlated with gray matter volume in the insular region. In asymptomatic middle-aged and older adults, lower self-reported sleep quality was associated with greater Aβ burden and lower volume in brain areas relevant in aging and AD, but not with glucose metabolism. These results highlight the potential relevance of preserving sleep quality in older adults and suggest that sleep may be a factor to screen for in individuals at risk for AD.
27102916	Genetic background and clinical picture of mood disorders (MD) are complex and may depend on many genes and their potential interactions as well as environmental factors. Therefore, clinical variations, or endophenotypes, were suggested for association studies. The aim of the study was to investigate association between the chronotype (CH) and quality of sleep characteristics with polymorphisms CLOCK, ARNTL, TIMELESS and PER3 genes in MD. We included a total sample of 111 inpatients and 126 healthy controls. To assess CH we applied Morningness-Eveningness Questionnaire (MEQ). Additionally, we defined the quality and patterns of sleep using The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). We applied Kruskal-Wallis test to determine associations. The main positive findings refer to associations between selected polymorphisms and: 1) chronotype with the ARNTL gene (rs11824092 and rs1481892) and the CLOCK (rs1268271) 2) sleep duration with the CLOCK gene (rs3805148) and the TIM gene (rs2291739) 3) daytime dysfunction with the PER3 gene (rs228727, rs228642, rs10864315) 4) subjective sleep quality with the ARNTL gene (rs11824092, rs1982350) 5) sleep disturbances with the ARNTL gene (rs11600996) We also found the significant epistatic interactions between polymorphism of the PER3 gene (rs2640909) & the CLOCK gene (rs11932595) and following sleep quality variables: sleep duration, habitual sleep efficiency and subjective sleep quality. The present study suggests a putative role of the analyzed clock genes polymorphisms in chronotype in the control group and in sleep quality disturbances in the course of MD. The results indicate that PSQI variables can be used to refine phenotype in association studies of clock genes in MD. 
27101434	We assessed salivary melatonin levels in renal transplant (RTx) recipients who participated in a randomised, multicentre wait-list controlled trial on the effect of bright light therapy on their sleep and circadian rhythms. A large proportion of RTx recipients in our cohort had unexpectedly low melatonin values, which precluded calculation of the dim-light melatonin onset (DLMO) as a circadian marker. Thus, the aim of this post hoc analysis was to describe the melatonin profile of home-dwelling RTx recipients diagnosed with sleep-wake disturbances (SWDs). The participants were characterised by means of sleep questionnaires, validated psychometric instruments [Pittsburgh sleep quality Index (PSQI), Epworth sleepiness scale (ESS), Morningness-Eveningness Questionnaire (MEQ) and Depression, Anxiety and Stress Scale (DASS)] in addition to melatonin assay in saliva. Data were analysed with descriptive statistics and group comparisons made with appropriate post hoc tests. RTx recipients [n = 29 (aged 54.83 ± 13.73, transplanted 10.62 ± 6.84 years ago)] were retrospectively grouped into two groups: RTx recipients whose dim light melatonin onset (DLMO) could be calculated (n = 11) and those whose DLMO could not be calculated (n = 18). RTx recipients having a measurable DLMO had a number of differences from those without DLMO: they were younger [46.4 ± 14.9 compared to 60.0 ± 10.3 (p = .007)], had higher haemoglobin values [135.36 ± 12.01 versus 122.82 ± 11.56 (p = .01)], less anxiety [4 (0;8) versus 12 (6.5;14) (p = .021)] and a better overall sense of coherence [SOC Score: 71.09 ± 12.78 versus 56.28 ± 15.48 (p = 0.013)]. These results suggest that RTx recipients whose DLMO could be calculated have less health impairments, underlying the relevance of a stable circadian system. 
27098168	The indirect association of childhood abuse with prevalent hypertension in adulthood through sleep disturbance and pro-inflammatory biomarkers was investigated in 589 community-dwelling, middle-aged adults. Participants completed the Childhood Trauma Questionnaire and self-reported current sleep disturbance and medical diagnoses including hypertension. Blood pressure was taken and blood samples were analyzed for C-reactive protein, interleukin-6, and fibrinogen. Hypertension was present in 41.3 % of the sample. In the full multiple mediation model, tested using structural equation modeling, all hypothesized pathways were significant (p's < 0.05). Childhood abuse was significantly related to both body mass index and sleep disturbance, which, both in turn, were significantly associated with inflammation, which was subsequently associated with hypertension status. The model demonstrated good fit [χ(2) (122) = 352.0, p < 0.001, CFI = 0.918, RMSEA = 0.057] and the indirect effect of all mediators was significant (indirect effect: 0.02, 95 % CI 0.005-0.03, p = 0.001). Sleep disturbance, body mass, and inflammation may be independent, intermediate steps between childhood abuse and subsequent hypertension that may be amenable to biobehavioral interventions.
27097817	Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered. 
27097227	This study examined the impact of competition on the sleep/wake behaviour of elite athletes. The sleep/wake behaviour of Australian Rules Football players was assessed with wrist activity monitors on the night immediately before, and the night immediately after, a day game and an evening game. The time of day that a game occurred had a marked influence on sleep/wake behaviour later that night. After the evening game, sleep onset was later, time in bed was shorter and total sleep obtained was less than after the day game. It is yet to be determined whether a reduction in sleep after evening games impairs recovery. 
27096291	The accuracy of sleep/wake estimates derived with actigraphy is often dependent on researchers being able to discern non-wear times from sleep or quiescent wakefulness when confronted by discrepancies in a sleep log. Without knowing when an accelerometer is being worn, non-wear could be inferred from periods of inactivity unlikely to occur while in bed. Data collected in our laboratory suggest that more than 50% of inactive periods during time in bed are <8 min in duration. This duration may be an appropriate minimum threshold for routine non-wear classification during self-reported wake. Higher thresholds could be chosen to derive non-wear definitions for self-reported bedtimes depending on the desired level of certainty. To determine non-wear at thresholds of 75%, 95% and 99%, for example, would require periods of inactivity lasting ≥18 min, ≥53 min and ≥85 min, respectively. 
27095159	Objective and self-reported sleep are only moderately correlated and it is uncertain if these two types of sleep measures are associated with distinct biological and psychological outcomes.Participants were 119 healthy women aged 26years on average. Cortisol and blood pressure assessed over one day were the measures of biological function. Psychological variables included optimism, life satisfaction, positive and negative affect as well as emotional distress. Sleep was assessed with the Pittsburgh Quality Index (PSQI), wrist actigraphy and sleep diaries.	Global sleep ratings on the PSQI were unrelated to objective sleep efficiency, duration or latency. Sleep duration derived from sleep diaries was highly correlated with objective duration but was unrelated to the PSQI measure. More disturbed sleep on the PSQI was associated with lower psychological wellbeing, as indicated by reduced levels of optimism, life satisfaction and positive affect as well as greater negative affect and emotional distress. Objective sleep efficiency was reduced among participants with lower positive and higher negative affect but there were no other associations between objective sleep indicators and psychological variables tested in our study. Participants with poorer self-reported sleep had lower cortisol awakening response while those with longer objective sleep latency had higher diastolic blood pressure, independently of covariates.	Our study reveals that self-reported and objective sleep measures, in particular those regarding sleep quality, are weakly associated but have different psychological and biological correlates. This suggests that findings relating self-reported sleep may not necessarily be corroborated by objective sleep indicators.	
27091961	The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.

27091533	Modafinil is a non-amphetaminic wake-promoting compound used as therapy against sleepiness and narcolepsy. Its mode of action is complex, but modafinil has been recently proposed to act as a cellular-coupling enhancer in glial cells, through modulation of gap junctions constituted by connexins. The present study investigated in mice the impact of connexins on the effects of modafinil using connexin inhibitors.Modafinil was administered alone or combined with inhibitors of astrocyte connexin, meclofenamic acid, or flecainide, respectively, acting on Cx30 and Cx43. Sleep-wake states were monitored in wild-type and narcoleptic orexin knockout mice. A spontaneous alternation task was used to evaluate working memory in wild-type mice. The effects of the compounds on astroglial intercellular coupling were determined using dye transfer in acute cortical slices.	Meclofenamic acid had little modulation on the effects of modafinil, but flecainide enhanced the wake-promoting and pro-cognitive effects of modafinil. Co-administration of modafinil/flecainide resulted in a marked decrease in the number and duration of direct transitions to rapid eye movement sleep, which are characteristic of narcoleptic episodes in orexin knockout mice. Furthermore, modafinil enhanced the connexin-mediated astroglial cell coupling, whereas flecainide reduced it. Finally, this modafinil-induced effect was reversed by co-administration with flecainide.	Our study indicates that flecainide impacts the pharmacological effects of modafinil, likely through the normalization of Cx30-dependent gap junctional coupling in astroglial networks. The enhancement of the wake-promoting, behavioral, and cognitive outcomes of modafinil demonstrated here with flecainide would open new perspectives in the management of sleep disorders such as narcolepsy.	A commentary on this article appears in this issue on page 1175.	
27091530	Disrupted sleep is one of the prominent but often overlooked presenting symptoms in the clinical course of psychotic disorders. The aims of this study were to examine the prevalence of sleep disturbances, particularly insomnia and nightmares, and their prospective associations with the risk of suicide attempts in patients with schizophrenia-spectrum disorders.A naturalistic longitudinal study was conducted in outpatients diagnosed with schizophrenia-spectrum disorders recruited from the psychiatric outpatient clinic of a regional university-affiliated public hospital in Hong Kong. A detailed sleep questionnaire was completed by 388 patients at baseline in May-June 2006. Relevant clinical information was extracted from clinical case notes from June 2007-October 2014.	Prevalence of frequent insomnia and frequent nightmares was 19% and 9%, respectively. Baseline frequent insomnia was significantly associated with an increased incidence of suicide attempts during the follow-up period (adjusted hazard ratio = 4.63, 95% confidence interval 1.40-15.36, P < 0.05). Nightmare complaint alone did not predict the occurrence of suicide attempts, but the comorbidity of nightmares and insomnia was associated with the risk of suicide attempt over follow-up (adjusted HR = 11.10, 95% confidence interval: 1.68-73.43, P < 0.05).	Sleep disturbances are common in patients with schizophrenia-spectrum disorders. The association between sleep disturbances and suicidal risk underscores the need for enhanced clinical attention and intervention on sleep disturbances in patients with schizophrenia.	
27091526	To analyze the temporal organization of the sleep-wake cycle under food entrainment in the rat.Eighteen male Sprague-Dawley rats were chronically implanted for polysomnographic recording. During the baseline (BL) protocol, rats were recorded under a 12:12 light-dark (LD) schedule in individual isolation chambers with food and water ad libitum. Food entrainment was performed by means of a 4-h food restriction (FR) protocol starting at photic zeitgeber time 5. Eight animals underwent a 3-h phase advance of the FR protocol (A-FR). We compared the mean curves and acrophases of wakefulness, NREM sleep, and REM sleep under photic and food entrainment and after a phase advance in scheduled food delivery. We further evaluated the dynamics of REM sleep homeostasis and the NREM sleep EEG delta wave profile.	A prominent food-anticipatory arousal interval was observed after nine or more days of FR, characterized by increased wakefulness and suppression of REM sleep propensity and dampening of NREM sleep EEG delta activity. REM sleep exhibited a robust nocturnal phase preference under FR that was not explained by a nocturnal REM sleep rebound. The mean curve of sleep-wake states and NREM sleep EEG delta activity remained phase-locked to the timing of meals during the A-FR protocol.	Our results support the hypothesis that under food entrainment, the sleep-wake cycle is coupled to a food-entrainable oscillator (FEO). Our findings suggest an unexpected interaction between FEO output and NREM sleep EEG delta activity generators.	
27091523	Our study aims to explore the associations between outdoor nighttime lights (ONL) and sleep patterns in the human population.Cross-sectional telephone study of a representative sample of the general US population age 18 y or older. 19,136 noninstitutionalized individuals (participation rate: 83.2%) were interviewed by telephone. The Sleep-EVAL expert system administered questions on life and sleeping habits; health; sleep, mental and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; International Classification of Sleep Disorders, Second Edition; International Classification of Diseases, 10(th) Edition). Individuals were geolocated by longitude and latitude. Outdoor nighttime light measurements were obtained from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS), with nighttime passes taking place between 19:30 and 22:30 local time. Light data were correlated precisely to the geolocation of each participant of the general population sample.	Living in areas with greater ONL was associated with delayed bedtime (P < 0.0001) and wake up time (P < 0.0001), shorter sleep duration (P < 0.01), and increased daytime sleepiness (P < 0.0001). Living in areas with greater ONL also increased the dissatisfaction with sleep quantity and quality (P < 0.0001) and the likelihood of having a diagnostic profile congruent with a circadian rhythm disorder (P < 0.0001).	Although they improve the overall safety of people and traffic, nighttime lights in our streets and cities are clearly linked with modifications in human sleep behaviors and also impinge on the daytime functioning of individuals living in areas with greater ONL.	
27091486	Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation. Then, we administrated a dopaminergic D2 receptor agonist, antagonist or vehicle directly in the striatum. After a period of 24 h of sleep-wake recording, we observed that the ibotenic acid infusion in the pedunculopontine tegmental nucleus blocked the so-called sleep rebound effect mediated by REM sleep deprivation, which was reversed by striatal D2 receptors activation. Rotenone infusion in the substantia nigra pars compacta also blocked the sleep rebound, however, striatal D2 receptors activation did not reverse it. In addition, rotenone administration decreased the time spent in NREM sleep, which was corroborated by positive correlations between dopamine levels in both substantia nigra pars compacta and striatum and the time spent in NREM sleep. These findings suggest a new circuitry for sleep regulation in Parkinson's disease, involving the triad composed by pedunculopontine nucleus, substantia nigra pars compacta and striatum, evidencing a potential therapeutic target for the sleep disturbances associated to this pathology. 
27090880	Circadian clocks are endogenous biochemical oscillators that control daily behavioral rhythms in all living organisms. In fruit fly, the circadian rhythms are typically studied using power spectra of multiday behavioral recordings. Despite decades of study, a quantitative understanding of the temporal shape of Drosophila locomotor rhythms is missing. Locomotor recordings have been used mostly to extract the period of the circadian clock, leaving these data-rich time series largely underutilized. The power spectra of Drosophila and mouse locomotion often show multiple peaks in addition to the expected at T ~ 24 h. Several theoretical and experimental studies have previously used these data to examine interactions between the circadian and other endogenous rhythms, in some cases, attributing peaks in the T < 24 h regime to ultradian oscillators. However, the analysis of fly locomotion was typically performed without considering the shape of time series, while the shape of the signal plays important role in its power spectrum. To account for locomotion patterns in circadian studies we construct a mathematical model of fly activity. Our model allows careful analysis of the temporal shape of behavioral recordings and can provide important information about biochemical mechanisms that control fly activity.Here we propose a mathematical model with four exponential terms and a single period of oscillation that closely reproduces the shape of the locomotor data in both time and frequency domains. Using our model, we reexamine interactions between the circadian and other endogenous rhythms and show that the proposed single-period waveform is sufficient to explain the position and height of >88 % of spectral peaks in the locomotion of wild-type and circadian mutants of Drosophila. In the time domain, we find the timescales of the exponentials in our model to be ~1.5 h(-1) on average.	Our results indicate that multiple spectral peaks from fly locomotion are simply harmonics of the circadian period rather than independent ultradian oscillators as previously reported. From timescales of the exponentials we hypothesize that model rates reflect activity of the neuropeptides that likely transduce signals of the circadian clock and the sleep-wake homeostat to shape behavioral outputs.	
27088753	The aim of this longitudinal study on novice police officers was to investigate inter-individual differences in sleep response to shift work, and to identify potential baseline predictors thereof. A total of 42 subjects were assessed at baseline, prior to commencing shift work. They were re-assessed during three follow-up sessions within the first 2 years of shift work exposure after approximately 4, 12, and 20 months of rotating shift work. Wrist actigraphy and sleep logs were used to investigate nocturnal sleep at baseline and daytime sleep after night shifts during the follow-up sessions. Actigraphically estimated total sleep time and subjective sleep quality were analyzed as outcome variables, using mixed-effects analysis of variance. Systematic inter-individual differences were observed in the overall response of these outcome variables to shift work. In this sample, flexibility of sleeping habits and gender were found to be predictors of daytime total sleep time in the first 2 years of shift work exposure. Flexibility of sleeping habits and subjective quality of nighttime sleep prior to shift work were found to be predictors of subjective quality of daytime sleep. These results suggest that it may be possible to detect and even predict sleep deficiencies in response to shift work early on, which could be a basis for the development of individualized interventions to improve shift work tolerance.
27087620	To assess the sleep quality in primary Sjögren's syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders.The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren's syndrome disease activity index (ESSDAI), the Sjögren's Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI).	The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged.	Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables.	
27086218	Fatigue and sleepiness are ubiquitous symptoms in various conditions and are frequently associated to impaired sleep quality. While separate fatigue and sleepiness scales exist, both constructs are often confused. Unraveling this issue requires estimating the instruments' measurement properties, potential scale recalibration and re-evaluation of symptom intensities on a comparable basis. This study aims at improving the assessment of these symptoms and quantifying their degree of overlap using common-person-equating (CPE). One hundred fifty-nine patients, either with complaints of fatigue, sleepiness and/or non-restorative sleep, addressed to an academic sleep unit for a full-night polysomnography (PSG), enrolled in the study. Symptom levels were measured with the Fatigue Severity (FSS) and Epworth Sleepiness (ESS) scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index, defining 'good' and 'poor' sleeper groups. Good and poor sleepers did not differ statistically regarding demographics and PSG parameters. Rasch analysis revealed that, considering proper calibration, the ESS and FSS generate reliable and valid, unidimensional linear measures and to be invariant to perceived sleep quality. CPE showed predominantly fatigued, rather than sleepy patients, being more likely to present as poor sleepers. A concordance diagram based on scale scores is provided, in order to improve the differentiation of both symptoms.
27085862	Within a chronobiological perspective, the present study aimed to describe 24 h of sleep-wake cycle, motor activity, and food intake patterns in different body mass index (BMI) categories of children through 7 days of actigraphic recording.Height and weight were objectively measured for BMI calculation in a sample of 115 Italian primary schoolchildren (10.21 ± 0.48 years, 62.61 % females). According to BMI values, 2.60 % were underweight, 61.70 % were of normal weight, 29.60 % were overweight and 6.10 % were obese. Participants wore a wrist actigraph continuously for 7 days to record motor activity and describe sleep-wake patterns. In addition, participants were requested to push the event-marker button of the actigraph each time they consumed food to describe their circadian eating patterns.	BMI group differences were found for sleep quantity (i.e. midpoint of sleep and amplitude), while sleep quality, 24-h motor activity and food intake patterns were similar between groups. Regression analyses showed that BMI was negatively predicted by sleep duration on schooldays. BMI was also predicted by motor activity and by food intake frequencies recorded at particular times of day during schooldays and at the weekend.	The circadian perspective seems to provide promising insight into childhood obesity, but this aspect needs to be further explored.	
27085090	Brain extracellular space (ECS) is an interconnected channel that allows diffusion-mediated transport of signaling molecules, metabolites, and drugs. We tested the hypothesis that β-adrenergic receptor (βAR) activation impacts extracellular diffusion-mediated transport of molecules through alterations in the morphology of astrocytes. Two structural parameters of ECS-volume fraction and tortuosity-govern extracellular diffusion. Volume fraction (α) is the volume of ECS relative to the total tissue volume. Tortuosity (λ) is a measure of the hindrance that molecules experience in the ECS, compared to a free medium. The real-time iontophoretic (RTI) method revealed that treatment of acutely prepared visual cortical slices of adult female rats with a βAR agonist, DL-isoproterenol (ISO), decreases α significantly, from 0.22 ± 0.03 (mean ± SD) for controls without agonist to 0.18 ± 0.03 with ISO, without altering λ (control: 1.64 ± 0.04; ISO: 1.63 ± 0.04). Electron microscopy revealed that the ISO treatment significantly increased the cytoplasmic area of astrocytic distal endings per unit area of neuropil by 54%. These findings show that norepinephrine decreases α, in part, through an increase in astrocytic volume following βAR activation. Norepinephrine is recognized to be released within the brain during the awake state and increase neurons' signal-to-noise ratio through modulation of neurons' biophysical properties. Our findings uncover a new mechanism for noradrenergic modulation of neuronal signals. Through astrocytic activation leading to a reduction of α, noradrenergic modulation increases extracellular concentration of neurotransmitters and neuromodulators, thereby facilitating neuronal interactions, especially during wakefulness. Synapse 70:307-316, 2016. © 2016 Wiley Periodicals, Inc. 
27084356	None of the proposed mechanisms of Alzheimer's disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5-20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.
27084236	Subjective reports of sleep disturbance are a common feature of Huntington's disease (HD); however, there is limited research investigating the relationship between sleep problems with changes in brain and behaviour. This study aimed to investigate whether subjective reports of sleep problems in HD are associated with brain volume, neurocognitive decline, and neuropsychiatric symptoms. This retrospective pilot study used brain volume, neurocognitive and neuropsychiatric data from premanifest (pre-HD) and symptomatic HD (symp-HD). Subjective sleep problem was measured using the sleep item of the Beck's Depression Inventory-II (BDI-II). Pre-HD individuals reporting sleep problems had significantly poorer neuropsychiatric outcomes compared to those not reporting sleep problems. In the symp-HD group, those with sleep problems had significantly accelerated thalamic degeneration and poorer neuropsychiatric outcomes compared to those without sleep problems. There was no relationship between subjective sleep problems and neurocognitive measures. These findings suggest an association between subjective sleep disturbance, neuropathology, and development of neuropsychiatric symptoms in HD. Further studies using quantitative EEG-based monitoring of sleep in HD and changes in the brain and behaviour will be necessary to establish the causal nature of this relationship. 
27083099	Allergic rhinitis is a highly prevalent and costly condition. The disease burden suffered by patients includes the morbidity of the nasal symptoms, the impairment of multiple domains of quality of life, and numerous comorbidities. The goal of therapy is long-term good control. 
27081381	The first-night effect is a well-known phenomenon resulting from an individual's maladaptation to the unfamiliar environment of a sleep laboratory. However, there have been no direct reports of the effect of previous sleep patterns on the first-night effect. We aimed to investigate the effect the previous week's sleep pattern on the first-night effect.Twenty-four young, healthy, male participants completed the study procedure. During one week prior to study, the participants kept sleep diaries and wore actigraphs to identify sleep-wake pattern. Two consecutive nights of polysomnography were conducted after that. Wilcoxon signed-rank tests were applied to compare sleep variables of the two nights. Variance (standard deviation) of sleep onset time during the previous week was used as an index of irregularity. A Kendall's ranked correlation analysis and a linear regression test were applied to detect correlation between sleep irregularity and the first-night effect measured by polysomnography.	There were significant differences in the values of sleep efficiency (p=0.011) and wake after sleep onset (WASO) (p=0.006) between the two nights. Sleep efficiency was lower and WASO was higher on the first night as compared to the second night. Sleep irregularity in the previous week was negatively correlated with sleep efficiency (p<0.001) of the first night, but was not significantly correlated with any other sleep parameters.	We replicated the existence of the first-night effect commonly observed in sleep studies. Sleep irregularity in the previous week may influence the first-night effect in polysomnographic studies.	
27079955	Sleep disorders and mild traumatic brain injury (mTBI) are among the most commonly occurring neurological problems clinicians encounter simultaneously. Each can cause the other, and both share common predisposing factors. An important question that remains to be addressed is whether high-risk groups can be defined. We observed an accumulation of considerable knowledge on sleep dysfunction in mTBI in recently published works. The results highlight sleep disturbances in mTBI as the product of diverse internal and external influences, acting on a genetically determined substrate. This may partially explain the clinical heterogeneity of mTBI, pointing to the importance of establishing an accurate history on the onset and course of a specific sleep disorder in the early stages post-mTBI in the individual patient. Such an approach will aid not only diagnosis and treatment but may also lead to identification of disorders whose symptoms mimic those of TBI and thereby direct the most suitable treatment and management. 
27078855	The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered key markers of neurological function in animal models of stress-induced sleep perturbation. 
27078269	The purpose of this study was to examine the effects of fundamental movement skills (FMS) training on FMS proficiency, self-perceived physical competence (SPC), physical activity (PA), and sleep disturbance in children with developmental coordination disorder (DCD) compared with children with typical development (TD). A total of 84 children were allocated into either experimental group (DCD[exp], TD[exp]) who received 6 weeks of FMS training or control groups (DCD[con], TD[con]). FMS were assessed using the Test of Gross Motor Development-2, whereas PA was monitored using accelerometers. SPC and sleep disturbance were evaluated using questionnaires. Results showed that the DCD[exp] group had significantly higher scores in FMS and SPC compared with the DCD[con] group at posttest. The DCD[exp] group scored lower in sleep disturbance at follow-up when compared with posttest. It is suggested that short-term FMS training is effective in improving FMS and SPC and reducing sleep disturbances for children with DCD. 
27078163	The way neurons process information depends both on their intrinsic membrane properties and on the dynamics of the afferent synaptic network. In particular, endogenously-generated network activity, which strongly varies as a function of the state of vigilance, significantly modulates neuronal computation. To investigate how different spontaneous cerebral dynamics impact single neurons' integrative properties, we developed a new experimental strategy in the rat consisting in suppressing in vivo all cerebral activity by means of a systemic injection of a high dose of sodium pentobarbital. Cortical activities, continuously monitored by combined electrocorticogram (ECoG) and intracellular recordings are progressively slowed down, leading to a steady isoelectric profile. This extreme brain state, putting the rat into a deep comatose, was carefully monitored by measuring the physiological constants of the animal throughout the experiments. Intracellular recordings allowed us to characterize and compare the integrative properties of the same neuron embedded into physiologically relevant cortical dynamics, such as those encountered in the sleep-wake cycle, and when the brain was fully silent. 
27076261	In most persons, blood pressure (BP) rises slowly during late sleep, increases rapidly upon morning awakening and commencement of diurnal activity, exhibits two - morning and afternoon/early evening - daytime peaks, shows a minor midday nadir, and undergoes a decline during nighttime sleep by 10-20% in systolic BP and somewhat lesser amount in diastolic BP relative to wake-time means. Nyctohemeral cycles of ambient temperature, light, noise and behaviorally driven temporal patterns in food, liquid, salt, and stimulant consumption, mental/emotional stress, posture, and physical activity intensity plus circadian rhythms of wake/sleep, pineal gland melatonin synthesis, autonomic and central nervous, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, renin-angiotensin-aldosterone, renal hemodynamic, endothelial, vasoactive peptide, and opioid systems constitute the key regulators and determinants of the BP 24 h profile. Environmental and behavioral cycles are believed to be far more influential than circadian ones. However, the facts that the: i) BP 24 h pattern of secondary hypertension, e.g., diabetes and renal disease, is characterized by absence of BP fall during sleep, and ii) scheduling of conventional long-acting medications at bedtime, rather than morning, results in much better hypertension control and vascular risk reduction, presumably because highest drug concentration coincides closely with the peak of most key circadian determinants of the BP 24 h profile, indicate endogenous rhythmic influences are of greater importance than previously appreciated.
27076073	One of the most predictable aspects of conscious life is the daily sleep-wake cycle, which is programmed by an internal clock that exerts broad effects on behavior and physiology. Studies of He et al. (2016) identify a small molecule clock modulator that improves metabolism, revealing that enhancing circadian function benefits health. 
27075044	This study investigated the relationship between somatic symptoms, sleep disturbance and psychological distress in women who underwent oocyte pick-up and in vitro fertilisation-embryo transfer.According to worldwide research, women receiving assisted reproductive technologies may suffer from somatic and psychological symptoms and even experience sleep disturbance. Apparently, the guilt of infecundity forces Asian women to conceal this scenario and delay the time at which they accept medical assistance and mental support.	A longitudinal study.	The subjects in this study were infertile female patients who received oocyte pick-up and in vitro fertilisation-embryo transfer therapies in a hospital in northern Taiwan. Data were collected via a structured questionnaire, including somatic symptoms, Pittsburgh Sleep Quality Index and a five-item brief symptom rating scale. Data were analysed using the McNemar's test, Wilcoxon Sign Rank and fully entered multiple regression with spss version 20.0 software.	The mean age of 100 participants was 34·54 (SD = 3·94) years old. They experienced abdominal distention, breast engorgement, nausea, faintness, diarrhoea, sleep disturbance and psychological distress when they received in vitro fertilisation-embryo transfer; these results were apparently higher than those receiving oocyte pick-up. In addition, sleep disturbance was the most significant factor involved in psychological distress during oocyte pick-up and in vitro fertilisation-embryo transfer therapies. The most serious indicator of the women's psychological distress during oocyte pick-up and in vitro fertilisation-embryo transfer treatment is anxiety.	Sleep disturbance was the most significant factor involved in the psychological distress of women having problems with conception.	Assisted reproductive technologies nurses can assess women's psychological distress by caring for their sleep disturbance without directly exploring their mood state. Moreover, these medical personnel should understand infertile female patients' psychological distress is mainly associated with their sleep disturbance. Developing various strategies to improve both sleep quality and psychological distress for infertile female patients should be recognised in future studies.	
27074935	Sleep disturbances related to reflux symptoms have a significant impact on the daily lives of affected individuals. These analyses identified clinical factors related to resolution of reflux-related sleep disturbance in subjects treated with esomeprazole 20 mg for 14 days.Data from the first 14 days of 2 similar randomized, double-blind studies were pooled for subjects experiencing frequent heartburn and related sleep disturbances receiving esomeprazole 20 mg (n = 357) or placebo (n = 346). A stepwise logistic regression analysis was performed with pooled and individual study data to evaluate relationships between clinical factors [treatment (esomeprazole vs. placebo), run-in sleep disturbance frequency, occurrence (yes/no) of 24-h, daytime, and nighttime heartburn (yes: ≥1 episode in 14-day treatment period)] and complete sleep disturbance resolution (no disturbances for 7 consecutive days).	Absence of daytime (p = 0.0018) or nighttime (p < 0.0001) heartburn during treatment was a significant predictor of complete sleep disturbance resolution at 14 days for the total population, while higher run-in sleep disturbance frequency (p < 0.0001) was associated with a lower likelihood of resolution. Esomeprazole treatment was an independent significant predictor of improvement across all endpoints (p < 0.0001). A significant treatment by run-in sleep disturbance interaction was observed for complete resolution (p = 0.0231), indicating greater therapeutic benefit with esomeprazole in subgroups with higher run-in symptom frequency.	Lower run-in sleep disturbance frequency, no occurrence of daytime or nighttime heartburn during therapy, and esomeprazole treatment predicted complete reflux-related sleep disturbance resolution. The magnitude of therapeutic benefit for esomeprazole 20 mg over placebo increased with increasing baseline sleep disturbance.	
27074002	The main objective of the study was to find out prevalence of depression and anxiety symptoms in the population of patients with AMI with ST-segment elevation (STEMI), treated with primary PCI (pPCI). Secondary target indicators included the incidence of sleep disorders and loss of interest in sex.The project enrolled 79 consecutive patients with the first AMI, aged <80 years (median 61 years, 21.5% of women) with a follow-up period of 12 months. Symptoms of depression or anxiety were measured using the Beck Depression Inventory II tests (BDI-II, cut-off value ≥14) and Self-Rating Anxiety Scale (SAS, cut-off ≥ 45) within 24 hours of pPCI, before the discharge, and in 3, 6 and 12 months). Results with the value p<0.05 were considered as statistically significant. The BDI-II positivity was highest within 24 hours after pPCI (21.5%) with a significant decline prior to the discharge (9.2%), but with a gradual increase in 3, 6 and 12 months (10.4%; 15.4%; 13.8% respectively). The incidence of anxiety showed a relatively similar trend: 8.9% after pPCI, and 4.5%, 10.8% and 6.2% in further follow-up.	Patients with STEMI treated by primary PCI have relatively low overall prevalence of symptoms of depression and anxiety. A significant decrease in mental stress was observed before discharge from the hospital, but in a period of one year after pPCI, prevalence of both symptoms was gradually increasing, which should be given medical attention.	
27073852	Recently it has been shown that acute sleep loss has a direct impact on emotional processing in healthy individuals. Here we studied the effect of chronically disturbed sleep on emotional processing by investigating two samples of patients with sleep disorders.25 patients with psychophysiologic insomnia (23 women and 2 men, mean age: 51.6 SD; 10.9 years), 19 patients with sleep apnea syndrome (4 women and 15 men, mean age: 51.9; SD 11.1) and a control sample of 24 subjects with normal sleep (15 women and 9 men, mean age 45.3; SD 8.8) completed a Facial Expressed Emotion Labelling (FEEL) task, requiring participants to categorize and rate the intensity of six emotional expression categories: anger, anxiety, fear, happiness, disgust and sadness. Differences in FEEL score and its subscales among the three samples were analysed using ANOVA with gender as a covariate.	Both patients with psychophysiologic insomnia and patients with sleep apnea showed significantly lower performance in the FEEL test as compared to the control group. Differences were seen in the scales happiness and sadness. Patient groups did not differ from each other.	By demonstrating that previously known effects of acute sleep deprivation on emotional processing can be extended to persons experiencing chronically disturbed sleep, our data contribute to a deeper understanding of the relationship between sleep loss and emotions.	
27073377	Traumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the SmartCage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact (CCI) injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated SmartCage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury. 
27073070	Kleine-Levin Syndrome [KLS] is often under-recognized and also misdiagnosed. When suspicion for KLS is raised, a thorough clinical evaluation should be performed, including detailed history from family members and a neurologic and psychiatric examination. Additional studies may include PSG, EEG, neuroimaging, as well as serological and CSF studies to rule out alternative diagnoses as clinically indicated. After arriving at a diagnosis of KLS, the foundation of care is supportive. Patients and their families should be provided with education about the disease. During symptomatic periods, patients should be allowed to rest at home under caregiver supervision. Caregivers should pay special attention to the patient's eating habits and mood. Patients should not be allowed to drive or operate heavy machinery during these episodes. In between episodes, avoidance of reported triggers, such as alcohol and infection are encouraged as is maintenance of a regular sleep-wake cycle. Pharmacologic therapy has not been well-studied and for most patients is not necessary. For more severe cases, targeted symptomatic therapy, such as modafinil or amantadine for somnolence or risperidone for psychosis may be considered depending on the patient's symptomatology. Lithium has the best data to support its use as a prophylactic agent and for patients with severe or frequent episodes, may be considered.
27072924	To investigate independent effects of various factors associated with sleep disturbance among community-dwelling elderly individuals.We analyzed data obtained from 3732 individuals aged ≥65 years who responded to a self-administered questionnaire and participated in a structured interview which assessed the Pittsburgh Sleep Quality Index (PSQI), subjective bodily pain, the Jichi Medical School Social Support Scale, the Geriatric Depression Scale (GDS-15), health status, and demographic characteristics. Sleep disturbance was defined as a global PSQI score >5.5, which was used as a dependent variable in multiple logistic regression analysis to determine adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) of related factors.	We identified a significant increase in the adjusted ORs for female (OR 1.56, 95 % CI 1.34-1.83), age ≥80 years (1.31, 1.01-1.69), history of stroke (1.44, 1.08-1.92), and a GDS-15 score ≥6 as compared to 0-2 (2.29, 1.86-2.81), with regard to sleep disturbance. Participants with severe or very severe bodily pain had the highest adjusted OR (3.00, 2.15-4.19), and those with very mild bodily pain also had a relatively high OR (1.30, 1.06-1.60), relative to those without subjective bodily pain. In addition, compared with participants with strong social support from spouse or family, those with weak social support had significantly increased adjusted ORs (1.21, 1.01-1.44, 1.44, 1.23-1.70, respectively).	The present study indicates that sleeping disturbances among the elderly are closely associated with social support from a spouse and family. They are also associated with pain, even at stages in which subjective bodily pain is very mild.	
27068547	Recent studies suggest that individuals with multiple sclerosis (MS) are at increased risk for sleep disturbances and that sleep disturbances contribute to fatigue and other chronic symptoms in MS. Although fatigue occurs commonly in people with MS, this symptom is often attributed to MS-specific pathology. Consequently, sleep disorders are often unrecognized and untreated in this population. Timely diagnosis and treatment of sleep problems in MS offer a new opportunity to ameliorate some of the daytime fatigue experienced by patients with MS. To increase this opportunity, the practitioner should be comfortable performing basic screening for common sleep complaints among patients with MS. The objectives of this review are to summarize the latest relevant data on sleep disorders in MS and offer a helpful approach to the identification and workup of the most common sleep problems in this population. Unexplored research avenues and opportunities to address important questions at the interface of sleep and MS are also discussed. 
27066526	Light therapy has shown promise as a nonpharmacological treatment to help regulate abnormal sleep-wake patterns and associated behavioral issues prevalent among individuals diagnosed with Alzheimer's disease and related dementia (ADRD). The present study investigated the effectiveness of a lighting intervention designed to increase circadian stimulation during the day using light sources that have high short-wavelength content and high light output.Thirty-five persons with ADRD and 34 caregivers completed the 11-week study. During week 1, subjective questionnaires were administered to the study participants. During week 2, baseline data were collected using Daysimeters and actigraphs. Researchers installed the lighting during week 3, followed by 4 weeks of the tailored lighting intervention. During the last week of the lighting intervention, Daysimeter, actigraph and questionnaire data were again collected. Three weeks after the lighting intervention was removed, a third data collection (post-intervention assessment) was performed.	The lighting intervention significantly increased circadian entrainment, as measured by phasor magnitude and sleep efficiency, as measured by actigraphy data, and significantly reduced symptoms of depression in the participants with ADRD. The caregivers also exhibited an increase in circadian entrainment during the lighting intervention; a seasonal effect of greater sleep efficiency and longer sleep duration was also found for caregivers.	An ambient lighting intervention designed to increase daytime circadian stimulation can be used to increase sleep efficiency in persons with ADRD and their caregivers, and may also be effective for other populations such as healthy older adults with sleep problems, adolescents, and veterans with traumatic brain injury.	
27066445	This study was performed to evaluate the quality of sleep in snoring obese children without obstructive sleep apnea (OSA); and to study the possible relationship between sleep interruption and gastroesophageal reflux (GER) in snoring obese children.Study subjects included 13 snoring obese children who were referred to our sleep lab for possible sleep-disordered breathing. Patients underwent multichannel intraluminal impedance and esophageal pH monitoring with simultaneous polysomnography. Exclusion criteria included history of fundoplication, cystic fibrosis, and infants under the age of 2 years. Significant association between arousals and awakenings with previous reflux were defined by symptom-association probability using 2-minute intervals.	Sleep efficiency ranged from 67-97% (median 81%). A total of 111 reflux episodes (90% acidic) were detected during sleep, but there were more episodes per hour during awake periods after sleep onset than during sleep (median 2.3 vs. 0.6, p=0.04). There were 279 total awakenings during the sleep study; 56 (20.1%) of them in 9 patients (69.2%) were preceded by reflux episodes (55 acid, 1 non-acid). In 5 patients (38.5%), awakenings were significantly associated with reflux.	The data suggest that acid GER causes sleep interruptions in obese children who have symptoms of snoring or restless sleep and without evidence of OSA.	
27065357	To (1) determine the frequency and severity of hot flashes, (2) examine the associations between hot flash frequency and severity and quality of life, and (3) identify the predictors of hot flash activity in breast cancer survivors.The study used a cross-sectional design and mailed survey of 253 breast cancer survivors recruited from a cancer wellness clinic. Participants provided information regarding cancer history, hot flashes, pain intensity, sleep problems, physical functioning, and psychological functioning.	About half of the survivors reported at least one hot flash in the past 24 h (45%) or past week (52%). The average frequency of hot flashes was 1.9 in the past 24 h and 1.8 in the past week. Hot flash severity was usually mild or asymptomatic. However, participants with hot flashes reported significantly more sleep problems and higher pain severity than those reporting no hot flashes. Moreover, the severity of hot flashes was associated with more sleep problems, higher pain severity, and more psychological dysfunction. History of hormonal suppression therapy and younger age predicted hot flash activity in the study sample.	In breast cancer survivors, hot flashes are common and are associated with unpleasant symptoms and poor quality of life. Research is needed to determine if treatments that reduce the frequency and severity of hot flashes in breast cancer survivors also result in improvements in symptoms such as sleep problems, pain, and psychological dysfunction.	
27064792	Although the chance of surviving an aneurysmal subarachnoid haemorrhage (aSAH) has increased steadily, disturbed sleep and persistent psychological complaints are frequently experienced post-ictus. To date, however, few studies have sought to determine whether physiological parameters, such as objectively measured sleep and cortisol secretion, interrelate significantly with low sleep quality and psychological complaints such as depression. Furthermore, there is little evidence as to whether post-ictal complaints differ between aSAH patients and other groups who have experienced stressful medical intervention.Data on objective and subjective sleep, sleep-related dysfunctional cognitions, psychological functioning and cortisol secretion were collected from 15 patients who had undergone medical intervention for aSAH. Data were also collected from a group of 16 individuals who had undergone surgery for a meningioma and a third group made up of 17 healthy participants.	aSAH patients and meningioma patients had significantly poorer subjective sleep than healthy controls and reported more sleep-related dysfunctional cognitions and hypochondriacal beliefs. They also had a significantly higher morning cortisol response. Finally, a non-significant trend was found showing that aSAH patients and meningioma patients reported poorer psychological functioning than healthy controls.	Following treatment, aSAH patients and meningioma patients experience poorer subjective sleep and some differences in objectively measured sleep, which might be attributable to increased sleep-related dysfunctional cognitions and poorer overall psychological functioning. Differences in cortisol production were also observed, suggesting that some physiological imbalances are still present post-ictus.	
27063430	Burnout is common among health care providers and doctors.The correlations between burnout and health, psychosomatic symptoms, life satisfaction and sleep were investigated.	An online quantitative cross-sectional questionnaire was administered to 186 doctors. Burnout was assessed by the means of the 21-item questionnaire of Pines and Aronson (1981). Data were analysed with chi-square probe, Mann-Whitney test, correlational analysis and linear regression.	Level of burnout correlated negatively with age (p = 0.040; r = -0.151), years spent in the health care system (p = 0.027; r = -0.162) and positive well-being (p<0.001, r = -0.670), while there was a negative correlation with negative well-being (p<0.001; r = 0.585) and life satisfaction (p<0.001; r = -0.532). Doctors with burnout reported worse health (p<0.001), more frequent psychosomatic symptoms (p<0.001), tumours (p = 0.007), allergies (p = 0.030), psychiatric disorders (p = 0.025) and sleep disturbances.	One-third of the doctors were affected by burnout in the present study. Higher age and having more children served as a protective factor.	
27062710	In this study, we addressed how sleep is related to acute stress disorder (ASD) symptoms, and how the presence of a trauma related-context moderates this relationship. This study (N = 140) was carried out during the 2014 Israel-Gaza conflict, during which 70% of Israelis were exposed to missile attacks. Findings show that participants with clinical ASD symptom levels reported more sleep disturbances than participants without clinical ASD symptom levels. More critically, this effect was only evident among respondents who had a reinforced security room in their houses. While reinforced security rooms offer protection against indirect missile damage, their relevance is salient in negative traumatic situations, which individuals with a clinical level of ASD are more sensitive to. Conversely, in houses without a reinforced security room, there was no difference in subjective sleep reports between individuals with or without clinical levels of ASD symptoms. Results are discussed in reference to trauma being activated by context and the ensuing effects on sleep. Theoretical and clinical implications are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
27060683	Rapid eye movement (REM) sleep is a recurring part of the sleep-wake cycle characterized by fast, desynchronized rhythms in the electroencephalogram (EEG), hippocampal theta activity, rapid eye movements, autonomic activation and loss of postural muscle tone (atonia). The brain circuitry governing REM sleep is located in the pontine and medullary brainstem and includes ascending and descending projections that regulate the EEG and motor components of REM sleep. The descending signal for postural muscle atonia during REM sleep is thought to originate from glutamatergic neurons of the sublaterodorsal nucleus (SLD), which in turn activate glycinergic pre-motor neurons in the spinal cord and/or ventromedial medulla to inhibit motor neurons. Despite work over the past two decades on many neurotransmitter systems that regulate the SLD, gaps remain in our knowledge of the synaptic basis by which SLD REM neurons are regulated and in turn produce REM sleep atonia. Elucidating the anatomical, cellular and synaptic basis of REM sleep atonia control is a critical step for treating many sleep-related disorders including obstructive sleep apnoea (apnea), REM sleep behaviour disorder (RBD) and narcolepsy with cataplexy. 
27057856	Migration flows from China are largely directed towards the South of Europe, Chinese being now the third largest overseas-born population in Italy. The aim of the study was to investigate hypertension burden and self-reported sleep disorders among 1608 first-generation Chinese migrants aged 16 to 59 years settled in Prato and recruited in a cross-sectional survey. Hypertension was defined as systolic BP ≥ 140  mm Hg and/or diastolic BP ≥ 90  mm Hg or self-reported antihypertensive treatment; potential impact of sleep disorders was analyzed by logistic regression adjusted for age, sex, marital status, education, health insurance, current smoking, parental hypertension, alcohol drinking, overweight or obesity, central obesity, diabetes, high total cholesterol, and high triglycerides. Among the 1608 participants, 21.7% were hypertensive (age-standardized prevalence 19.2%; 95% Cl: 18.5-20.0); 54% of hypertensive subjects were aware of their condition; 70% of aware hypertensive subjects received drugs, and 39% of treated subjects had blood pressure controlled. Self-reported snoring increased the risk of hypertension; when compared with no snoring, the age- and sex-adjusted OR for hypertension of snoring 3 to 6  d/week was 2.11 (95% Cl: 1.48-3.01) and 2.48 (95% Cl: 1.79-3.46) of snoring every day. When compared with a sleep duration ≤ 5  hours, subjects with sleep duration of 7  hours had reduced risk of high triglycerides (adjusted OR: 0.66; 95% Cl: 0.43-0.95).Despite a high level of awareness, low treatment rates for hypertension were observed among Chinese participants, independently of health insurance. Sleep history is to be considered in screening and prevention programs.
27055793	To investigate the prevalence and influencing factors of visual hallucinations in patients with Parkinson's disease(PD), and to analyze the relationship between visual hallucinations and sleep disorders.We recruited 187 patients with PD(H-Y Ⅰ-Ⅲ) from outpatient department in Beijing Hospital. The patients were investigated for general information and the use of medicine. The patients were divided into visual hallucination(VH) group and non-hallucination(non-VH) group. A comparison study was conducted between two groups. We investigated the sleep disorders of PD patients according to Non Motor Symptom Quest(NMSquest) and Parkinson's disease sleep scale(PDSS). Logistic stepwise multiple regression procedures were used to determine the best predictive model of visual hallucinations in patients with PD.	(1) 42 cases(22.5%) of PD patients were accompanied by visual hallucinations; (2) the VH group and non-VH group had no difference in age, sex, duration of illness, the scores of Minimum Mental State Examination(MMSE) and levodopa equivalent doses (LED). The scores of Unified Parkinson's Disease Rating Scale(UPDRS) Ⅰ, the Hamilton Rating Scale for Anxiety(HAMA) and the Hamilton Rating Scale for Depression(HAMD) in VH group were significantly higher than those in non-VH group[3.5(2, 5) vs 2 (1, 3); 10(6.75, 15) vs 8(5, 11); 11(7.75, 17) vs 9(5, 13); P<0.05]; (3) the incidences of vivid dreams and REM sleep behavior disorder(RBD) in VH group were significantly higher than those in non-VH group(61.9% vs 40.7%, 71.4% vs 47.6%, P<0.05). There were no significant differences in incidences of excessive daytime sleepiness and restless legs between two groups(P>0.05). The score of PDSS in VH group was significantly lower than that in non-VH group[111(92.75, 128.25) vs 123(109, 135), P<0.05]; (4) the Logistic stepwise multiple regression revealed that vivid dreams(P=0.045) and the score of PDSS(P=0.006) were the independent influencing factors for VH in PD patients.	The incidence of VH in PD with H-Y staging Ⅰ-Ⅱ is 22.5%. The presence of vivid dreams and severe sleep disorder are independently associated with VH in PD.	
27051324	Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep-wake regulation came from narcolepsy-cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep-wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep-wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders. 
27050849	Carpal tunnel syndrome (CTS) is a condition involving nerve entrapment that often leads to chronic neuropathic pain. We aimed to evaluate sleep quality and related parameters in diabetic and non-diabetic CTS patients.This study included a total of 366 patients with chronic CTS. These patients' sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) and depression using the Beck Depression Inventory (BDI). The severity of neuropathic pain was evaluated using the Douleur Neuropathique-4 (DN4) questionnaire and a visual analogue scale (VAS).	In the non-diabetic patient group, the total PSQI score was found to affect BDI and VAS, while in the diabetic patient group, the duration of symptoms affected VAS, BDI and fasting glucose levels.	For diabetic patients, hyperglycemia depression and chronification of neuropathic pain may lead to deterioration of sleep quality. Therefore, consideration of these parameters in the treatment may break a vicious cycle.	
27049562	Neuromyelitis optica spectrum disorder (NMOSD) is associated with reduced health-related quality of life (HRQOL). This study aimed to investigate factors that impact HRQOL in NMOSD.A series of questionnaires were completed by 73 patients to assess the relationships between HRQOL and fatigue, depression, anxiety and sleep disorder. We also evaluated the contributions of clinical characteristics to HRQOL. Correlation and regression analysis were conducted to identify factors that negatively impact HRQOL in NMOSD.	Pearson's correlation analysis showed that reduced HRQOL was strongly correlated with anxiety (r=-0.77, P=0.000), fatigue (r=-0.75, P=0.000) and depression (r=-0.73, P=0.000); and moderately correlated with disability (r=-0.53, P=0.000) and sleep disorder (r=-0.59, P=0.000). Stepwise regression analysis further revealed that anxiety was the best predictor of both the global and physical composite scores of HRQOL, followed by disability, fatigue and depression (global composite, r(2)=0.76, P=0.000; physical composite, r(2)=0.71, P=0.000). Depression, fatigue and anxiety were the main predictors of the mental health composite score of HRQOL (r(2)=0.69, P=0.000). Other factors did not have an effect on HRQOL.	This study revealed factors that impact HRQOL in NMOSD and provided the first demonstration that anxiety, disability, fatigue and depression are independent predictors of poor HRQOL in NMOSD.	

27043528	Sleep disturbance is common in children with atopic dermatitis (AD). It is a major factor leading to impaired quality of life in these patients and could have negative effects on neurocognitive function and behavior. However, the pathophysiology of sleep disturbance in children with AD is poorly understood, and there is no consensus on how to manage sleep problems in these patients. Pruritus and scratching could lead to sleep disruption but is unlikely the sole etiology. The circadian rhythm of cytokines, the immune system, and skin physiology such as transcutaneous water loss and skin blood flow might also play a role. Recent studies have suggested that melatonin could also be involved due to its multiple effects on sleep, immunomodulation, and anti-oxidant ability. Environmental factors should also be considered. In this review, we summarize the current understanding of the pathophysiology of sleep disturbance in children with AD, and discuss possible therapeutic implications. 


27040118	Bio-mathematical models that predict fatigue and/or sleepiness have proved a useful adjunct in the management of what has been typically referred to as fatigue-related risk. Codifying what constitutes appropriate use of these models will be increasingly important over the next decade. Current guidelines for determining a safe working time arrangement based on model outputs generally use a single upper threshold and are, arguably, over-simplistic. These guidelines fail to incorporate explicitly essential aspects of the risk assessment process - namely, the inherent uncertainty and variability in human sleep-wake behavior; the non-linear relationship between fatigue, task performance and safety outcomes; the consequence of a fatigue-related error and its influence on overall risk; and the impact of risk mitigation or controls in reducing the likelihood or consequence of a fatigue-related error. As industry and regulatory bodies increasingly move toward performance-based approaches to safety management, any fatigue risk management system that includes a bio-mathematical model should specify what exactly is measured by the model, and how the model can be used in the context of a safety management system approach. This will require significant dialog between the various parties with an interest in bio-mathematical models, i.e. developers, vendors, end-users, and regulators.
27039083	Female doctors in Hungary have worse indicators of physical and mental health compared with other professional women. We aimed to cast light on possible indicators of mental health, workload, and burnout of female physicians.Two time-points (T) were compared, in 2003 (T1 n = 408) and 2013 (T2 n = 2414), based on two nationally representative surveys of female doctors, and comparison made with data from other professional control groups. Independent samples t test or chi-squared test was used both for the two time-point comparison and the comparison between the index and the control groups. The background factors of sleep disorders and burnout were assessed by binary logistic regression analysis.	No significant differences in the rates of depressive symptoms and suicidal thoughts and attempts were detected between the 2003 and 2013 cohorts, but the prevalence of sleep disorders increased. The workload increased, and there was less job satisfaction in 2013 than in 2003, coupled to more stressful or difficult work-related situations. The personal accomplishment component of burnout significantly decreased in line with the declining work-related satisfaction. Compared to the professional control groups, the prevalence of depressive symptoms, suicide attempts, and sleep disorders was higher among female physicians at both time-points. The number of workplaces, frequency of work-related stressful situations, and intensive role conflict was associated with sleep disorders and decreased personal accomplishment.	In comparison with the other professional groups, female doctors had worse mental health indicators with regard to depression, suicidal ideas, and sleep disorders both in 2003 and 2013 while within professional strata the changes seemed to be less. Increasing workload had a clear impact on sleep disorders and the personal accomplishment dimension of burnout.	
27038330	Muscarinic m2 receptors (M2Rs) are implicated in autoregulatory control of cholinergic output neurons located within the pedunculopontine (PPT) and laterodorsal tegmental (LTD) nuclei of the mesopontine tegmentum (MPT). However, these nuclei contain many noncholinergic neurons in which activation of M2R heteroceptors may contribute significantly to the decisive role of the LTD and PPT in sleep-wakefulness. We examined the electron microscopic dual immunolabeling of M2Rs and the vesicular acetylcholine transporter (VAchT) in the MPT of rat brain to identify the potential sites for M2R activation. M2R immunogold labeling was predominately seen in somatodendritic profiles throughout the PPT/LTD complex. In somata, M2R immunogold particles were often associated with Golgi lamellae and cytoplasmic endomembrannes, but were rarely in contact with the plasma membrane, as was commonly seen in dendrites. Approximately 36% of the M2R-labeled somata and 16% of the more numerous M2R-labeled dendrites coexpressed VAchT. M2R and M2R/VAchT-labeled dendritic profiles received synapses from inhibitory- and excitatory-type axon terminals, over 88% of which were unlabeled and others contained exclusively M2R or VAchT immunoreactivity. In axonal profiles M2R immunogold was localized to plasmalemmal and cytoplasmic regions and showed a similar distribution in many VAchT-negative glial profiles. These results provide ultrastructural evidence suggestive of somatic endomembrane trafficking of M2Rs, whose activation serves to regulate the postsynaptic excitatory and inhibitory responses in dendrites of cholinergic and noncholinergic neurons in the MPT. They also suggest the possibility that M2Rs in this brain region mediate the effects of acetylcholine on the release of other neurotransmitters and on glial signaling. J. Comp. Neurol. 524:3084-3103, 2016. © 2016 Wiley Periodicals, Inc. 
27038292	The aims of the present study were to detect serum brain-derived neurotrophic factor (BDNF) protein concentrations in healthy and diabetic subjects with sleep disorders and to explore correlations among serum BDNF concentrations, metabolic parameters and inflammation.In all, 377 eligible subjects were recruited to the study and underwent a 75-g oral glucose tolerance test. Various clinical parameters of metabolic disorders and cytokines were measured. Sleep disorders were assessed using the Pittsburgh Sleep Quality Index (PSQI). Subjects were grouped into those with normal glucose tolerance (NGT), those with NGT and sleep disorders (NGT-SDi), those with newly diagnosed type 2 diabetes mellitus (T2DM), and those with newly diagnosed T2DM and sleep disorders (T2DM-SDi).	Serum BDNF levels were higher in the NGT-SDi and T2DM-SDi subgroups than in the NGT and T2DM groups, respectively. Multiple linear regression analysis revealed that serum BDNF concentrations were independently correlated with PSQI scores, homeostasis model assessment of insulin resistance, and HbA1c, interleukin 6 and tumor necrosis factor-α concentrations (P < 0.05 for all). Binary logistic regression analysis revealed that significant associations remained between serum BDNF concentrations and sleep disorders after adjustment for glucose- and metabolic-related factors in both the NGT-SDi and T2DM-SDi subgroups.	Serum BDNF concentrations were higher in patients with sleep disorders and were associated with various metabolic parameters and inflammatory cytokines.	
27034850	Measurement of sleep microarchitecture and neural oscillations is an increasingly popular technique for quantifying EEG sleep activity. Many studies have examined sleep spindle oscillations in sleep-disordered adults; however reviews of this literature are scarce. As such, our overarching aim was to critically review experimental studies examining sleep spindle activity between adults with and without different sleep disorders. Articles were obtained using a systematic methodology with a priori criteria. Thirty-seven studies meeting final inclusion criteria were reviewed, with studies grouped across three categories: insomnia, hypersomnias, and sleep-related movement disorders (including parasomnias). Studies of patients with insomnia and sleep-disordered breathing were more abundant relative to other diagnoses. All studies were cross-sectional. Studies were largely inconsistent regarding spindle activity differences between clinical and nonclinical groups, with some reporting greater or less activity, while many others reported no group differences. Stark inconsistencies in sample characteristics (e.g., age range and diagnostic criteria) and methods of analysis (e.g., spindle bandwidth selection, visual detection versus digital filtering, absolute versus relative spectral power, and NREM2 versus NREM3) suggest a need for greater use of event-based detection methods and increased research standardization. Hypotheses regarding the clinical and empirical implications of these findings, and suggestions for potential future studies, are also discussed. 
27034174	Nonalcoholic fatty liver (NAFLD) usually has worse cardiovascular risk factors. Given the potential association between deterioration of sleep and arterial stiffness, we aim to investigate the association between deterioration of sleep and arterial stiffness in a middle-aged Chinese population with NAFLD. In this cross-sectional study, 15,372 Chinese aged 40-60 years who participated in periodic health checkups in central south China, were included. Self-reported sleep duration and sleep quality, anthropometric, biochemical, and liver ultrasound scan were analyzed and brachial-ankle pulse wave velocity (baPWV) was used as the indicator of arterial stiffness. Poor sleep quality was found to be associated with increased arterial stiffness, with odds ratios and 95 % confidence intervals (CIs) of 2.28 (95 % CI, 1.53-3.38) compared with good sleep quality. Using sleep duration ≥ 8 h as the reference, there was no significant association between sleep duration of ≤ 6 or 6-8 h and arterial stiffness after multivariable-adjusted. In additional analyses, further investigation of the association of different combinations of sleep duration and quality in relation to arterial stiffness indicated participants with poor sleep quality and sleep duration ≤ 6 h were more likely to have arterial stiffness than those with good quality sleep who sleep for ≥ 8 h (OR 2.59, 95 % CI 1.58-4.24). The present study indicates that short sleep duration, poor sleep quality in individuals with NAFLD correlate with increased arterial stiffness. 
27033540	Behavioral microsleeps are associated with complete disruption of responsiveness for [Formula: see text][Formula: see text]s to 15[Formula: see text]s. They can result in injury or death, especially in transport and military sectors. In this study, EEGs were obtained from five nonsleep-deprived healthy male subjects performing a 1[Formula: see text]h 2D tracking task. Microsleeps were detected in all subjects. Microsleep-related activities in the EEG were detected, characterized, separated from eye closure-related activity, and, via source-space-independent component analysis and power analysis, the associated sources were localized in the brain. Microsleeps were often, but not always, found to be associated with strong alpha-band spindles originating bilaterally from the anterior temporal gyri and hippocampi. Similarly, theta-related activity was identified as originating bilaterally from the frontal-orbital cortex. The alpha spindles were similar to sleep spindles in terms of frequency, duration, and amplitude-profile, indicating that microsleeps are equivalent to brief instances of Stage-2 sleep. 
27033453	Human postmortem studies reported increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Lithium (Li(+)) has been shown to effectively treat the mood disturbances in bipolar disorder patients and was proposed to act by inhibiting the interaction betweenNCS-1 and inositol 1,4,5-triphosphate receptor protein (InsP3R).NCS-1 is known to enhance the activity of InsP3R, and of Ca(2+)-mediated gamma oscillatory activity in the pedunculopontine nucleus (PPN), part of theRAS This study aimed to determine the nature of some of the intracellular mechanisms of Li(+)on ratPPNcells and to identify the interaction between Li(+)andNCS-1. Since Li(+)has been shown to act by inhibiting the enhancing effects ofNCS-1, we tested the hypothesis that Li(+)would reduced the effects of overexpression ofNCS-1 and prevent the downregulation of gamma band activity. Li(+)decreased gamma oscillation frequency and amplitude by downregulating Ca(2+)channel activity, whereasNCS-1 reduced the effect of Li(+)on Ca(2+)currents. These effects were mediated by a G-protein overinhibition of Ca(2+)currents. These results suggest that Li(+)affected intracellular pathways involving the activation of voltage-gated Ca(2+)channels mediated by an intracellular mechanism involving voltage-dependent activation of G proteins, thereby normalizing gamma band oscillations mediated by P/Q-type calcium channels modulated byNCS-1. 
27032628	Citalopram has been shown to improve agitation in patients with Alzheimer's disease. The authors evaluated whether other neuropsychiatric symptoms improve with citalopram treatment compared with placebo.In this planned secondary analysis of the Citalopram for Agitation in Alzheimer's Disease study, the authors evaluated the effect of citalopram on the 12 neuropsychiatric symptom domains assessed by the Neuropsychiatric Inventory (NPI). They compared caregiver-reported NPI scores at week 9 in patients receiving citalopram (30 mg/day) or placebo with regard to both the presence or absence of individual neuropsychiatric symptoms and individual domain scores (reflecting severity) in participants who had symptoms at week 9.	At week 9, participants treated with citalopram were significantly less likely to be reported as showing delusions (odds ratio=0.40), anxiety (odds ratio=0.43), and irritability/lability (odds ratio=0.38). A comparison of median scores of participants with symptoms present at week 9 showed significant differences favoring citalopram for hallucinations and favoring placebo for sleep/nighttime behavior disorders.	While dosage constraints must be considered because of citalopram's adverse effect profile, this agent's overall therapeutic effects in patients with Alzheimer's disease and agitation, in addition to efficacy for agitation/aggression, included reductions in the frequency of irritability, anxiety, and delusions; among patients who had these symptoms at week 9, they included a reduction in the severity of hallucinations but an increase in the severity of sleep/nighttime behavior disorders.	
27031975	Pittsburg Sleep Quality Index (PSQI) is a widely used standardized instrument to assess sleep quality in clinical and research settings. Objective of the study was to translate the PSQI into Sinhala language and validate using a combined qualitative and quantitative approach.Every fifth patient aged 18-60 years who attended the out-patients department of a tertiary care hospital was recruited. PSQI was translated into Sinhala using a combined qualitative and quantitative approach. Internal consistency was measured using Cronbach's alpha. Construct validity was assessed by comparing the scores in patients who were identified as having depressive disorder according to the Centre for Epidemiologic Studies Depression Scale (CES-D) and those without depressive disorder.	Forty-six participants with depression were compared with 159 non depressed controls. Mean PSQI component scores were significantly higher in depressed patients in 5 components. Factor analysis identified a single component explaining 53.53% of the variance. Cronbach's alpha of 0.85 indicated a high internal consistency.	The Sinhala translation of the PSQI is a valid and reliable tool to assess sleep quality.	
27028801	The median raphe is a key subcortical modulatory centre involved in several brain functions, such as regulation of the sleep-wake cycle, emotions and memory storage. A large proportion of median raphe neurones are glutamatergic and implement a radically different mode of communication compared to serotonergic cells, although their in vivo activity is unknown. We provide the first description of the in vivo, brain state-dependent firing properties of median raphe glutamatergic neurones identified by immunopositivity for the vesicular glutamate transporter type 3 (VGluT3) and serotonin (5-HT). Glutamatergic populations (VGluT3+/5-HT- and VGluT3+/5-HT+) were compared with the purely serotonergic (VGluT3-/5-HT+ and VGluT3-/5-HT-) neurones. VGluT3+/5-HT+ neurones fired similar to VGluT3-/5-HT+ cells, whereas they significantly diverged from the VGluT3+/5-HT- population. Activity of the latter subgroup resembled the spiking of VGluT3-/5-HT- cells, except for their diverging response to sensory stimulation. The VGluT3+ population of the median raphe may broadcast rapidly varying signals on top of a state-dependent, tonic modulation.Subcortical modulation is crucial for information processing in the cerebral cortex. Besides the canonical neuromodulators, glutamate has recently been identified as a key cotransmitter of numerous monoaminergic projections. In the median raphe, a pure glutamatergic neurone population projecting to limbic areas was also discovered with a possibly novel, yet undetermined function. In the present study, we report the first functional description of the vesicular glutamate transporter type 3 (VGluT3)-expressing median raphe neurones. Because there is no appropriate genetic marker for the separation of serotonergic (5-HT+) and non-serotonergic (5-HT-) VGluT3+ neurones, we utilized immunohistochemistry after recording and juxtacellular labelling in anaesthetized rats. VGluT3+/5-HT- neurones fired faster, more variably and were permanently activated during sensory stimulation, as opposed to the transient response of the slow firing VGluT3-/5-HT+ subgroup. VGluT3+/5-HT- cells were also more active during hippocampal theta. In addition, the VGluT3-/5-HT- population, comprising putative GABAergic cells, resembled the firing of VGluT3+/5-HT- neurones but without any significant reaction to the sensory stimulus. Interestingly, the VGluT3+/5-HT+ group, spiking slower than the VGluT3+/5-HT- population, exhibited a mixed response (i.e. the initial transient activation was followed by a sustained elevation of firing). Phase coupling to hippocampal and prefrontal slow oscillations was found in VGluT3+/5-HT- neurones, also differentiating them from the VGluT3+/5-HT+ subpopulation. Taken together, glutamatergic neurones in the median raphe may implement multiple, highly divergent forms of modulation in parallel: a slow, tonic mode interrupted by sensory-evoked rapid transients, as well as a fast one capable of conveying complex patterns influenced by sensory inputs.	
27028261	Clinicians should periodically assess their menopausal patients' alcohol use. Specific health hazards from excessive alcohol consumption, as well as potential benefits of low-level consumption (for cardiovascular disease, bone health, and type 2 diabetes), should be discussed with their patients who drink. The information in this Practice Pearl can help clinicians provide evidence-based guidance about alcohol consumption and its relationship to common health concerns. 
27026556	應用耳穴貼壓改善產婦睡眠之成效.產婦普遍睡眠品質不佳，過去有研究運用耳穴按壓於護理人員、大學生及原住民老年婦女等健康群體，發現可有效改善睡眠品質，但尚未見探討耳穴按壓對於失眠產婦之成效的相關研究，故引發進行研究之動機。.	探討耳穴貼壓措施介入對產婦睡眠品質之成效。.	本研究採前瞻性類實驗性設計，共收案有睡眠品質不佳產婦共60人，實驗組（30人）施予神門穴、心穴、腎穴之耳穴貼壓，控制組（30人）則接受一般常規照顧。運用Chinese version of the Pittsburgh Sleep Quality Index（CPSQI）於介入措施前及介入後第21天後，追蹤兩組產婦睡眠品質之改變，以廣義估計方程（generalized estimating equation）統計法比較耳穴貼壓介入後睡眠品質之改善成效。.	耳穴貼壓於介入後第21天，實驗組之睡眠品質比控制組有顯著改善。於總分、主觀睡眠品質、睡眠時數及睡眠困擾等變項，實驗組改善程度均顯著大於控制組（p < .05）。.	本研究發現，運用耳穴按壓三週，能有效改善產婦失眠的問題，且此非藥物性與非侵入之措施，可增加產婦睡眠之品質。.	Puerperae exhibit generally poor sleep quality. Previous studies have shown auricular acupressure as effective in improving the sleep problems of nurses, college students, and elderly indigenous Taiwanese women. However, no study has yet examined the effectiveness of auricular acupressure in improving the sleep quality of postpartum women.	To explore the efficacy of auricular acupressure (AA) on puerperae who were affected by sleep disturbance.	A prospective quasi-experimental design was used and 60 puerperae with insomnia who scored at least 5 on the Chinese of version of the Pittsburgh Sleep Quality Index (CPSQI) were recruited at one postpartum centre (a "doing-the-month" care centre) in northern Taiwan. The experimental group (n=30) received pasted auricular magnetic beads and acupressure on the Shenmen, Xin, and Shen points. The control group (n=30) received general nursing directions about insomnia only. All participants were assessed using the CPSQI prior to the intervention and on the 21st post-intervention day. The intervention effects were analysed using the Generalized Estimating Equation (GEE).	After three weeks of the AA intervention, the mean global PSQI score had decreased significantly more in the experimental group than in the control group (p<.05). Furthermore, experimental-group participants reported better sleep quality (p<.05), longer total sleep time (p<.001) and lower sleep disturbance (p<.05) than their control-group peers.	The present pilot study found complementary AA to be an effective intervention for treating puerperae with insomnia. This non-pharmacological and nonintrusive intervention for improving sleep disturbance in puerperae promotes the quality of sleep.	
27025152	Health-related quality of life (HRQOL) of children and adolescents with chronic health conditions is a multifactorial concept that combines a child's perception and adaptation to physical, social, emotional, and school environments regardless of particular medical diagnosis. Children with chronic kidney disease (CKD) experience non-kidney specific co-morbidities, including depression, body image alterations, and sleep disturbance, that impair their daily lives. This article reviews the pediatric nephrology literature to highlight the evidence identifying these riskr to HRQOL and suggesting ways in which nurses in both nephrology and primary care are poised to identify and modify these risk factors.
27023587	Chronic sleep disturbance induced by traffic noise is considered to cause environmental sleep disorder, which increases the risk of cardiovascular disease, stroke, diabetes and other stress-related diseases. However, noise indices for the evaluation of sleep disturbance are not based on the neurophysiological process of awakening regulated by the brainstem. In this study, through the neurophysiological approach, we attempted (1) to investigate the thresholds of awakening due to external stimuli in the brainstem; (2) to evaluate the dynamic characteristics in the brainstem and (3) to verify the validity of existing noise indices. Using the mathematical Phillips-Robinson model, we obtained thresholds of awakening in the brainstem for different durations of external stimuli. The analysis revealed that the brainstem seemed insensitive to short stimuli and that the response to external stimuli in the brainstem could be approximated by a first-order lag system with a time constant of 10-100 s. These results suggest that the brainstem did not integrate sound energy as external stimuli, but neuroelectrical signals from auditory nerve. To understand the awakening risk accumulated in the brainstem, we introduced a new concept of "awakening potential" instead of sound energy. 
27023005	To examine the associations of Intimate partner violence (IPV) with stress-related sleep disturbance (measured using the Ford Insomnia Response to Stress Test [FIRST]) and poor sleep quality (measured using the Pittsburgh Sleep Quality Index [PSQI]) during early pregnancy.This cross-sectional study included 634 pregnant Peruvian women. In-person interviews were conducted in early pregnancy to collect information regarding IPV history, and sleep traits. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CIs) were calculated using logistic regression procedures.	Lifetime IPV was associated with a 1.54-fold increased odds of stress-related sleep disturbance (95% CI: 1.08-2.17) and a 1.93-fold increased odds of poor sleep quality (95% CI: 1.33-2.81). Compared with women experiencing no IPV during lifetime, the aOR (95% CI) for stress-related sleep disturbance associated with each type of IPV were: physical abuse only 1.24 (95% CI: 0.84-1.83), sexual abuse only 3.44 (95%CI: 1.07-11.05), and physical and sexual abuse 2.51 (95% CI: 1.27-4.96). The corresponding aORs (95% CI) for poor sleep quality were: 1.72 (95% CI: 1.13-2.61), 2.82 (95% CI: 0.99-8.03), and 2.50 (95% CI: 1.30-4.81), respectively. Women reporting any IPV in the year prior to pregnancy had increased odds of stress-related sleep disturbance (aOR = 2.07; 95% CI: 1.17-3.67) and poor sleep quality (aOR = 2.27; 95% CI: 1.30-3.97) during pregnancy.	Lifetime and prevalent IPV exposures are associated with stress-related sleep disturbance and poor sleep quality during pregnancy. Our findings suggest that sleep disturbances may be important mechanisms that underlie the lasting adverse effects of IPV on maternal and perinatal health.	
27022957	To characterize and compare the sleep-wake behavior of individuals following a mild traumatic brain injury (mTBI) with that of noninjured healthy controls.Community.	Fourteen participants with a recent mTBI (Mage = 28.07; SD = 10.45; n = 10 females) and 34 noninjured controls (Mage = 23.70; SD = 7.30; n = 31 females).	Cross-sectional.	Battery of subjective sleep measures and 14 days of sleep-wake monitoring via actigraphy (objective measurement) and concurrent daily sleep diary.	Participants who had sustained an mTBI self-reported significantly higher sleep-related impairment, poorer nightly sleep quality, and more frequently met criteria for clinical insomnia, compared with controls (d = 0.76-1.11, large effects). The only significant between-group difference on objective sleep metrics occurred on sleep timing. On average, people with a recent history of mTBI fell asleep and woke approximately 1 hour earlier than did the controls (d = 0.62-0.92, medium to large effects).	Participants with a history of mTBI had several subjective sleep complaints but relatively few objective sleep changes with the exception of earlier sleep timing. Future research is needed to understand the clinical significance of these findings and how these symptoms can be alleviated. Interventions addressing subjective sleep complaints (eg, cognitive behavior therapy for insomnia) should be tested in this population.	
27022631	Hypocretin 1 and 2 (Hcrts; also known as orexin A and B), excitatory neuropeptides synthesized in cells located in the tuberal hypothalamus, play a central role in the control of arousal. Hcrt inputs to the locus coeruleus norepinephrine (LC NE) system and the posterior hypothalamic histaminergic tuberomammillary nuclei (TMN HA) are important efferent pathways for Hcrt-induced wakefulness. The LC expresses Hcrt receptor 1 (HcrtR1), whereas HcrtR2 is found in the TMN. Although the dual Hcrt/orexin receptor antagonist almorexant (ALM) decreases wakefulness and increases NREM and REM sleep time, the neural circuitry that mediates these effects is currently unknown. To test the hypothesis that ALM induces sleep by selectively disfacilitating subcortical wake-promoting populations, we ablated LC NE neurons (LCx) or TMN HA neurons (TMNx) in rats using cell-type-specific saporin conjugates and evaluated sleep/wake following treatment with ALM and the GABAA receptor modulator zolpidem (ZOL). Both LCx and TMNx attenuated the promotion of REM sleep by ALM without affecting ALM-mediated increases in NREM sleep. Thus, eliminating either HcrtR1 signaling in the LC or HcrtR2 signaling in the TMN yields similar effects on ALM-induced REM sleep without affecting NREM sleep time. In contrast, neither lesion altered ZOL efficacy on any measure of sleep-wake regulation. These results contrast with those of a previous study in which ablation of basal forebrain cholinergic neurons attenuated ALM-induced increases in NREM sleep time without affecting REM sleep, indicating that Hcrt neurotransmission influences distinct aspects of NREM and REM sleep at different locations in the sleep-wake regulatory network. 
27021240	Long-term adverse effects of propranolol treatment for infantile hemangioma (IH) in young children have been suggested.To compare growth and development in children treated with propranolol for IH with nontreated healthy controls.	Eighty two (73%) children with IH aged 43 to 51 months treated with propranolol for 6 months or longer, and without other developmental risk factors, were recruited (cases) and matched with 4 twin counterparts and 78 children from a community-based cohort (control subjects). Parents completed the 48-months Ages and Stages Questionnaire (ASQ). Percentages of children with abnormal ASQ results were compared using χ(2) analyses. Mean ASQ scores and growth were compared using Mann-Whitney U tests.	Six (7.3%) cases had abnormal ASQ results, compared with 10 (12.2%) controls (P = .292). Mean ASQ total score (25th-75th percentile) was 52.9 (50.8-57.0) for cases and 51.9 (49.0-56.0) for controls (P = .383). Height and weight of cases and controls were comparable.	A parent-completed screening instrument was used. The exclusion of children born at gestational age less than 36 weeks and/or children born small for gestational age partly limits generalizability.	We found no increased developmental risk or growth impairment at age 4 years in patients with IH treated with propranolol.	
27020314	The purpose of the current study was to examine the influence of "time" on isometric elbow flexion torque, body temperature and muscle size without interrupting the sleep wake cycle in college aged males. Two hours following the participants normal wake time, oral temperature was measured, followed by muscle thickness of the upper and lower body using ultrasound, as well as elbow flexor torque via a maximal voluntary contraction (MVC). Measurements were repeated every 2h for 12h (Time points 1-7). To examine the repeatability of the rhythm, participants returned and completed the same procedures as before within 14days of their first circadian visit (Circadian visit 2). There was no time×day interaction for body temperature (p=0.29), nor were there main effects for time (p=0.15) or day (p=0.74). For MVC, there was no time×day interaction (p=0.93) or main effect for day (p=0.50), however, there was a main effect for time (p=0.01). MVC at time points 1 (86.4±6.4Nm) and 2 (87.1±6.2Nm) was greater than time points 4 (84.2±6.6Nm) and 6 (83.4±6.8Nm, p<0.05). Additionally, time point 5 MVC was greater than time point 4. For upper body muscle thickness, there was no time×day interaction (p=0.34), nor was there a main effect for day (p=0.38), or time (p=0.06). For lower body muscle thickness, there was no time×day interaction (p=0.57), nor was there a main effect for day (p=0.75), or time (p=0.13). Cosinor analyses revealed no group level rhythms for oral temperature, muscle thickness or strength (p>0.05), however, there were some individual rhythms noted for muscle thickness and strength. Results suggest that, when accounting for an individuals normal wake time, circadian rhythms of strength, temperature and muscle thickness are not apparent in most individuals. 
27020079	Tinnitus is often associated with disturbed sleep, but there are also patients without sleep problems. The mechanisms for developing insomnia or not in tinnitus patients are still unknown. The aim of the present study was to extract possible tinnitus specific factors that increase the risk of developing insomnia based on the analysis of a large patient cohort suffering from chronic tinnitus.173 patients presenting at the multidisciplinary tinnitus center of a University Hospital completed a questionnaire measuring specific psychological symptoms of insomnia (RIS) and a tinnitus questionnaire (TQ). The scores of all ten RIS items were compared between tinnitus patients and 94 healthy individuals by separate ANOVAs in order to specify the extent of insomnia specific symptoms in the tinnitus group. In a second step a multiple linear regression analysis was performed in the tinnitus sample with subscales of the TQ (excluding the TQ sleep scale), age and duration of tinnitus as independent variables and the RIS score as the dependent variables.	Tinnitus patients differed from healthy controls not only in impaired sleep quality but also in insomnia specific concerns and anxiety. Tinnitus related emotional and cognitive distress and somatic complaints correlated with severity of insomnia, whereas no association of age or duration of tinnitus with severity of insomnia was found.	Our results suggest that chronic tinnitus patients have more sleeping difficulties and associated worries about sleep or negative emotions in contrast to healthy controls. Tinnitus-related distress is related to insomnia.	
27020069	Fibromyalgia is a chronic condition of unknown aetiology, characterised by widespread pain, sleep disturbances, and fatigue. In this paper we examined the relationship metacognitions and the impact of Fibromyalgia in a German sample, detailing the translation and validation of a self-report metacognitive instrument.The Metacognitions about Symptoms Control Scale (MaSCS) was translated into German using the back-forward translation process. A total of 348 patients (316 female and 26 male) with Fibromyalgia contributed data to the study to test the structure and psychometric properties of the MaSCS.	Confirmatory factor analyses, informed by modification indices, resulted in a 16-item scale consisting of two factors pertaining to positive and negative metacognitions about symptoms control. Further analyses revealed that both factors had good internal consistency. Correlation analyses established convergent validity, indicating that both factors were significantly associated with: (1) established positive and negative metacognitions scales; and (2) with symptoms severity in Fibromyalgia. Regression analyses revealed that positive metacognitions about symptoms control significantly predicted impairment in physical functioning while negative metacognitions about symptoms control significantly predicted the overall Fibromyalgia impact value, when controlling for stress, anxiety, and depression and a general metacognitions.	The findings support the potential relevance of metacognitions, and utility of the German version of MaSCS, in examining the role of metacognitions in Fibromyalgia and other chronic health conditions.	
27019198	Sleep restriction causes impaired cognitive performance that can result in adverse consequences in many occupational settings. Individuals may rely on self-perceived alertness to decide if they are able to adequately perform a task. It is therefore important to determine the relationship between an individual's self-assessed alertness and their objective performance, and how this relationship depends on circadian phase, hours since awakening, and cumulative lost hours of sleep. Healthy young adults (aged 18-34) completed an inpatient schedule that included forced desynchrony of sleep/wake and circadian rhythms with twelve 42.85-hour "days" and either a 1:2 (n = 8) or 1:3.3 (n = 9) ratio of sleep-opportunity:enforced-wakefulness. We investigated whether subjective alertness (visual analog scale), circadian phase (melatonin), hours since awakening, and cumulative sleep loss could predict objective performance on the Psychomotor Vigilance Task (PVT), an Addition/Calculation Test (ADD) and the Digit Symbol Substitution Test (DSST). Mathematical models that allowed nonlinear interactions between explanatory variables were evaluated using the Akaike Information Criterion (AIC). Subjective alertness was the single best predictor of PVT, ADD, and DSST performance. Subjective alertness alone, however, was not an accurate predictor of PVT performance. The best AIC scores for PVT and DSST were achieved when all explanatory variables were included in the model. The best AIC score for ADD was achieved with circadian phase and subjective alertness variables. We conclude that subjective alertness alone is a weak predictor of objective vigilant or cognitive performance. Predictions can, however, be improved by knowing an individual's circadian phase, current wake duration, and cumulative sleep loss. 

27017288	Research supports the distinctness of sluggish cognitive tempo (SCT) (e.g., mental confusion and slowed behavior/thinking) from other psychopathologies. However, the relation between SCT and sleep functioning has not been adequately studied. We examined the association between SCT and sleep functioning in 325 children (62% male) ages 6-10 years referred to a pulmonary-based, accredited Sleep Disorders Center. Correlations between caregiver ratings of SCT, other psychopathologies (i.e., inattention/hyperactivity, oppositionality, depression, anxiety), sleep functioning (both behavioral and organic symptoms), as well as sleep disorder diagnoses, were examined. Unique effects of SCT and other psychopathologies on sleep problem severity controlling for child demographics were assessed using regressions. Regression analyses were also conducted to examine the unique effects of SCT on impairment (i.e., academic difficulties, parenting stress, and other psychopathologies) controlling for child demographics, sleep problem severity, and other psychopathology symptoms. SCT was weakly to moderately correlated with most measures of sleep (rs = .07-.39) and moderately to strongly correlated with measures of daytime sleepiness (rs = .33 and .53). In the regression analyses, SCT was uniquely associated with greater sleep functioning severity and impairment in academic functioning. SCT was also uniquely associated with higher levels of depression and inattention/hyperactivity, but not anxiety, and negatively associated with oppositionality. Finally, SCT symptoms were uniquely associated with greater parent-child dysfunctional interaction. Findings demonstrate that SCT is related to, but not redundant with, sleep problems and daytime sleepiness specifically. Further, SCT remained associated with several domains of functional impairment in sleep-disordered children after controlling for clinically-relevant variables, highlighting the potential value in assessing SCT symptoms in children with sleep problems.
27014592	Sleep analysis in animal models typically involves recording an electroencephalogram (EEG) and electromyogram (EMG) and scoring vigilance state in brief epochs of data as Wake, REM (rapid eye movement sleep) or NREM (non-REM) either manually or using a computer algorithm. Computerized methods usually estimate features from each epoch like the spectral power associated with distinctive cortical rhythms and dissect the feature space into regions associated with different states by applying thresholds, or by using supervised/unsupervised statistical classifiers; but there are some factors to consider when using them:•Most classifiers require scored sample data, elaborate heuristics or computational steps not easily reproduced by the average sleep researcher, who is the targeted end user.•Even when prediction is reasonably accurate, small errors can lead to large discrepancies in estimates of important sleep metrics such as the number of bouts or their duration.•As we show here, besides partitioning the feature space by vigilance state, modeling transitions between the states can give more accurate scores and metrics. An unsupervised sleep segmentation framework, "SegWay", is demonstrated by applying the algorithm step-by-step to unlabeled EEG recordings in mice. The accuracy of sleep scoring and estimation of sleep metrics is validated against manual scores. 
27013946	Panax quinquefolius (American Ginseng) is known for its therapeutic potential against various neurological disorders, but its plausible mechanism of action still remains undeciphered. GABA (Gamma Amino Butyric Acid) plays an important role in sleep wake cycle homeostasis. Thus, there exists rationale in exploring the GABA-ergic potential of Panax quinquefolius as neuroprotective strategy in sleep deprivation induced secondary neurological problems.The present study was designed to explore the possible GABA-ergic mechanism in the neuro-protective effect of Panax quinquefolius against 72-h sleep deprivation induced anxiety like behavior, oxidative stress, mitochondrial dysfunction, HPA-axis activation and neuroinflammation.	Male laca mice were sleep deprived for 72-h by using Grid suspended over water method. Panax quinquefolius (American Ginseng 50, 100, and 200 mg/kg) was administered alone and in combination with GABA modulators (GABA Cl(-) channel inhibitor, GABA-benzodiazepine receptor inhibitor and GABAA agonist) for 8 days, starting 5 days prior to 72-h sleep deprivation period. Various behavioral (locomotor activity, mirror chamber test), biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels), mitochondrial complexes, neuroinflammation marker (Tumor Necrosis Factor, TNF-alpha), serum corticosterone, and histopathological sections of brains were assessed.	Seventy two hours sleep deprivation significantly impaired locomotor activity, caused anxiety-like behavior, conditions of oxidative stress, alterations in mitochondrial enzyme complex activities, raised serum corticosterone levels, brain TNFα levels and led to neuroinflammation like signs in discrete brain areas as compared to naive group. Panax quinquefolius (100 and 200 mg/kg) treatment restored the behavioral, biochemical, mitochondrial, molecular and histopathological alterations. Pre-treatment of GABA Cl(-) channel inhibitor as well as GABA-benzodiazepine receptor inhibitor, significantly reversed the protective effect of P. quinquefolius (100 mg/kg) in 72-h sleep deprived animals (P < 0.05). However, pretreatment with GABAA agonist, potentiated Panax quinquefolius's protective effect which was significant as compared to their effect per se (p < 0.05).	GABA-ergic mechanism could be involved in the neuroprotective effect of P.quinquefolius against sleep deprivation induced anxiety-like behavior, oxidative stress, mitochondrial dysfunction, HPA axis activation and neuroinflammation.	
27013526	Poor sleep quality impairs immune responses and pain tolerance, both key to recovery from acute illness. Hospitalised children and their co-sleeping parents also risk emotional lability and impaired coping skills when sleep-deprived. We aimed to study the experiences of children and parents during hospital admissions.Semi-structured interviews were conducted with parents within a week of their child's discharge. Questions explored parent and child sleep quality, factors contributing to this, perceived impact on day-time functioning and suggested improvements to ward sleep environment.	Southampton Children's Hospital, UK.	17 co-sleeping parents of 16 children aged 3-12 years completed interviews. Children admitted for surgical procedures and those with established sleep disorders or nocturnal seizures were excluded.	Constant comparative methods identified themes within the data using a grounded theory approach.	Parents reported that they, and to a lesser extent their children, experienced reduced sleep quality. Noise and light as well as ward schedules were identified as key factors disrupting sleep. Parents reported that lack of sleep caused difficulties with their own emotional regulation and that of their child, affecting daytime parent-child relationships. Furthermore, they reported a negative impact of sleep deprivation on decision-making about their child's medical care.	Parents identified poor sleep in hospital as a significant additional burden to their child's hospital admission. Importantly, they identified potential improvements to the ward sleep environment. Intervention studies that target modifiable, child-centred alterations to night-time ward culture are recommended, focusing on measurable child and parental outcomes.	
27013460	We previously reported that dietary heat-killed Lactobacillus brevis SBC8803 affects sleep rhythms in mice. The present study evaluated the effect of consumption of heat-killed SBC8803 on sleep architecture in humans. A non-randomised, placebo-controlled, double blind, and crossover pilot study was conducted using volunteers who scored at a slightly high level (i.e. ≥6) on the Athens Insomnia Scale (AIS). Male subjects (n=17; age 41-69 y) consumed placebo or SBC8803 capsules (25 mg/day of heat-killed SBC8803) for 10 days. Electroencephalograms (EEG) were recorded using a mobile, one-channel system, providing objective data on sleep. Subjects' sleep journals and administration of the AIS provided subjective data on sleep. Three subjects were excluded from the statistical analysis. Analysis of the remaining 14 volunteers revealed no significant differences between placebo and SBC8803 consumption in either the AIS or the sleep EEG. The sleep journals revealed an improvement in 'waking' for the SBC8803 consumption periods (P=0.047), and there was a marginally significant effect on 'drowsiness during the following day' (P=0.067). Effects on the EEG delta power value (μV(2)/min) were revealed by a stratified analysis based on age, AIS, and the Beck Depression Inventory (BDI). Specifically, effects were found among subjects in their 40s who consumed the SBC8803 capsules (P=0.049) and among subjects with a BDI score less than the all-subjects average (13.3) (P=0.045). A marginally significant effect was found among subjects with an AIS score less than the all-subjects average (11.6) (P=0.065). The delta power value of 5 subjects with both BDI and AIS scores less than the average increased significantly (P=0.017). While the number of subjects was limited, a beneficial effect on sleep due to consumption of heat-killed L. brevis SBC8803 was found in subjects with slightly challenged sleep. 
27012745	Pediatric sleep disturbances are regularly diagnosed on the basis of parental reports. However, the impact of parental sleeping problems on parental perceptions and reports of their child's sleep has not yet been studied. We hypothesized that poor parental sleep decreases the parent-reported child sleep quality.A 1-week actigraph recording was performed in 100 children aged 2 to 6 years recruited in 16 day care centers. Their biological parents completed a sleep diary and a Sleep Disturbance Scale for Children (SDSC) on children's sleep. The parents also completed the Jenkins' sleep scale on their own sleep, the 12-item General Health Questionnaire, and questions on demographic factors. Linear regression analyses were performed to study the association of the parental Jenkins' score on their child's total SDSC score. Analyses were also performed for 3 of the subscales of the SDSC: disorders of excessive somnolence, disorders of initiating and maintaining sleep, and sleep-wake transition disorders.	Parental sleeping problems were associated with more frequent reporting of children's sleeping problems. This association was unexplained by the actigraph measures of children's sleep, such as actual 24-hour sleep time and sleep efficiency, parental mental health problems, or any other tested potential confounder or mediator. Similar correlations were seen for the 3 analyzed subscales.	Parental sleep quality was associated with overreporting of sleep problems in their children. This finding emphasizes the importance of considering parental sleep quality in the diagnosis, treatment, and research of pediatric sleeping problems.	
27011178	Chronic pruritus is a debilitating condition with numerous etiologies. Many patients suffer from nocturnal pruritus, which can decrease quality of life and affect mortality in hemodialysis patients. Nocturnal pruritus may occur in all sleep stages but is most prevalent in stages N1 and N2. Further research is needed to elucidate the pathophysiology of nocturnal itch, which will aid in the development of tailored management strategies. 
27011157	Healthcare systems are increasingly looking to integrate aromatherapy (essential oils) as a safe, low-cost, and nonpharmacologic option for patient care to reduce pain, nausea, and anxiety and to improve sleep. This article describes the development and implementation of a healthcare system-wide program of nurse-delivered essential oil therapeutic interventions to inpatients throughout an acute care setting. In addition, we provide lessons learned for nursing administrators interested in developing similar nurse-delivered aromatherapy programs. 
27010071	Daytime sleepiness and sleep disorders are frequently reported in Parkinson's disease (PD). However, their impact on quality of life has been underestimated and few clinical trials have been performed.We aimed to assess the efficacy and safety of pharmacological interventions for daytime sleepiness and sleep disorders in PD.	Systematic review of randomized controlled trials comparing any pharmacological intervention with no intervention or placebo for the treatment of daytime sleepiness and sleep problems in PD patients.	Ten studies (n = 338 patients) were included. Four trials addressed interventions for excessive daytime sleepiness. Meta-analysis of the three trials evaluating modafinil showed a significant reduction in sleepiness, as assessed by the Epworth Sleepiness Scale (ESS) (- 2.24 points, 95% CI - 3.90 to - 0.57, p < 0.05). In one study, treatment with caffeine was associated with a non-significant improvement of 1.71 points in ESS (95% CI, - 3.57 to 0.13). The six remaining trials assessed interventions for insomnia and REM sleep Behaviour Disorder (RBD). Single study results suggest that doxepin and YXQN granules might be efficacious, while pergolide may be deleterious for insomnia and that rivastigmine may be used to treat RBD in PD patients. However, there is insufficient evidence to support or refute the efficacy of any of these interventions. No relevant side effects were reported.	Whilst providing recommendations, this systematic review depicts the lack of a body of evidence regarding the treatment of sleep disorders in PD patients; hence, further studies are warranted.	
27005534	To investigate the sleep quality and related factors among medical students in China, understand the association between dormitory environment and sleep quality, and provide evidence and recommendations for sleep hygiene intervention.A total of 555 undergraduate students were selected from a medical school of an university in Beijing through stratified-cluster random-sampling to conduct a questionnaire survey by using Chinese version of Pittsburgh Sleep Quality Index (PSQI) and self-designed questionnaire. Analyses were performed by using multiple logistic regression model as well as multilevel linear regression model.	The prevalence of sleep disorder was 29.1%(149/512), and 39.1%(200/512) of the students reported that the sleep quality was influenced by dormitory environment. PSQI score was negatively correlated with self-reported rating of dormitory environment (γs=-0.310, P<0.001). Logistic regression analysis showed the related factors of sleep disorder included grade, sleep regularity, self-rated health status, pressures of school work and employment, as well as dormitory environment. RESULTS of multilevel regression analysis also indicated that perception on dormitory environment (individual level) was associated with sleep quality with the dormitory level random effects under control (b=-0.619, P<0.001).	The prevalence of sleep disorder was high in medical students, which was associated with multiple factors. Dormitory environment should be taken into consideration when the interventions are taken to improve the sleep quality of students.	
27003694	Tasimelteon (Hetlioz(®)) is a dual melatonin receptor agonist indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24) (free-running disorder). In two randomized, double-masked, multicentre, phase III trials, totally blind individuals with Non-24 who received oral tasimelteon 20 mg once nightly were significantly more likely than those receiving placebo to entrain the circadian pacemaker (the SET trial) and maintain entrainment (the RESET trial). Sleep/wake parameters and functioning were also improved with tasimelteon. Oral tasimelteon was generally well tolerated in totally blind patients with Non-24. In conclusion, tasimelteon is a useful drug for the treatment of Non-24 in totally blind individuals. 
27003163	Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller's surface material. We examined the efficacy of gentle skin stimuli for treating nocturia.The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79-89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3-day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period.	Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean ± standard deviation, -0.74 ± 0.7 times) was significantly greater than that during placebo stimuli periods (-0.15 ± 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13).	These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life.	UMIN Clinical Trial Registry (CTR) UMIN000015809.	
27002812	Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders. 
27002678	Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.
27002665	Subacromial impingement syndrome (SIS) is characterized by pain and disability of shoulder. Various treatment methods have been used for SIS.The aim of our study was to evaluate efficacy of therapeutic ultrasound (US) on pain, disability, anxiety, depression, sleep quality and quality of life in patients with SIS.	Patients with SIS were randomly divided into two groups, including the group 1 (continuous US group; 3 MHz, 1.5 W/cm2, n = 26) and group 2 (sham US group, n = 24). Additionally, transcutaneous electrical nerve stimulation (TENS) + exercise program were added in both groups. Pain and disability of the shoulder were assessed by the Shoulder Pain and Disability Index (SPADI), while anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality. Quality of life was evalutaed by the Nottingham Health Profile (NHP). Patients were evaluated at baseline and after end of three weeks.	Both groups had significantly improvements in terms of SPADI-pain, SPADI-disability, SPADI-total, NHP-pain and NHP-sleep scores after the three weeks interventions. There were significantly improvements in the Group 1 in terms of PSQI-total, and NHP-physical activity. Group 2 had significantly improvements in terms of anxiety-HADS, depression-HADS and NHP-emotional reaction scores. In the inter-group comparison, there were no significantly differences in the change scores were observed in any domains of SPADI scores, anxiety, depression and sleep scores, or any NHP scores.	Our study showed that US does not have any benefits on SIS. TENS + exercise program are not effective on anxiety, depression and fatigue, however TENS +$ exercise program are effective on pain, disability and sleep disturbance in patients with SIS.	
26998996	Our aim was to study not only the prevalence but more importantly the severity and the correlation between sleep quality and restless legs syndrome (RLS) in a large population of well-defined migraine patients as poor sleep presumably triggers migraine attacks.In a large cross-sectional and observational study, data on migraine and RLS were collected from 2385 migraine patients (according to the International Classification of Headache Disorders ICHD-IIIb) and 332 non-headache controls. RLS severity (International RLS Study Group severity scale) and sleep quality (Pittsburgh Sleep Quality Index) were assessed. Risk factors for RLS and RLS severity were calculated using multivariable-adjusted regression models.	Restless legs syndrome prevalence in migraine was higher than in controls (16.9% vs. 8.7%; multivariable-adjusted odds ratio 1.83; 95% confidence interval 1.18-2.86; P = 0.008) and more severe (adjusted severity score 14.5 ± 0.5 vs. 12.0 ± 1.1; P = 0.036). Poor sleepers were overrepresented amongst migraineurs (50.1% vs. 25.6%; P < 0.001). Poorer sleep quality was independently associated with RLS occurrence (odds ratio 1.08; P < 0.001) and RLS severity (P < 0.001) in migraine patients.	Restless legs syndrome is not only twice as prevalent but also more severe in migraine patients, and associated with decreased sleep quality.	
26996255	During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.
26994361	To evaluate how insomnia is associated with seizure control and quality of life in patients with epilepsy.Consecutive patients with epilepsy attending clinical visits were surveyed with the Insomnia Severity Index (ISI). Patients had to be treated with at least one anticonvulsant and could not have had documented psychogenic pseudoseizure. The presence or absence of seizures and quality of life (QOLIE-P-10) within the past 4 weeks was recorded. Other variables included demographic and clinical data, sleep-wake timing, the Hörne-Östberg Morningness-Eveningness Questionnaire (MEQ), sleepiness (Epworth Sleepiness Scale (ESS), and mood (Center for Epidemiologic Studies Depression Scale, CES-D).	207 patients completed surveys. 43% had clinically significant insomnia, and 51% had at least mild insomnia. 58% were seizure free. Mean ISI scores were significantly worse for those with continuing seizures, and more severe ISI scores correlated strongly with worse QOL. Younger age, shorter duration of epilepsy, use of sedative/hypnotics, medical and sleep comorbidities, delayed sleep timing and chronotype, excessive sleepiness, and depression were all associated with more severe insomnia. Those with unexpected health care visits over the most recent 4 weeks had worse insomnia. After adjustment for these covariates, more severe insomnia remained significantly associated with lack of seizure freedom and with worse QOL.	Insomnia is common in epilepsy, and is associated with short term poor seizure control and worse QOL. Future studies must evaluate cause-and-effect relationships. Assessment of insomnia may be important in the comprehensive care of epilepsy and may influence control of epileptic seizures.	
26993564	Sleep disorders are diverse in Parkinson's disease. We aimed to assess the quality of sleep in patients with Parkinson's disease in an African population.In a transversal and prospective study from April to June 2014, all parkinsonian patients followed at the Fann Teaching Hospital Neurology Clinic (Dakar, Senegal) were assessed using the Hoehn and Yahr's scale and filled out the following questionnaires: Parkinson's disease sleep scale (PDSS), the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). A PDSS score<82 (or a subscore<5) and a PSQI score>5 indicated poor quality or impaired sleep. An ESS score>10 indicated excessive daytime sleepiness. We used the Pearson coefficient to search for correlation between age, disease stage, disease duration, and the importance of sleep impairment.	Hoehn and Yahr staging was 2.42±0.90 in the 35 patients (60% male, mean age 65.7±7.4years, disease duration 32.4±23.4months). The mean total PDSS score was 99.5±24.1 and 74.3% of the patients had an abnormally high PSQI score, indicating high frequency and intensity of sleep disorders. Most frequent disorders were pain or cramps interrupting sleep, night waking to urinate and fatigue or sleepiness on waking. Patients exhibited excessive diurnal sleepiness in 22.9% of the cases; they often had an abnormal PSQI score. Both the total PDSS score and the difficulty to sleep increased with disease stage, but not with age or disease duration.	We found evidence of major alteration of sleep quality in Senegalese Parkinson patients.	
26991850	To compare parent and adolescent reports in exploring adolescent sleep problems and to identify the factors associated with adolescent sleep problem disclosures.Parent (n = 5185) and adolescent reports (n = 5171, age=13.9 ± 0.3 years), from a birth cohort were used to explore adolescent sleep problems. Kappa coefficients were used to assess the agreement, whereas, conditional agreement and disagreement ratios were used to identify the optimal informant. Logistic regression analysis was used to determine the factors affecting adolescent sleep problem disclosure.	Parental reports identified only about one-third of the sleep problems reported by adolescents. Whereas adolescent reports identified up to two-thirds of the sleep problems reported by parents. Combined reports of parents and adolescent did not show any considerable difference from the adolescent report. Adolescent and parent health, maternal depression, and family communication were significantly associated with adolescents sleep problem disclosures.	Adolescent reports could be used as the preferred source to explore adolescent sleep problems. Parental reports should be used when parents as observers are more reliable reporters, or where adolescents are cognitively unable to report sleep problems. Additionally, the impact of poor health, maternal depression and family communication on sleep problems disclosure should be considered for adolescent sleep problem diagnosis.	
26991592	To determine how intensive care unit evaluations of patients' sleep by nurses correspond to polysomnography and if changes in patients' physiologic parameters could be helpful in sleep evaluation.The evaluations of patients' sleep by nurses have not corresponded very well with objective sleep recordings, so there is a need for further knowledge in this field.	Correlational study of patients' sleep, nurses' sleep evaluations and the sleep-related heart rate and blood pressure changes.	The standard overnight polysomnography was recorded on 21 patients. Simultaneously, nurses marked into an electronic patient care documentation system all the changes noted in the patients' sleep status. Patients' arterial blood pressure and heart-rate data were automatically saved into the electronic patient care documentation.	The evaluations of patients' sleep/wake state by nurses corresponded to polysomnography 68% of the time. A correlation was found between nurses' evaluations and polysomnography recordings only on total sleep time. There was no correlation in the other sleep aspects (sleep latency, amount of awakenings or movements during sleep). Most patients' blood pressures and heart rate varied according to sleep/wake state. There was less variation if the patient had received noradrenalin for blood pressure control.	The evaluations of patients' sleep/wake state by nurses only correspond to the polysomnography two-thirds of the time. Thus, more sophisticated evaluation methods should be developed to aid nurses in sleep evaluations. Sleep-related changes in blood pressure and heart rate can be seen in intensive care unit patients, so using these parameters as part of the patients' sleep evaluation should be further explored.	The nurses' evaluation practices of intensive care unit patients' sleep need further development. Monitoring the changes in patients' heart rate and blood pressure may aid in evaluating his/her sleep.	
26986132	Nonapnea sleep disorders (NASDs) and associated problems, which are highly prevalent in patients with kidney diseases, are associated with unfavorable medical sequelae. Nonetheless, whether NASDs are associated with acute kidney injury (AKI) development has not been thoroughly analyzed. We examined the association between NASD and AKI. We conducted a population-based study by using 1,000,000 representative data from the Taiwan National Health Insurance Research Database for the period from January 1, 2000, to December 31, 2010. We studied the incidence and risk of AKI in 9178 newly diagnosed NASD patients compared with 27,534 people without NASD matched according to age, sex, index year, urbanization level, region of residence, and monthly income at a 1:3 ratio. The NASD cohort had an adjusted hazard ratio (hazard ratio [HR]; 95% confidence interval [CI] = 1.15-2.63) of subsequent AKI 1.74-fold higher than that of the control cohort. Older age and type 2 diabetes mellitus were significantly associated with an increased risk of AKI (P < 0.05). Among different types of NASDs, patients with insomnia had a 120% increased risk of developing AKI (95% CI = 1.38-3.51; P = 0.001), whereas patients with other sleep disorders had a 127% increased risk of subsequent AKI (95% CI = 1.07-4.80; P = 0.033). Men with NASDs were at a high risk of AKI (P < 0.05). This nationwide population-based cohort study provides evidence that patients with NASDs are at higher risk of developing AKI than people without NASDs.
26986095	Lack of sleep can compromise the immune system, which may reactivate latent varicella-zoster virus. Studies on sleep disorders and the risk of herpes zoster (HZ) are scant.We conducted a population-based cohort study to evaluate the risk of HZ in patients with sleep disorders and potential risk factors for HZ development. We identified patients with sleep disorders without apnea from 2002 to 2005 by using the Taiwan Longitudinal Health Insurance Database. The patients without sleep disorders were randomly selected and frequency matched with patients with sleep disorders according to age, sex, and index year. We estimated the follow-up time in person-years for the patients from the entry date until HZ diagnosis, loss to follow-up, or the end of 2010. We used Cox proportional hazards regression models and a sensitivity analysis to estimate the risk of HZ while controlling for demographic characteristics and comorbidities. A total of 131,001 study participants (follow-up, 948,177 person-years; mean age, 51.2 ± 16.5 years; 62.2% women) were included in the study. Patients with sleep disorders exhibited a higher incidence of HZ compared with a comparison cohort when stratified by age, sex, and comorbidities. After adjustment for covariates, the sleep disorder cohort exhibited a 1.23-fold greater risk of HZ compared with the comparison cohort (95% confidence interval [CI] = 1.17-1.30). The incidence of HZ increased with age. Adults ages 65 years and older exhibited a 6.11-fold greater risk of HZ development compared with their younger counterparts (95% CI = 5.34-7.00). Cancers and autoimmune diseases were independent risk factors of HZ development. The patients with sleep disorders may carry an increased risk of developing HZ.
26985900	The primary aim of this study was to examine associations between problematic Internet use, depression and sleep disturbance, and explore whether there were differential effects of problematic Internet use and depression on sleep disturbance. A total of 1772 adolescents who participated in the Shantou Adolescent Mental Health Survey were recruited in 2012 in Shantou, China. The Chinese version of the Internet Addiction Test (IAT) was used to evaluate the prevalence and severity of Internet addiction. The Chinese version of the Pittsburgh Sleep Quality Index (PSQI), a 10-item version of the Center for Epidemiologic Studies Depression Scale (CESD-10), and other socio-demographic measures were also completed. Multiple regression analysis was used to test the mediating effect of problematic Internet use and depression on sleep disturbance. Among the participants, 17.2% of adolescents met the criteria for problematic Internet use, 40.0% were also classified as suffering from sleep disturbance, and 54.4% of students had depressive symptoms. Problematic Internet use was significantly associated with depressive symptoms and sleep disturbance. The correlation between depressive symptoms and sleep disturbance was highly significant. Both problematic Internet use (β = 0.014; Sobel test Z = 12.7, p < 0.001) and depression (β = 0.232; Sobel test Z = 3.39, p < 0.001) had partially mediating effects on sleep disturbance and depression was of greater importance for sleep disturbance than problematic Internet use. There is a high prevalence of problematic Internet use, depression and sleep disturbance among high school students in southern China, and problematic Internet use and depressive symptoms are strongly associated with sleep disturbance. This study provides evidence that problematic Internet use and depression have partially mediating effects on sleep disturbance. These results are important for clinicians and policy makers with useful information for prevention and intervention efforts. 
26985725	Sleep problems are the most common non-motor symptoms in Parkinson's disease (PD), and are more difficult to treat than the motor symptoms. In the current study, the role of human leucine-rich repeat kinase 2 (hLRRK2), the most common genetic cause of PD, was investigated with regards to sleep problems, and the therapeutic potential of melatonin in hLRRK2‑associated sleep problems was explored in Drosophila. hLRRK2 was selectively expressed in the mushroom bodies (MBs) in Drosophila and sleep patterns were measured using the Drosophila Activity Monitoring System. MB expression of hLRRK2 resulted in sleep problems, presynaptic dysfunction as evidenced by reduced miniature excitatory postsynaptic current (mEPSC) and excitatory postsynaptic potential (EPSP) frequency, and excessive synaptic plasticity such as increased axon bouton density. Treatment with melatonin at 4 mM significantly attenuated the sleep problems and rescued the reduction in mEPSC and EPSP frequency in the hLRRK2 transgenic flies. The present study demonstrates that MB expression of hLRRK2 in flies recapitulates the clinical features of the sleep disturbances in PD, and that melatonin attenuates hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of melatonin in PD patients carrying LRRK2 mutations. 
26983091	Intense itch associated with atopic dermatitis (AD) can negatively impact sleep. However, the nature of sleep disturbance and fatigue in AD has not been fully elucidated.The aim of this study was to determine the burden of sleep disturbance and fatigue in US adults with AD.	This study used a cross-sectional, questionnaire-based survey using a nationally representative sample of 5563 adults from the 2005 to 2006 National Health and Nutrition Examination Survey. Respondents were asked about history of AD, sleep disturbance, and fatigue-related instrumental activity of daily living (IADL) impairment.	There was no significant association between having AD and having a diagnosed sleep disorder (10.44% vs 7.27%; odds ratio [OR] [95% confidence interval (CI)], 1.49 [0.84-2.64]; P = 0.23); however, respondents were more likely to report sleep disturbances to clinicians (33.38% vs 23.67%; OR [95% CI], 1.62 [1.10-2.38]; P = 0.04). In multivariate regression models controlling for sociodemographic and lifestyle factors, adults with AD had higher odds of sleep disturbances, including shorter sleep duration (adjusted OR [95% CI], 1.61 [1.16-2.25]), trouble falling asleep (adjusted OR [95% CI], 1.57 [1.10-2.24]), and early morning awakenings (adjusted OR [95% CI], 1.86 [1.24-22.78]). Those with AD also had significantly higher odds of feeling unrested and feeling too tired to perform IADLs.	United States adults with AD have significantly impaired sleep and fatigue affecting IADLs, and sleep disturbances may be underdiagnosed in this population.	
26980820	Cardiovascular disease (CVD) is the leading cause of death in the United States. Although the role of habitual lifestyle factors such as physical activity and dietary patterns in increasing CVD risk has long been appreciated, less is known about how acute daily activities may cumulatively contribute to long-term disease risk. Here, the term acute refers to metabolic responses occurring in a short period of time after eating, and the goal of this article is to review recently identified stressors that can occur after meals and during the sleep-wake cycle to affect macronutrient metabolism. It is hypothesized that these events, when repeated on a regular basis, contribute to the observed long-term behavioral risks identified in population studies. In this regard, developments in research methods have supported key advancements in 3 fields of macronutrient metabolism. The first of these research areas is the focus on the immediate postmeal metabolism, spanning from early intestinal adsorptive events to the impact of incretin hormones on these events. The second topic is a focus on the importance of meal components on postprandial vasculature function. Finally, some of the most exciting advances are being made in understanding dysregulation in metabolism early in the day, due to insufficient sleep, that may affect subsequent processing of nutrients throughout the day. Key future research questions are highlighted which will lead to a better understanding of the relations between nocturnal, basal (fasting), and early postmeal events, and aid in the development of optimal sleep and targeted dietary patterns to reduce cardiometabolic risk. 
26980095	Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.
26980087	Evidence suggests that patients with bipolar disorder (BD) experience biological rhythm disturbances; however, no studies have examined the impact of this disruption on quality of life (QOL). The aim of this study is to investigate the influence of biological rhythm, depressive symptoms, sleep quality, and sleep medication use on QOL in BD.Eighty BD subjects (44 depressed and 36 euthymic) completed questionnaires assessing QOL (WHOQOL-BREF), biological rhythm disruption (BRIAN), depressive symptoms (MADRS), and sleep quality (PSQI). The impact of biological rhythm disturbance, depressive symptoms severity, sleep quality, and sleep medication use on QOL was determined with multiple regression analyses.	BRIAN (β = -0.31, t = -2.73, p < 0.01), MADRS (β = -0.30, t = -2.93, p < 0.01), and sleep medication use (β = -0.45, t = -2.55, p < 0.05) were significant predictors of QOL in this model (F 4, 75 = 20.28; p < 0.0001). The relationship of these factors with subdomains of QOL showed that poorer social QOL was associated with greater biological rhythm disturbance (β = -0.43, t = -3.66, p < 0.01) and sleep medication use (β = -0.49, t = -2.35, p < 0.01), providing support for the social rhythm theory of BD. Physical QOL was associated with depression (β = -0.30, t = -2.93, p < 0.01) and biological rhythm disruption (β = -0.31, t = -2.73, p < 0.01). Main limitations include the cross-sectional assessment and the lack of objective measures of biological rhythms in relation to QOL.	Disruption in biological rhythm is associated with poor QOL in BD, independent of sleep disturbance, sleep medication use, and severity of depression. Treatment strategies targeting regulation of biological rhythms, such as sleep/wake cycles, eating patterns, activities, and social rhythms, are likely to improve QOL in this population.	
26978182	Disturbances in sleep and circadian rest-activity rhythms are key features of depression. Actigraphy, a non-invasive method for monitoring motor activity, can be used to objectively assess circadian rest-activity rhythms and sleep patterns. While recent studies have measured sleep and daytime activity of depressed patients using wrist-worn actigraphy, the actigraphic 24-h rest-activity rhythm in depression has not been well documented. We aimed to examine actigraphically measured sleep and circadian rest-activity rhythms in depressed outpatients. Twenty patients with DSM-IV major depressive episode and 20 age- and sex-matched healthy controls participated in this study. Participants completed 7 consecutive days of all-day actigraphic activity monitoring while engaging in usual activities. For sleep parameters, total sleep time, wake after sleep onset, and sleep fragmentation index were determined. Circadian rhythms were estimated by fitting individual actigraphy data to a cosine curve of a 24-h activity rhythm using the cosinor method, which generated three circadian activity rhythm parameters, i.e., MESOR (rhythm-adjusted mean), amplitude, and acrophase. Subjective sleep was also assessed using a sleep diary and the Pittsburgh Sleep Quality Index. Patients showed significantly lower MESOR and more dampened amplitude along with significant sleep disturbances. Logistic regression analysis revealed that lower MESOR and more fragmented sleep emerged as the significant predictors of depression. Correlations between subjectively and actigraphically measured parameters demonstrated the validity of actigraphic measurements. These results indicate marked disturbances in sleep and circadian rest-activity rhythms of depression. By simultaneously measuring sleep and rest-activity rhythm parameters, actigraphy might serve as an objective diagnostic aid for depression. 
26978077	Bench testing is a useful method to characterize the response of different automatic positive airway pressure (APAP) devices under well-controlled conditions. However, previous models did not consider the diversity of obstructive sleep apnea (OSA) patients' characteristics and phenotypes. The objective of this proof-of-concept study was to design a new bench test for realistically simulating an OSA patient's night, and to implement a one-night example of a typical female phenotype for comparing responses to several currently-available APAP devices. We developed a novel approach aimed at replicating a typical night of sleep which includes different disturbed breathing events, disease severities, sleep/wake phases, body postures and respiratory artefacts. The simulated female OSA patient example that we implemented included periods of wake, light sleep and deep sleep with positional changes and was connected to ten different APAP devices. Flow and pressure readings were recorded; each device was tested twice. The new approach for simulating female OSA patients effectively combined a wide variety of disturbed breathing patterns to mimic the response of a predefined patient type. There were marked differences in response between devices; only three were able to overcome flow limitation to normalize breathing, and only five devices were associated with a residual apnea-hypopnea index of <5/h. In conclusion, bench tests can be designed to simulate specific patient characteristics, and typical stages of sleep, body position, and wake. Each APAP device behaved differently when exposed to this controlled model of a female OSA patient, and should lead to further understanding of OSA treatment. 
26977123	Fatigue and other treatment-related symptoms (e.g., sleep disturbance) are critical targets for improving quality of life in patients undergoing chemotherapy. Yoga may reduce the burden of such symptoms. This study investigated the feasibility of conducting a randomized controlled study of a brief yoga intervention during chemotherapy for colorectal cancer.We randomized adults with colorectal cancer to a brief Yoga Skills Training (YST) or an attention control (AC; empathic attention and recorded education).	The interventions and assessments were implemented individually in the clinic while patients were in the chair receiving chemotherapy.	Both interventions consisted of three sessions and recommended home practice.	The primary outcome was feasibility (accrual, retention, adherence, data collection). Self-reported outcomes (i.e., fatigue, sleep disturbance, quality of life) and inflammatory biomarkers were also described to inform future studies.	Of 52 patients initially identified, 28 were approached, and 15 enrolled (age Mean = 57.5 years; 80% White; 60% Male). Reasons for declining participation were: not interested (n = 6), did not perceive a need (n = 2), and other (n = 5). Two participants were lost to follow-up in each group due to treatment changes. Thus, 75% of participants were retained in the YST and 71% in the AC arm. Participants retained in the study adhered to 97% of the in-person intervention sessions and completed all questionnaires.	This study demonstrated the feasibility of conducting a larger randomized controlled trial to assess YST among patients receiving chemotherapy for colorectal cancer. Data collected and challenges encountered will inform future research.	
26976740	Williams-Beuren syndrome (WBS), a neurodevelopmental disorder caused by a microdeletion on chromosomic region 7q11.23, presents with peculiar behavioral and neurocognitive phenotypes that are marked by apparently preserved social and communicative abilities, which contrasts with low overall cognitive and particularly visuospatial performance. In addition, parents often report complaints of sleep disorders and behavioral problems of unknown cause. Sleep is a biological phenomenon that is modulated by the plasma concentration of melatonin and with influence on behavioral aspects and memory. Thus, this study sought to investigate the behavior, memory and the presence of sleep disorders in WBS and to correlate these factors with each other and with the plasma melatonin content. We used the Child Behavior Checklist for ages 6-18 (CBCL), the digit subtest of the Wechsler scale for auditory memory, the visual sequential memory subtest of the Illinois Test of Psycholinguistic Abilities (ITPA) and the Sleep Disturbance Scale for Children (SDSC). Determination of urinary aMT6s, an indirect measure of plasma melatonin content, was held for 72h by ELISA, and the analysis of the circadian rhythm of this content was performed by the Cosinor method. The results of the CBCL showed that 87% of the WBS group presented with a clinical score on the overall competence and total behavioral problems. Furthermore, the behavioral problems that were most frequently reported by parents were anxiety and problems of thought. All individuals with WBS presented with impairments in auditory memory and 47% with impairments in visual sequential memory; 65% of the WBS group presented with an indicative of at least one sleep disorder, where respiratory, initiation and maintenance of sleep (DIMS) and hyperhidrosis were the most frequent disorders. The night time aMT6s levels were lower in individuals with WBS when compared with controls; 53% of the WBS group did not present with circadian rhythm variations in aMT6s levels. In addition, there was a negative correlation between the scores of auditory memory and the total score of sleep disorders and between the DIMS and nocturnal aMT6s content. In conclusion, in the present study, individuals with WBS showed a high frequency of behavioral and memory problems, sleep disturbances and no rhythm variation in aMT6s levels. The low melatonin content may be related with sleep disorders in this population, which, in turn, can have an adverse effect on specific cognitive skills such as memory. 
26975614	Nightmare frequency in adult ADHD patients has not yet been studied systematically. In a sample of 65 patients, it could be shown that nightmare frequency was elevated in ADHD patients compared to a sample representative for Germany. Frequent nightmares (once a week or more often) were reported by 4.62 % of the patients and 1.77 % of the controls. This increase was neither explained by the increased dream recall in general nor by the presence of a comorbid mental disorder. Questions about nightmares should be included in the diagnostic procedures for ADHD patients, and it should be tested whether well-established nightmare treatment strategies like imagery rehearsal treatment might be beneficial to those patients with nightmares.

26973592	The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S), which rises linearly during the day, and a circadian process C, which determines the timing of sleep in a ~24-h rhythm in accordance to the external light-dark (LD) cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the suprachiasmatic nucleus ("master clock") of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation. While the phase length (tau) of the cycle is relatively stable and genetically determined, the phase of the clock is reset by external stimuli ("zeitgebers"), the most important being the LD cycle. Misalignments of the internal rhythm with the LD cycle can lead to various somatic complaints and to the development of circadian rhythm sleep disorders (CRSD). Non-24-hour sleep-wake disorders (N24HSWD) is a CRSD affecting up to 50% of totally blind patients and characterized by the inability to maintain a stable entrainment of the typically long circadian rhythm (tau > 24.5 h) to the LD cycle. The disease is rare in sighted individuals and the pathophysiology less well understood. Here, we present the case of a 40-year-old sighted male, who developed a misalignment of the internal clock with the external LD cycle following the treatment for Hodgkin's lymphoma (ABVD regimen, four cycles and AVD regimen, four cycles). A thorough clinical assessment, including actigraphy, melatonin profiles and polysomnography led to the diagnosis of non-24-hour sleep-wake disorders (N24HSWD) with a free-running rhythm of tau = 25.27 h. A therapeutic intervention with bright light therapy (30 min, 10,000 lux) in the morning and melatonin administration (0.5-0.75 mg) in the evening failed to entrain the free-running rhythm, although a longer treatment duration and more intense therapy might have been successful. The sudden onset and close timely connection led us to hypothesize that the chemotherapy might have caused a mutation of the molecular clock components leading to the observed elongation of the circadian period. 
26973111	The orexin system has been investigated in patients affected by mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by measuring orexin-A concentrations in the cerebrospinal fluid (CSF), and correlated to subjective and objective sleep parameters, quantified by questionnaires and polysomnography, respectively. Twenty drug-naïve patients with MCI due to AD were studied and compared with a population of 26 age and/or sex matched controls, divided into subgroups on the basis of the Pittsburgh Sleep Quality Index (PSQI) score. Increased CSF-orexin levels were detected in patients with MCI due to AD in comparison with controls (p < 0.05). In particular, CSF-orexin concentrations were higher in MCI patients suffering from sleep complaints (PSQI ≥5, n = 10) compared with MCI patients with a regular sleep-wake cycle (PSQI <5, n = 10, p < 0.001) and compared with both control groups (with sleep complaints, PSQI ≥5, n = 11, p < 0.001; without sleep complaints, PSQI <5, n = 15, p < 0.001). Moreover, REM sleep was reduced in MCI patients compared with controls (p < 0.01), and had a negative correlation coupled with a reciprocal influence at the multiple regression analysis with CSF-orexin levels (R = -0.65; β = -8.90). REM sleep disruption and sleep fragmentation are related to higher CSF-orexin levels in patients with MCI due to AD, thus suggesting that the orexin system may be involved even in the earliest stages of AD, resulting in prolonged sleep latency, reduced sleep efficiency, and REM sleep impairment.
26972685	Light is the major stimulus for the synchronization of circadian clocks with day-night cycles. The light-driven entrainment of the clock that controls rest-activity rhythms in Drosophila relies on different photoreceptive molecules. Cryptochrome (CRY) is expressed in most brain clock neurons, whereas six different rhodopsins (RH) are present in the light-sensing organs. The compound eye includes outer photoreceptors that express RH1 and inner photoreceptors that each express one of the four rhodopsins RH3-RH6. RH6 is also expressed in the extraretinal Hofbauer-Buchner eyelet, whereas RH2 is only found in the ocelli. In low light, the synchronization of behavioral rhythms relies on either CRY or the canonical rhodopsin phototransduction pathway, which requires the phospholipase C-β encoded by norpA (no receptor potential A). We used norpA(P24) cry(02) double mutants that are circadianly blind in low light and restored NORPA function in each of the six types of photoreceptors, defined as expressing a particular rhodopsin. We first show that the NORPA pathway is less efficient than CRY for synchronizing rest-activity rhythms with delayed light-dark cycles but is important for proper phasing, whereas the two light-sensing pathways can mediate efficient adjustments to phase advances. Four of the six rhodopsin-expressing photoreceptors can mediate circadian entrainment, and all are more efficient for advancing than for delaying the behavioral clock. In contrast, neither RH5-expressing retinal photoreceptors nor RH2-expressing ocellar photoreceptors are sufficient to mediate synchronization through the NORPA pathway. Our results thus reveal different contributions of rhodopsin-expressing photoreceptors and suggest the existence of several circuits for rhodopsin-dependent circadian entrainment. J. Comp. Neurol. 524:2828-2844, 2016. © 2016 Wiley Periodicals, Inc. 
26972036	This article provides an overview of common pediatric sleep disorders encountered in the neurology clinic, including restless legs syndrome, narcolepsy, parasomnias, sleep-related epilepsy, and sleep and headaches. An overview of each is provided, with an emphasis on accurate diagnosis and treatment. It is important in comprehensive neurologic care to also obtain a sleep history, because treating the underlying sleep condition may improve the neurologic disorder. 
26972034	Sleep and circadian rhythms significantly impact almost all aspects of human behavior and are therefore relevant to occupational sleep medicine, which is focused predominantly around workplace productivity, safety, and health. In this article, 5 main factors that influence occupational functioning are reviewed: (1) sleep deprivation, (2) disordered sleep, (3) circadian rhythms, (4) common medical illnesses that affect sleep and sleepiness, and (5) medications that affect sleep and sleepiness. Consequences of disturbed sleep and sleepiness are also reviewed, including cognitive, emotional, and psychomotor functioning and drowsy driving. 
26972033	Sleep disorders in neuromuscular disorders are generally caused by respiratory dysfunction associated with these diseases. Hypoventilation in neuromuscular diseases results from both respiratory muscle weakness and reduced chemoreceptor sensitivity, which is required for ventilatory drive. This condition results in repeated arousals, sleep fragmentation, and nocturnal hypoxemia, manifesting most commonly as excessive daytime somnolence. Polysomnography can identify sleep disordered breathing in patients with neuromuscular disorders and treatment with noninvasive ventilation may improve quality of life. 
26972032	Evidence increasingly suggests sleep disorders are associated with higher risk of cardiovascular events, including stroke. Strong data correlate untreated sleep apnea with poorer stroke outcomes and more recent evidence implicates sleep disruption as a possible etiology for increased cerebrovascular events. Also, sleep duration may affect incidence of cardiovascular events. In addition, sleep-disordered breathing, insomnia, restless legs syndrome, and parasomnias can occur as a result of cerebrovascular events. Treatment of sleep disorders improve sleep-related symptoms and may also improve stroke recovery and risk of future events. 
26972031	Sleep plays an intricate role in the disease process of epilepsy. Despite the complexity of this relationship, the prognosis is a favorable one for patients presenting with sleep disorders and epilepsy. Clinicians need to be vigilant about asking about and addressing sleep complaints in patients with epilepsy. Ultimately, improving sleep and optimizing seizure control can have significant positive effects on the quality of life of these patients. 
26972030	Post-traumatic sleep-wake disturbances are frequent and often chronic complications after traumatic brain injury. The most prevalent sleep-wake disturbances are insomnia, excessive daytime sleepiness, and pleiosomnia, (i.e., increased sleep need). These disturbances are probably of multifactorial origin, but direct traumatic damage to key brain structures in sleep-wake regulation is likely to contribute. Diagnosis and treatment consist of standard approaches, but because of misperception of sleep-wake behavior in trauma patients, subjective testing alone may not always suffice.
26972029	Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. 
26971242	Several small studies found night-time awakenings due to COPD symptoms were associated with decreased health status. In this study, night-time awakenings in patients with COPD were examined and effects of tiotropium therapy evaluated.This study was a post hoc, exploratory, pooled analysis of twin, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. Patients with stable moderate-to-severe COPD were randomized to tiotropium HandiHaler® (n = 550) or placebo (n = 371) and followed for 13 weeks. During a 2-week, pre-treatment baseline period and for 13 weeks on treatment, self-reported night-time awakenings due to COPD symptoms, rescue medication (albuterol) use, and morning and evening peak expiratory flow rate (PEFR) were recorded daily. Nightly, COPD-related awakenings were scored: 0 = no awakenings; 1 = 1 awakening; 2 = 2-3 awakenings; or 3 = awake most of the night. Health-related quality-of-life (HRQoL) and energy-fatigue questionnaires were completed at baseline and during treatment.	Patients were aged 65.2 ± 8.7 years (mean ± SD), with a mean pre-bronchodilator FEV1 of 36.1 ± 13.5 % predicted normal at baseline. Data for night-time awakenings and albuterol use were available for 543 (99 %) patients on tiotropium and 352 (95 %) on placebo. At baseline, 280 (51.5 %) patients on tiotropium and 179 (50.1 %) on placebo reported ≥1 COPD-related night-time awakening per week. Over the 13-weeks' treatment, tiotropium was associated with fewer night-time awakenings, with mean ± SE overall awakening scores per week of 0.356 ± 0.006 compared with 0.421 ± 0.007 for placebo (p < 0.001); means were significantly lower for tiotropium versus placebo in patients with baseline awakenings (p < 0.001), but not for those without baseline awakenings. COPD-related night-time awakenings were associated with increased nocturnal rescue medication use and lower HRQoL ratings in both treatment arms. Following start of treatment, tiotropium decreased patients' use of rescue medication compared with placebo, and morning and evening adjusted means for PEFR were higher for tiotropium compared with placebo.	Tiotropium is associated with decreased COPD-related night-time awakenings. Night-time awakenings are associated with increased nocturnal rescue medication use and may be a surrogate marker of symptom control in patients with COPD.	
26970995	Restless Legs Syndrome (RLS) is a common disorder characterized by an irresistible urge to move the legs particularly during rest in the evenings often leading to insomnia and daytime impairment. No prior studies estimate the prevalence of RLS in a diverse sample of adults with epilepsy using standard diagnostic criteria.A total of 225 patients with epilepsy (61.8% female; mean age 33.3 ± 12.3 years) seen in the epilepsy clinic of Çukurova University Neurology Department were included. Restless Legs Syndrome diagnosis was based on structured interviews using internationally accepted criteria. Demographic and epilepsy-related variables were obtained through medical record review.	The prevalence of RLS was 5.8% (n=13). Mean score on the International RLS Study Group rating scale for these subjects was 9.3 ± 3.6 (6-18). Ten (76.9%) patients with RLS scored in the mild range and the remainder in the moderate range of severity. Patients with RLS were not significantly different from others in terms of demographics, epilepsy classification or duration, treatment regimen (polytherapy vs. monotherapy), patient-reported sleep assessment, or relevant laboratory data.	The prevalence of RLS in adults with epilepsy was similar to that observed in the adult general Turkish population (3.18-5.2%), although we excluded subjects with conditions associated with RLS, rendering ours a conservative estimate. While preliminary, these findings support the need for future studies exploring RLS in epilepsy given the potential impact of untreated sleep disorders and sleep deprivation on seizures and quality of life in people with epilepsy.	
26970937	There is a bidirectional association between sleep disorders and addiction. Sleep problems negatively impact the quality of life of subjects with addictions (psychological state, pain perception, drug use). Sleep disorders are associated with a higher risk of relapse among sujects with addiction. The association between sleep disorders and relapse may be related to poor quality of life or to a higher level of craving. Maintaining abstinence and reducing craving episodes among subjects with addiction is the first-line treatment to reduce sleep disorders. Specific interventions focused on sleep disorders are needed when sleep disorders persist during abstinence and may improve global addiction outcome.
26969345	Sleep and its disorders are known to affect the functions of essential organs and systems in the body. However, very little is known about how the blood-brain barrier (BBB) is regulated. A few years ago, we launched a project to determine the impact of sleep fragmentation and chronic sleep restriction on BBB functions, including permeability to fluorescent tracers, tight junction protein expression and distribution, glucose and other solute transporter activities, and mediation of cellular mechanisms. Recent publications and relevant literature allow us to summarize here the sleep-BBB interactions in five sections: (1) the structural basis enabling the BBB to serve as a huge regulatory interface; (2) BBB transport and permeation of substances participating in sleep-wake regulation; (3) the circadian rhythm of BBB function; (4) the effect of experimental sleep disruption maneuvers on BBB activities, including regional heterogeneity, possible threshold effect, and reversibility; and (5) implications of sleep disruption-induced BBB dysfunction in neurodegeneration and CNS autoimmune diseases. After reading the review, the general audience should be convinced that the BBB is an important mediating interface for sleep-wake regulation and a crucial relay station of mind-body crosstalk. The pharmaceutical industry should take into consideration that sleep disruption alters the pharmacokinetics of BBB permeation and CNS drug delivery, being attentive to the chrono timing and activation of co-transporters in subjects with sleep disorders.
26968471	Prior work has shown that symptoms leading to restrictions in daily activities are common at the end of life. Hospice is a Medicare benefit designed to alleviate distressing symptoms in the last 6 months of life. The effect of hospice on the burden of such symptoms is uncertain.From an ongoing cohort study of 754 community-dwelling older persons, aged ≥70 years, we evaluated 241 participants who were admitted to hospice from March 1998 to December 2013. A set of 15 physical and psychological symptoms leading to restricted activity (ie, cut down on usual activities or spend at least half the day in bed) were ascertained during monthly telephone interviews in the year before and 3 months after hospice admission.	The prevalence and mean number of restricting symptoms increased progressively until about 2 months before hospice admission, before increasing precipitously to a peak around the time of hospice admission. After the start of hospice, both the prevalence and the mean number of restricting symptoms dropped markedly. For several symptoms deemed most amenable to hospice treatment, including depression and anxiety, the prevalence dropped to levels comparable to or lower than those observed 12 months before the start of hospice. The trends observed in symptom prevalence and mean number of symptoms before and after hospice did not differ appreciably according to hospice admission diagnosis or sex. The median duration of hospice (before death) was only 15 days.	The burden of restricting symptoms increases progressively several months before the start of hospice, peaks around the time of hospice admission, and decreases substantially after the start of hospice. These results, coupled with the short duration of hospice, suggest that earlier referral to hospice may help to alleviate the burden of distressing symptoms at the end of life.	
26967200	Several studies have identified an association between Pandemrix(TM), an AS03 adjuvanted pandemic influenza A(H1N1) vaccine, and narcolepsy, a rare and under-diagnosed sleep disorder with a median onset-to-diagnosis interval of ten years. This paper reviews potential sources of bias in published studies and aims to provide, through simulation, methodological recommendations for assessment of vaccine safety signals. Our simulation study showed that in the absence of an association between the vaccine and the outcome, presence of detection bias and differential exposure misclassification could account for elevated risk estimates. These may play a major role, particularly in alert situations when observation times are limited and the disease has a long latency period. Estimates from the case-control design were less inflated than those from the cohort design when these biases were present. Overall, these simulations provide useful insights for the design and interpretation of future studies. 
26964685	In homeotherms, the hypothalamus controls thermoregulatory and adaptive mechanisms in energy balance, sleep-wake and locomotor activity to maintain optimal body temperature. Orexin neurons may be involved in these functions as they promote thermogenesis, food intake and behavioral arousal, and are sensitive to temperature and metabolic status. How thermal and energy balance signals are integrated in these neurons is unknown. Thus, we investigated the cellular mechanisms of thermosensing in orexin neurons and their response to a change in energy status using whole-cell patch clamp on rat brain slices. We found that warming induced an increase in miniature excitatory postsynaptic current (EPSC) frequency, which was blocked by the transient receptor potential vanilloid-1 (TRPV1) receptor antagonist AMG9810 and mimicked by its agonist capsaicin, suggesting that the synaptic effect is mediated by heat-sensitive TRPV1 channels. Furthermore, warming inhibits orexin neurons by activating ATP-sensitive potassium (KATP) channels, an effect regulated by uncoupling protein 2 (UCP2), as the UCP2 inhibitor genipin abolished this response. These properties are unique to orexin neurons in the lateral hypothalamus, as neighboring melanin-concentrating hormone neurons showed no response to warming within the physiological temperature range. Interestingly, in rats fed with western diet for 1 or 11weeks, orexin neurons had impaired synaptic and KATP response to warming. In summary, this study reveals several mechanisms underlying thermosensing in orexin neurons and their attenuation by western diet. Overeating induced by western diet may in part be due to impaired orexin thermosensing, as post-prandial thermogenesis may promote satiety and lethargy by inhibiting orexin neurons. 
26964485	Sleep disturbances are common in older adults. Little is known about the sleep of cognitively intact older adults and its relationship to subsequent cognitive impairment. The objective of this study was to examine the association between objective sleep-wake measures and risk of incident cognitive impairment.In this prospective cohort study encompassing four U.S. sites, 1,245 women (mean age: 82.6 years) without dementia participated in the Study of Osteoporotic Fractures and completed actigraphy at the baseline visit and comprehensive cognitive assessment at follow-up. The association between sleep-wake patterns measured by actigraphy and risk of incident mild cognitive impairment (MCI) and dementia was examined.	A total of 473 women (38%) developed cognitive impairment during an average (SD) follow-up of 4.9 (0.6) years; 290 (23.3%) developed MCI and 183 (14.7%) developed dementia. After controlling for multiple potential confounders, women in the lowest quartile of average sleep efficiency (<74%) had a 1.5-fold higher odds of developing MCI or dementia compared with women in the highest quartile of sleep efficiency (>86%) (odds ratio: Q1 versus Q4 1.53; 95% CI: 1.07, 2.19; Wald χ(2) [1, N = 1,223] = 5.34 for p for trend = 0.03). Longer average sleep latency, but not total sleep time, was also associated with higher odds of developing cognitive impairment. Greater variability in both sleep efficiency and total sleep time was associated with an increased odds of developing MCI or dementia.	Lower average sleep efficiency, longer average sleep latency, and greater variability in sleep efficiency and total sleep time are associated with increased odds of developing cognitive impairment. Further research is needed to explore the mechanisms underlying these associations.	
26963362	Coexistence of multiple chronic conditions (i.e., multimorbidity) is the most common chronic health problem in adults. However, clinical practice guidelines have primarily focused on patients with a single disease, resulting in uncertainty about the care of patients with multimorbidity. The American Thoracic Society convened a workshop with the goal of establishing a strategy to address multimorbidity within clinical practice guidelines. In this Workshop Report, we describe a framework that addresses multimorbidity in each of the key steps of guideline development: topic selection, panel composition, identifying clinical questions, searching for and synthesizing evidence, rating the quality of that evidence, summarizing benefits and harms, formulating recommendations, and rating the strength of the recommendations. For the consideration of multimorbidity in guidelines to be successful and sustainable, the process must be both feasible and pragmatic. It is likely that this will be achieved best by the step-wise addition and refinement of the various components of the framework. 
26960782	The association of wind turbine noise (WTN) with sleep and physical/mental health has not been fully investigated. To investigate the relationship of WTN with the prevalence of self-reported symptoms of sleep and health problems, a socioacoustic survey of 1079 adult residents was conducted throughout Japan (2010-2012): 747 in 34 areas surrounding wind turbine plants and 332 in 16 control areas. During face-to-face interviews, the respondents were not informed of the purpose of the survey. Questions on symptoms such as sleeplessness and physical/mental complaints were asked without specifying reasons. Insomnia was defined as having one or any combination of the following that occurs three or more times a week and bothers a respondent: Difficulty initiating sleep, difficulty maintaining sleep, premature morning awakening, and feeling of light overnight sleep. Poor health was defined as having high scores for health complaints, as determined using the Total Health Index, exceeding the criteria proposed by the authors of the index. The noise descriptor for WTN was LAeq,n outdoor, estimated from the results of actual measurement at some locations in each site. Multiple logistic analysis was applied to the LAeq,n and insomnia or poor health. The odds ratio (OR) of insomnia was significantly higher when the noise exposure level exceeded 40 dB, whereas the self-reported sensitivity to noise and visual annoyance with wind turbines were also independently associated with insomnia. OR of poor health was not significant for noise exposure, but significant for noise sensitivity and visual annoyance. The above two moderators appear to indicate the features of respondents who are sensitive to stimuli or changes in their homeostasis. 
26959668	Evaluate sleep quality, its correlates, and the effect of telephone-based problem-solving treatment (PST) in active duty postdeployment service members with mild traumatic brain injury (mTBI) SETTING:: Randomized clinical trial.Active duty service members with combat-related mTBI.	Education-only (EO) and PST groups (N = 178 each) received printed study materials and 12 educational brochures. The PST group additionally received up to 12 PST telephone calls addressing participant-selected issues. Outcomes were evaluated postintervention (6 months) and at 12 months.	Pittsburgh Sleep Quality Index.	Sleep quality was manifestly poor in both groups at baseline (Pittsburgh Sleep Quality Index = 12.5 ± 4). Overall sleep quality was significantly different between the PST and EO groups at 6 months (P = .003) but not at 12 months. Longitudinally, PST significantly improved sleep quality at 6 months (P = .001) but not over the follow-up. Low sleep quality was associated with concussion symptoms, pain, depression, and posttraumatic stress disorder at all time points (P < .0001).	Sleep disorders, common in postdeployment service members with mTBI, are strongly associated with the presence of pain, posttraumatic stress disorder, and depression. Telephone-based PST may be an effective therapeutic approach for reducing sleep disorders in this population. Research should focus on maintenance of treatment gains.	
26959667	To examine the discrepancy between sleep diary and actigraphic measures of sleep in Veterans with moderate-severe post-acute traumatic brain injury (TBI) and to explore whether these discrepancies vary according to participant characteristics.VA Medical Center in the Rocky Mountain United States.	Nineteen males with moderate-severe post-acute TBI and insomnia symptoms as measured by the Insomnia Severity Index.	Descriptive, cross-sectional.	Sleep diary, wrist actigraphy, Ohio State University TBI-Identification Method, Insomnia Severity Index, and Hospital Anxiety and Depression Scale.	There was poor agreement between actigraphic and sleep diary measurements of (1) total sleep time, (2) wake after sleep onset, and (3) sleep onset latency. On average, actigraphy measured greater duration of all 3 sleep parameters. Discrepancies were not found to be associated with specific TBI characteristics or mood-related symptoms.	When measuring sleep-related outcomes among Veterans with moderate-severe post-acute TBI, notable mismatches were found between actigraphic and self-reported sleep diary data. Knowledge regarding measure-related limitations is important for both clinical and research practices among those with moderate-severe post-acute TBI.	
26959666	Examine sleep-wake disturbance (SWD) characteristics, factors, consequences, and management strategies from the perspective of veterans with chronic stage, moderate/severe traumatic brain injury (TBI).VA Medical Center, Rocky Mountain.	Nineteen male veterans with post-acute TBI and SWD in the VA Health Administration.	Qualitative descriptive.	Semistructured interviews, Ohio State University TBI-Identification Method, Insomnia Severity Index.	Two main dimensions emerged: "Messed up sleep" and Surviving and Managing SWD. Sleep-wake disturbance has long-term multidimensional features, etiology, consequences, and practice implications. Although SWD may not be consistently discussed with providers, the problem appears to be pervasive in many aspects of the lives of the informants. Difficulty falling asleep, frequent awakenings, and poor sleep quality were common symptoms that were described as intrusive, isolating, and difficult to self-manage. Veterans discussed a host of physical symptoms, mental health issues, environmental, and behavioral factors that contributed to SWD. Medications, sleep apnea treatment, and self-imposed isolation were frequent management strategies. Veterans expressed a willingness to try new approaches and work with providers.	Sleep-wake disturbance among veterans with chronic stage TBI is a multidimensional phenomenon with interplay between comorbidities, contributing factors, effects on functioning, and sleep management strategies. Implications for practice include early and routine evaluation, monitoring, and treatment of SWD. Research is needed to test interventions that address SWD and common TBI comorbidities.	
26959665	To examine concordance of accelerometer-based actigraphy (ACG) with polysomnography (PSG) in the determination of sleep states in inpatients with traumatic brain injury (TBI), and examine the impact of injury severity and comorbid conditions (spasticity, apnea) on concordance.This was a convenience sample of 50 participants with primarily severe TBI.	This was a retrospective chart review of concurrent administration of PSG with ACG in nonconsecutive rehabilitation admissions with TBI.	Total sleep time and sleep efficiency were measured by PSG and ACG.	Moderate to strong correlations between ACG and PSG were observed for total sleep time (r = 0.78, P < .01) and sleep efficiency (r = 0.66, P < .01). PSG and ACG estimates of total sleep time (316 minutes vs 325 minutes, respectively) and sleep efficiency (78% vs 77%, respectively) were statistically indistinguishable.	Actigraphy is a valid proxy for monitoring of sleep in this population across injury severity and common comorbidity groups. However, further research with larger sample sizes to examine concordance in patients with TBI with disorder of consciousness and spasticity is recommended.	

26959472	Nurses are accustomed to helping others with their sleep problems and dealing with issues such as pain that may delay or interrupt sleep. However, they may be less familiar with what constitutes a healthy night's sleep. This article examines what is known about the process and purpose of sleep, and examines the ways in which factors that promote wakefulness and sleep combine to help establish a normal circadian rhythm. Theories relating to the function of sleep are discussed and research is considered that suggests that sleep deficit may lead to metabolic risks, including heart disease, obesity, type 2 diabetes mellitus and several types of cancer. 
26959327	Aims Since 1956, more than 100,000 Swedish soldiers have served abroad on various international missions. The aim of this paper was to determine whether there was a connection between military service abroad and sleep disorders among Swedish soldiers. Methods The prevalence of sleep disturbances among 1,080 veterans from Kosovo and Afghanistan was compared with almost 27,000 Swedes from a general population sample, using propensity score matching and logistic regression. The sleep disturbances studied were habitual snoring, difficulty inducing sleep (DIS), difficulty maintaining sleep (DMS), early morning awakenings (EMA), and excessive daytime sleepiness (EDS). Insomnia was defined as having at least one of DIS, DMS, or EMA. The covariates used in the matching and adjustments were age, gender, smoking habits, BMI, education, ever having had asthma, moist snuff, and exercise habits. Results The veterans had a significantly lower prevalence of insomnia (26.2% versus 30.4%) and EDS (22.7% versus 29.4%) compared with a matched group from the reference population, using propensity score matching. Analyses with logistic regression showed that belonging to the military population was related to a lower risk of having DMS (adjusted OR (95% CI) 0.77 (0.64-0.91)), insomnia (OR 0.82 (0.71-0.95)), and EDS (OR 0.74 (0.63-0.86)), whereas no significant difference was found for snoring, DIS, and EMA. Conclusion Swedish veterans have fewer problems with insomnia and daytime sleepiness than the general Swedish population. The explanation of our findings may be the selection processes involved in becoming a soldier and when sampling personnel for military assignments abroad. 
26956161	Primary insomnia (PI) is commonly defined as a state of having disturbed daytime activities due to poor night-time sleep quality. Studies have demonstrated that it is a disorder of 24 h hyperarousal, expressed in terms of physiological, cognitive and cortical activation. Acupuncture is considered to be beneficial to restore the normal sleep-wake cycle. The aim of the trial is to assess the therapeutic effects of acupuncture on sleep quality and hyperarousal state in patients with PI.This study is a randomised, patient-assessor-blinded, sham controlled trial. -88 eligible patients with PI will be randomised in a ratio of 1:1 to the intervention group (real acupuncture) and control group (sham acupuncture, superficial insertion at irrelevant acupuncture points). Acupuncture intervention will be given to all participants three times a week for 4 weeks, followed up for 8 weeks.The primary outcome measures are the Pittsburgh Sleep Quality Index (PSQI) and Hyperarousal scale (HAS). The secondary outcomes are Fatigue scale-14 (FS-14), polysomnography (PSG), heart rate variability (HRV) and Morning Salivary Cortisol Level (MSCL). Outcomes will be evaluated at baseline, post-treatment period and 8 weeks follow-up. All main analyses will be carried out on the basis of the intention-to-treat principle.	This protocol has been approved by the Medical Ethical Committee of Beijing Traditional Chinese Medicine Hospital (Beijing TCM Hospital) on 5 January 2015. The permission number is 2014BL-056-02. The study will present data concerning the clinical effects of treating primary insomnia with acupuncture. The results will help to demonstrate if acupuncture is an effective therapy for improving sleep quality in association with a decreased hyperarousal level as a possible underlying mechanism. The findings from this study will be shared with the healthcare professionals, general public and relevant organisations through publication of manuscripts and conference presentations.	ISRCTN16079489; Pre-results.	
26954979	Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. 
26954978	Sleep disturbance and depression are common, particularly in females, and sleep disturbance is a well-known risk factor for depression. Systemic inflammation has been suggested as a potential mechanism of this association. This study examined whether preexisting sleep disturbance acted as a vulnerability factor for depressed mood induced by an inflammatory challenge in healthy females vs males. In a randomized double-blind placebo-controlled design, volunteers aged 18-50 (N = 111; 67 females) were assigned to placebo or low-dose endotoxin. Before substance administration, sleep disturbance was assessed using the Pittsburgh Sleep Quality Index and dichotomized using median split (⩾ 3 vs < 3). Self-reported depressed mood (profile of mood states) and circulating proinflammatory cytokines (interleukin-6, tumor necrosis factor-α) were repeatedly assessed over 6 h. Among females, moderation of depressed mood by sleep disturbance was significant even after adjustment for covariates (X(2) = 12.73, df = 6, P < 0.05). There was a robust time-by-condition interaction in females with sleep disturbance (X(2) = 26.22, df = 6, P < 0.001), but not in females without sleep disturbance (X(2) = 8.65, df = 6, P = 0.19). Although cytokines increased equally in all females, the correlations between cytokines and depressed mood were significantly stronger in females with sleep disturbance. Among males, no moderating effect of sleep disturbance was observed. Inflammation-induced depressed mood was considerably more severe among females reporting mild sleep disturbance compared with those reporting no sleep disturbance, suggesting that even mild sleep disturbance may increase vulnerability for inflammation-induced depression in females. Furthermore, sleep disturbance appears to increase the vulnerability to depression by augmenting affective sensitivity to cytokines rather than by enhancing cytokine responses to inflammatory challenge in females.
26951421	There is currently no questionnaire-based pre-screening tool available to detect non-24-hour sleep-wake rhythm disorder (N24HSWD) among blind patients. Our goal was to develop such a tool, derived from gold standard, objective hormonal measures of circadian entrainment status, for the detection of N24HSWD among those with visual impairment.We evaluated the contribution of 40 variables in their ability to predict N24HSWD among 127 blind women, classified using urinary 6-sulfatoxymelatonin period, an objective marker of circadian entrainment status in this population. We subjected the 40 candidate predictors to 1,000 bootstrapped iterations of a logistic regression forward selection model to predict N24HSWD, with model inclusion set at the p < 0.05 level. We removed any predictors that were not selected at least 1% of the time in the 1,000 bootstrapped models and applied a second round of 1,000 bootstrapped logistic regression forward selection models to the remaining 23 candidate predictors. We included all questions that were selected at least 10% of the time in the final model. We subjected the selected predictors to a final logistic regression model to predict N24SWD over 1,000 bootstrapped models to calculate the concordance statistic and adjusted optimism of the final model. We used this information to generate a predictive model and determined the sensitivity and specificity of the model. Finally, we applied the model to a cohort of 1,262 blind women who completed the survey, but did not collect urine samples.	The final model consisted of eight questions. The concordance statistic, adjusted for bootstrapping, was 0.85. The positive predictive value was 88%, the negative predictive value was 79%. Applying this model to our larger dataset of women, we found that 61% of those without light perception, and 27% with some degree of light perception, would be referred for further screening for N24HSWD.	Our model has predictive utility sufficient to serve as a pre-screening questionnaire for N24HSWD among the blind.	
26951412	In March 2014, the American Academy of Sleep Medicine (AASM) Board of Directors requested the Scoring Manual Editorial Board develop rules, terminology, and technical specifications for scoring sleep/wake states in full-term infants from birth to 2 mo of age, cognizant of the 1971 Anders, Emde, and Parmelee Manual for Scoring Sleep in Newborns. On July 1, 2015, the AASM published rules for scoring sleep in infants, ages 0-2 mo. This evidence-based review summarizes the background information provided to the Scoring Manual Editorial Board to write these rules. The Anders Manual only provided criteria for coding physiological and behavioral state characteristics in polysomnograms (PSG) of infants, leaving specific sleep scoring criteria to the individual investigator. Other infant scoring criteria have been published, none widely accepted or used. The AASM Scoring Manual infant scoring criteria incorporate modern concepts, digital PSG recording techniques, practicalities, and compromises. Important tenets are: (1) sleep/wake should be scored in 30-sec epochs as either wakefulness (W), rapid eye movement, REM (R), nonrapid eye movement, NREM (N) and transitional (T) sleep; (2) an electroencephalographic (EEG) montage that permits adequate display of young infant EEG is: F3-M2, F4-M1, C3-M2, C4-M1, O1-M2, O2-M1; additionally, recording C3-Cz, Cz-C4 help detect early and asynchronous sleep spindles; (3) sleep onsets are more often R sleep until 2-3 mo postterm; (4) drowsiness is best characterized by visual observation (supplemented by later video review); (5) wide open eyes is the most crucial determinant of W; (6) regularity (or irregularity) of respiration is the single most useful PSG characteristic for scoring sleep stages at this age; (7) trace alternant (TA) is the only relatively distinctive EEG pattern, characteristic of N sleep, and usually disappears by 1 mo postterm replaced by high voltage slow (HVS); (8) sleep spindles first appear 44-48 w conceptional age (CA) and when present prompt scoring N; (9) score EEG activity in an epoch as "continuous" or "discontinuous" for inter-scorer reliability; (10) score R if four or more of the following conditions are present, including irregular respiration and rapid eye movement(s): (a) low chin EMG (for the majority of the epoch); (b) eyes closed with at least one rapid eye movement (concurrent with low chin tone); (c) irregular respiration; (d) mouthing, sucking, twitches, or brief head movements; and (e) EEG exhibits a continuous pattern without sleep spindles; (11) because rapid eye movements may not be seen on every page, epochs following an epoch of definite R in the absence of rapid eye movements may be scored if the EEG is continuous without TA or sleep spindles, chin muscle tone low for the majority of the epoch; and there is no intervening arousal; (12) Score N if four or more of the following conditions are present, including regular respiration, for the majority of the epoch: (a) eyes are closed with no eye movements; (b) chin EMG tone present; (c) regular respiration; and (d) EEG patterns of either TA, HVS, or sleep spindles are present; and (13) score T sleep if an epoch contains two or more discordant PSG state characteristics (either three NREM and two REM characteristics or two NREM and three REM characteristics). These criteria for ages 0-2 mo represent far more than baby steps. Like all the other AASM Manual rules and specifications none are fixed in stone, all open for debate, discussion and revision with the fundamental goal to provide standards for comparison of methods and results.A commentary on this article appears in this issue on page 291.	
26951410	While women report sleep interruption secondary to nighttime hot flashes, the sleep disrupting impact of nocturnal hot flashes (HF) is not well characterized. We utilized a model of induced HF to investigate the relationship of nighttime HF to sleep architecture and sleep-stage transitions.Twenty-eight healthy, premenopausal volunteers received the depot gonadotropin-releasing hormone agonist (GnRHa) leuprolide to rapidly induce menopause, manifesting with HF. Sleep disruption was measured on 2 polysomnograms conducted before and after 4-5 weeks on leuprolide, when HF had developed.	165 HF episodes were recorded objectively during 48 sleep studies (mean 3.4 HF/night). After standardizing to sleep-stage time distribution, the majority of HF were recorded during wake (51.0%) and stage N1 (18.8%). Sixty-six percent of HF occurred within 5 minutes of an awakening, with 80% occurring just before or during the awakening. Objective HF were not associated with sleep disruption as measured by increased transitions to wake or N1, but self-reported nocturnal HF correlated with an increase from pre- to post-leuprolide in the rate of transitions to wake (p = 0.01), and to N1 (p = 0.008).	By isolating the effect of HF on sleep in women without the confound of age-related sleep changes associated with natural menopause, this experimental model shows that HF arise most commonly during N1 and wake, typically preceding or occurring simultaneously with wake episodes. Perception of HF, but not objective HF, is linked to increased sleep-stage transitions, suggesting that sleep disruption increases awareness of and memory for nighttime HF events.	
26950542	Obesity is a common disorder with many complications. Although chronodisruption plays a role in obesity, few epidemiological studies have investigated the association between artificial light at night (ALAN) and obesity. Since sleep health is related to both obesity and ALAN, we investigated the association between outdoor ALAN and obesity after adjusting for sleep health. We also investigated the association between outdoor ALAN and sleep health. This cross-sectional survey included 8526 adults, 39-70 years of age, who participated in the Korean Genome and Epidemiology Study. Outdoor ALAN data were obtained from satellite images provided by the US Defense Meteorological Satellite Program. We obtained individual data regarding outdoor ALAN; body mass index; depression; and sleep health including sleep duration, mid-sleep time, and insomnia; and other demographic data including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking status and consumption of caffeine or alcohol before sleep. A logistic regression model was used to investigate the association between outdoor ALAN and obesity. The prevalence of obesity differed significantly according to sex (women 47% versus men 39%, p < 0.001) and outdoor ALAN (high 55% versus low 40%, p < 0.001). Univariate logistic regression analysis revealed a significant association between high outdoor ALAN and obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.14-1.35, p < 0.001). Furthermore, multivariate logistic regression analyses showed that high outdoor ALAN was significantly associated with obesity after adjusting for age and sex (OR 1.25, 95% CI 1.14-1.37, p < 0.001) and even after controlling for various other confounding factors including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking, consumption of caffeine or alcohol before sleep, delayed sleep pattern, short sleep duration and habitual snoring (OR 1.20, 95% CI 1.06-1.36, p = 0.003). The findings of our study provide epidemiological evidence that outdoor ALAN is significantly related to obesity. 
26949891	The aim of the study was to examine association of shift work with sleep quality in police officers.Data were obtained from the Buffalo Cardio-Metabolic Occupational Police Stress study (n = 363). An electronic work history database was used to define shift as day, afternoon, or night for three durations: past month, 1 year, and 15 years. Sleep quality was determined using the Pittsburgh Sleep Quality Index.	The overall prevalence of poor sleep quality was 54%; 44% for day, 60% for afternoon, and 69% for night shift. Poor sleep quality was 70% more prevalent among night-shift officers (P < 0.001) and 49% higher among those on the afternoon shift (P = 0.003) relative to officers working on the day shift.	Night and evening work schedules are associated with elevated prevalence of poor sleep quality among police officers.	
26949263	The prevalence of resistant hypertension is seemingly much lower than had been reported in early studies. Recent analyses suggest that <5 % of treated hypertensive patients remain uncontrolled if fully adherent to an optimized antihypertensive treatment. However, these patients do have increased cardiovascular risk and need effective therapeutic approaches. Drug development is a high-risk, complex, lengthy, and very expensive process. In this article, we discuss the factors that should be considered in the process of developing a new agent for treatment of resistant hypertension. 
26949152	A growing body of research reveals strong relationships between sleep disturbance, sleep architecture, and neuropsychological functioning in children. Children with epilepsy experience numerous neuropsychological comorbidities, including cognitive deficiencies and emotional/behavioral difficulties; thus, it is reasonable to consider the moderating role of sleep in this population. This review summarizes findings involving the prevalence and characteristics of sleep problems often experienced by children with epilepsy. The complex and bidirectional relationship between sleep and seizure frequency is discussed. Research pertaining to the relationship between sleep disturbance and daytime cognition as well as behavior reveals a substantial association between these variables. Clinically relevant practices related to the assessment and treatment of sleep-related complications are reviewed, and directions for further research involving intervention and assessment are also reviewed. 
26948972	There is a complex bidirectional relationship between sleep and epilepsy. Sleep/wake timing of seizures has been investigated for several individual seizure types and syndromes, but few large-scale studies of the timing of seizures exist in people with varied epilepsy types. In addition, the genetic contributions to seizure timing have not been well studied.Sleep/wake timing of seizures was determined for 1,395 subjects in 546 families enrolled in the Epilepsy Phenome/Genome Project (EPGP). We examined seizure timing among subjects with different epilepsy types, seizure types, epilepsy syndromes, and localization. We also examined the familial aggregation of sleep/wake occurrence of seizures.	Seizures in nonacquired focal epilepsy (NAFE) were more likely to occur during sleep than seizures in generalized epilepsy (GE), for both convulsive (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.59-7.52) and nonconvulsive seizures (OR 4.2, 95% CI 2.48-7.21). Seizures occurring within 1 h of awakening were more likely to occur in patients with GE than with NAFE for both convulsive (OR 2.3, 95% CI 1.54-3.39) and nonconvulsive (OR 1.7, 95% CI 1.04-2.66) seizures. Frontal onset seizures were more likely than temporal onset seizures to occur during sleep. Sleep/wake timing of seizures in first-degree relatives predicted timing of seizures in the proband.	We found that sleep/wake timing of seizures is associated with both epilepsy syndrome and seizure type. In addition, we provide the first evidence for a genetic contribution to sleep/wake timing of seizures in a large group of individuals with common epilepsy syndromes.	
26947521	Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders. 

26945921	Propranolol has been widely used in the treatment of infantile hemangiomas since 2008. This study aimed to investigate complications of systemic propranolol therapy for infantile hemangiomas, especially its effect on infants' physical growth. In this study, propranolol was given at a dose of 2 mg/kg per day. Abnormal symptoms and growth parameters were recorded in detail during the therapy. Follow-up visits were arranged to continue at least through the age of 2 years. A total of 76 patients with complete growth parameters were enrolled into the study. Complications of propranolol were minor, and mainly included sleeping disorders, diarrhea, decrease in fasting glucose, bronchial hyperactivity and hyperkalemia. Four (5.26%) patients' growth curve dropped off more than 20 percentiles during therapy and half of them returned to normal after withdrawal of the medications. None of them suffered from underweight, wasting or stunning when medication was stopped. Systemic propranolol was proved to be a safe treatment for problematic infantile hemangiomas and did not affect the physical growth.
26944397	To replicate and expand upon the relationship of somatic symptoms and posttraumatic stress disorder (PTSD) by comparing symptoms among service eras in US Veterans.Data were collected from 226 Vietnam and 132 Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans who were referred to a Veterans Affairs (VA) hospital PTSD outpatient clinic between 2005 and 2013. Veterans were administered self-report inventories and a clinical interview to measure somatic symptoms and PTSD severity. A subset of Veterans (n=185) screening positive for PTSD were administered the Clinician Administered PTSD Scale (CAPS) to measure PTSD severity. Multiple moderated linear regressions were used to examine the influence of service era on the relationship between somatic and PTSD symptoms.	There were no significant differences between service eras in pain severity, pain interference, and total somatic symptoms reported. Vietnam Veterans were more likely to report limb/join pain (p<.05), fainting (p<.01), and shortness of breath (p<.001), whereas OIF/OEF Veterans were more likely to complain of headaches (p<.001). A significant interaction effect occurred between service era and dizziness (p<.05) and chest pain (p<.01), with OIF/OEF Veterans reporting higher levels of these symptoms significantly more likely than Vietnam Veterans to also experience more severe PTSD.	Findings are consistent with previous research demonstrating the relationship of somatic symptoms and PTSD across service eras but provide additional data concerning similarities and differences of somatic symptoms between eras. Potential explanations for observed service era differences in somatic symptoms are discussed.	
26943712	Abnormal nocturnal behavior can have many causes, including primary sleep disorder, nocturnal seizures, and underlying medical or neurological disorders. A 79-year-old woman with type 2 diabetes was admitted for evaluation of abnormal nocturnal behavior. Every night at around 04:30 she was observed displaying abnormal behavior including leg shaking, fumbling with bedclothes, crawling around the room with her eyes closed, and non-responsiveness to verbal communication. Polysomnography with 20-channel electroencephalography (EEG) was performed. EEG showed that the posterior dominant rhythm was slower than that observed in the initial EEG, with diffuse theta and delta activities intermixed, and no epileptiform activity. The serum glucose level was 35 mg/dL at that time, and both the EEG findings and clinical symptoms were resolved after an intravenous injection of 50 mL of 50% glucose. These results indicate that nocturnal hypoglycemia should be considered as one of the possible etiologies in patients presenting with abnormal nocturnal behavior.


26943473	The mechanisms linking sleep disordered breathing with impairment of sleep and bone metabolism/architecture are poorly understood. Here, we explored the role of the neuropeptide orexin, a respiratory homeostasis modulator, in growth retardation induced in an upper airway obstructed (AO) rat model.The tracheae of 22-day-old rats were narrowed; AO and sham-control animals were monitored for 5 to 7 w. Growth parameters, food intake, sleep/wake activity, and serum hormones were measured. After euthanasia, growth plate (GP) histology, morphometry, orexin receptors (OXR), and related mediators were analyzed. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and GP histology were also investigated.	The AO group slept 32% less; the time spent in slow wave and paradoxical sleep during light period and slow wave activity was reduced. The AO group gained 46% less body weight compared to the control group, despite elevated food intake; plasma ghrelin increased by 275% and leptin level decreased by 44%. The impediment of bone elongation and bone mass was followed by a 200% increase in OX1R and 38% reduction of local GP ghrelin proteins and growth hormone secretagogue receptor 1a. Sry-related transcription factor nine (Sox9), a molecule mediating cartilage ossification, was downregulated and the level of transcription factor peroxisome proliferator-activated receptor gamma was upregulated, explaining the bone architecture abnormalities. Administration of almorexant restored sleep and improved GP width in AO animals.	In AO animals, enhanced expression of orexin and OX1R plays a role in respiratory induced sleep and growth abnormalities.	
26943464	Frontal intermittent rhythmic delta activity (FIRDA) has long been considered to be an abnormal variant in the electroencephalogram (EEG) among older adults. Prior work also indicates a predominance of slow wave EEG activity among patients with dementia. However, instability of state control occurring with aging generally and among many neurodegenerative diseases raises the possibility that FIRDA might represent the intrusion of sleep related elements of the EEG into the waking state. We examined delta activity at sleep onset (DASO) in community-dwelling, older adults without dementia, and examined whether this activity is related to poorer cognitive performance.153 community-dwelling, older adults without dementia underwent overnight polysomnography and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, and visuospatial ability. Delta activity during sleep/wake transitions (scored either as Waking or N1) was analyzed visually.	Participants were 83 women and 70 men, mean age 71.3 ± 0.6 y. DASO was present in 30 participants (19.6%). Age, years of education, sex, and body mass index did not differ between DASO (+) and (-) groups. Multiple regression analyses indicated faster reading of the Stroop color words in DASO (+) subjects (P = 0.007). None of the other cognitive domains differed between the two groups.	DASO was relatively common in our sample of community-dwelling, older adults without dementia. DASO was not associated with poorer performance on any cognitive domain. Instead, individuals with DASO demonstrated better performance on a simple reading task. Although these findings suggest that an abnormal EEG activity may represent normal variation, our work underscores the importance of distinguishing DASO from FIRDA when examining sleep in older adults.	A commentary on this article appears in this issue on page 725.	
26942630	Concerns about health problems due to the increasing use of mobile phones are growing. Excessive use of mobile phones can affect the quality of sleep as one of the important issues in the health literature and general health of people. Therefore, this study investigated the relationship between the excessive use of mobile phones and general health and quality of sleep on 450 Occupational Health and Safety (OH&S) students in five universities of medical sciences in the North East of Iran in 2014. To achieve this objective, special questionnaires that included Cell Phone Overuse Scale, Pittsburgh's Sleep Quality Index (PSQI) and General Health Questionnaire (GHQ) were used, respectively. In addition to descriptive statistical methods, independent t-test, Pearson correlation, analysis of variance (ANOVA) and multiple regression tests were performed. The results revealed that half of the students had a poor level of sleep quality and most of them were considered unhealthy. The Pearson correlation co-efficient indicated a significant association between the excessive use of mobile phones and the total score of general health and the quality of sleep. In addition, the results of the multiple regression showed that the excessive use of mobile phones has a significant relationship between each of the four subscales of general health and the quality of sleep. Furthermore, the results of the multivariate regression indicated that the quality of sleep has a simultaneous effect on each of the four scales of the general health. Overall, a simultaneous study of the effects of the mobile phones on the quality of sleep and the general health could be considered as a trigger to employ some intervention programs to improve their general health status, quality of sleep and consequently educational performance. 

26940700	Disruption of sleep/wake cycles is common in patients with schizophrenia and correlates with cognitive and affective abnormalities. Mice deficient in stable tubule only polypeptide (STOP) show cognitive, behavioral, and neurobiological deficits that resemble those seen in patients with schizophrenia, but little is known about their sleep phenotype. We characterized baseline sleep/wake patterns and recovery sleep following sleep deprivation in STOP null mice. Polysomnography was conducted in adult male STOP null and wild-type (WT) mice under a 12:12 hours light:dark cycle before, during, and after 6 hours of sleep deprivation during the light phase. At baseline, STOP null mice spent more time awake and less time in non-rapid eye movement sleep (NREMS) over a 24-hour period, with more frequent transitions between wake and NREMS, compared to WT mice, especially during the dark phase. The distributions of wake, NREMS and REMS across the light and the dark phases differed by genotype, and so did features of the electroencephalogram (EEG). Following sleep deprivation, both genotypes showed homeostatic increases in sleep duration, with no significant genotype differences in the initial compensatory increase in sleep intensity (EEG delta power). These results indicate that STOP null mice sleep less overall, and their sleep and wake periods are more fragmented than those of WT mice. These features in STOP null mice are consistent with the sleep patterns observed in patients with schizophrenia. 
26940117	Most studies of sleep and health outcomes rely on self-reported sleep duration, although correlation with objective measures is poor. In this study, we defined sociodemographic and sleep characteristics associated with misreporting and assessed whether accounting for these factors better explains variation in objective sleep duration among 2,086 participants in the Hispanic Community Health Study/Study of Latinos who completed more than 5 nights of wrist actigraphy and reported habitual bed/wake times from 2010 to 2013. Using linear regression, we examined self-report as a predictor of actigraphy-assessed sleep duration. Mean amount of time spent asleep was 7.85 (standard deviation, 1.12) hours by self-report and 6.74 (standard deviation, 1.02) hours by actigraphy; correlation between them was 0.43. For each additional hour of self-reported sleep, actigraphy time spent asleep increased by 20 minutes (95% confidence interval: 19, 22). Correlations between self-reported and actigraphy-assessed time spent asleep were lower with male sex, younger age, sleep efficiency <85%, and night-to-night variability in sleep duration ≥1.5 hours. Adding sociodemographic and sleep factors to self-reports increased the proportion of variance explained in actigraphy-assessed sleep slightly (18%-32%). In this large validation study including Hispanics/Latinos, we demonstrated a moderate correlation between self-reported and actigraphy-assessed time spent asleep. The performance of self-reports varied by demographic and sleep measures but not by Hispanic subgroup. 

26938911	There is much research concerning the psychological and physical effects of sleep deprivation on patients in healthcare systems, yet interrupted sleep on hospital wards at night remains a problem. Staff at Plymouth Hospitals NHS Trust, Devon, wanted to identify the factors that prevent patients from sleeping well at night. Two audits were carried out, between April and August 2015, to assess noise and light levels on wards at night, and to engage nurses in ways of reducing these. A number of recommendations were made based on the audit findings, many of which have been put into practice. 
26937653	Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1β and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1β CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1β TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1β levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1β-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1β-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance. 
26935441	We investigated the influence of nocturia and sleep disturbance on health-related quality of life(HRQOL) using the Medical Outcomes Study 8-item Short Form Health Survey (SF-8) in patients with nocturia. We also assessed the effect of therapeutic intervention by means of an anticholinergic agent on the results of the SF-8. One hundred and eighty-four patients who voided at least once per night were surveyed using the SF-8, Overactive Bladder Symptom Score (OABSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). These parameters were also evaluated before and after 12 weeks of imidafenacin treatment in 51 patients with OAB accompanied by nocturia. The SF-8 physical component summary score (PCS) showed a significant decrease as nighttime voiding frequency increased. The mental health component summary score was 47.1 and 47.6 (which were lower than the standard value of 50) in the group with a nighttime frequency of once and ≥3/night, respectively. The SF-8 PCS and 6 subscales were negatively associated with nighttime voiding frequency, while the PSQI global score was positively associated with it. Imidafenacin significantly improved the OABSS, PSQI, and ESS, as well as the SF-8 score. This is the first study using the SF-8 to show that nocturia and sleep disturbance have a major influence on comprehensive HRQOL and that the SF-8 can be used to monitor HRQOL in OAB patients receiving treatment for nocturia. 
26934877	Whether the temporal correlation between inter-leads Electroencephalogram (EEG) that located on the boundary between left and right brain hemispheres is associated with sleep stages or not is still unknown. The purpose of this paper is to evaluate the role of correlation coefficients between EEG leads Fpz-Cz and Pz-Oz for automatic classification of sleep stages. A total number of 39 EEG recordings (about 20 h each) were selected from the expanded sleep database in European data format for temporal correlation analysis. Original waveform of EEG was decomposed into sub-bands δ (1-4 Hz), θ (4-8 Hz), α (8-13 Hz) and β (13-30 Hz). The correlation coefficient between original EEG leads Fpz-Cz and Pz-Oz within frequency band 0.5-30 Hz was defined as r(EEG) and was calculated every 30 s, while that between the two leads EEG in sub-bands δ, θ, α and β were defined as r(δ), r(θ), r(α) and r(β), respectively. Classification of wakefulness and sleep was processed by fixed threshold that derived from the probability density function of correlation coefficients. There was no correlation between EEG leads Fpz-Cz and Pz-Oz during wakefulness (|r| < 0.1 for r(θ), r(α) and r(β), while 0.3 > r > 0.1 for r(EEG) and r(δ)), while low correlation existed during sleep (r ≈ -0.4 for r(EEG), r(δ), r(θ), r(α) and r(β)). There were significant differences (analysis of variance, P < 0.001) for r(EEG), r(δ), r(θ), r(α) and r(β) during sleep when in comparison with that during wakefulness, respectively. The accuracy for distinguishing states between wakefulness and sleep was 94.2, 93.4, 89.4, 85.2 and 91.4% in terms of r(EEG), r(δ), r(θ), r(α) and r(β), respectively. However, no correlation index between EEG leads Fpz-Cz and Pz-Oz could distinguish all five types of wakefulness, rapid eye movement (REM) sleep, N1 sleep, N2 sleep and N3 sleep. In conclusion, the temporal correlation between EEG bipolar leads Fpz-Cz and Pz-Oz are highly associated with sleep-wake stages. Moreover, high accuracy of sleep-wake classification could be achieved by the temporal correlation within frequency band 0.5-30 Hz between EEG leads Fpz-Cz and Pz-Oz.
26934362	Our goal was to model the temporal dynamics of sleep-wake transitions, represented by transitions between rest and activity obtained from actigraphic data, in patients with bipolar disorder using a probabilistic state transition approach.We collected actigraphic data for 14 days from 20 euthymic patients with bipolar disorder, who had been characterized clinically, demographically, and with respect to their circadian preferences (chronotype). We processed each activity record to generate a series of transitions in both directions between the states of rest (R) and activity (A) and plotted the estimated transition probabilities (pRA and pAR). Each 24-hour period was also divided into a rest phase consisting of the eight consecutive least active hours in each day and an active phase consisting of the 16 consecutive most active hours in each day. We then calculated separate transition probabilities for each of these phases for each participant. We subsequently modeled the rest phase data to find the best fit for rest-activity transitions using maximum likelihood estimation. We also examined the association of transition probabilities with clinical and demographic variables.	The best-fit model for rest-activity transitions during the rest phase was a mixture (bimodal) of exponential functions. Of those patients with rapid cycling, 75% had an evening-type chronotype. Patients with bipolar II disorder taking antidepressants had a lower probability of transitioning back to rest than those not on antidepressants [mean ± SD = 0.050 ± 0.006 versus 0.141 ± 0.058, F(1,15) = 3.40, p < 0.05].	The dynamics of transitions between rest and activity in bipolar disorder can be accounted for by a mixture (bimodal) of exponential functions. Patients taking antidepressants had a reduced probability of sustaining and returning to sleep.	
26933456	We hypothesized that if we control for lifestyle changes during Ramadan, Ramadan Islamic intermittent fasting (IF) reduces oxidative stress. This study was conducted to examine the effect of Islamic IF during and outside of Ramadan on the circadian changes in lipid peroxidation marker malondialdehyde (MDA) during and outside while controlling for potential confounders.Serum MDA concentration was measured in eight healthy male volunteers at baseline (BL), after fasting for 1 week before Ramadan (BL fasting), and during Ramadan. Blood samples were drawn at 22:00, 02:00, 04:00, 06:00, and 11:00. The participants were admitted to the sleep laboratory and monitored for 24 h on the day of the measurements. In the laboratory, each participant received meals of fixed compositions and caloric contents based on their ideal body weights. Light exposure, physical activity, and total sleep duration were uniformly maintained during the three study periods.	The participants had a mean age of 26.6 ± 4.9 years and a mean body mass index of 23.7 ± 3.5 kg/m(2). No significant changes were observed in MDA levels and blood glucose during BL, BL fasting, or Ramadan.	In this pilot study, under conditions of fixed sleep-wake schedules and caloric intake, Ramadan IF does not alter serum MDA levels in healthy subjects. Larger studies are needed to confirm these findings.	
26932938	Non-motor symptoms (NMS) of Parkinson Disease (PD) are common and can cause severe disability. They are often under-recognized and remain untreated. Tools to evaluate these symptoms in Arabic-speaking patients are still lacking. The objective of this study was to evaluate an Arabic version of the non-motor symptoms scale (NMSS) of PD as an instrument for measuring NMS in Arabic-speaking patients. Sixty-two PD patients clustered around Hoehn & Yahr Stages 2-3 were evaluated by the Arabic version of NMSS. They also underwent a battery of standard psychometric assessment measures that included the scales for outcomes of Parkinson's disease-autonomic (SCOPA-AUT), the Pittsburgh sleep quality index (PSQI), the Beck depression inventory, the geriatric depression scale (GDS), the mini-mental state examination (MMSE), the visual analogical scale for pain(VAS) and the neuro-psychiatric inventory (NPI). The metric properties of the NMSS were studied as well as its correlation with other standard tests evaluating NMS. The mean NMSS score was 82 ± 56 (skewness 0.88). There were highly significant correlations between the NMSS and the SCOPA-AUT as well as the NMSS and PSQI scores. Significant positive correlations between NMSS and GDS, BECK and VAS were also observed. The sleep/fatigue domain significantly correlated with the PSQI, the cardiovascular/urinary/sexual function/gastrointestinal domains significantly correlated with the SCOPA-AUT, the mood/cognition domain significantly correlated with the GDS and BECK findings. The mean Cronbach's alpha coefficient was 0.87, showing a satisfactory internal consistency. The Arabic version of NMSS can be considered a comprehensive and reliable measure for non-motor symptoms in Arabic-speaking PD patients. 
26937548	Hartsfield syndrome comprises two core features: holoprosencephaly (HPE) spectrum disorders and ectrodactyly spectrum disorders. HPE spectrum disorders, resulting from failed or incomplete forebrain division early in gestation, include alobar, semilobar, or lobar HPE. Other brain malformations observed in persons with Hartsfield syndrome include corpus callosum agenesis, absent septum pellucidum, absent olfactory bulbs and tracts, and vermian hypoplasia. Varying degrees of developmental delay are observed. Microcephaly, spasticity, seizures, and feeding difficulties are common. Hypothalamic dysfunction (manifest as temperature dysregulation and erratic sleep patterns) can occur, as well as hypogonadotropic hypogonadism and central insipidus diabetes. Ectrodactyly spectrum disorders are unilateral or bilateral malformations of the hands and/or feet characterized by a median cleft of hand or foot due to absence of the longitudinal central rays (also called split hand/foot malformation). The number of digits on the right and left can vary. Polydactyly and syndactyly can also be seen.The diagnosis is established in a proband with the two core features: an HPE spectrum disorder and an ectrodactyly spectrum disorder. It can be confirmed by identification of either an FGFR1 heterozygous pathogenic variant (in those with autosomal dominant inheritance) or FGFR1 biallelic pathogenic variants (in those with autosomal recessive inheritance).	Treatment of manifestations: Medically refractory epilepsy typically requires multiple antiepileptic drugs. Spasticity can be treated with physical and occupational therapy and bracing, as well as muscle relaxants (when moderate or severe). Sometimes surgery may be required. Diabetes insipidus may need treatment with desmopressin; temperature dysregulation can be managed by modifying the environment; disturbance of sleep-wake cycles can be managed with good sleep hygiene and, if needed, with use of melatonin or other sleep aids such as clonidine. Some children may require a gastrostomy and/or a tracheostomy.	Hartsfield syndrome is inherited most commonly in an autosomal dominant (AD) and less commonly in an autosomal recessive (AR) manner. AD inheritance: Most probands have a de novoFGFR1 pathogenic variant. Germline mosaicism has been observed in two unrelated families. AR inheritance: At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FGFR1 pathogenic variant(s) have been identified in an affected family member, prenatal testing or preimplantation genetic diagnosis for a pregnancy at increased risk is possible.	
26930172	Research on chronotypic differences has been conducted for many years, however, until recently, little attention has been paid to young children. The current study examined the influence of morningness-eveningness in the daily lives of 2 to 4 year olds (291 females, 230 males, 8 gender not given) via an online survey completed by 529 mothers from across the United States. The results replicated previous findings on chronotypic differences in sleep-wake patterns and the development of morningness-eveningness in early childhood. The influence of chronotype on sleep habits, daily routines and schedules was also explored. At both bed and wake times, mothers of evening type (E-type) children were more likely to report challenges. For a while, morning type (M-type) children tended to fall asleep easily and wake themselves up in the morning, E-types were more likely to show bedtime resistance, wake in a negative mood and have conflicts with their parents. In the morning, mothers of M-type children often stuck to their normal routine on days when the child had to be somewhere at 7:00 am, whereas mothers of E-type children employed different strategies to get their child up and out the door. Bedtime routines and daily schedules also differed by chronotype. Individual differences in morningness-eveningness and their impact on sleep-wake patterns and social interactions are evident early on. A greater understanding of how they affect the lives of young children and their future development is needed. 
26928255	Electroencephalogram (EEG) and electromyogram (EMG) recordings are often used in rodents to study sleep architecture and sleep-associated neural activity. These recordings must be scored to designate what sleep/wake state the animal is in at each time point. Manual sleep-scoring is very time-consuming, so machine-learning classifier algorithms have been used to automate scoring.Instead of using single classifiers, we implement a multiple classifier system. The multiple classifier is built from six base classifiers: decision tree, k-nearest neighbors, naïve Bayes, support vector machine, neural net, and linear discriminant analysis. Decision tree and k-nearest neighbors were improved into ensemble classifiers by using bagging and random subspace. Confidence scores from each classifier were combined to determine the final classification. Ambiguous epochs can be rejected and left for a human to classify.	Support vector machine was the most accurate base classifier, and had error rate of 0.054. The multiple classifier system reduced the error rate to 0.049, which was not significantly different from a second human scorer. When 10% of epochs were rejected, the remaining epochs' error rate dropped to 0.018.	Compared with the most accurate single classifier (support vector machine), the multiple classifier reduced errors by 9.4%. The multiple classifier surpassed the accuracy of a second human scorer after rejecting only 2% of epochs.	Multiple classifier systems are an effective way to increase automated sleep scoring accuracy. Improvements in autoscoring will allow sleep researchers to increase sample sizes and recording lengths, opening new experimental possibilities.	
26927330	The aim of the present study was to evaluate sleep and mood disorders in patients with irritating ocular diseases. The study design was a cross-sectional/case-control study conducted in six eye clinics. Out of 715 outpatients diagnosed with irritating ocular surface diseases and initially enrolled, 301 patients with dry eye disease (DED) and 202 age-matched control participants with other ocular surface diseases were analyzed. The mean Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) scores were 6.4 ± 3.2 and 11.1 ± 5.7 for severe DED (n = 146), 5.5 ± 3.3 and 9.8 ± 4.0 for mild DED (n = 155), 5.5 ± 3.1 and 9.5 ± 6.6 for chronic conjunctivitis (n = 124), and 5.0 ± 3.3 and 8.9 ± 5.3 for allergic conjunctivitis (n = 78). There were significant differences among these diagnostic groups for PSQI (P < 0.05). Regression analysis of patients with DED revealed the PSQI and HADS scores were significantly correlated with the severity of DED (P < 0.05). Our results demonstrate that sleep quality in patients with DED is significantly worse than in patients with other irritating ocular surface diseases and it is correlated with the severity of DED. 
26926327	Most midlife women report vasomotor symptoms (VMS), yet their physiology remains poorly understood. This study tested whether acute decreases in cardiac vagal control would occur with VMS in a large sample of women monitored during wake and sleep.Two hundred and fifteen nonsmoking women aged 40 to 60 years with evidence of VMS were included. Women were free of a history of clinical cardiovascular disease or arrhythmia; or use of insulin, beta blockers, calcium channel blockers, or medications impacting VMS. Women underwent 24 hours of ambulatory monitoring for physiological (sternal skin conductance) and self-report (electronic diary) measurement of VMS; heart rate variability (electrocardiogram); and respiratory rate. Changes in cardiac vagal control as assessed by respiratory sinus arrhythmia during VMS, relative to periods before and after VMS, were tested in linear mixed models.	Significant decreases in respiratory sinus arrhythmia were observed during physiologically measured VMS relative to periods preceding (b[SE] = 0.13 (0.004), P < 0.0001) and after the vasomotor symptoms (b[SE] = 0.13 (0.004), P < 0.0001), adjusted for age, race, body mass index, and sleep/wake status. Decreases were observed for women not aware of their VMS, and differences persisted controlling for respiration rate. Interactions indicated that respiratory sinus arrhythmia decreases were most pronounced during sleep and for younger women.	Physiologically measured VMS were accompanied by an inhibition of cardiac vagal control in a large sample of women. Changes were observed irrespective of whether the VMS were reported, were most pronounced during sleep, and were greatest among younger women. These findings contribute to the understanding of vasomotor symptom physiology.	
26924827	Exploring neural activity behind synchronization and time locking in brain circuits is one of the most important tasks in neuroscience. Our goal was to design and characterize a microelectrode array (MEA) system specifically for obtaining in vivo extracellular recordings from three deep-brain areas of freely moving rats, simultaneously. The target areas, the deep mesencephalic reticular-, pedunculopontine tegmental-and pontine reticular nuclei are related to the regulation of sleep-wake cycles.The three targeted nuclei are collinear, therefore a single-shank MEA was designed in order to contact them. The silicon-based device was equipped with 3 × 4 recording sites, located according to the geometry of the brain regions. Furthermore, a microdrive was developed to allow fine actuation and post-implantation relocation of the probe. The probe was attached to a rigid printed circuit board, which was fastened to the microdrive. A flexible cable was designed in order to provide not only electronic connection between the probe and the amplifier system, but sufficient freedom for the movements of the probe as well.	The microdrive was stable enough to allow precise electrode targeting into the tissue via a single track. The microelectrodes on the probe were suitable for recording neural activity from the three targeted brainstem areas.	The system offers a robust solution to provide long-term interface between an array of precisely defined microelectrodes and deep-brain areas of a behaving rodent. The microdrive allowed us to fine-tune the probe location and easily scan through the regions of interest.	
26923809	Given the limitations of treatments for dementia, the characterisation of the early stages of dementia is crucial for the development of preventive programmes and interventions. We aimed to estimate the prevalence of mild cognitive impairment (MCI) and examine its medical and lifestyle correlates in a nationally representative sample of the Spanish population.A total of 3625 participants (≥50 years of age) were interviewed in a cross-sectional study. MCI was defined as the presence of cognitive concerns, the objective evidence of impairment in one or more cognitive domains, the preservation of independence in functional abilities and no dementia. Participants were also asked to provide sociodemographic, health status and lifestyle information. Logistic regression analyses were performed using the overall sample and by age groups.	The overall prevalence of MCI was 9.6%, with higher rates in older people and women. In the overall model, after adjustment for potential confounders, depression [odds ratio (OR) = 1.79; 95% confidence interval (CI) = 1.21, 2.66], diabetes (OR = 1.43; 95% CI = 1.05, 1.95), sleep disturbances (OR = 1.66; 95% CI = 1.09, 2.55) and low level of physical activity (OR = 1.71; 95% CI = 1.26, 2.31) were associated with significantly higher odds for MCI. When stratified by age groups, depression (OR = 2.41; 95% CI = 1.35, 4.31), stroke (OR = 3.77; 95% CI = 1.44, 9.83) and obesity (OR = 2.06; 95% CI = 1.20, 3.53) were significantly associated with MCI in middle-aged participants (50-64 years), whereas low level of physical activity (OR = 1.85; 95% CI = 1.32, 2.59) and sleep disturbances (OR = 1.79; 95% CI = 1.05, 3.05) were associated with MCI in individuals aged 65+ years.	Significant associations between MCI and psychological, cardiovascular and lifestyle factors were found. Targeting modifiable risk factors might reduce the risk for MCI and subsequent dementia.	
26921923	Chronic diseases may aggravate or simulate climacteric symptoms. Although acknowledged in clinical practice, there is a lack of research systematically analysing the association between chronic diseases and climacteric symptoms.Our study was a cross-sectional population-based study, which included 3421 women, aged 41-54 years. Climacteric symptoms were evaluated using the Women's Health Questionnaire (WHQ), of which we included seven symptom domains (vasomotor, sleep, depressive, anxiety/fears, cognitive, sexual, and menstrual) and a question concerning whether the women were worried about growing old. The occurrence of various diseases (cardiovascular, neurological, sensory organ, bronchopulmonary, musculoskeletal, gastrointestinal, urological, dermatological, and thyroid disease, diabetes, and cancer) was recorded. The associations between the diseases and symptoms were defined with multivariable analyses, adjusting for various confounding factors.	The women with the diseases had more symptoms. Vasomotor symptoms and sleep problems were associated only with gastrointestinal diseases, and lower sexual functioning only with diabetes. The remaining symptoms were associated with several diseases, except being worried about growing old, which was not associated with any.	Many symptoms connected to the climacteric may manifest also due to chronic diseases. Thus, health-care professionals should consider the origin of the symptoms when treating middle-aged women with chronic diseases.	
26921599	The purpose of this study was to document the frequency of sleep problems including poor sleep quality, excessive daytime sleepiness, and insomnia in subjects with epilepsy compared with healthy controls and to determine the factors associated with these sleep disturbances.We recruited 180 patients with epilepsy (age: 43.2 ± 15.6 years, men: 50.0%) and 2836 healthy subjects (age: 44.5 ± 15.0 years, men: 49.8%). Sleep and the anxiety/mood profiles were measured using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index, Goldberg Anxiety Scale, and Patient Health Questionnaire-9 depression scale. Associations of sleep problems with epilepsy and other factors were tested by multiple logistic regression analysis, adjusted for age, gender, body mass index, alcohol intake, smoking, perceived sleep insufficiency, and habitual snoring.	Sleep disturbances were more common in the group with epilepsy than in the controls (53.3% vs. 25.5%; p<0.001). Poor sleep quality, excessive daytime sleepiness, and insomnia were significantly associated with epilepsy (odds ratio [95% confidence interval]: 3.52 [2.45-5.05], 2.10 [1.41-3.12], 5.91 [3.43-10.16], respectively). Depressive mood, anxiety, and perceived sleep insufficiency contributed to the presence of sleep disturbances. In the group with epilepsy, seizure remission for the past year related to a lower frequency of insomnia, whereas age, sex, type of epilepsy, and number of antiepileptic drugs were not correlated with sleep problems.	Epilepsy was significantly associated with the higher frequency of sleep disturbances, which supports the importance of screening sleep problems in patients with epilepsy and providing available intervention.	
26921272	Previous studies reported lower health-related quality of life (HRQOL) scores in overweight and obese adolescents compared to their normal weight counterparts; however, few studies investigated the association between obesity-related behaviors including physical activity and sedentary behaviors and HRQOL in adolescents. This study aimed at investigating the relationship between physical activity, sedentary behaviors, sleep duration and body mass index-for-age (BMI-for-age) and HRQOL among high school Tehranian students.A total of 465 high school students (48.8 % girls) were recruited from three different socio-economic zones in Tehran. The BMI-for-age was determined and physical activity and HRQOL were assessed using validated questionnaires including Quantification de l'Activite Physique en Altitude Chez les Enfants (QAPACE) and Pediatric Quality of Life Inventory (PedsQL) respectively.	Over one third of students (38.5 %) were either overweight or obese. The means of all self- and parent-reported HRQOL scores were significantly lower in girls, compared to boys, except for the parent-reported social functioning subscale. Mean hours of daily sleeping were significantly higher in girls, compared to boys (8.16 ± 1.27 vs. 7.73 ± 1.22 respectively; p < 0.05). Both girls and boys spent more time on sedentary activities than engaging in sport activities. During school and vacation periods, boys had significantly higher daily energy expenditure (DEE) compared to girls (p < 0.05). Only DEE during school period had a significant inverse correlation with BMI-for-age in boys but not girls (r = -0.14, p < 0.05). In addition, self-reported HRQOL scores were significantly associated with weekly hours adolescents spent on videogames/internet, listening to music and reading, watching TV, sports as well as DEE through sex-specific patterns. However according to parents' perspective only weekly hours spent on listening to music and readings and sport activities were significantly associated with their children HRQOL scores.	In summary, time spent on physical and sedentary activities were not associated with BMI-for-age, although both of these were associated with the HRQOL of high school students. The potential role of sedentary activities and physical activity should be considered in future interventions aimed at improving HRQOL in adolescents.	
26918668	Children's sleep problems and self-regulation problems have been independently associated with poorer adjustment to school, but there has been limited exploration of longitudinal early childhood profiles that include both indicators.This study explores the normative developmental pathway for sleep problems and self-regulation across early childhood and investigates whether departure from the normative pathway is associated with later social-emotional adjustment to school.	This study involved 2,880 children participating in the Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) - Infant Cohort from Wave 1 (0-1 years) to Wave 4 (6-7 years).	Mothers reported on children's sleep problems, emotional, and attentional self-regulation at three time points from birth to 5 years. Teachers reported on children's social-emotional adjustment to school at 6-7 years. Latent profile analysis was used to establish person-centred longitudinal profiles.	Three profiles were found. The normative profile (69%) had consistently average or higher emotional and attentional regulation scores and sleep problems that steadily reduced from birth to 5 years. The remaining 31% of children were members of two non-normative self-regulation profiles, both characterized by escalating sleep problems across early childhood and below mean self-regulation. Non-normative group membership was associated with higher teacher-reported hyperactivity and emotional problems, and poorer classroom self-regulation and prosocial skills.	Early childhood profiles of self-regulation that include sleep problems offer a way to identify children at risk of poor school adjustment. Children with escalating early childhood sleep problems should be considered an important target group for school transition interventions.	
26918226	Despite continued research and growing public awareness, the incidence of non-communicable diseases (NCD) continues to accelerate. While a person may have a genetic predisposition to certain NCDs, the rapidly changing epidemiology of NCDs points to the importance of environmental, social, and behavioural determinants of health. Specifically, three lifestyle behaviours expose children to important environmental cues and stressors: physical activity, nutritional intake, and sleep behaviour. Failure to expose children to proper gene-environment interactions, through the aforementioned lifestyle behaviours, can and will predispose children to the development of NCDs. Reengineering the environments of children can induce a paradigm shift, from a predominantly biomedical health model of treating symptomology, to a more holistic model based on encouraging appropriate behavioral decisions and optimal health. 
26913940	Restless legs syndrome (RLS), a burdensome sleep disorder, has been associated with cardiovascular disease (CVD), hypertension, diabetes, and related disorders. However, the relationship of RLS to history of pregnancy-induced hypertension (PIH), a predictor of subsequent CVD, diabetes, and associated conditions, remains little explored. In this study, we investigated the relationship of RLS to history of PIH in a sample of primary care patients.Participants were women aged ≥40 years drawn from an anonymous survey study of West Virginia primary care patients. Data collected included detailed information on demographics, lifestyle factors, sleep patterns, and reproductive/medical history; the survey also included an RLS diagnostic questionnaire. Women who were pregnant or unsure about their pregnancy status were excluded from the analyses.	Of the 498 participants in the final analytic sample, 24.5% met diagnostic criteria for RLS (17.9% with symptoms ≥once/week, 11.9% with symptoms ≥3 times/week); 73 (16.5% of parous women) reported a history of PIH, defined as physician-diagnosed preeclampsia or gestational hypertension. After adjustment for demographics, lifestyle characteristics, obesity, reproductive history, health conditions, and other factors, those reporting a history of PIH were approximately twice as likely to meet criteria for RLS (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.1, 3.6). These associations increased in magnitude with increasing symptom frequency (adjusted OR for RLS with symptoms ≥3 times/week = 3.8; CI 1.9, 7.6; p for trend = 0.003).	History of PIH was strongly and positively related to current RLS in this study of primary care patients; these findings further support a possible role for metabolic dysregulation in RLS etiology.	
26913197	In the face of chronic stress, some individuals can maintain normal function while others go on to develop mental illness. Addiction, affecting one in every twelve people in America, is a substance use disorder long associated with stressful life events and disruptions in the sleep/wake cycle. The circadian and stress response systems have evolved to afford adaptability to environmental changes and allow for maintenance of functional stability, or homeostasis. This mini-review will discuss how circadian rhythms and stress individually affect drug response, affect each other, and how their interactions may regulate reward-related behavior. In particular, we will focus on the interactions between the circadian clock and the regulation of glucocorticoids by the hypothalamic-pituitary-adrenal (HPA) axis. Determining how these two systems act on dopaminergic reward circuitry may not only reveal the basis for vulnerability to addiction, but may also illuminate potential therapeutic targets for future investigation. 
26911837	The dorsal pons has long been implicated in the generation of rapid eye movement (REM) sleep, but the underlying circuit mechanisms remain poorly understood. Using cell-type-specific microendoscopic Ca(2+) imaging in and near the laterodorsal tegmental nucleus, we found that many glutamatergic neurons are maximally active during REM sleep (REM-max), while the majority of GABAergic neurons are maximally active during wakefulness (wake-max). Furthermore, the activity of glutamatergic neurons exhibits a medio-lateral spatial gradient, with medially located neurons more selectively active during REM sleep. 

26908691	Delirium in children is common but not widely understood by pediatric practitioners, often leading to underdiagnosis and lack of treatment. This presents a significant challenge in the young patients in the PICU who are most at risk for delirium and in whom the core features of delirium are difficult to assess and treat. However, because of the potential increased morbidity and mortality associated with untreated delirium in adults and children, it remains important to address it promptly. The literature for delirium in this age group is limited. Here we present the case of an infant with multiple underlying medical risk factors who exhibited waxing and waning motor restlessness with disrupted sleep-wake cycles contributing significantly to destabilization of vital parameters. Making a diagnosis of delirium was key to guiding further treatment. After appropriate environmental interventions are implemented and underlying medical causes are addressed, antipsychotic medications, although not Food and Drug Administration-approved in infants, are the mainstay of pharmacotherapy for delirium in older age groups. They may lengthen corrected QT interval (QTc) intervals, presenting a challenge in infants who frequently have other coexisting risks for QTc prolongation, as in our case. The risk from QTc prolongation needs to be balanced against that from untreated delirium. Low doses of risperidone were successfully used in this patient and without side effects or worsening of QTc interval. This case illustrates the importance of increased recognition of delirium in children, including infants, and the role for cautious consideration of atypical antipsychotics in the very young. 
26905794	The symptom profile of alcohol withdrawal delirium (AWD), relative to deliriums of other etiology, remains uncertain.To evaluate the factor structure of symptoms in patients with AWD, as assessed by the Delirium Rating Scale-Revised-98 (DRS-R-98).	A total of 112 patients aged 18 years or more with AWD were assessed on DRS-R-98.	The mean age of participants was 44.2 years. About two-third of the patients developed delirium within 24 hours of the last intake of alcohol and the mean duration of delirium at the time of assessment was 3.9 days. In 46% of cases the delirium was attributed solely to alcohol withdrawal; in the remaining subjects alcohol withdrawal was a major contributory factor. Three separate principal component analysis (whole sample, pure AWD and AWD with associated etiologies) were carried out. In all the factor analyses, one of the factors included cognitive symptoms (attention, orientation and visuospatial disturbances) along with or without short- and long-term memory impairment; the second factor included motoric symptoms along with sleep-wake cycle disturbances; the third factor included psychotic symptoms. For the whole group and subgroup of AWD with associated etiologies, items of higher level thinking (i.e. language disturbances and thought process abnormality) loaded along with cognitive symptoms. In pure AWD group, these items along with memory disturbances loaded with psychotic symptoms.	Results of the current factor analyses suggest that the factor structure of pure AWD is different from AWD with associated etiologies. Hence, attention to the symptom profile of patients with AWD may provide clues to delirium etiology.	
26903630	In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes. 
26903420	Noradrenergic neurons of the brainstem extend projections throughout the neuraxis to modulate a wide range of processes including attention, arousal, autonomic control and sensory processing. A spinal projection from the locus coeruleus (LC) is thought to regulate nociceptive processing. To characterize and selectively manipulate the pontospinal noradrenergic neurons in rats, we implemented a retrograde targeting strategy using a canine adenoviral vector to express channelrhodopsin2 (CAV2-PRS-ChR2-mCherry). LC microinjection of CAV2-PRS-ChR2-mCherry produced selective, stable, transduction of noradrenergic neurons allowing reliable opto-activation in vitro. The ChR2-transduced LC neurons were opto-identifiable in vivo and functional control was demonstrated for >6 months by evoked sleep-wake transitions. Spinal injection of CAV2-PRS-ChR2-mCherry retrogradely transduced pontine noradrenergic neurons, predominantly in the LC but also in A5 and A7. A pontospinal LC (ps:LC) module was identifiable, with somata located more ventrally within the nucleus and with a discrete subset of projection targets. These ps:LC neurons had distinct electrophysiological properties with shorter action potentials and smaller afterhyperpolarizations compared to neurons located in the core of the LC. In vivo recordings of ps:LC neurons showed a lower spontaneous firing frequency than those in the core and they were all excited by noxious stimuli. Using this CAV2-based approach we have demonstrated the ability to retrogradely target, characterise and optogenetically manipulate a central noradrenergic circuit and show that the ps:LC module forms a discrete unit. This article is part of a Special Issue entitled SI: Noradrenergic System. 
26901675	Current research on the effects of pharmacological agents on human neurophysiology finds its roots in animal research, which is also reflected in contemporary animal pharmaco-electroencephalography (p-EEG) applications. The contributions, present value and translational appreciation of animal p-EEG-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. After the pioneering years in the late 19th and early 20th century, animal p-EEG research flourished in the pharmaceutical industry in the early 1980s. However, around the turn of the millennium the emergence of structurally and functionally revealing imaging techniques and the increasing application of molecular biology caused a temporary reduction in the use of EEG as a window into the brain for the prediction of drug efficacy. Today, animal p-EEG is applied again for its biomarker potential - extensive databases of p-EEG and polysomnography studies in rats and mice hold EEG signatures of a broad collection of psychoactive reference and test compounds. A multitude of functional EEG measures has been investigated, ranging from simple spectral power and sleep-wake parameters to advanced neuronal connectivity and plasticity parameters. Compared to clinical p-EEG studies, where the level of vigilance can be well controlled, changes in sleep-waking behaviour are generally a prominent confounding variable in animal p-EEG studies and need to be dealt with. Contributions of rodent pharmaco-sleep EEG research are outlined to illustrate the value and limitations of such preclinical p-EEG data for pharmacodynamic and chronopharmacological drug profiling. Contemporary applications of p-EEG and pharmaco-sleep EEG recordings in animals provide a common and relatively inexpensive window into the functional brain early in the preclinical and clinical development of psychoactive drugs in comparison to other brain imaging techniques. They provide information on the impact of drugs on arousal and sleep architecture, assessing their neuropharmacological characteristics in vivo, including central exposure and information on kinetics. In view of the clear disadvantages as well as advantages of animal p-EEG as compared to clinical p-EEG, general statements about the usefulness of EEG as a biomarker to demonstrate the translatability of p-EEG effects should be made with caution, however, because they depend on the particular EEG or sleep parameter that is being studied. The contribution of animal p-EEG studies to the translational characterisation of centrally active drugs can be furthered by adherence to guidelines for methodological standardisation, which are presently under construction by the International Pharmaco-EEG Society (IPEG). 
26901055	Narcolepsy-cataplexy is a sleep-wake disorder and suggested to be immune-mediated, involving genetic and environmental factors. The autoimmune process eventually leads to a loss of hypocretin neurons in the lateral hypothalamus. Epidemiological studies in several countries proved an increased incidence of narcolepsy after H1N1 flu vaccination and infection. This survey in 30 sleep centers in Switzerland led to the identification of 9 H1N1-vaccinated children and adults as newly diagnosed narcolepsy. Clinical features included the abrupt and severe onset of sleepiness, cataplexy and sleep fragmentation. 
26900739	Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD). The aim of this study was to estimate the correlates of NPS in patients with PD in the initial motor stage of the disease (hemiparkinsonism). A total of 111 patients with PD and 105 healthy control participants were assessed. Patients with PD experienced apathy, depression, and anxiety more frequently compared with healthy controls. Sleep disturbances occurred commonly in early PD patients. Patients with PD and mild cognitive impairment (MCI) had depression and anxiety more frequently, but not apathy, compared with patients with PD without MCI. The results of this study confirm a high burden of NPS even in the earliest motor stage of PD. 
26900637	Efavirenz is part of the first-line treatment for HIV patients including those in South Africa with approximately 50% experiencing neuropsychiatric side effects. A systematic review of papers reporting neuropsychiatric side effects with efavirenz published between January 2001 and December 2014 was performed, to provide guidance. 13 articles were reviewed. Patient ages ranged between 37 to 41 years, with a high percentage males. Scales used to measure incidence and severity of side effects were varied; with disease severity or stage not reported. Patients with psychoses were excluded. Most commonly reported side effects were a reduction in sleep quality, depression, dizziness and anxiety. These were generally mild and not warranting discontinuation of efavirenz. It is difficult to directly compare the studies. Standardised methods need to be introduced and all patient groups represented including the elderly, children, patients with active symptomatic illness and more women especially among the African population. 
26896878	Research on self-reported experiences of discrimination and health has grown in recent decades, but has largely focused on racial discrimination or overall mistreatment. Less is known about reports of discrimination on the basis of socioeconomic status (SES), despite the fact that SES is one of the most powerful social determinants of health.We sought to examine the cross-sectional association between self-reported SES discrimination and subjective sleep quality, an emerging risk factor for disease. We further examined whether associations differed by race or SES.	We used logistic and linear regression to analyze data from a population-based cohort of 425 African-American and White middle-aged adults (67.5% female) in the Southeastern United States. SES discrimination was assessed with a modified Experiences of Discrimination Scale and poor subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index.	In logistic regression models adjusted for age, gender, and education, reports of SES discrimination were associated with poor sleep quality among African-Americans (OR = 2.39 95%, CI = 1.35, 4.24), but not Whites (OR = 1.03, 95% CI = 0.57, 1.87), and the race × SES discrimination interaction was significant at p = 0.04. After additional adjustments for reports of racial and gender discrimination, other psychosocial stressors, body mass index and depressive symptoms, SES discrimination remained a significant predictor of poor sleep among African-Americans, but not Whites. In contrast to findings by race, SES discrimination and sleep associations did not significantly differ by SES.	Findings suggest that reports of SES discrimination may be an important risk factor for subjective sleep quality among African-Americans and support the need to consider the health impact of SES-related stressors in the context of race.	
26894478	Sleep disturbances are more common among sarcoidosis patients than in the general population. The influence of organ involvement on the subjective sleep quality was investigated in a large group of sarcoidosis patients.In collaboration with the German Sarcoidosis Association, 1197 sarcoidosis patients were examined with a specially developed questionnaire with the Pittsburgh sleep quality index (PSQI) integrated into it.	91 % had pulmonary involvement, 65 % extra-pulmonary sarcoidosis. In 61 %, two or more organs were involved. Subjective sleep quality in PSQI declined significantly (p < 0.001) with the increase in the number of organs involved; there was a significant increase in the prevalence of known sleep apnea (p < 0.005), restless legs syndrome (RLS), percentage of women and comorbidities (all p < 0.001). In at least 33 % of patients with bone, muscle, nerve, kidney or heart involvement, the PSQI scores were > 10.	In sarcoidosis patients with involvement of at least 2 organs, sleeping behaviour that includes RLS and sleep apnea should be evaluated.	
26892580	Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. The specific threshold of muscle weakness that leads to mobility limitations has not been identified.To determine the best cutoff point of handgrip strength for identifying mobility limitation and to investigate the factors associated with muscle weakness and mobility limitation in community-dwelling older people.	Transversal study.	Cities of Belo Horizonte, Barueri and Santa Cruz in Brazil.	1374 community-dwelling older people from the Frailty study in Brazilian older people (FIBRA Study).	Outcomes included muscle weakness determined according to gender-specific handgrip strength cutoff points generated by Receiver Operating Characteristic curves, mobility limitation defined as a gait speed ≤ 0.8 m/s; and a combination of both muscle weakness and mobility limitation. Associated factors included socio-demographic variables, lifestyle, anthropometrics, health conditions, use of health services and disability.	The cutoff points of handgrip strength with the best balancing between sensitivity and specificity for mobility limitation were 25.8 kgf for men (sensitivity 69%, specificity 73%) and 17.4 kgf (sensitivity 60%, specificity 66%) for women. Age and disability in instrumental activities of daily living were associated with all outcomes. Women had greater odds of mobility limitation than men. Physical inactivity, body fat, diabetes, depression, sleeping disturbances, number of medications and occurrence of falls remained as significant associated factors in the final model.	Handgrip strength can be a useful tool to identify mobility limitation in clinical practice. Interventions to prevent or minimize impacts of sarcopenia should stimulate physical activity and improvement of body composition in addition to the management of chronic diseases and disabilities.	
26891336	Light of short wavelengths has been shown to play a key role in non-image forming responses. Due to aging, the ocular lens becomes more yellow reducing the transmission of short wavelengths in the elderly. In the present study, we make use of cataract surgery to investigate the effects of a relative increase of short wavelength transmission on melatonin- and sleep-wake rhythms (N = 14). We observed, on average, a delay of the sleep-wake and the nocturnal melatonin rhythms after cataract surgery. This delay is tentatively attributed to a relatively large increase of light transmittance in the evening hours more than an increase of the already relatively high light intensities found in the daytime. The later phase that we observed after cataract surgery (clear lens) as compared to the earlier phase observed before cataract (yellowish lens) is in agreement with the general later phase reported in the young (clear lens) population. 
26889894	This commentary is intended to supplement the accompanying review of sleep problems in childhood psychiatric disorders by Gregory and Sadeh. A number of considerations are outlined because of their relevance to both clinical practice and research concerning assessment and treatment of sleep disturbance in children in general and especially those with psychiatric and/or neurological conditions. These considerations (which illustrate the importance of combined medical and psychological involvement) are as follows: the importance of screening for sleep disturbance which otherwise may well be overlooked; the need to specify sleep disorders rather than simply nonspecific sleep problems as this will guide choice of appropriate advice and treatment; the risk of sleep disorders being misdiagnosed because of clinicians' unfamiliarity with the sleep disorders field; the possibility that a child's sleep disturbance is of multiple aetiology; a wide range of treatments for disturbed sleep is now described from which a choice is possible given an accurate diagnosis; sleep problems may be intensified if a child's condition is complicated by intellectual disability but the same principles of assessment and management apply as in other children in the expectation that treatment can be effective. 
26889812	Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.
26888725	The purpose of our study was to evaluate the association between short and long sleep duration and all-cause and cardiovascular mortality among elderly individuals.Systematic review and meta-analysis of population-based cohort studies.	Articles were retrieved from international and national electronic databases.	Studies were identified in PubMed, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), IBECS (Bibliographic Index on Health Sciences from Spain) and CAPES (PhD thesis repository) between 1980 and 2015. Studies which met all criteria were eligible: participants aged 60 years or over, assessment of sleep duration as 24 h, nighttime or daytime sleep, evaluation of all-cause or cause-specific mortality, population-based cohort studies conducted on representative samples. There was no language restriction and studies published as abstracts were excluded.	Data were analysed using the Comprehensive Meta-Analysis software (V.3.3.070), and summary estimates (relative risk (RR), 95% CI) were calculated using a random effects model. Heterogeneity and consistency were evaluated through Cochran's Q and the I(2) statistics, respectively, and sensitivity analyses were conducted.	All-cause and cardiovascular mortality.	Overall, 27 cohort studies were selected, comprising >70,000 elderly individuals, and followed up from 3.4 to 35 years. In the pooled analysis, long and short sleep duration were associated with increased all-cause mortality (RR 1.33; 95% CI 1.24 to 1.43 and RR 1.07; 95% CI 1.03 to 1.11, respectively), compared with the reference category. For cardiovascular mortality, the pooled relative risks were 1.43 (95% CI 1.15 to 1.78) for long sleep, and 1.18 (95% CI 0.76 to 1.84) for short sleep. Daytime napping ≥ 30 min was associated with risk of all-cause mortality (RR 1.27; 95% CI 1.08 to 1.49), compared with no daytime sleep, but longer sleep duration (≥ 2.0 h) was not (RR 1.34; 95% CI 1.95 to 1.90).	Among elderly individuals, long and short sleep duration are associated with increased risk for all-cause mortality. Long sleep duration is associated with cardiovascular mortality.	
26887433	Fatigue is considered as a common symptom in patients with end-stage renal disease (ESRD) and can significantly decrease patients' quality of life. This study aimed to assess fatigue in hemodialysis patients and to investigate risk factors of fatigue in Chinese patients receiving maintenance hemodialysis (MHD) in China.Eligible patients completed questionnaires including demographic information, a Chinese version of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), the Family APGAR Index (APGAR), the medical outcomes study health status-Social Functioning subscale (SF-36,SocF), and the Pittsburgh sleep quality index (PSQI). Laboratory parameters were abstracted by medical records review. The multiple linear regression model was used to relate parameters with the FACIT-Fatigue score.	A total of 345 MHD patients (216 men and 129 women, age 55.6 ± 12.8) were recruited in this study. The score of FACIT-Fatigue was 39 (Interquartile Range, 31-44). Fatigue was correlated with PSQI scores (p < 0.001), SocF scores (p < 0.001), comorbidity (p = 0.006), exercise time <1 hour per day (p = 0.003), adequacy of dialysis (Kt/V) < 1.2 (p = 0.016), APGAR scores (p = 0.014), and high Scr (p = 0.043).	Fatigue is related to sleep disturbance, social and family functioning, taking physical exercise time, comorbidity condition, Kt/V and serum creatinine level in Chinese MHD patients. Future studies and interventions should focus on developing strategies and improving the quality of life in patients by addressing these significant contributing factors.	
26885786	Psoriasis is a debilitating skin disease associated with substantial pruritus, work impairment, and sleep disturbance.This study evaluated associations between pruritus and work productivity, and the role of sleep problems as a possible mediator of the relationship between the two.	Data from a pruritus visual analog scale (Itch VAS), the Medical Outcomes Study Sleep Scale (MOS-SS), and the Work Productivity and Activity Impairment Questionnaire (WPAI) were collected in a phase 2 clinical trial in patients with psoriasis treated with ixekizumab or placebo. Mediating effects of sleep were tested in multiple regressions with pruritus severity (independent variable) and work productivity (dependent variable). Sobel tests evaluated the significance of sleep's effect.	Several MOS-SS domains were significantly associated with the WPAI presenteeism, work productivity, and activity impairment scores, and decreased the effect of pruritus. Sobel tests indicated that the Sleep Problems Index I had a significant effect (P<.05) in mediating the relationship between pruritus and presenteeism, work productivity, and activity impairment.	Sleep may mediate the role of pruritus on work productivity, but both factors appear to have independent negative effects on work.	
26885400	Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states. 
26884049	This randomised controlled trial (RCT) aimed to evaluate the efficacy of a self-guided internet-based stress management intervention (iSMI) for employees compared to a 6-month wait-list control group (WLC) with full access for both groups to treatment as usual.A sample of 264 employees with elevated symptoms of perceived stress (Perceived Stress Scale, PSS-10 ≥22) was randomly assigned to either the iSMI or to the WLC. The iSMI consisted of seven sessions and one booster session including problem-solving and emotion regulation techniques. Self-report data were assessed at baseline, at 7 weeks and at 6 months following randomisation. The primary outcome was perceived stress (PSS-10). The secondary outcomes included other relevant mental-related and work-related health outcomes. Data were analysed based on intention-to-treat principles.	The iSMI participants showed a significantly higher reduction in perceived stress from baseline to post-treatment at 7 weeks (d=0.96, 95% CI 0.70 to 1.21) and to the 6-month follow-up (d=0.65, 95% CI 0.40 to 0.89) compared to the WLC. Significant differences with small to moderate effect sizes were also found for depression, anxiety, emotional exhaustion, sleeping problems, worrying, mental health-related quality of life, psychological detachment, emotion regulation skills and presenteeism, in favour of the experimental group. At the 6 -month follow-up, all outcomes remained significantly better for the experimental group with the exception of work engagement, physical health-related quality of life and absenteeism, which were not found to significantly differ between the iSMI and WLC groups.	The iSMI investigated in this study was found to be effective in reducing typical mental-related and work-related health symptoms of stressed employees. Internet-based self-guided interventions could be an acceptable, effective and potentially cost-effective approach to reduce the negative consequences associated with work-related stress.	

26881786	The transition due to immigration from one country to another country (referred to as immigration transition henceforth) is inherently stressful, placing an additional dimension of stress to midlife women in the menopausal transition. However, few studies have examined the association of immigration to sleep-related symptoms experienced by midlife women in the menopausal transition. The authors' purpose for this study was to explore the associations of immigration to sleep-related symptoms among four major racial/ethnic groups of 1,054 midlife women in the United States. This was a secondary analysis of data from two national surveys that were collected from 2005 to 2013. The instruments included questions on background characteristics, health and menopausal status, immigration transition, and the Sleep Index for Midlife Women. The data were analyzed using t-tests, chi-square tests, correlation analyses, and hierarchical multiple regression analyses. Immigrants reported fewer total numbers of and lower total severity scores of sleep-related symptoms than non-immigrants (p < .01). Yet, when background characteristics and health and menopausal status were controlled, self-reported racial/ethnic identity was the only significant factor associated with sleep-related symptoms (ΔR2 = 0.02, p < .01). Health-care providers need to consider self-reported racial/ethnic identity as a factor significantly related to sleep-related symptoms during the menopausal transition.
26881294	HIV infection has been historically considered a disease of young adults; however, adults aged 50 years and older represent now an increasing proportion of HIV cases worldwide, including in Portugal. In this context, given the considerable burden associated with living with HIV, the topic of quality-of-life (QoL) assessment has become increasingly relevant. The aims of this study were to examine the age-related differences in QoL and depressive symptoms of younger and middle-aged and older adults with HIV as well as the sociodemographic, HIV-related and depressive symptoms (cognitive-affective and somatic) associated with QoL domains. The sample consisted of 1194 HIV-infected patients, recruited from 10 Portuguese hospitals. QoL data were collected using the WHOQOL-HIV-Bref questionnaire. Patients also completed the Beck Depression Inventory. Of the 1194 patients, 185 (15.5%) were over 50 years old. Middle-aged and older patients reported significantly lower QoL in the physical, independence and social relationships domains. Regarding the specific facets of QoL, middle-aged and older patients reported significantly lower scores in seven of the 29 specific facets of the WHOQOL-HIV-Bref and higher scores in one facet (financial resources). Overall, among middle-aged and older patients, higher education, being employed, a shorter time since HIV diagnosis, use of combination anti-retroviral therapy and fewer depressive symptoms were significantly associated with higher QoL ratings. Our findings suggest that both cognitive-affective and somatic depressive symptoms account for significant variability in QoL scores in middle-aged and older patients. Because an important feature of healthy ageing is maintaining QoL, these data may provide useful information for tailoring age-appropriate and effective interventions to improve the mental health and QoL of middle-aged and older patients living with HIV.
26879311	Migraine clinical presentation and life-time course can be highly heterogeneous, with a subgroup of patients developing chronic migraine; moreover, migraine clinical spectrum is expanded by the association with different coexisting conditions and interictal dysfunctions. The aim of this study was to systematically evaluate migraine clinical features, daily functioning parameters, sleep pattern, presence of depressive-anxiety symptoms and body mass index (BMI) in a sample of 75 episodic and 75 chronic migraine without aura patients. Migraine-related disability, fatigue, daily sleepiness, subjective sleep quality, anxiety and depressive symptoms were, respectively, evaluated using the following questionnaires: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire 9-item Scale (PHQ-9). Mean FSS score (p < 0.001), PSQI score (p = 0.015), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.012) were significantly higher in chronic compared to episodic migraineurs. Additionally, a correlation analysis carried out in the total sample of 150 migraine patients documented a statistically significant, positive correlation between monthly frequency of migraine attacks and FSS score (p < 0.001), PSQI score (p = 0.006), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.049). Data from the present report seem to expand the concept of migraine as a continuum or spectrum, with greater occurrence of fatigue, poor sleep quality, anxiety-depressive symptoms and higher BMI score in chronic compared to episodic migraine patients; further investigation is certainly necessary to better define the biological basis and mechanisms associated with migraine transformation from episodic to chronic pattern. 
26878399	BACKGROUND Nasal septal perforation (NSP) may alter nasal airflow patterns and physiology. To the best of our knowledge, no studies in the English literature have investigated the effect of NSP and its treatment on polysomnographic parameters. In this study, we aimed to investigate polysomnographic parameters in patients with NSP as well as changes in those parameters after treatment of NSP. MATERIAL AND METHODS Nineteen patients diagnosed with NSP were included in the study. All patients had baseline and post-procedure polysomnographies (PSG) after insertion of silicone septal button for closure of NSP. RESULTS Both median AHI [5.30 (14.40) vs. 2.40 (14.50)] and median supine AHI [10.00 (42.10) vs. 6.60 (37.00)] decreased after correction of the perforation. There was a large reduction in median supine AHI in patients with a perforation size >66 mm2 [10.10 (34.15) vs. 1.60 (28.30)]. CONCLUSIONS We conclude that NSP did not cause any deterioration in objective sleep parameters as determined by PSG, other than a decrease in REM sleep duration and an increase in supine AHI. Correction of NSP did not affect REM duration and supine AHI decreased after treatment. 
26873990	Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers. 
26869817	Sleep-wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep-wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep-wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer's disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson's disease, and the insomnia and circadian dysregulation associated with Huntington's disease. 
26869781	The aim was to assess and compare reported sleep disturbances and objectively measured sleep in men and women with COPD compared with controls and also explore sex differences.A total of 96 patients with COPD and 90 age- and sex-matched controls answered a sleep questionnaire, underwent ambulatory polysomnography, a post-bronchodilatory spirometry, and blood sampling.	Of the patients with COPD, 51% reported sleep disturbances as compared with 31% in controls (P=0.008). Sleep disturbances were significantly more prevalent in males with COPD compared with controls, whereas there was no significant difference in females. The use of hypnotics was more common among patients with COPD compared with controls, both in men (15% vs 0%, P=0.009) and women (36% vs 16%, P=0.03). The men with COPD had significantly longer recorded sleep latency than the male control group (23 vs 9.3 minutes, P<0.001), while no corresponding difference was found in women. In men with COPD, those with reported sleep disturbances had lower forced vital capacity, higher C-reactive protein, myeloperoxidase, and higher prevalence of chronic bronchitis.	The COPD was associated with impaired sleep in men while the association was less clear in women. This was also confirmed by recorded longer sleep latency in male subjects with COPD compared with controls.	
26869622	We present a case of a man who experienced night sweats, abdominal pain and fever for over 3 months, with incomplete response to broad-spectrum intravenous antibiotics. Although CT imaging was insufficient to identify the cause for his chronic abdominal pain, the abnormality of a 'misty mesentery' was crucial in guiding further investigation. The final diagnosis of chronic appendicitis was made through laparoscopic and pathological examination. This case highlights the utility of a collaborative diagnostic effort between disciplines. Chronic appendicitis can cause lingering abdominal pain. Early recognition and appropriate referral can save patients months and even years of unnecessary suffering. 
26869012	Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers.Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks.	Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times.	These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action.	
26868675	Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine. 
26868467	The aim of the study was to characterize pain associated with oral mucosal lesions.A cross-sectional study was performed in patients diagnosed with localized mucosal pain originating from acute ulcers (AUs), herpes infections (HIs), and immune-mediated chronic diseases (IMCDs). Pain-related features, including intensity (VAS-I), perceived unpleasantness (VAS-U), functional impairment (VAS-F), and effect on quality of life (VAS-Q), were recorded using a 10-cm visual analogue scale (VAS). Waking from sleep, provoking, and alleviating factors were assessed by questionnaires.	Sixty-three patients aged 19 to 82 years (47.22 ± 17.20 years) were examined over the study period. These included 18 patients with AUs, 21 with HIs, and 24 with IMCDs. At rest, VAS-U was significantly higher than VAS-I for all groups, and VAS-F was higher for lesions located on the tongue or lips. Up to 80% of patients described the pain as "burning." Differences between groups were not observed for all other parameters measured. Pain woke the patients from sleep in almost half of cases. VAS-I and VAS-U were not related to size or number of lesions.	Mucosal pain is generally burning in quality, with a higher level of pain-related unpleasantness than pain intensity. In about half of the cases, pain awakens the person from sleep, a feature that correlated to female gender and pain intensity. Pain intensity or unpleasantness was not related to the size or number of lesions.	
26866932	Integration of knowledge concerning circadian rhythms, metabolic networks, and sleep-wake cycles is imperative for unraveling the mysteries of biological cycles and their underlying mechanisms. During the last decade, enormous progress in circadian biology research has provided a plethora of new insights into the molecular architecture of circadian clocks. However, the recent identification of autonomous redox oscillations in cells has expanded our view of the clockwork beyond conventional transcription/translation feedback loop models, which have been dominant since the first circadian period mutants were identified in fruit fly. Consequently, non-transcriptional timekeeping mechanisms have been proposed, and the antioxidant peroxiredoxin proteins have been identified as conserved markers for 24-hour rhythms. Here, we review recent advances in our understanding of interdependencies amongst circadian rhythms, sleep homeostasis, redox cycles, and other cellular metabolic networks. We speculate that systems-level investigations implementing integrated multi-omics approaches could provide novel mechanistic insights into the connectivity between daily cycles and metabolic systems. 
26865627	Understanding the control of sleep-wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep-wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that "selective" stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of "selective" optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons.Optogenetics is a revolutionary tool to assess the roles of particular groups of neurons in behavioral functions, such as control of sleep and wakefulness. However, the interpretation of optogenetic experiments requires knowledge of the effects of stimulation on local neurotransmitter levels and effects on neighboring neurons. Here, using a novel "opto-dialysis" probe to couple optogenetics and in vivo microdialysis, we report that optical stimulation of basal forebrain (BF) cholinergic neurons in mice increases local acetylcholine levels and wakefulness. Reverse microdialysis of cholinergic antagonists within BF prevents the wake-promoting effect. This important result challenges the prevailing dictum that BF cholinergic projections to cortex directly control wakefulness and illustrates the utility of "opto-dialysis" for dissecting the complex brain circuitry underlying behavior.	
26864839	The purpose of this qualitative study was to explore psychiatric inpatients' reflections on their experiences with sleep throughout their lives. Fourteen patients in an acute care behavioral health unit agreed to participate in this study. Participants met individually with a researcher to reflect on times in their lives when they experienced good sleep; times when they had difficulty sleeping; and times when difficult sleep was resolved. The major findings of the study indicated that feeling alone with life problems triggered difficult sleep; while feelings of belonging and purpose were associated with good sleep.
26863894	Athletes at different skill levels perform strenuous physical activity at high altitude for a variety of reasons. Multiple team and endurance events are held at high altitude and may place athletes at increased risk for developing acute high altitude illness (AHAI). Training at high altitude has been a routine part of preparation for some of the high level athletes for a long time. There is a general belief that altitude training improves athletic performance for competitive and recreational athletes.A review of relevant publications between 1980 and 2015 was completed using PubMed and Google Scholar.	Clinical review.	Level 3.	AHAI is a relatively uncommon and potentially serious condition among travelers to altitudes above 2500 m. The broad term AHAI includes several syndromes such as acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). Athletes may be at higher risk for developing AHAI due to faster ascent and more vigorous exertion compared with nonathletes. Evidence regarding the effects of altitude training on athletic performance is weak. The natural live high, train low altitude training strategy may provide the best protocol for enhancing endurance performance in elite and subelite athletes. High altitude sports are generally safe for recreational athletes, but they should be aware of their individual risks.	Individualized and appropriate acclimatization is an essential component of injury and illness prevention.	
26863349	Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the homeodynamics and circuitry of sleep-wake regulation. In many laboratories, a cable-based sleep recording system is used to monitor the EEG and EMG in freely behaving mice in combination with computer software for automatic scoring of the vigilance states on the basis of power spectrum analysis of EEG data. A description of this system is detailed herein. Steel screws are implanted over the frontal cortical area and the parietal area of 1 hemisphere for monitoring EEG signals. In addition, EMG activity is monitored by the bilateral placement of wires in both neck muscles. Non-rapid eye movement (Non-REM; NREM) sleep is characterized by large, slow brain waves with delta activity below 4 Hz in the EEG, whereas a shift from low-frequency delta activity to a rapid low-voltage EEG in the theta range between 6 and 10 Hz can be observed at the transition from NREM to REM sleep. By contrast, wakefulness is identified by low- to moderate-voltage brain waves in the EEG trace and significant EMG activity. 
26861410	The sleep-wake cycle is regulated by a fine-tuned interplay between sleep-homeostatic and circadian mechanisms. Compelling evidence suggests that adenosine plays an important role in mediating the increase of homeostatic sleep pressure during time spent awake and its decrease during sleep. Here, we summarize evidence that adenosinergic mechanisms regulate not only the dynamic of sleep pressure, but are also implicated in the interaction of homeostatic and circadian processes. We review how this interaction becomes evident at several levels, including electrophysiological data, neuroimaging studies and behavioral observations. Regarding complex human behavior, we particularly focus on sleep-wake regulatory influences on working memory performance and underlying brain activity, with a specific emphasis on the role of adenosine in this interplay. We conclude that a change in adenosinergic mechanisms, whether exogenous or endogenous, does not only impact on sleep-homeostatic processes, but also interferes with the circadian timing system. 
26859995	The results of study of sleep-wakefulness cycle in experimental models of pre-clinical and early clinical stages of Parkinson's disease present and compared to some clinical examples. The conclusion is, the increase in activity level and decrease in total amount of slow wave and paradoxical sleep in model animals are taking place at the same circadian period of the secretion of pineal melatonin as sleep disorders in patients.
26857307	Children with Down syndrome (DS) have a high prevalence of sleep problems, including behavioural sleep disturbances and obstructive sleep apnea. Sleep problems are associated with a wide range of adverse health effects. Since children with DS are already known to have many comorbidities, they are particularly susceptible for the negative impact of sleep problems. Aim of this study is (1) to evaluate the prevalence of sleep problems in children with DS, (2) compare the prevalence of sleep problems in children with DS with a community sample of typical developing school-aged children, and (3) to correlate the existence of sleep problems in children with DS and OSA.Children enrolled at the multidisciplinary Down team of the University Hospital Antwerp and seen at the ENT department were eligible for this study. The prevalence of sleep problems was evaluated by the use of the Child Sleep Habits Questionnaire (CSHQ) and a full overnight polysomnography was performed to screen for obstructive sleep apnea.	Parents of fifty-four children with DS, aged 7.5 years (5.4-11.6), completed the CSHQ and an overall prevalence of sleep problems was found in 74.1%. In 57.1% of the children OSA was diagnosed with a median obstructive apnea-hypopnea index (oAHI) 7.25/h (5.7-9.8). Overall sleep problems were not age-or gender related, however boys suffer more from daytime sleepiness. Symptoms of sleep disordered breathing correlate with parasomnias, a longer sleep duration and more daytime sleepiness. No correlation was found between sleep problems and underlying OSA.	Children with Down syndrome have a significantly higher prevalence of sleep problems, compared to normal developing healthy school-aged children. We didn't find any correlation between the parental report of sleep problems and underlying OSA, or OSA severity.	
26857057	To compare sleep/wake patterns in children born preterm in Australia vs Canada and determine cultural differences in the relationship between parental perception of sleep and actual sleep behaviors.Australian and Canadian children born preterm were recruited from the Caffeine for Apnea of Prematurity trial (n = 188, 5-12 y) and underwent 14 days actigraphy monitoring. Parents completed the National Sleep Foundation 2004 Sleep in America questionnaire. Cross-cultural differences in sleep characteristics assessed by actigraphy and parent-reported questionnaire were examined. Correlational analyses determined the associations between parental perceptions of child sleep need and sleep behavior.	Actigraphy showed preterm children obtained, on average, 8 h sleep/night, one hour less than population recommendations for their age. There was no difference in total sleep time (TST) between Australian and Canadian cohorts; however, bed and wake times were earlier in Australian children. Bedtimes and TST varied by 60 minutes from night to night in both cohorts. Parent-reported child TST on the National Sleep Foundation questionnaire was 90 minutes longer than recorded by actigraphy. Both bedtime and TST on weekdays and weekends were related to parental perception of child sleep need in the Australian cohort. Only TST on weekdays was related to parental perception of child sleep need in the Canadian cohort.	This study suggests that short sleep duration and irregular sleep schedules are common in children born preterm. Cultural differences in the association between parental perception of child sleep need and actual sleep behaviors provide important targets for future sleep health education.	

26856852	Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy.Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy.	Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior.	Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone + pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated.	These data suggest that cortisol, progesterone, and ALLO + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses.	
26856810	Symptoms of sleep disturbance, particularly nightmares and insomnia, are a central feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that specific treatment of PTSD-related sleep disturbance improves other symptoms of the disorder, which in turn suggests that such disturbance may be fundamental to development and maintenance of the disorder. This mini-review focuses on pharmacological treatment of sleep disturbance in adult PTSD (specifically, studies testing the efficacy of antidepressants, adrenergic inhibiting agents, antipsychotics and benzodiazepine and non-benzodiazepine hypnotics). We conclude that only prazosin, an adrenergic inhibiting agent, has had its efficacy established by multiple randomised controlled trials. There is also high-level evidence supporting use of eszopiclone, as well as risperidone and olanzapine as adjunct therapy. Antidepressants such as sertraline, venlafaxine and mirtazapine, benzodiazepines such as alprazolam and clonazepam and non-benzodiazepine hypnotics such as zolpidem appear ineffective in treating PTSD-related sleep disturbance. Most studies that report reduced frequency of nightmares and insomnia also report decreases in overall symptom severity. Such findings suggest that (i) sleep disruption is central to PTSD; (ii) treating sleep disruption may be an effective way to address other symptoms of the disorder and (iii) PTSD symptoms tend to cluster together in predictable ways.
26856133	Mass introduction of lighting devices according to the concept of "maximum coverage area" and multistoried buildings of cities gave rise to light pollution, which became a problem for astronomers, ecologists and hygienists. Analysis of modern lighting devices and installations has shown that about 30-45% of the luminous flux becomes the light pollution. Night lighting of cities causes both direct and indirect damage to the environment, leads to unnecessary energy wastes. So in the USA due to excessive light there is wasted about 2 million barrels of oil per day. Light pollution affects the human hormonal system, causing various health disorders, such as insomnia and depression as a consequence. The light pollution through the ganglion cells of the retina affects the synthesis of melatonin by the pineal gland (epiphysis) and contributes to its calcification, which greatly affects the human psyche. At present, many countries have been paying much state attention to this problem via delivery of national documents and change of the concept of the designing of lighting devices and installations. The essence of this concept--to shine with a preset quality of light only in the right place at the specified time interval. This reduces the light pollution, saves energy and increases the environmental safety of lighting. There is presented an example of a technical solution to reduce the light pollution in the application of the light panel in the form of the gradient of the light guide generator project development.
26855610	The purpose of this article was to provide an overview of the effects of the sleep education with self-help treatment for student, teacher, and local resident and sleep health promotion for mental and physical wellness for elderly with actual examples of public health from the community and schools. Sleep education with self-help treatment in schools revealed that delayed or irregular sleep/wake patterns were significantly improved. Also, it was effective for improving sleep-onset latency, sleep satisfaction, mood during the morning, and daytime sleepiness. The strategy of this sleep education included the acquisition of the correct knowledge about sleep and the sleep-related behaviors that are important for improving sleep. Sleep health promotion that included short naps and exercise in the evening (Sleep health class) was effective in promoting sleep and mental health with elderly people. The interventions demonstrated that the proper awakening maintenance, keeping proper arousal level during the evening was effective in improving sleep quality. Furthermore, sleep management that included sleep education and cognitive-behavioral interventions improved sleep-related habits and the quality of sleep. In this study, a sleep educational program using minimal cognitive-behavioral modification techniques was developed. Mental and physical health was also improved with better sleep in the elderly. These results suggest that sleep health promotion is effective for mental and physical wellness for the elderly.
26855327	Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, and a medical treatment for narcolepsy and other neuropsychiatric disorders. Its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are endogenously converted to GHB and thereby exert their psychobehavioural effects. In humans, GHB has a wide spectrum of properties ranging from stimulation and euphoria in lower doses, to sedation, deep sleep, and coma after ingestion of high doses. However, behavioural studies in healthy volunteers remain scarce and are usually limited to psychomotor performance testing. Most available data arise from either qualitative studies with illicit users or clinical trials examining therapeutic properties of GHB (then usually termed sodium oxybate). Here, we present an overview of the behavioural effects of GHB, GBL, and 1,4-BD in these three populations. GHB and its precursors strongly influence behaviours related to core human autonomic functions such as control of food intake, sexual behaviour, and sleep-wake regulation. These effects are instrumentalised by illicit users and clinically utilised in neuropsychiatric disorders such as narcolepsy, fibromyalgia, and binge-eating syndrome. Considering the industry withdrawal from psychopharmacology development, repurposing of drugs according to their behavioural and clinical profiles has gained increasing relevance. As such, GHB seems to be an attractive candidate as an experimental therapeutic in depression.
26855097	To examine the association of acupuncture with sleep disturbances and serum sex hormone levels in perimenopausal and postmenopausal women and whether there are associated changes in sex hormone levels.We systematically searched electronic databases (EMBASE, PubMed, PsycINFO, CINAHL, ClinicalTrials.gov, Wanfang Data Chinese Database, and China Knowledge Resource Integrated Database) and the reference lists of the identified studies.	Randomized controlled trials that examined the effects of acupuncture on sleep disturbances in perimenopausal and postmenopausal women were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed.	We identified 31 randomized controlled trials with 34 effect sizes involving a total of 2,433 participants. Acupuncture is associated with a significant reduction in the likelihood of sleep disturbances (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.14-0.31), a significant increase in the secretion of serum estradiol (pooled difference in means 7.56 pg/mL, 95% CI 4.03-11.08), and reduction in the secretion of serum follicle-stimulating hormone (-6.75 milli-international units/mL, 95% CI -12.16 to -1.34) and luteinizing hormone (-2.71 milli-international units/mL, 95% CI -4.22 to -1.20). Studies with a large effect size of acupuncture-associated changes in serum estradiol had a significantly lower odds of sleep disturbances than did those with a small-to-moderate effect sizes (ORs 0.07 and 0.36, P=.02).	Acupuncture is associated with a significant reduction in sleep disturbances in women experiencing menopause-related sleep disturbances. Our findings suggest that acupuncture should be adopted as part of a multimodal approach for improving sleep disturbances in perimenopausal and postmenopausal women.	
26853999	Disruptions to sleep and circadian rhythms have now been recognized as common comorbidities in patients with medical illnesses. We aimed to determine if the diurnal rhythms for rest and activity were disrupted in parallel with the development of diabetic complications. Ninety outpatients in our diabetes clinic who had a body mass index <25 kg m(2) wore an actigraph for 7 consecutive days (42 men; mean age 68.7 ± 8.2 years). Patients with neuropsychiatric diseases, liver cirrhosis, renal failure, chronic obstructive pulmonary disease or blindness, or those who performed shiftwork were excluded. We grouped the actigraph recordings into 1-h periods and counted the number of minutes that showed activity. Stepwise regression analysis showed an association between a diabetic clinical background and measurements of circadian rhythms such as daytime activity, night-time activity, phase, interdaily stability, intradaily variability and relative amplitude. Higher age, body mass index, total cholesterol levels and insulin usage were associated with lower daytime activity and higher intradaily variability, whereas higher haemoglobin A1c levels and the presence of neuropathy were associated with greater daytime activity. The presence of proliferative retinopathy and increased levels of microalbuminuria were associated with higher intradaily variability and lower interdaily stability and amplitude. The presence of cardiovascular disease was associated with advanced phase, whereas painful neuropathy was associated with delayed phase. Our study demonstrated that different diabetic complications were associated independently with a variety of alterations in the circadian rest and activity rhythms. Our findings have provided novel insights that may be helpful in developing interventions for sleep-wake disorders associated with diabetes. 
26853813	In preeclampsia and gestational diabetes, the sympathetic nerves are activated, leading to disrupted sleep. Melatonin, which transmits information to regulate the sleep-wake rhythm and other such biorhythms, has been implicated in insulin resistance, antioxidant behaviors, and metabolic syndrome. In addition, its reduced secretion increases the risk of hypertension and diabetes. The aim of this study was to elucidate the features of melatonin secretion, sleep quality, and sleep-wake rhythms in pregnant women with complications. Fifty-eight pregnant women with pregnancy complications (hypertensive or glucose metabolic disorders) and 40 healthy pregnant women completed questionnaires, including sleep logs and the Pittsburgh Sleep Quality Index (PSQI), during the second to third trimesters. Their salivary melatonin levels were also measured. Pregnant women with complications had significantly lower morning (p < 0.001), daytime (p < 0.01), evening (p < 0.001), night (p < 0.01), daily mean (p < 0.001), peak (p < 0.001), and bottom (p < 0.01) melatonin values than healthy pregnant women. Pregnant women with complications also had significantly smaller melatonin amplitudes than healthy pregnant women (p < 0.001). Among pregnant women with complications, the duration (p < 0.05) and frequency (p < 0.01) of wake after sleep-onset were significantly greater in the poor sleep group than in the favorable sleep group which was divided by PSQI cutoff value. Pregnant women with hypertensive or glucose metabolic disorder complications had smaller circadian variation in salivary melatonin secretion, and their values were lower throughout the day than healthy pregnant women. 
26853244	To investigate the effects of non-drug interventions on the sleep quality of patients after mechanical cardiac valve implantation.In this prospective, randomized, controlled trial, 64 patients scheduled for mechanical mitral valve replacement were recruited. Patients underwent cognitive behavioral therapy and wore noise cancelling earplugs and eye mask. Sleep quality was evaluated on the 4th after admission and the 5th days after operation. The primary outcome was the total sleep quality score differences between the 4th day after admission and the 5th day after operation.	All patients had been suffering from poor sleep quality for a month before admission. There was no difference between both groups on the 4th day after admission. Overall sleep quality in the intervention group was better than in the control group on the 5th day after operation. The subjective sleep quality of the patients in each group was significantly lower on the 5th day after the operation than on the 4th day after admission (P <0.05).	Non-drug intervention could improve the sleep quality of patients after mechanical cardiac valve implantation and help the postoperative recovery of the patients. (	ChiCTR-TRC-14004405, 21 March 2014.).	
26852225	Anchoring vignettes are brief texts describing a hypothetical character who illustrates a certain fixed level of a trait under evaluation. This research uses vignettes to elucidate factors associated with sleep disorders in adult Japanese before and after adjustment for reporting heterogeneity in self-reports. This study also evaluates the need for adjusting for reporting heterogeneity in the management of sleep and energy related problems in Japan.We investigated a dataset of 1002 respondents aged 18 years and over from the Japanese World Health Survey, which collected information through face-to-face interview from 2002 to 2003. The ordered probit model and the Compound Hierarchical Ordered Probit (CHOPIT) model, which incorporated anchoring vignettes, were employed to estimate and compare associations of sleep and energy with socio-demographic and life-style factors before and after adjustment for differences in response category cut-points for each individual.	The prevalence of self-reported problems with sleep and energy was 53 %. Without correction of cut-point shifts, age, sex, and the number of comorbidities were significantly associated with a greater severity of sleep-related problems. After correction, age, the number of comorbidities, and regular exercise were significantly associated with a greater severity of sleep-related problems; sex was no longer a significant factor. Compared to the ordered probit model, the CHOPIT model provided two changes with a subtle difference in the magnitude of regression coefficients after correction for reporting heterogeneity.	Sleep disorders are common in the general adult population of Japan. Correction for reporting heterogeneity using anchoring vignettes is not a necessary tool for proper management of sleep and energy related problems among Japanese adults. Older age, gender differences in communicating sleep-related problems, the presence of multiple morbidities, and regular exercise should be the focus of policies and clinical practice to improve sleep and energy management in Japan.	
26852189	Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).	We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies	Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.	Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.	We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.	Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.	
26851463	Although additive combinations of age and work environment characteristics have been found to predict sleep impairment, possible age x work environment interactions have been largely disregarded. The present study examined linear and curvilinear interactions of age with work environment measures in relation to sleep quality and duration. Survey data were collected from offshore day-shift personnel (N = 901). Main effects and interactions of the age terms with work environment measures (job demand, control, and social support, physical environment and strenuous work) were evaluated. Sleep duration was predicted by a curvilinear interaction, age(2) x job demand (p < .005), and by the age x social support interaction (p < .002); sleep quality was predicted by age x job demand (p < .002). Job control and physical environment showed significant additive effects. At a time when older employees are encouraged to remain in the workforce, the findings serve to increase understanding of how ageing and work demands jointly contribute to sleep impairment.
26850806	To document the use of aromasticks to facilitate sleep in a cancer centre in the UK. Sleep disturbance is a common problem amongst patients diagnosed with cancer. Essential oils may be inhaled by means of an aromastick (a personal inhaler device containing essential oils) as a means of improving sleep. A prospective audit of aromasticks given to help facilitate sleep. Sixty-five aromasticks were given out over a 13 week period. 94% of patients reported that they did use their aromastick to help them sleep and 92% reported that they would continue to do so. An improvement of at least one point on a Likert scale measuring sleep quality was shown by 64% of patients following the use of an aromastick. Bergamot (Citrus bergamia) and sandalwood (Santalum austrocaladonicum); and frankincense (Boswellia carterii), mandarin (Citrus reticulata) and lavender (Lavandula angustifolia) were the essential oils used in the two blends chosen by patients. 
26848569	Post-stroke sleep disturbances (PSSD) are common and associated with various adverse outcomes. However, PSSD in the sub-acute stages of stroke have been scarcely studied. We aimed to evaluate the characteristics of and the factors related to PSSD in stroke patients 3 months post stroke.A total of 199 patients were evaluated for PSSD at 3 months after stroke. The qualities of nighttime sleep and excessive daytime sleepiness (EDS) were assessed using the Verran Snyder-Halpern sleep scale and Epworth Sleepiness Scale, respectively. Presence of motor dysfunction and post-stroke pain, post-stroke depression, fatigue and social support were evaluated.	Eighty-eight patients (44.2%) had poor quality of nighttime sleep. Twenty-eight patients (14.4%) reported EDS. Poor quality of nighttime sleep was independently associated with depression (p = 0.044) and EDS (p = 0.041) whereas fatigue (p < 0.001) and poor nighttime sleep (p = 0.045) were independently associated with EDS. Post-stroke pain and social support showed no association with PSSD.	We found that the occurrence of PSSD 3 months after stroke is common. Although causality remained to be determined, depression and nighttime sleep disturbances were related, whereas fatigue and nighttime sleep disturbances were related to EDS.	
26847980	Sleep is important for optimal cognitive functioning across the lifespan. Among older adults (≥55 years), self-reported short and long sleep durations have been repeatedly, albeit inconsistently, reported to elevate the risk for poor cognitive function. This meta-analytic review quantitatively summarizes the risk for poorer cognitive function among short and long sleepers in older adults. Eligible publications were searched online and manually. A total of 35 independent samples (N = 97,264) from 11 cross-sectional and seven prospective cohort studies were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) were derived using random-effects models. Self-reported short and long sleep increased the odds for poor cognitive function by 1.40 (CI = 1.27-1.56) and 1.58 times (CI = 1.43-1.74), respectively. Effect sizes varied across studies and may have been moderated by both study type (cross-sectional and prospective) and cognitive domain assessed. For cross-sectional studies, extreme sleep durations were significantly associated with poorer multiple-domain performance, executive functions, verbal memory, and working memory capacity. Prospective cohort studies revealed the significant long-term impact of short and long sleep on multiple-domain performance only. These findings establish self-reported extreme sleep duration as a risk factor for cognitive aging. 
26847978	To investigate the prevalence of bed-sharing and examine correlates of bed-sharing habits in early adolescents.Participants were 1452 early adolescents from 10 primary schools in Shanghai, China. Children's health status and past history, family environment and parents' attitude towards bed-sharing, and children's sleep arrangements were surveyed. Sleep was assessed by the Children's Sleep Habit Questionnaire. Tanner stage was determined by the endocrinologist.	The median of age was 10.83 years (range: 9.42-12.92; 95% confidence interval [CI]: 10.79-10.83) and boys accounted for 51.17%. The prevalence of bed-sharing was 16.8%. Positive parental attitude toward bed-sharing (OR: 9.87; 95% CI: 6.57-14.83), asthma (OR: 2.15; 95% CI: 1.16-3.98), smaller residential space (OR: 1.90; 95% CI: 1.17-3.09), extended family (OR: 1.59; 95% CI: 1.16-2.18), and being physically less mature (OR: 2.39; 95% CI: 1.16-4.91) increased the likelihood of bed-sharing. Bed-sharers were more likely to have bedtime resistance (OR: 12.20; 95% CI: 8.59-17.33), sleep anxiety (OR: 3.76; 95% CI: 2.74-5.15), and poor sleep quality (OR: 3.21; 95% CI: 2.28-4.81) compared to non-bed-sharers. Furthermore, bed-sharing was associated with daytime sleepiness (OR: 1.53; 95% CI: 1.10-2.13) but not with sleep duration.	Bed-sharing is highly prevalent among Chinese early adolescents and is significantly related to sleep quality. Parental positive attitude toward bed-sharing was the most determining factor.	
26847977	To examine the association between self-reported sleep quality and cognitive decline one year later.A longitudinal study of 1010 cognitively intact adults, aged 65-80 years at baseline, from two urban communities in China was performed. Sleep quality at baseline was measured using the Pittsburgh Sleep Quality Index (PSQI). Cognitive function was determined by using the Chinese version of Mini-Mental State Examination (CMMSE) at the baseline and one year later. Substantial CMMSE decline was defined as the CMMSE score decreases by three or more points during the follow-up. Potential confounders, such as age, sex, education, baseline CMMSE score, depression, physical activity level, drinking status, smoking status, body mass index, snoring frequency, history of hypertension, diabetes, and coronary heart disease were measured via questionnaires or physical examination.	After adjusting for potential confounders, individuals with poor sleep quality (PSQI > 7), relative to whose with good sleep quality, had 0.32 (95% CI: -0.62, -0.02; p = 0.04) CMMSE-points more decline and tended to have a higher likelihood of developing substantial CMMSE decline (OR = 1.46; 95% CI: 0.97, 2.18; p = 0.06). Among seven subscales of the PSQI, poor sleep efficiency was associated with greater CMMSE decline (beta = -0.16, 95% CI: -0.29, -0.03; p = 0.01) and higher risk of substantial CMMSE decline (OR = 1.24, 95% CI: 1.05, 1.46; p = 0.01). Short sleep duration (sleeping ≤5 h/night) was also significantly associated with more CMMSE decline and a higher likelihood of developing substantial CMMSE decline (p <0.05 for both).	Self-reported poor sleep quality may be an indicator of early cognitive decline for elderly people and should be paid particular attention by clinicians.	
26847976	Sleep disorders (SD) and erectile dysfunction (ED) both play crucial roles in quality of life and have received increasing attention in the general population and among physicians.This study investigated the risk of ED in people diagnosed with SD compared with that in age- and sex-matched unaffected people. This longitudinal, nationwide, population-based cohort study was conducted using data in the Taiwan National Health Insurance Research Database (NHIRD) from January 1998 to December 2011. The sample consisted of 603 people with sleep apnea, 17,182 people with non-apnea SD, and 35,570 matched comparisons as controls. A Cox proportional hazard regression was used to compute the risk of ED in people with SD relative to that in people without SD.	The ED incidences were 9.44-fold higher (95% CI 6.49-13.7) in the sleep apnea cohort and 3.72-fold higher (95% CI 3.13-4.41) in the non-apnea SD cohort than in the control cohort, respectively, after age, sex, and comorbidities were adjusted for. The incidence of ED was higher in younger adults (adjusted hazard ratio (HR), 10.4 (95% CI 5.93-18.4) in the sleep apnea cohort and adjusted HR, 4.20 (95% CI 3.07-5.76) in non-apnea SD cohort) and those using benzodiazepine (adjusted HR, 9.69 (95% CI 5.48-10.6) in the sleep apnea cohort and adjusted HR, and 3.83 (95% CI 3.20-4.59) in the non-apnea SD cohort).	This nationwide population-based cohort study provides evidence that people with SD, particularly those with sleep apnea, exhibit an increased risk of subsequent ED.	
26847974	Research indicates that physicians may frequently use pharmacotherapy to treat pediatric insomnia despite minimal safety data and very limited indications. Canadian data on the subject are lacking. This study aimed to determine physicians' views on and prescribing habits for sleep-promoting over-the-counter medication (OTCM) and prescription (RXM) medications for children.A modified 26-item version of the 'Pediatric Sleep Medication Survey', originally developed by Judith Owens and colleagues, was sent to 100 pediatricians and a random sample of 421 family physicians in Southwestern Ontario, Canada.	A total of 67 returned surveys were sufficiently complete for analysis. Sixty-one respondents indicated their specialty (28 pediatricians, 33 family physicians). In a typical 6-month period, 89% and 66% of respondents have recommended OTCM and RXM, respectively, for children with sleep problems. Only 20% have received any formal training on pediatric sleep disorders. The most common circumstances and sleep problems for which OTCM or RXM were recommended were mood disorders, developmental delay and attention deficit hyperactivity disorder (ADHD) (56, 40, and 39%, respectively), and insomnia, bedtime struggles/delayed sleep onset and circadian rhythm disorders (52, 48, and 28%, respectively). A total of 30% recommended OTCM or RXM to otherwise healthy children with sleep problems. Melatonin (73%), OTC antihistamines (41%), antidepressants (37%), and benzodiazepines (29%) were the most commonly recommended OTCM and RXM, respectively.	Respondents in our sample frequently use pharmacotherapy to treat pediatric sleep problems; few have received any training in this area. Our findings indicate the need for evidence-based guidelines and regular physician training in the management of pediatric sleep disorders.	
26847973	Behavioral sleep problems are common in children with attention deficit hyperactivity disorder (ADHD), and longitudinal studies have found sleep problems to be both a predictor and outcome of internalizing and externalizing problems. We investigated the potential bidirectional relationship between sleep problems and internalizing/externalizing problems.Children with ADHD, aged 5-13 years, were recruited from 21 pediatric practices across Victoria, Australia (N = 270). Across a 12-month period, at three time points, parents reported on their child's sleep problems (Children's Sleep Habits Questionnaire) and emotional and behavioral functioning (Strengths and Difficulties Questionnaire). Data were analyzed using autoregressive cross-lagged panel models.	Sleep problem severity and emotional/behavioral problem severity were very stable across the 12-month period. Sleep problems at baseline predicted emotional problems at six months (r = 0.17, p < 0.01), and emotional problems at baseline predicted sleep problems at six months (r = 0.07, p < 0.05). However, there was no predictive relationship between sleep problems and emotional problems from 6-12 months. No bidirectional relationship was observed between sleep problems and conduct problems.	In children with ADHD, there is weak evidence of a bidirectional relationship between sleep problems and emotional problems. These symptoms are also very stable over time; therefore, the best treatment approach to improve overall functioning may be to target both sleep and emotional functioning in these children.	
26847969	Children with Down syndrome (DS) have a high rate of pulmonary hypertension and sleepiness. They also have a high prevalence of obstructive sleep apnea syndrome (OSAS). We hypothesized that OSAS was associated with cardiovascular dysfunction and sleepiness in children with DS, and that this dysfunction was partly reversible.A total of 23 children with DS, aged 8-19 years, were evaluated with polysomnography, echocardiography, and measurement of brain natriuretic peptide (BNP). Children having OSAS were randomized to four months of actual or sham continuous positive airway pressure (CPAP) in a double-blinded fashion.	Of the total participants, 20 (87%) had OSAS. On echocardiography, no participant was found to have pulmonary hypertension, and all participants had a BNP <10 pg/mL. The early/tissue Doppler (E/e') of the lateral mitral annulus, a measure of worse left ventricular (LV) diastolic function, correlated with the arousal index (r = 0.42, p = 0.043) and apnea hypopnea index (AHI; r = 0.61, p = 0.002) and inversely with the SpO2 nadir (r = -0.61, p = 0.002). Participants with OSAS had a high pediatric Epworth score [median interquartile range (IQR) = 8(4,9)],correlating with the arousal index (r = 0.49, p = 0.016). At four months, there were no changes in cardiovascular outcomes or sleepiness between those on actual versus sham CPAP. Hours of actual CPAP use was associated with improved E/e' mitral lateral (r = -0.48, p = 0.044), but surprisingly also correlated with LV mass z-score (r = 0.54, p = 0.018).	In children with DS, LV diastolic function correlated with OSAS severity, with improvement with CPAP use. There was a tendency towards increased sleepiness in those with OSAS, which correlated with the arousal index. Larger studies are warranted to confirm these findings.	
26846456	Studies of chronic pain show sleep disturbances to be a prevalent symptom in 50-88% of patients and studies show improved pain to correspond with improved sleep. The impact of spinal cord stimulation (SCS) on sleep in failed back surgery syndrome, complex regional pain syndrome, and neuropathic pain patients has not been studied prospectively.We prospectively assess the impact of SCS on sleep quality using the Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS). Further we examine the correlations between sleep and pain.	Patients who underwent permanent SCS implantation completed six validated questionnaires to compare sleep patterns, pain intensity, and quality of life at baseline and six months postoperatively. Results were analyzed via paired samples t-tests and bivariate analysis.	Data from 27 patients were collected. We saw a significant decrease in ISI scores (n = 23, t(df)=2.9(22), p = 0.008), and noted a trend in the percentage improvement between ISI and ESS (n = 12, t(df)=2.0(10), p = 0.078). We did not see any significant improvement in ESS. However, improvements in insomnia correlated with pain intensity as measured through visual analog scale score and McGill Pain Questionnaire (R = 0.546, p = 0.007 and R = 0.559, p = 0.006, respectively).	We demonstrate that insomnia scores on ISI improve with SCS at six-month follow-up. Further, we find that improvements in pain correlate with these ISI improvements.	
26843036	Parkinson's disease is a neurodegenerative disorder. Parkinson's clinical feature is characterized by its motor manifestations, although its many nonmotor symptoms occur earlier and have more profound impact on the quality of patient's life. Acupuncture has been increasingly popular and has been used to treat patients with Parkinson's. In this article, we have studied the clinical reports of acupuncture treatment for Parkinson's, which were listed in Medline, PubMed, EMBASE, CNKI, and CINAHL databases in the past 15 years. It was found that acupuncture either manual or electroacupuncture stimulation at specific acupoints relieved some motor symptoms in patients with Parkinson's and markedly improved many nonmotor symptoms such as psychiatric disorders, sleep problems, and gastrointestinal symptoms. When it was used as an adjunct for levodopa, acupuncture improved therapeutic efficacy and reduced dosage and the occurrence of side effects of levodopa. However, the results were constrained by small sample sizes, methodological flaws, and blinding methods of studies. Although the evidence for the effectiveness of acupuncture for treating Parkinson's is inconclusive, therapeutic potential of acupuncture seems quite promising. More studies, either comparative effectiveness research or high-quality placebo-controlled clinical studies are warranted.
26839481	The purpose of this study was to examine sleep patterns in a large sample of infants and toddlers (ages birth to 36 months) in Korea, and to compare sleep patterns, sleep problems, sleep ecology, and parental behaviors to global sleep data on young children in both predominantly Asian (P-A) and predominantly Caucasian (P-C) countries/regions. We additionally examined parent and child demographic information, parental behaviors, and aspects of the sleep ecology as predictors of sleep patterns among infants and toddlers in Korea. Parents/caregivers of 1,036 Korean infants and toddlers completed an expanded, internet-based version of the brief infant sleep questionnaire. Consistent with other studies of sleep in early childhood, sleep/wake patterns became increasingly consolidated with older child age for the Korea sample. Compared to both P-A and P-C infants and toddlers, children in Korea had the latest bedtimes, shortest total sleep and daytime sleep durations, and the least frequent rates of napping. Even though half of parents perceive their children's sleep problematic, parental perceptions of severe child sleep problems were the lowest. Within Korea, breastfeeding and bottle-feeding at sleep resumption were associated with increased nocturnal awakenings. Evening television viewing was associated with later bedtimes, which may have implications for sleep hygiene recommendations in clinical practice. The current study provides important information about sleep/wake patterns, parental behaviors, and aspects of the sleep ecology for infants and toddlers for physicians to support healthy sleep in Korea.
26836644	Crying and unsettled behavior in infancy is common. Prolonged disturbed infant sleep can have significant negative effects on the development of the child, and on the psychological well-being of the mother. Compared to studies examining the effects of behavioral sleep programs such as extinction-based techniques in infants over 6 months of age, fewer studies have looked at such strategies in infants under 6 months of age. The aim of this article is to summarize the literature examining the effects of behavioral techniques on infant sleep outcomes in the first 6 months of life and provide evidence based recommendations for the management of infant sleep disturbance.An electronic search of the literature was performed to identify studies which examined the effects of a behavioral intervention aimed at improving sleep in infants under 6 months of age.	Eleven studies were identified, of which 8 demonstrated improvements in infant sleep outcomes subsequent to the implementation of an educational behavioral program.	Education directed to parents about the use of simple, prescriptive, behavioral techniques is effective in improving infant sleep. Long term follow-up studies have failed to find any negative effects on the child, either from a psychological or physical perspective.	
26833569	Longitudinal analyses are crucial for understanding long-term processes such as development and behavioral rhythms. For a complete understanding of such processes, both organism-level observations as well as single-cell observations are necessary. Sleep is an example for a long-term process that is under developmental control. This behavioral state is induced by conserved sleep-active neurons, but little is known about how sleep neurons control the physiology of an animal systemically. In the nematode C. elegans, sleep induction crucially requires the single RIS interneuron to actively induce a developmentally regulated sleep behavior. Here, we used RIS-induced sleep as an example of how longitudinal analyses can be automated. We developed methods to analyze both behavior and neural activity in larva across the sleep-wake cycle. To image behavior, we used an improved DIC contrast to extract the head and detect the nose. To image neural activity, we used GCaMP3 expression in a small number of neurons including RIS combined with a neuron discrimination algorithm. Thus, we present a comprehensive platform for automatically analyzing behavior and neural activity in C. elegans exemplified by using RIS-induced sleep during C. elegans development.
26833349	Sleep complaints and the consumption of medications for sleep are common in older adults. Falls are also a significant concern for older adults and sedative use has been identified as a risk factor for falls. Sleep quality is a potential confounder in studies evaluating the relationship between sleep medication use and falls. However, very few studies have assessed the combined impact of sleep medication use and sleep quality on the risk of falls.The objective of this study was to evaluate the association between sleep medication use, poor sleep quality, and falls in community-dwelling older adults.	This was a multicenter, 6-month prospective cohort study conducted in senior housings settings in central Virginia, USA. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and a medication review was conducted. Data regarding falls were collected over 6 months by use of a diary. Logistic regression modeling was used to examine the effects of poor sleep quality, sleep medication use, and both, on the risk of falls.	Among 113 independently living older adults (mean age ± standard deviation 81.1 ± 8.6), 46.9 % fell at least once during a 6-month period; 62.8 % (n = 71) had poor sleep quality, and 44.2 % (n = 50) used medications or treatments to aid sleep. Compared with participants reporting good sleep quality and no sleep medication use, those who reported poor sleep quality and sleep medication use had an increased risk of falls after adjusting for covariates (odds ratio 3.23, 95 % confidence interval 1.05-9.91). The group with good sleep quality and sleep medication use, as well as the group with poor sleep quality and no sleep medication use had no significantly greater risk for falls compared with the group with good sleep quality and no sleep medication use.	A combined effect of sleep quality and sleep medication use on the risk of falls suggests that medication effectiveness may be an important factor to consider in understanding the risk of falls associated with sedative medications.	

26833134	Autism spectrum disorders (ASDs) are a group of devastating neurodevelopmental syndromes that affect up to 1 in 68 children. Despite advances in the identification of ASD risk genes, the mechanisms underlying ASDs remain unknown. Homozygous loss-of-function mutations in Contactin Associated Protein-like 2 (CNTNAP2) are strongly linked to ASDs. Here we investigate the function of Cntnap2 and undertake pharmacological screens to identify phenotypic suppressors. We find that zebrafish cntnap2 mutants display GABAergic deficits, particularly in the forebrain, and sensitivity to drug-induced seizures. High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems. Finally, we find that estrogen receptor agonists elicit a behavioral fingerprint anti-correlative to that of cntnap2 mutants and show that the phytoestrogen biochanin A specifically reverses the mutant behavioral phenotype. These results identify estrogenic compounds as phenotypic suppressors and illuminate novel pharmacological pathways with relevance to autism.
26832348	The orexins are hypothalamic neuropeptides involved in an array of functions such as regulation of sleep/wake states and chemoreception to CO2/pH. The locus coeruleus (LC) is a chemosensitive site and expresses an extensive population of orexin receptor 1 (OX1R). We tested the hypothesis that OX1Rs located in the LC participate in the ventilatory response to hypercapnia in a vigilance state and diurnal cycle-dependent manner. For this, we performed unilateral injections of SB-334867 (OX1R antagonist, 5 mM) into the LC of male Wistar rats and evaluated the ventilatory response to 7 % CO2 during wakefulness and sleep in the dark and light phases of the diurnal cycle. Hypercapnia induced an increase in ventilation (V E) in all groups compared to normocapnic values. However, during the dark phase, but not in the light phase, SB-334867 injection promoted an attenuation of the hypercapnic chemoreflex during wakefulness (V E: vehicle, 1502.6 ± 100 mL kg(-1) min(-1) vs SB-334867, 1200.3 ± 70.0 mL kg(-1) min(-1)) but not during sleep (V E: vehicle, 1383.0 ± 113.9 vs SB-334687, 1287.6 ± 92.1 mL kg(-1) min(-1)), due to changes in tidal volume (V T). We suggest that projections of orexin-containing neurons to the LC contribute, via OX1Rs, to the hypercapnic chemoreflex during wakefulness in the dark phase.
26832127	To assess the effect of age in the association between poor sleep quality and frailty status.Population-based, cross-sectional study conducted in Atahualpa, a rural village located in coastal Ecuador.	Out of 351 Atahualpa residents aged ≥ 60 years, 311 (89%) were interviewed with the Pittsburgh Sleep Quality Index (PSQI) and the Edmonton Frail Scale (EFS). The independent association between PSQI and EFS scores was evaluated by the use of a generalized linear model adjusted for relevant confounders. A contour plot with Shepard interpolation was constructed to assess the effect of age in this association.	Mean score in the PSQI was 5 ± 2 points, with 34% individuals classified as poor sleepers. Mean score in the EFS was 5 ± 3 points, with 46% individuals classified as robust, 23% as prefrail, and 31% as frail. In the fully adjusted model, higher scores in the PSQI were significantly associated with higher scores in the EFS (β 0.23; 95% CI 0.11-0.35; P < .0001). Several clusters depicted the strong effect of age in the association between PSQI and EFS scores. Older individuals were more likely to have high scores in the EFS and the PSQI, and younger individuals had low EFS scores and were good sleepers. Clusters of younger individuals who were poor sleepers and had high EFS scores accounted for the independent association between PSQI and EFS scores.	This study shows the strong effect of age in the association between poor sleep quality and frailty status.	
26831120	The study aimed to investigate the relationship between quality of sleep and psychiatric disorders including anxiety and depression in patients with subjective tinnitus. Early intervention is associated with improved therapeutic outcomes. We used Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and tinnitus handicap inventory (THI) in 543 patients [224 male (41.3 %); 319 female (58.7 %)] with subjective tinnitus enrolled in the ENT outpatient clinic from 2013 to 2015. Tinnitus characteristics and hearing status were recorded. A binary step-wise logistic regression analysis was performed. Two hundred cases (36.8 %) including 65 men (32.5 %) and 135 women (67.5 %) were diagnosed with sleep disorders. The PSQI score was the highest in patients with anxiety plus depression. Prolonged sleep latency and daytime dysfunction were positively associated with anxiety and depression. Increased sleep latency score was associated with 1.521- and 1.667-fold increased risk of anxiety and depression. Increase in the daytime dysfunction score was associated with 1.941- and 1.477-fold increases in the risk of anxiety and depression, respectively. Psychiatric and sleep disorders are highly prevalent in patients with subjective tinnitus. The most severe sleep impairment was found in patients with anxiety plus depression, resulting from prolonged sleep latency and severe daytime dysfunction. Acute duration, young people, hearing loss, impaired sleep, and severity of tinnitus were the major risk factors for tinnitus accompanied with anxiety symptoms. Severity of tinnitus and sleep impairment appeared to be the major risk factors of tinnitus accompanied with depression symptoms. 
26828002	Anxiety and sleep disorders (SDS) are frequently treated with psychotropic drugs. Health authorities in France have been advised to improve access to alternative treatments such as homeopathic medicines. Our aim was to describe the socio-demographic characteristics and clinical progression of patients prescribed homeopathic medicine Passiflora Compose (PC) for anxiety and/or SDS.This was an open-label, observational study. Randomly selected general practitioners (GPs) known to prescribe homeopathic medicines recruited consecutive patients (≥18-years) prescribed PC. The following data were recorded at inclusion by the GP: socio-demographic data and anxiety severity (Hamilton anxiety rating scale or HAM-A); and by the patients: level of anxiety (STAI Spielberger self-assessment questionnaire) and SDS (Jenkins sleep scale or JSS). Anxiety and SDS were reassessed after 4 weeks of treatment using the same scales.	A total of 639 patients (mean age: 46.3 ± 17.5 years; 78.6% female) were recruited by 98 GPs. Anxiety was present in 85.4% (HAM-A) and 93.3% (Spielberger State) at inclusion (mean scores: 17.8 ± 8.91 and 54.59 ± 11.69, respectively) and SDS was present in 74.0% (mean score: 15.24 ± 5.28). A total of 401 (62.7%) patients received PC alone and 167 (26.1%) PC + psychotropics. After 4 weeks, mean anxiety scores decreased by more than 7, 12 and 6 points (HAM-A, Spielberger State and Trait respectively), and SDS score by more than 4 points (JSS).	Anxiety and/or SDS improved significantly in patients included on this study. PC could be an alternative to the use of psychotropic drugs for first intention treatment of anxiety and SDS. Further studies are needed to confirm those results.	
26826649	Internalizing symptoms increase the risk for disordered eating; however, the mechanism through which this relationship occurs remains unclear. Sleep-related problems may be a potential link as they are associated with both emotional functioning and disordered eating. The present study aims to evaluate the mediating roles of two sleep-related problems (sleep disturbance and daytime sleepiness) in the relationship between youth internalizing symptoms and disordered eating, and to explore if age moderates these relations.Participants were 225 youth (8-17years) attending a primary care appointment. Youth and legal guardians completed questionnaires about youth disordered eating attitudes and behaviors, internalizing symptoms, sleep disturbance, and daytime sleepiness. Mediation and moderated mediation analyses were utilized.	The mediation model revealed both youth sleep disturbance and daytime sleepiness independently mediated the association between internalizing symptoms and disordered eating attitudes and behaviors, and explained 18% of the variance in disordered eating. The moderated mediation model including youth age accounted for 21% of the variance in disordered eating; youth age significantly interacted with sleep disturbance, but not with daytime sleepiness, to predict disordered eating. Sleep disturbance only mediated the relationship between internalizing symptoms and disordered eating in youth 12years old and younger, while daytime sleepiness was a significant mediator regardless of age.	As sleep-related problems are frequently improved with the adoption of health behaviors conducive to good sleep, these results may suggest a relatively modifiable and cost-effective target to reduce youth risk for disordered eating.	
26826370	It is an important public health problem to identify risk factors of health-related quality of life (HRQoL) among the elderly. We recruited subjects from Ansan, Korea, as a subset of the Korean Genome and Epidemiology Study (KoGES), which is an ongoing population study, and followed up their sleep quality for 6 years. Mixed effect models were used to estimate the association between sleep quality and HRQoL, and we found that overall HRQoL was significantly lower to the elderly having poor sleep quality with adjustment for significant covariates although sleep quality showed a significant interaction effect with time for the mental component summary of SF-12. In particular, the elderly having lack of quality sleep appeared to have good general health, but their functional performances were significantly poor. 
26826022	The circadian system regulates biological rhythmicity in the human body. The role of the circadian system in neurological disorders is a theme that is attracting an increasing amount of interest from the scientific community. This has arisen, in part, from emerging evidence that disorders such as Parkinson's disease (PD) are multifactorial with many features exhibiting diurnal fluctuations, thereby suggestive of circadian involvement. Although the importance of fluctuating motor and nonmotor manifestations in PD have been well acknowledged, the role of the circadian system has received little attention until recently. It is proposed that intervening with circadian function provides a novel research avenue down which new strategies for improving symptomatic treatment and slowing of the progressive degenerative process can be approached to lessen the burden of PD. In this article we review the literature describing existing circadian research in PD and its experimental models.

26825619	The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insula (AI) has strong reciprocal connectivity with wake and sleep-promoting hypothalamic and brainstem regions, and we hypothesized that the AI regulates patterns of sleep and wakefulness. To test this hypothesis, we lesioned the AI in rats (n = 8) and compared sleep, wake, and activity regulation in these animals with nonlesioned controls (n = 8) with 24-h sleep recordings and chronic infrared activity monitoring. Compared to controls, animals with AI lesions had decreased wakefulness and increased rapid eye movement (REM) sleep and non-REM (NREM) sleep. AI-lesioned animals had shorter wake bouts, especially during the active dark phase. AI-lesioned animals also had more transitions from NREM to REM sleep, especially during the inactive light phase. Chronic infrared monitoring revealed that AI-lesioned animals also had a disturbed temporal organization of locomotor activity at multiple time scales with more random activity fluctuations from 4 to 12 h despite intact circadian rhythms. These results suggest that the AI regulates sleep and activity and contributes to the regulation of sleep and motor behavior rhythmicity across multiple time scales. Dysfunction of the AI may underlie changes in sleep-wake patterns in neurological diseases. 
26823076	Children with autism spectrum disorder (ASD) are at high risk for sleep disturbance and behavioral dysregulation. However, the relationships between these difficulties are not fully understood. The current study examined the relationships between specific types of sleep and behavioral problems among 81 children with ASD. Sleep problems were significantly associated with physical aggression, irritability, inattention, and hyperactivity. In multivariate analyses, distinct sets of sleep problems accounted for between 22 and 32 % of the variance in behavior problems across models. These results indicate that sleep disturbance is associated with behavioral dysregulation among children with ASD. Of note, night awakenings had the most consistently strong association with daytime behavior problems, even after controlling for the effects of age and sex.
26821967	Pelvic inflammatory disease (PID) a common infection in women that is associated with significant morbidity and is a major cause of infertility. A clear temporal causal relationship between PID and psychiatric disorders has not been well established. We used a nationwide population-based retrospective cohort study to explore the relationship between PID and the subsequent development of psychiatric disorders. We identified subjects who were newly diagnosed with PID between 1 January 2000 and 31 December 2002 in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed for patients without PID. A total of 21 930 PID and 21 930 matched control patients were observed until diagnosed with psychiatric disorders, or until death, withdrawal from the NHI system, or until 31 December 2009. Adjusted hazard ratio (HR) of bipolar disorder, depressive disorder, anxiety disorder and sleep disorder in subjects with PID were significantly higher (HR: 2.671, 2.173, 2.006 and 2.251, respectively) than that of the controls during the follow-up. PID may increase the risk of subsequent newly diagnosed bipolar disorder, depressive disorder, anxiety disorder and sleep disorder, which will impair life quality. Our findings highlight that clinicians should pay particular attention to psychiatric comorbidities in PID patients. 
26821511	The importance of the sleep related breathing disorders (obstructive sleep apnea syndrome, central sleep apnea, and Cheyne-Stokes breathing) in the pathophysiology crebro- and cardiovascular disorders is well known. The relationship of sleep related breathing abnormalities and epilepsy is also important but underestimated in the daily practice. The relation is bidirectional. The breathing abnormalities in sleep may play important role in generating epileptic seizure, but the adverse effect of seizure and antiepileptic therapy (generation of apneas and hypopneas) may worsen the seizure control. The effect of new therapies (vagal nerve and deep brain stimulation) on the sleep architecture and sleep disordered breathing must be examined and discussed. Here we present a brief case of epileptic patient with deep brain stimulation therapy on sleep as well. The examination of the sleep related breathing abnormalities in epilepsy patient may help improve the effectiveness of antiepileptic therapy.
26821185	There is a growing need for free-living monitoring of the full 24 h spectrum of behaviors with a single or integrated set of sensors. The validity of field standard wearable monitors in sleep and physical activity have yet to be assessed for the complementary behavior in the context of 24 h continuous monitoring. We conducted a free-living comparison study of the Actigraph GT3X+ (GT3X+) to assess sleep parameters as compared with the Actiwatch-64 (AW-64) and concurrently, the AW-64 to assess sedentary and physical activity behaviors as compared with the GT3X+. Thirty young adults (15 female, 19.2±0.86 years) wore both monitors for 3 consecutive days and 2 consecutive nights. Agreement of sleep, sedentary, and physical activity metrics were evaluated using analyses of variance, intraclass correlation coefficients, Bland-Altman plots with associated confidence limits, mean absolute percentage of errors and equivalence tests. For sleep, the GT3X+ showed high agreement for total sleep time and sleep efficiency, but underestimated wakefulness after sleep onset and sleep onset latency relative to the AW-64. For sedentary behavior and physical activity, the AW-64 showed a moderate agreement for activity energy expenditure, but not for sedentary, light or moderate-vigorous physical activities relative to the GT3X+. Overall our results showed good agreement of the GT3X+ with AW-64 for assessing sleep but a lack of agreement between AW-64 and GT3X+ for physical activity and sedentary behaviors. These results are likely due to the monitor placement (wrist vs hip), as well as the algorithm employed to score the data. Future validation work of existing and emerging technologies that may hold promise for 24 h continuous monitoring is needed.
26818148	Sleeping difficulty has been associated with type 2 diabetes in some prior studies. Whether the observed associations are independent of health behaviours, other cardiovascular risk factors or other sleep disorders is unclear.We analysed data from 133,353 women without diabetes, cardiovascular disease and cancer at baseline in the Nurses' Health Study (NHS, 2000-2010) and the NHSII (2001-2011). Sleeping difficulty was assessed as having difficulty falling or staying asleep 'all of the time' or 'most of the time' at baseline (2000 in NHS and 2001 in NHSII).	We documented 6,407 incident cases of type 2 diabetes during up to 10 years of follow-up. After adjustment for lifestyle factors at baseline, comparing women with and without sleeping difficulty, the multivariate-adjusted HR (95% CI) for type 2 diabetes was 1.45 (95% CI 1.33, 1.58), which changed to 1.22 (95% CI 1.12, 1.34) after further adjustment for hypertension, depression and BMI based on the updated repeated measurements. Women who reported all four sleep conditions (sleeping difficulty, frequent snoring, sleep duration ≤6 h and sleep apnoea in NHS or rotating shift work in NHSII) had more than a fourfold increased likelihood of type 2 diabetes (HR 4.17, 95% CI 2.93, 5.91).	Sleeping difficulty was significantly associated with type 2 diabetes. This association was partially explained by associations with hypertension, BMI and depression symptoms, and was particularly strong when combined with other sleep disorders. Our findings highlight the importance of sleep disturbance in the development and prevention of type 2 diabetes.	
26818096	The aim of this study was to test the efficacy and safety of mirtazapine in the treatment of sleep disorders in patients with Alzheimer's disease by means of a randomized, double-blind, placebo-controlled trial. Measurements were obtained for 7 days before intervention (baseline) and for 2 weeks after the onset of treatment.Alzheimer's disease patients with sleep disorders (n = 24) received 15-mg mirtazapine (n = 8) or placebo (n = 16) once daily at 2100 hours for 2 weeks. Patients were evaluated with actigraphy and structured scales before and after intervention. Historical control was employed.	Treatment with mirtazapine or placebo had no effect on cognitive and functional status as assessed by the Mini-Mental State Examination and the Katz scale, respectively. There were no differences between groups in the frequency or severity of the adverse events reported. Compared with the placebo group, mirtazapine users showed increased daytime sleepiness but no improvement in the duration or efficiency of nocturnal sleep after treatment.	This study showed no significant therapeutic effects of 15-mg mirtazapine in community-dwelling Alzheimer's disease patients with sleep disorders. Instead, this study found evidence of worsening of daytime sleep patterns.	
26817213	Sleep problems can have a significant effect on children behaviors, emotional and cognitive developments. However, limited information is available regarding the sleep behaviors and sleep problems of school-aged children in Thailand. The purposes of this study were to examine the prevalence of sleep problems and to describe sleep/wake pattern of Thai children.The school-based, cross-sectional study was conducted in 5 primary public schools selected from Bangkok and three regions of Thailand. The samples were selected from the first and fourth grades of each school. The Children's Sleep Habits Questionnaire (CSHQ) was used to evaluate sleep behaviors and sleep problems.	Grade 1 children went to bed earlier and had longer weekday sleep duration comparing with grade 4 children. Sleep duration was significantly shorter in children living in Bangkok, comparing with those living in rural areas. Mean total CSHQ score was significant higher in grade 1 children, when comparing with grade 4 children (51.30 vs. 50.18; p = 0.026). Grade 1 children scored significantly higher on bedtime resistance (10.96 vs. 10.39; p = 0.004) and sleep anxiety subscale (6.68 vs. 6.41; p = 0.022), while grade 4 children scored significantly higher on sleep-onset delay subscale (1.41 vs. 1.23; p < 0.001). Prevalence of sleep problems was highest in the category of "falling asleep while riding in car or bus" (69.5%), followed by "awakening by others in the morning" (68.5%).	Sleep problems were common in Thai school-aged children. The most common sleep problems were in the domains of daytime sleepiness and bedtime resistance and anxiety.	
26817030	To assess the degree and interrelationship of sleep disturbance and plasma cytokine levels in temporomandibular disorder (TMD) pain patients.Forty female TMD patients and 20 age-, sex-, and body mass index (BMI)-matched healthy subjects were enrolled. TMD was diagnosed using the Research Diagnostic Criteria for TMD. The TMD patients were classified as having low or high disability according to Graded Chronic Pain Scale findings. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality. Plasma concentrations of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured from blood samples collected between 9 am and noon. Statistical analyses included Kruskal-Wallis and one-way analysis of variance tests to compare results between different groups and multivariate general linear models to evaluate the effect of sleep status on cytokine levels.	The high-disability group had the highest PSQI and ESS scores (P < .001). Plasma levels of IL-1β, IL-6, IL-10, and TNF-α were significantly higher in the patient groups, with the high-disability group exhibiting the highest values (P ≤ .001). The plasma cytokine levels were significantly correlated with PSQI scores (P < .05). Plasma levels of IL-10 and TNF-α were significantly associated with the disability level after adjusting for both sleep indices (both P < .05).	Patients with TMD, especially those with high disability, had elevated plasma cytokine levels and increased ESS and PSQI scores suggestive of sleep disturbance.	

26815930	Sleeping too much or too little has been associated with adverse health outcomes including total mortality, cardiovascular disease, Type 2 diabetes, and hypertension. This study explored the relationship between sleep patterns and age-related macular degeneration (AMD).One thousand and three consecutive patients in a retina practice were prospectively surveyed regarding sleep histories. Each patient then had a masked ophthalmic examination and was graded on the modified Wisconsin Age-Related Maculopathy System. The relationship between AMD grade and sleep hours was analyzed in a logistic regression model. Multivariable analysis was performed after adjustment for age, gender, and smoking history.	In multivariable analysis, controlling for age, gender, and smoking history, sleep hours are not associated with neovascular AMD (P = 0.97) but are associated with geographic atrophy (P = 0.02). Sleeping >8 hours is associated with geographic atrophy (age-adjusted odds ratio, 7.09; 95% confidence interval, 1.59-31.6) compared with patients without AMD.	Longer sleep duration is associated with geographic atrophy secondary to AMD. These altered sleep patterns may be another morbidity of AMD, but further study is necessary.	
26813728	To explore the influence of occupational stress related factors on depression symptoms among 244 policemen in a city in China.In May 2011, 287 policemen from a city public security bureau were recruited to this survey by cluster sampling method. We deleted questionnaires which include missing variables on demographic characteristics and factors associated with occupational stress questionnaires which include over 3 missing items. 244 policemen were included in this study. Depression symptoms and occupational stressors were measured using Chinese version of depression self-reported questionnaire, job content questionnaire, Chinese version of effort-reward imbalances questionnaire, job hazard scale and occupational stress inventory. Depression symptom scores and the relationship between the variables and occupational stress were analyzed by Spearman correlation analysis and multiple regression analysis.	The Median (P25-P75) of depression symptom scores of all respondents was 16.50 (11.00-25.00). 144 were policemen with no depression symptoms and 100 were with depression symptoms. The median (P25-P75) of depression symptoms scores among policemen with length of serves <10, 10-19, 20-29 and ≥30 was 17.00 (8.00-26.00), 16.00 (11.00-24.50), 19.00 (12.00-27.00), and 12.00 (6.25-15.00), respectively. The difference of scores was significant among length of serves groups (χ2=9.52, P=0.023). The scores of psychological demands, sleep disorder, daily life stress and negative affectivity among policemen with depression symptoms were 17.00 (8.00-26.00), 16.00 (11.00-24.50), 19.00 (12.00-27.00), and 12.00 (6.25-15.00), respectively, which were higher than those with no depression symptoms (24.00 (22.00-25.00), 8.00 (5.00-13.00), 8.00 (6.00-10.00), 1.00 (0-2.75)), and the differences were significant (Z=3.82, 5.39, 5.15, 6.41, P<0.001). Spearman correlation analysis revealed that depression symptoms score was positively related to sleep disorder, commitment effort, psychological demands, daily life stress, negative affectivity and job hazards scores. Correlations coefficient were 0.44, 0.28, 0.28, 0.33, 0.38, 0.44, and 0.38, respectively (P<0.001). Multiple linear regression analysis indicated that self-esteem, daily life stress and negative affectivity had bigger contribution on the depression symptoms scores. The standard regression coefficient was -0.46, 0.19 and 0.13, respectively (P<0.001, P=0.001, P=0.030).	Sleep disorder, commitment effort, psychological demands, daily life stress, negative affectivity and job hazards scores were the inducement of depression symptoms for policemen. To reduce the daily life stress, negative affectivity and improve the quality of sleep, add to self-esteem, reward and social support have positive effects on reducing the occurrence of depressive symptoms for police.	


26812659	Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.
26812513	To describe three-year trends in nutritional status and sleep quality and their impact on hospital utilisation in the oldest old (80 +) with heart failure (HF).Single-centred longitudinal observational study.	South-eastern Sweden.	90 elderly (80+) with objectively verified HF.	Baseline data from the Mini Nutritional Assessment (MNA) and on sleep quality were collected through structured interviews following the HF diagnosis (n=90) and at a three-year follow-up (n=41). Data on hospital utilisation during the three years following the HF diagnosis were also collected.	Nineteen percent of the participants were found to have impaired nutritional status, a condition that increased hospital utilisation by four bed days per year. A majority (85%) had impaired sleep quality, but no impact on hospital utilisation was found. Nutritional status and sleep quality were stable over the three-year period.	In the oldest old with HF, impaired nutritional status and impaired sleep quality are already common at HF diagnosis. Impaired nutritional status increases hospital utilisation significantly. Therefore, it is of supreme importance to systematically evaluate nutritional status and sleep quality in the oldest old when they are diagnosed with HF, as well as to take action if impairments are present.	
26812192	In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups.In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-x03B3; and IL-2 were measured prior to the EEG.	Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant.	The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways.	
26810497	Poor sleep quality during pregnancy is associated with adverse obstetric and neuropsychiatric outcomes. Despite its routine use as a sleep quality assessment scale among men and non-pregnant women, the psychometric properties of the Pittsburgh Sleep Quality Index (PSQI) have not been assessed among US pregnant women. We sought to evaluate the construct validity and factor structure of the PSQI among 1488 pregnant women.A structured interview was used to collect information about demographics and sleep characteristics in early pregnancy. The Patient Health Questionnaire-9 (PHQ-9) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) were used to assess symptoms of depression, anxiety, and stress. Consistency indices, exploratory and confirmatory factor analyses (EFA and CFA), correlations, and logistic regression procedures were used.	The reliability coefficient, Cronbach's alpha for the PSQI items was 0.74. Results of the EFA showed that a rotated factor solution for the PSQI contained two factors with eigenvalues >1.0 accounting for 52.8 % of the variance. The PSQI was significantly positively correlated with the PHQ-9 (r s = 0.48) and DASS-21 (r s = 0.42) total scores. Poor sleepers (PSQI global score >5) had increased odds of experiencing depression (OR = 6.47; 95 % CI = 4.56-9.18), anxiety (OR = 3.59; 95 % CI = 2.45-5.26), and stress (OR = 4.37; 95 % CI = 2.88-6.65) demonstrating evidence of good construct validity. CFA results corroborated the two-factor structure finding from the EFA and yielded reassuring measures indicating goodness of fit (comparative fit index = 0.975) and accuracy (root mean square error of approximation = 0.035).	The PSQI has good construct validity and reliability for assessing sleep quality among pregnant women.	
26810291	Infants and children with upper respiratory tract infection (URI) often have concurrent acute otitis media (AOM). Young infants have fewer specific symptoms than older children. The purpose of this study was to evaluate the usefulness of symptoms and other risk factors in predicting the presence of AOM in infants.Healthy infants, age less than four weeks, were enrolled and followed prospectively for up to age one year. Infants were scheduled for a research visit when their parents noted the onset of symptoms. At each URI visit, parents first reported the severity of symptoms. An investigator then diagnosed the presence or absence of concurrent AOM. Risk factors and symptom scores for infants with and without AOM were studied.	Infants (N=193, mean age at first URI 3.9±2.5 months) experienced 360 URI episodes and 63 AOM events. Symptoms consisting of fever, earache, poor feeding, restless sleep, and irritability together (ETG-5) were statistically associated with the prediction of AOM (P=0.006). A multiple variable statistical model (J-Score) that included day care attendance, age, severity of cough and earache best predicted AOM (P<0.001), with 95% specificity. Both ETG-5 and J-score yielded relatively low sensitivity for AOM prediction.	In infants with URI in the first year of life, severity of symptoms was significantly associated with concurrent AOM. Daycare attendance, presence and severity of earache and cough added to better correlation. These observations may have clinical application in identification of infants at risk for AOM.	
26809504	Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials. 
26809462	Identification of non-traditional risk factors is an important component of cardiac rehabilitation (CR). However, the prevalence and predictors of sleep-disordered breathing (SDB) and its influence on exercise performance in patients attending CR remain poorly described.Patients enrolled in a national CR centre were eligible for a comprehensive SDB screening program. Screening questionnaires for SDB, overnight sleep study, and the 6-minute walk test (6MWT) were conducted.	We recruited 332 patients (mean age 62±10 years, 62.4% male) attending CR for primary (29.2%) or secondary (70.8%) prevention, of which 209 successfully completed the overnight sleep study. Sleep-disordered breathing group patients (n=68, 32.5%) were older and had a higher body mass index (BMI) and neck and waist circumferences than the non-SDB group patients. After adjusting for neck and waist circumference, age (OR=1.06; 95% CI 1.02-1.10; p=0.001) and BMI (OR=1.19; 95% CI 1.10-1.30; p<0.001) remained independent predictors of SDB. A high risk of SDB based on the Berlin Questionnaire (43.4% versus 35.5%, p=0.277) or STOP-BANG questionnaire (63.2% versus 53.2%, p=0.170) and excessive daytime sleepiness (Epworth Sleepiness Scale >10, 23.9% versus 17.7%, p=0.297) were similar between the groups. The 6MWT scores were significantly lower in the SDB than non-SDB group (mean difference -32 m; 95% CI -57-7; p=0.013). The relationship was no longer significant after adjusting for age, sex, and waist circumference.	Sleep-disordered breathing is prevalent in CR patients and is independently predicted by ageing and obesity. The association between SDB and poorer exercise performance may be explained by age, sex, and waist circumference.	
26805423	Sleep and electroencephalogram abnormalities are prominent early features of Huntington's disease (HD) that typically appear before the onset of characteristic motor symptoms. The changes in sleep and electroencephalogram seen in HD patients are largely recapitulated in mouse models of HD such as transgenic R6/2 lines. To test whether or not drugs with hypnotic properties can correct the sleep and electroencephalogram abnormalities seen in HD mice, we treated male wild-type (WT; N = 7) and R6/2 mice (N = 9) acutely with intraperitoneal injections of vehicle, zolpidem (5, 10 or 20 mg/kg) or amitriptyline (5, 10 or 20 mg/kg), and then monitored their sleep-wake behavior. In R6/2 mice, both zolpidem and amitriptyline suppressed the abnormally high REM sleep amount and electroencephalographic gamma (30-46 Hz) oscillations in a dose-dependent manner. Amitriptyline's effect on sleep was similar in both genotypes, whereas zolpidem showed significant genotype differences. Zolpidem exerted a strong hypnotic effect in WT mice by increasing electroencephalographic delta power, doubling the mean bout duration and the total amount of non-rapid eye movement sleep. However, no such effect was seen in R6/2 mice. Our study demonstrates that the pathophysiological changes seen in sleep and electroencephalogram are not 'hard-wired' in HD brain and can be reversed even at late stages of the disease. The diminished hypnotic effect of zolpidem suggests that the GABAergic control of sleep-wake states is impaired in HD mice. A better understanding of the neurochemical basis underlying these abnormalities should lead to more effective and rational therapies for HD. 
26805412	Sleep disturbances have been linked to psychotic experiences in the general adult populations of multiple countries, but this association has yet to be confirmed in the United States using robust diagnostic measures. We analyzed a subsample (n=2304) of the National Comorbidity Survey Replication, and found that when compared with those who did not report any sleep problems, individuals with sleep disturbances lasting two weeks or longer over the past 12months were significantly more likely to report at least one psychotic experience during that same time frame. Specifically, difficulty falling asleep, waking up during the night, early morning awakenings, and feeling sleepy during the day were each associated with greater odds of reporting psychotic experiences over the past year after controlling for socio-demographic variables. However, only difficulty falling asleep and early morning awakenings were still significant after adjusting for DSM comorbid disorders. Reporting three or four types of sleep disturbances was especially predictive of psychotic experiences. Our findings underscore the importance of detecting and reducing sleep problems among individuals who report PE. 
26803484	Therapeutic sleep deprivation (SD) is a rapid acting treatment for major depressive disorder (MDD). Within hours, SD leads to a dramatic decrease in depressive symptoms in 50-60% of patients with MDD. Scientifically, therapeutic SD presents a unique paradigm to study the neurobiology of MDD. Yet, up to now, the neurobiological basis of the antidepressant effect, which is most likely different from today's first-line treatments, is not sufficiently understood. This article puts the idea forward that sleep/wake-dependent shifts in synaptic plasticity, i.e., the neural basis of adaptive network function and behavior, represent a critical mechanism of therapeutic SD in MDD. Particularly, this article centers on two major hypotheses of MDD and sleep, the synaptic plasticity hypothesis of MDD and the synaptic homeostasis hypothesis of sleep-wake regulation, and on how they can be integrated into a novel synaptic plasticity model of therapeutic SD in MDD. As a major component, the model proposes that therapeutic SD, by homeostatically enhancing cortical synaptic strength, shifts the initially deficient inducibility of associative synaptic long-term potentiation (LTP) in patients with MDD in a more favorable window of associative plasticity. Research on the molecular effects of SD in animals and humans, including observations in the neurotrophic, adenosinergic, monoaminergic, and glutamatergic system, provides some support for the hypothesis of associative synaptic plasticity facilitation after therapeutic SD in MDD. The model proposes a novel framework for a mechanism of action of therapeutic SD that can be further tested in humans based on non-invasive indices and in animals based on direct studies of synaptic plasticity. Further determining the mechanisms of action of SD might contribute to the development of novel fast acting treatments for MDD, one of the major health problems worldwide.
26802809	A small body of developing research has found evidence for sleep disturbance in obsessive-compulsive disorder (OCD) and links between sleep disturbance and obsessive-compulsive symptoms (OCS) in unselected samples. However, the link between sleep disturbance and OCS is yet to be examined in a nationally representative sample. Furthermore, the extent to which the link between sleep disturbance and OCS is accounted for by symptoms of depression remains unclear. To address this gap in the literature, the present study examined the relationship between sleep disturbance and OCS in a nationally representative sample. Participants were assessed in the National Comorbidity Survey Replication (NCS-R; n = 2073). Consistent with predictions, results revealed that individuals with sleep disturbance reported increased OCS severity compared to individuals without sleep disturbance. Further, sleep disturbance severity was associated with OCS severity, even when controlling for depression (and other anxiety-related disorders). This study is the first to link sleep disturbance and OCS in a nationally representative sample, and these findings highlight the unique role of sleep disturbance in the experience of OCS. Future research is necessary to delineate specific mechanisms that may account for this relationship.
26802484	Infant rats switch randomly between the sleeping and waking states; during early infancy (up to postnatal day 8), sleep and wake bouts are random, brief (with means on the order of several seconds) and exponentially distributed, with the length of a particular bout independent of the length of prior bouts. As the rat ages during this early period, mean sleep and wake bout lengths gradually increase, though sleep and wake bouts remain exponentially distributed. Additionally, sleep and wake bouts are regulated independently of each other - alterations in the development of sleep (wake) bouts has no impact on the regulation wake (sleep) bouts. Sleep and wake bout behavior is associated with the activity of mutually inhibitory sleep-active and wake-active brainstem populations. In this work, I employ a simplified biophysical model of two mutually inhibitory populations consisting of ten integrate-and-fire neurons each and a noise-based switching mechanism. I show that such a noise-based switching mechanism naturally accounts for the experimentally observed features of sleep-wake switching during early infancy - random alternating activity bouts occur as a consequence of noise (provided inhibition is strong relative to excitation), bout durations are exponential (due to a lack of memory within the system), and cross-population inhibition or intrapopulation excitatory coupling provide mechanisms for changing and independently regulated sleep and wake bout means. 
26800634	Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples.29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures).	Data were available for 7041 UK and 1392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: 'full' polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; 'pain-only' (muscle/joint) 20.3%; 'sore throat/painful lymph node' 4.5%; and 'oligosymptomatic' (median 1, IQR 0-2 symptoms) 4.7%. Two 'partial' polysymptomatic phenotypes were similar to the 'full' phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data.	Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments.	
26799351	Neurodevelopmental disorders (NDDs) are defined as a group of disorders caused by changes in early brain development, resulting in behavioral and cognitive alterations in sensory and motor systems, speech, and language. NDDs affect approximately 1-2% of the general population. Up to 80% of children with NDDs are reported to have disrupted sleep; subsequent deleterious effects on daytime behaviors, cognition, growth, and overall development of the child are commonly reported. Examples of NDDs discussed in this review include autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome. The etiology of sleep disorders in children with NDDs is largely heterogeneous and disease specific. The diagnosis and management of sleep disorders in this population are complex, and little high-quality data exist to guide a consistent approach to therapy. Managing sleep disorders in children with NDDs is critical both for the child and for the family but is often frustrating due to the refractory nature of the problem. Sleep hygiene must be implemented as first-line therapy; if sleep hygiene alone fails, it should be combined with pharmacologic management. The available evidence for the use of common pharmacologic interventions, such as iron supplementation and melatonin, as well as less common interventions, such as melatonin receptor agonists, clonidine, gabapentin, hypnotics, trazodone, and atypical antipsychotics is reviewed. Further, parents and caregivers should be provided with appropriate education on the nature of the sleep disorders and the expectation for modest pharmacologic benefit, at best. Additional data from well-designed trials in children with NDDs are desperately needed to gain a better understanding of sleep pharmacotherapy including efficacy and safety implications. Until then, clinicians must rely on the limited available data, as well as clinical expertise, when managing sleep disorders in the population of children with NDDs. 
26797291	Leg ulcers commonly emerge as a symptom of other comorbidities, often in older people. As a consequence of the ulcer, pain and sleep disturbances might occur. Due to the complex illness, the responsibility of treatment is unclear between health caregivers. The interaction between ulcer type, sleep and pain has not previously been investigated. This study aimed to explore pain in older men and women (65 years and older) with different diagnoses of leg ulcers and to investigate the associations of sleep disturbances and pain in people with leg ulcer diagnosis.The study used a cross-sectional design and data from the Swedish Registry of Ulcer Treatment, collected between May 2009 and December 2013. One thousand and eight hundred and twenty four people were included, and 62.9% were women. The mean age was 83.4 years (SD 8.8). For the analyses, the chi-square test, Mann-Whitney U-test, t-test, one-way ANOVA and logistic regression was performed. Pain was measured by the Numeric Rating Scale (NRS), and sleep disturbances was assessed dichotomously.	We found the prevalence of pain intensity ≥ 5 on the NRS to be 34.8% in those reporting pain. Additionally, the pain intensity was associated with the number of ulcers (p = 0.003). Sleep disturbances were associated with pain (p < 0.001) and were found in 34.8% of the total sample. Although more women than men reported pain and scored higher on the NRS, no significant gender difference in sleep disturbances was found (p = 0.606). The mean NRS scores did not differ significantly between the ulcer types; however, arterial and venous-arterial ulcers increased the risk of sleep disturbances, as did higher pain scores.	The majority of the participants were of advanced age (>80 years) and frequently suffered from pain and sleep disturbances. Further research is needed regarding pain, sleep and wound healing in the oldest old with leg ulcers. Ulcer pain sometimes appears to receive less attention in ulcer management, as do sleep disturbances, implying that individual needs might not be satisfactorily met. National guidelines in managing leg ulcers, which also consider consequences such as sleep disturbances, pain and discomfort, are needed.	
26797244	The basal forebrain (BF) cholinergic neurons have long been thought to be involved in behavioral wakefulness and cortical activation. However, owing to the heterogeneity of BF neurons and poor selectivity of traditional methods, the precise role of BF cholinergic neurons in regulating the sleep-wake cycle remains unclear. We investigated the effects of cell-selective manipulation of BF cholinergic neurons on the sleep-wake behavior and electroencephalogram (EEG) power spectrum using the pharmacogenetic technique, the 'designer receptors exclusively activated by designer drugs (DREADD)' approach, and ChAT-IRES-Cre mice. Our results showed that activation of BF cholinergic neurons expressing hM3Dq receptors significantly and lastingly decreased the EEG delta power spectrum, produced low-delta non-rapid eye movement sleep, and slightly increased wakefulness in both light and dark phases, whereas inhibition of BF cholinergic neurons expressing hM4Di receptors significantly increased EEG delta power spectrum and slightly decreased wakefulness. Next, the projections of BF cholinergic neurons were traced by humanized Renilla green fluorescent protein (hrGFP). Abundant and highly dense hrGFP-positive fibers were observed in the secondary motor cortex and cingulate cortex, and sparse hrGFP-positive fibers were observed in the ventrolateral preoptic nucleus, a known sleep-related structure. Finally, we found that activation of BF cholinergic neurons significantly increased c-Fos expression in the secondary motor cortex and cingulate cortex, but decreased c-Fos expression in the ventrolateral preoptic nucleus. Taken together, these findings reveal that the primary function of BF cholinergic neurons is to inhibit EEG delta activity through the activation of cerebral cortex, rather than to induce behavioral wakefulness. 
26795630	Sleep problems affect 30% to 80% of patients with mild traumatic brain injury. We assessed the prevalence of sleep disorders after mild traumatic brain injury and its correlation with other symptoms.Individuals with mild traumatic brain injury were assessed at the New York University Concussion Center during 2013-2014 with the Sports Concussion Assessment Tool, third edition, data following mild traumatic brain injury. The relationship between sleep problems (drowsiness, difficulty falling asleep, fatigue or low energy), psychiatric symptoms (sadness, nervousness or anxiousness), headache, and dizziness were analyzed by Spearman correlation and logistic regression using moderate to severe versus none to mild categorization.	Ninety-three patients were retrospectively considered. The most common injury causes were falls (34.4%) and motor vehicle accidents (21.5%). There was a positive correlation between dizziness, headache, psychiatric problems (sadness, anxiety, irritability), and sleep problems (fatigue, drowsiness, and difficulty falling asleep) (P < 0.001). Logistic regression showed a significant association between moderate to severe psychiatric symptoms and moderate to severe sleep symptoms (P < 0.05). Sleep symptoms became more severe with increased time interval from mild traumatic brain injury to Sport Concussion Assessment Tool 3 administration (odds ratio = 1.005, 1.006, and 1.008, P < 0.05). There was significant correlation between motor vehicle accident and drowsiness and difficulty falling asleep (P < 0.05). Medications given in the emergency department had a positive correlation with drowsiness (P < 0.05).	Individuals who report moderate to severe headache, dizziness, and psychiatric symptoms have a higher likelihood of reporting moderate to severe sleep disorders following mild traumatic brain injury and should be counseled and initiated with early interventions.	
26794719	There is a growing interest in monitoring the sleep of elite athletes. Polysomnography is considered the gold standard for measuring sleep, however this technique is impractical if the aim is to collect data simultaneously with multiple athletes over consecutive nights. Activity monitors may be a suitable alternative for monitoring sleep, but these devices have not been validated against polysomnography in a population of elite athletes.Participants (n=16) were endurance-trained cyclists participating in a 6-week training camp.	A total of 122 nights of sleep were recorded with polysomnography and activity monitors simultaneously. Agreement, sensitivity, and specificity were calculated from epoch-for-epoch comparisons of polysomnography and activity monitor data. Sleep variables derived from polysomnography and activity monitors were compared using paired t-tests. Activity monitor data were analysed using low, medium, and high sleep-wake thresholds.	Epoch-for-epoch comparisons showed good agreement between activity monitors and polysomnography for each sleep-wake threshold (81-90%). Activity monitors were sensitive to sleep (81-92%), but specificity differed depending on the threshold applied (67-82%). Activity monitors underestimated sleep duration (18-90min) and overestimated wake duration (4-77min) depending on the threshold applied.	Applying the correct sleep-wake threshold is important when using activity monitors to measure the sleep of elite athletes. For example, the default sleep-wake threshold (>40 activity counts=wake) underestimates sleep duration by ∼50min and overestimates wake duration by ∼40min. In contrast, sleep-wake thresholds that have a high sensitivity to sleep (>80 activity counts=wake) yield the best combination of agreement, sensitivity, and specificity.	
26793010	Sleep and energy balance are essential for health. The two processes act in concert to regulate central and peripheral homeostasis. During sleep, energy is conserved due to suspended activity, movement, and sensory responses, and is redirected to restore and replenish proteins and their assemblies into cellular structures. During wakefulness, various energy-demanding activities lead to hunger. Thus, hunger promotes arousal, and subsequent feeding, followed by satiety that promotes sleep via changes in neuroendocrine or neuropeptide signals. These signals overlap with circuits of sleep-wakefulness, feeding, and energy expenditure. Here, we will briefly review the literature that describes the interplay between the circadian system, sleep-wake, and feeding-fasting cycles that are needed to maintain energy balance and a healthy metabolic profile. In doing so, we describe the neuroendocrine, hormonal/peptide signals that integrate sleep and feeding behavior with energy metabolism. 
26792830	To describe the prevalence of symptoms of depression and anxiety, and the level of life stress and worry in late pregnancy for Māori and non-Māori women.In late pregnancy, women completed a questionnaire recording their prior history of mood disorders; self-reported current depressive symptoms (⩾13 on the Edinburgh Postnatal Depression Scale), current anxiety symptoms (⩾6 on the anxiety items from the Edinburgh Postnatal Depression Scale), significant life stress (⩾2 items on life stress scale) and dysfunctional worry (>12 on the Brief Measure of Worry Scale).	Data were obtained from 406 Māori women (mean age = 27.6 years, standard deviation=6.3 years) and 738 non-Māori women (mean age = 31.6 years, standard deviation=5.3 years). Depressive symptoms (22% vs 15%), anxiety symptoms (25% vs 20%), significant life stress (55% vs 30%) and a period of poor mood during the current pregnancy (18% vs 14%) were more prevalent for Māori than non-Maori women. Less than 50% of women who had experienced ⩾2 weeks of poor mood during the current pregnancy had sought help. Being young was an independent risk factor for depressive symptoms, significant life stress and dysfunctional worry. A prior history of depression was also consistently associated with a greater risk of negative affect in pregnancy.	Antenatal mental health requires at least as much attention and resourcing as mental health in the postpartum period. Services need to specifically target Māori women, young women and women with a prior history of depression.	
26791323	Many factors contribute to sleep disturbance among young adults. Social media (SM) use is increasing rapidly, and little is known regarding its association with sleep disturbance.In 2014 we assessed a nationally representative sample of 1788 U.S. young adults ages 19-32. SM volume and frequency were assessed by self-reported minutes per day spent on SM (volume) and visits per week (frequency) using items adapted from the Pew Internet Research Questionnaire. We assessed sleep disturbance using the brief Patient-Reported Outcomes Measurement Information System (PROMIS®) sleep disturbance measure. Analyses performed in Pittsburgh utilized chi-square tests and ordered logistic regression using sample weights in order to estimate effects for the total U.S.	In models that adjusted for all sociodemographic covariates, participants with higher SM use volume and frequency had significantly greater odds of having sleep disturbance. For example, compared with those in the lowest quartile of SM use per day, those in the highest quartile had an AOR of 1.95 (95% CI=1.37-2.79) for sleep disturbance. Similarly, compared with those in the lowest quartile of SM use frequency per week, those in the highest quartile had an AOR of 2.92 (95% CI=1.97-4.32) for sleep disturbance. All associations demonstrated a significant linear trend.	The strong association between SM use and sleep disturbance has important clinical implications for the health and well-being of young adults. Future work should aim to assess directionality and to better understand the influence of contextual factors associated with SM use.	
26790580	To examine sleep-wake cycle (SWC) composition of healthy term infants in the immediate postnatal period using EEG, and investigate factors that might influence it.Multichannel video-EEG was recorded for a median of 61.9 min (IQR: 60.0-69.3). The absolute and relative scores of sleep states were calculated for each infant's recording. Parametric/non-parametric statistical tests and multiple linear regression analysis were used to investigate the influence of perinatal factors on SWC composition.	Eighty healthy term infants aged 1-36 h were studied. A well-developed SWC was evident as early as within the first 6h after birth. The mean (SD) percentage of active sleep (AS) was 52.1% (12.9) and quiet sleep (QS) was 38.6% (12.5). AS was longer and QS shorter in infants delivered by elective caesarean section (CS) compared to infants delivered by vaginal delivery or emergency CS.	This is the first large cohort EEG study that has quantified neonatal sleep. SWC is clearly present immediately after birth, it is dominated by AS, and is influenced by mode of delivery.	This knowledge of the early neonatal EEG/SWC can be used as reference data for EEG studies of neurologically compromised infants.	
26788969	Anxiety Sensitivity (AS) has been associated with sleep difficulties in certain anxiety disorder populations, but no studies have examined cross-diagnostically the role of anxiety sensitivity in sleep dysfunction. Three hundred one participants with generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD) completed an ancillary questionnaire-based study. Linear regression was used to examine AS and sleep dysfunction, and mediation analyses were used to examine whether AS was a mediator of the effect of primary diagnosis on sleep. AS was associated with increased sleep dysfunction across anxiety disorders, and primary anxiety disorder diagnosis was significantly associated with sleep dysfunction. However, after controlling for AS, primary diagnosis was no longer significant. AS significantly mediated the effects of PD versus SAD and of PD versus GAD on sleep dysfunction, but did not significantly mediate the effect of GAD versus SAD on sleep dysfunction. Taken together, AS appears to be a more important predictor of sleep dysfunction overall, emphasizing the cross-diagnostic nature of AS and bolstering the RDoC initiative approach for treating psychological dysfunction.
26786476	To examine the relationship between self-reported sleep duration and neovascular age-related macular degeneration (nAMD).This case-control study comprised 165 subjects (57 patients with nAMD and 108 controls). Controls were matched to cases by age and sex. Participants completed a questionnaire that included questions about sleep duration and quality. Four categories of sleep duration were established; <6 hours, 6-7 hours, 7-8 hours and >8 hours. Association of sleep duration and nAMD was assessed by logistic regression analysis. Multiple logistic regression models were performed to control for possible confounders.	We found a significant association between short sleep duration and nAMD (for <6 hours, odds ratio, OR, 3.29, 95% confidence interval, CI, 1.32-8.27; for 6-7 hours, OR 2.25, 95% CI 0.80-6.32; and for >8 hours, OR 1.39, 95% CI 0.53-3.73) compared with the reference category of 7-8 hours. This association remained significant after adjustment for confounders (<6 hours, OR 3.09, 95% CI 1.20-7.97). In addition, a borderline significant association was observed between self-reported very bad sleep quality and nAMD (OR 2.84, 95% CI 1.02-7.88). The highest rate of sleep medication use was found in the nAMD group (p < 0.001).	Our findings provide evidence to support an association between short sleep duration and nAMD. Considering strategies to improve sleep in these patients may prevent the negative effects of sleep deficiency.	
26785837	The aim of this work was to study the sleep characteristics, blood pressure (BP) and heart rate (HR) of the police officers working during out-of-phase (OP) and in-phase (IP) duty schedules with respect to their chronotypes. Adult male and female police officers (n = 85) were asked to answer Hindi/English version of different questionnaires to assess their chronotype (morningness-eveningness questionnaire; MEQ), PSQI scores (Pittsburgh sleep quality index), daytime sleepiness (Epworth sleepiness scale, ESS) and fatigue levels (fatigue severity scale, FSS) and fill a sleep log. Based on their PSQI scores, the participating subjects (n = 85) were divided into two categories: good sleepers (58/85) and poor sleepers (27/85). Of these 85 subjects, 23 subjects (good sleepers n = 13; poor sleepers n = 10) volunteered for the next part of the study. At the beginning of the study, the existing duty schedule of these subjects was OP and lasted for 4 days (OP1). Thereafter, they were allotted their preferred (IP) duty schedule for 4 days, followed by OP2 for further 4 days. Over the 12-day period, subjects were monitored for their BP and sleep-wake cycle. Results showed that the poor sleepers improved their sleep quality and HR during IP duty schedule; however, good sleepers were not affected significantly. 
26785726	Various characteristics of the sleep-wake cycle can determine the success or failure of individual adjustment to certain temporal conditions of the today's society. However, it remains to be explored how many such characteristics can be self-assessed and how they are inter-related one to another. The aim of the present report was to apply a three-dimensional structural representation of the sleep-wake adaptability in the form of "rugby cake" (scalene or triaxial ellipsoid) to explain the results of analysis of the pattern of correlations of the responses to the initial 320-item list of a new inventory with scores on the six scales designed for multidimensional self-assessment of the sleep-wake adaptability (Morning and Evening Lateness, Anytime and Nighttime Sleepability, and Anytime and Daytime Wakeability). The results obtained for sample consisting of 149 respondents were confirmed by the results of similar analysis of earlier collected responses of 139 respondents to the same list of 320 items and responses of 1213 respondents to the 72 items of one of the earlier established questionnaire tools. Empirical evidence was provided in support of the model-driven prediction of the possibility to identify items linked to as many as 36 narrow (6 core and 30 mixed) adaptabilities of the sleep-wake cycle. The results enabled the selection of 168 items for self-assessment of all these adaptabilities predicted by the rugby cake model. 
26779564	The overall objective of the 2014 National Sleep Foundation Sleep in America Poll "Sleep in the Modern Family" was to obtain a current picture of sleep in families with at least 1 school-aged child.Cross-sectional poll.	Internet-based interview.	Nationally representative Internet panel of US households with a child 6-17 years.	Primary measures included parental perception of the importance of sleep, parental and child sleep quality, child sleep duration and habits, technology in bedroom, and family rules. Parents/guardians (n= 1103; mean age, 42; 54% female) completed the survey. Although the majority of parents endorsed the importance of sleep, 90% of children obtain less sleep than recommended. Significant predictors of age-adjusted sufficient sleep duration (estimated conservatively as ≥9 hours for ages 6-11 years and ≥8 hours for ages 12-17 years) included parent education, regular enforcement of rules about caffeine, and whether children left technology on in their bedroom overnight. Significant predictors of excellent sleep quality included whether a bedtime was always enforced and whether children left technology on overnight.	Children generally have better age-appropriate sleep in the presence of household rules and regular sleep-wake routines. Sufficient sleep quantity and adequate sleep quality were protected by well-established rules of sleep hygiene (limited caffeine and regular bedtime). In contrast, sleep deficiency was more likely to be present when parents and children had electronic devices on in the bedroom after bedtime. Public health intervention goals for sleep health might focus on reducing the encroachment of technology and media into time for sleep and supporting well-known sleep hygiene principles.	
26777774	To determine whether the increase in slow-wave sleep associated with modafinil treatment in chronic cocaine users mediates improved clinical outcomes.57 cocaine dependent participants were randomized to receive modafinil 400mg or placebo daily during a period of inpatient treatment followed by six weeks of outpatient treatment. Participants underwent polysomnographic sleep recording during inpatient treatment prior to and after starting modafinil. Outpatient treatment consisted of weekly cognitive behavioral therapy. Contingency management was used to promote participation in treatment and research demands, including thrice weekly visits during the outpatient phase for urine toxicology screens and other assessments. The primary clinical outcome was the percent of urine toxicology screens that were negative for cocaine.	Modafinil treatment was associated with a higher mean percentage (52% vs. 26%) of cocaine-free urine screens (p=0.02) and an increase in N3 sleep time (p=0.002). The change in N3 sleep time mediated the higher rate of cocaine-free urine screens. Modafinil treatment was also associated with more consecutive days abstinent during outpatient treatment, greater survival of abstinence, higher daily rates of abstinence, and less sleep degradation typically associated with abstinence from chronic cocaine use.	Morning-dosed modafinil improves slow-wave sleep in abstinent cocaine users in the inpatient setting, and this effect is a statistical mediator of improved clinical outcomes associated with continued modafinil treatment. The high rates of abstinence achieved in this trial suggest that promoting healthy sleep physiology in an inpatient setting may be important in the effective treatment of cocaine dependence.	
26777427	Bright nocturnal light has been shown to suppress melatonin secretion. However, bright light exposure during the day might reduce light-induced melatonin suppression at night. The human circadian system is sensitive to short wavelength light. This study evaluated the preventive effect of different wavelengths of daytime light on light-induced melatonin suppression at night. Twelve male subjects were exposed to various light conditions (dim, white, and bluish white light) between the hours of 09:00 and 10:30 (daytime light conditions). They were then exposed to light (300lx) again between 01:00 and 02:30 (night-time light exposure). Subjects provided saliva samples before (00:55) and after night-time light exposure (02:30). A two-tailed paired t-test yielded significant decrements in melatonin concentrations after night-time light exposure under daytime dim and white light conditions. No significant differences were found in melatonin concentrations between pre- and post-night-time light exposure with bluish-white light. Present findings suggest that daytime blue light exposure has an acute preventive impact on light-induced melatonin suppression in individuals with a general life rhythm (sleep/wake schedule). These findings may be useful for implementing artificial light environments for humans in, for example, hospitals and underground shopping malls to reduce health risks.
26777273	The suppression of inappropriate actions is critical for flexible behavior. Cortical-basal ganglia networks provide key gating mechanisms for action suppression, yet the specific roles of neuronal subpopulations are poorly understood. Here, we examine Arkypallidal (‘‘Arky’’) and Prototypical (‘‘Proto’’) globus pallidus neurons during a Stop task, which requires abrupt cancellation of an imminent action. We first establish that Arky neurons can be identified by their firing properties across the natural sleep/wake cycle. We then show that Stop responses are earlier and stronger in the Arky compared to the Proto subpopulation. In contrast to other basal ganglia neurons, pallidal Stop responses are selective to Stop, rather than Go, cues. Furthermore, the timing of these Stop responses matches the suppression of developing striatal Go-related activity. Our results support a two-step model of action suppression: actions-inpreparation are first paused via a subthalamic-nigral pathway, then cancelled via Arky GABAergic projections to striatum.
26776447	The maternal postpartum period is characterized by sleep fragmentation, which is associated with daytime impairment, mental health disturbances, and changes in melatonin patterns. In addition to sleep fragmentation, women undergo a complex set of physiological and environmental changes upon entering the postpartum period, confounding our understanding of effects of postpartum sleep disturbance. The primary study aim was to understand the basic impact of a single night of postpartum-like sleep fragmentation on sleep architecture, nocturnal melatonin levels, mood, daytime sleepiness, and neurobehavioral performance.For one week prior to entry into the laboratory, eleven healthy nulliparous women kept a stable sleep-wake schedule (verified via actigraphy). Participants contributed three consecutive nights of laboratory overnight polysomnography: (1) a habituation/sleep disorder screening night; (2) a baseline night; and (3) a sleep fragmentation night, when participants were awakened three times for ~30min each. Self-reported sleep quality and mood (Profile of Mood States survey) both decreased significantly after sleep fragmentation compared to baseline measurements. Unexpectedly, daytime sleepiness (Multiple Sleep Latency Test) decreased significantly after sleep fragmentation. Experimental fragmentation had no significant effect on time spent in nocturnal sleep stages, urinary 6-sulfatoxymelatonin concentration, or psychomotor vigilance test performance. Participants continued to provide actigraphy data, and daily PVTs and self-reported sleep quality assessments at home for one week following sleep fragmentation; these assessments did not differ from baseline values.	While there were no changes in measured physiological components of a single night of postpartum-like experimental sleep fragmentation, there were decreases in self-reported measures of mood and sleep quality. Future research should examine the effects of multiple nights of modeling postpartum-like sleep fragmentation on objective measures of sleep and daytime functioning.	
26776072	Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterised by impulsivity, inattention and hyperactivity. Aside from these core psychopathologies, sleep disturbances are found to be highly comorbid with ADHD, and indeed dysregulated sleep may contribute to some of the symptoms of the disorder. It is not clear how sleep disturbances come to be so common in ADHD, but one putative mechanism is through the circadian timekeeping system. This system underpins the generation of near 24-hour rhythms in a host of physiological, behavioural and psychological parameters, and is a key determinant of the sleep/wake cycle. In this paper we review the evidence for sleep and circadian rhythm disturbance in ADHD, examine the possible mechanistic links between these factors and the disorder and discuss future directions through which the circadian clock can be targetted for ADHD symptom relief. 
26775112	Sleep-wake behavior is altered in response to immune challenge. Although the precise mechanisms that govern sickness-induced changes in sleep are not fully understood, interleukin-1β (IL-1) is one mediator of these responses. To better understand mechanisms underlying sleep and inflammatory responses to immune challenge, we used two transgenic mouse strains that express IL-1 receptor 1 (IL1R1) only in the central nervous system and selectively on neurons or astrocytes. Electroencephalographic recordings from transgenic and wild-type mice reveal that systemic challenge with lipopolysaccharide (LPS) fragments sleep, suppresses rapid eye movement sleep (REMS), increases non-REMS (NREMS), diminishes NREM delta power, and induces fever in all genotypes. However, the magnitude of REMS suppression is greater in mice expressing IL1R1 on astrocytes compared with mice in which IL1R1 is selectively expressed on neurons. Furthermore, there is a delayed increase in NREM delta power when IL1R1 is expressed on astrocytes. LPS-induced sleep fragmentation is reduced in mice expressing IL1R1 on neurons. Although LPS increases IL-1 and IL-6 in brain of all genotypes, this response is attenuated when IL1R1 is expressed selectively on neurons or on astrocytes. Collectively, these data suggest that in these transgenic mice under the conditions of this study it is neuronal IL1R1 that plays a greater role in LPS-induced suppression of REMS and NREM delta power, whereas astroglial IL1R1 is more important for sleep fragmentation after this immune challenge. Thus, aspects of central responses to LPS are modulated by IL1R1 in a cell type-specific manner.
26774862	To examine the association between sleep and social-emotional development in two-year-old toddlers.The study is part of a longitudinal cohort study, the Akershus Birth Cohort Study, which targeted all women giving birth at Akershus University Hospital in Norway. The current study is from the fourth round of the study, including 2014 women two years after delivery. The Brief Infant Sleep Questionnaire (BISQ) and the Ages and Stages Questionnaire: Social Emotional (ASQ:SE) were filled out by the mothers and were used to assess toddler sleep, and social-emotional development, respectively. Other domains of development (communication problems, gross motor problems, and fine motor problems) were assessed with the Ages and Stages Questionnaire (ASQ). Confirmatory factor analysis was conducted on the ASQ:SE, and logistic regression analyses were used to examine both crude associations between sleep variables and social-emotional problems, and adjusting for potential confounders.	The mean sleep duration of the toddlers was 12h and 27 min; the majority of the children (54%) had 1-2 awakenings per night, while 10% of the children had a sleep onset latency of more than 30 min. All sleep parameters, including short sleep duration, nocturnal awakenings and sleep onset problems, were significantly associated with social-emotional problems in a dose-response manner. For example, sleeping less than 11h per night was associated with a five-fold increase in the odds of social-emotional problems, compared to sleeping 13-14 h per night. Adjusting for potential confounders, including maternal age, maternal education, marital status, parity, gestational age, child birth-weight and other developmental problems, did not, or only slightly, attenuate the associations between any of the sleep variables and social-emotional problems.	Short sleep duration, nocturnal awakenings and sleep onset problems were all associated with higher odds of social-emotional problems, even after accounting for developmental problems and demographic factors. Thus, a broad assessment of sleep and social-emotional problems when toddlers present with either can be useful.	
26774754	Huntington's disease (HD) is an inherited neurodegenerative disorder that is well recognised as producing progressive deterioration of motor function, including dyskinetic movements, as well as deterioration of cognition and ability to carry out activities of daily living. However, individuals with HD commonly suffer from a wide range of additional symptoms, including weight loss and sleep disturbance, possibly due to disruption of circadian rhythmicity. Disrupted circadian rhythms have been reported in mice models of HD and in humans with HD. One way of assessing an individual's circadian rhythmicity in a community setting is to monitor their sleep/wake cycles, and a convenient method for recording periods of wakefulness and sleep is to use accelerometers to discriminate between varied activity levels (including sleep) during daily life. Here we used Actiwatch(®) Activity monitors alongside ambulatory EEG and sleep diaries to record wake/sleep patterns in people with HD and normal volunteers. We report that periods of wakefulness during the night, as detected by activity monitors, agreed poorly with EEG recordings in HD subjects, and unsurprisingly sleep diary findings showed poor agreement with both EEG recordings and activity monitor derived sleep periods. One explanation for this is the occurrence of 'break through' involuntary movements during sleep in the HD patients, which are incorrectly assessed as wakeful periods by the activity monitor algorithms. Thus, care needs to be taken when using activity monitors to assess circadian activity in individuals with movement disorders. 
26774552	Children with medical complexity have a high prevalence of sleep disorders. However, outpatient polysomnography to evaluate for these conditions may be difficult to perform because of lack of skilled nursing care. The aim of this study was to explore polysomnography indications in hospitalized children and assess its impact on patient care.Data from 85 inpatient polysomnographies of 70 children hospitalized between March and December 2014 were retrospectively collected.	Sixty percent of patients were boys with ages 6.5 ± 6 years. Chronic respiratory failure was present in 33.8%, airway obstruction due to defects of the tracheobronchial tree or craniofacial abnormalities in 54.3%, neurological complications of the perinatal period in 22.9%, genetic syndromes and neurodegenerative disorders in 31.4%, congenital myopathies in 5.7%, metabolic diseases in 4.3% and congenital cyanotic heart defects in 4.3%. Indications for polysomnography included assessment of chronic pulmonary disease (60%), ventilator requirements (41.2%), apnea/desaturation (23.5%), and acute life-threatening events (1.2%). Abnormal results were found in 89.4%. The observed diagnosis was obstructive sleep apnea in 64.7%, signs of chronic lung disease in 34.1%, hypoventilation in 9.4%, periodic breathing in 3.5%, and periodic limb movement of sleep in 4.7%. The following interventions were performed: adjustment of ventilator parameters (45.8%), positive airway pressure initiation (24.7%), otorhinolaryngology referral (30.6%), supraglottoplasty (2.4%), tracheostomy decannulation (2.4%), and tracheostomy placement (3.5%). Nine patients had available follow-up polysomnograms, all showing improvement in sleep variables after adherence to recommended interventions.	In individuals with complex medical disorders, inpatient polysomnographies give invaluable information to guide immediate medical decision making and should be strongly considered if resources allow this.	
26774535	The influence of approaching death in addition to age and their interaction on the course of a broad spectrum of nondopaminergic features in Parkinson's disease (PD) has not been well studied. This study addresses this issue in a prospectively designed study.During five years, the severity of axial symptoms, cognitive impairment, psychotic symptoms, autonomic dysfunction, depressive symptoms, and daytime sleepiness was annually evaluated in PD patients. For each domain a linear mixed-effect model was used to examine changes during follow-up and relations with age and death.	Of 378 included patients, 43 died during follow-up. Higher age was associated with increased severity of all nondopaminergic features except depression, and with a higher rate of progression of axial symptoms and cognitive impairment. Patients who died during follow-up had a higher severity of all nondopaminergic features except autonomic dysfunction, and a higher rate of progression of axial symptoms, cognitive impairment, and psychotic symptoms, compared to patients who survived.	This study shows that the severity of most nondopaminergic features and the progression rate of axial and psychotic symptoms and cognitive impairment increase before PD patients die, independent of the influence of age. An interaction between age and approaching death did not have a significant effect on the course of the symptoms. Improving our understanding of the fundamental biology underlying these factors and the interaction with factors intrinsic to the disease, may have profound implications for the treatment of PD.	
26774482	The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%-100%). In addition, we developed a respiration-based fully automated non-invasive sleep phenotyping system, the Snappy Sleep Stager (SSS), for high-performance (95.3% accuracy) sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA) receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research. 
26771699	Anti-N-methyl-D-Aspartate encephalitis is a recently diagnosed autoimmune disorder with increasing significance. During this disease antibodies are produced against the subunit of the NMDA receptor, which cause different symptoms, both psychiatric and neurological. The aim of this publication is to introduce this disease, to facilitate the diagnosis and to recommend therapeutical guideline.In this review we summarized the relevant literature published between 2007 and 2015 giving emphasis on etiopathogenesis, diagnosis, differential diagnosis, treatment and prognosis.	In the etiology an underlying tumor or a viral agent should be considered. During the disease we can discern 3 periods: first prodromal viral infections-like symptoms can be seen, 1-2 weeks later psychiatric symptoms, such as aggression, sleep and behavior disturbances appear. After that neurological symptoms (tonic-clonic convulsions, aphasia, catatonia, orofacial dyskinesia, autonom lability, altered mental state) are typical, and the patient's condition deteriorates. For the correct diagnosis it is necessary to detect antibodies against the NMDA receptor from the serum and the liquor. Steroids, immunoglobulins and plasmaheresis are the first-line therapies. If the disease is unresponsive, then as a second-line therapy anti-CD 20 (Rituximab) and cyclophosphamid can be useful. Most of the patients are improving without any neurological sequale with prompt detection and appropriate therapy.	It is important to be familiar with the symptoms, diagnosis and therapy of this disease as a practicing clinician, especially as a psychiatrist or neurologist. 75 percentage of the patients are admitted to psychiatric departments first because of the leading symptoms. Autoimmune NMDA encephalitis is a reversible disease after early diagnosis and treatment.	
26771556	Personal psychosocial resources (e.g., positive affect, social support, perceived mastery, meaning in life) are associated with better sleep in noncancer populations, but there have been few studies in cancer patients. The present study examined psychosocial resources and sleep in gynecological cancer patients. Before chemotherapy, 72 participants completed self-report measures of sleep and psychosocial resources; 63 also completed actigraphic monitoring. Subjective sleep was associated with positive affect, social support, perceived mastery, and meaning in life; objective sleep was associated with social support. Future studies should examine whether interventions to enhance psychosocial resources result in improved sleep in this population. 
26769785	We determined whether crowding at emergency shelters is associated with a higher incidence of sleep disturbance among disaster evacuees and identified the minimum required personal space at shelters.Retrospective review of medical charts.	30 shelter-based medical clinics in Ishinomaki, Japan, during the 46 days following the Great Eastern Japan Earthquake and Tsunami in 2011.	Shelter residents who visited eligible clinics.	Based on the result of a locally weighted scatter-plot smoothing technique assessing the relationship between the mean space per evacuee and cumulative incidence of sleep disturbance at the shelter, eligible shelters were classified into crowded and non-crowded shelters. The cumulative incidence per 1000 evacuees was compared between groups, using a Mann-Whitney U test. To assess the association between shelter crowding and the daily incidence of sleep disturbance per 1000 evacuees, quasi-least squares method adjusting for potential confounders was used.	The 30 shelters were categorised as crowded (mean space per evacuee <5.0 m(2), 9 shelters) or non-crowded (≥ 5.0 m(2), 21 shelters). The study included 9031 patients. Among the eligible patients, 1079 patients (11.9%) were diagnosed with sleep disturbance. Mean space per evacuee during the study period was 3.3 m(2) (SD, 0.8 m(2)) at crowded shelters and 8.6 m(2) (SD, 4.3 m(2)) at non-crowded shelters. The median cumulative incidence of sleep disturbance did not differ between the crowded shelters (2.3/1000 person-days (IQR, 1.6-5.4)) and non-crowded shelters (1.9/1000 person-days (IQR, 1.0-2.8); p=0.20). In contrast, after adjusting for potential confounders, crowded shelters had an increased daily incidence of sleep disturbance (2.6 per 1000 person-days; 95% CI 0.2 to 5.0/1000 person-days, p=0.03) compared to that at non-crowded shelters.	Crowding at shelters may exacerbate sleep disruptions in disaster evacuees; therefore, appropriate evacuation space requirements should be considered.	
26768728	Dementia-related sleep problems can be complex and challenging. Environmental interventions which resynchronise the sleep/wake cycle have been trialled with promising results for people with dementia in institutionalised settings. However, there is less research concerning community-dwelling people with dementia and their family carers. This study involved a five-week feasibility study including timed light therapy, exercise and sleep education. Sleep and physical and mental functioning were measured at the beginning and end of the trial using objective measures, standardised questionnaires and structured participant feedback. Of 15 community-dwelling pairs who participated, nine completed the trial. The case studies presented here reveal that it is feasible for this population to use non-pharmacological interventions, with positive outcomes. However, there are also issues that can mask benefits or prevent compliance. The options for treating dementia are limited. Environmental interventions may help manage dementia-related sleep problems and further trials would be worthwhile to improve compliance and evaluate effectiveness.
26768391	To compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI).The prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans.	Women Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans.	Efforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population.	
26767328	Children with cancer are known to have sleep problems. Although hospitalization and psychosocial factors are considered to be the factors affecting children's sleep, few studies have confirmed these effects. The aims of this study were to describe the sleep status of hospitalized children with cancer and to explore the correlates.The sleep status of 11 hospitalized children (aged 2-12 years) with cancer was measured using actigraph and sleep diary during hospitalization and a short home stay. Possible correlates were assessed using a questionnaire.	The participants had significantly longer sleep onset latency, earlier bedtime, and poorer self-evaluated sleep quality during hospitalization than the short home stay. They had shorter total sleep time, longer wake time after sleep onset, and less sleep efficiency at home, compared with healthy historical controls. Children's age, symptoms, hospitalization period, Cognitive Fatigue, Procedural Anxiety, Treatment Anxiety, Social Anxiety, and Separation Anxiety, as well as caregiver anxiety, Receptive and Focused Attitude, and Regimented Attitude were significantly correlated with sleep variables.	Hospitalization decreased self-evaluated sleep quality, and difficulty falling asleep. The sleep of the participants at home was disturbed compared with that of healthy children. Hospitalization, patient characteristics, disease-related, and some psychosocial factors were associated with sleep variables. Medical professionals should develop a favorable environment for falling asleep in hospital for individual children. Children with cancer in the early period of hospitalization need increased care to facilitate good sleep.	
26766187	Data from the National Health Interview Survey, 2013-2014. Single parents, especially women, were more likely than adults in other types of families to have short sleep duration, frequently have trouble falling asleep and staying asleep, and frequently wake up feeling not well-rested. Within family types, women were more likely than men to frequently have trouble falling asleep and staying asleep, and to frequently wake up feeling not well-rested. Overall, adults in two-parent families were less likely than adults in other types of families to have taken sleep medication four times or more in the past week.
26762786	Extensive studies focus on the cognitive and motor impairments after perinatal hypoxic-ischemia (HI). Sleep problems, although reported to be associated with cerebral palsy (CP), are often overlooked in non-severe HI patients. Here, by investigating the sleep qualities of children with different degrees of HI, we discovered that sleep initiation and maintenance, sleep-related breathing problems, or circadian rhythmic issues were highly associated with children of moderate or mild HI, respectively. Follow-up MRI studies in 2-year old patients showed that periventricular white matter lesions including periventricular leukomalacia (PVL) were prevalent in moderate, but not mild, HI children. In contrast, the occurrence of pineal cysts had a high risk in children with mild HI. Our study provides novel insights into the mechanisms of distinctive sleep problems associated with children of different degrees of HI, and therefore sheds light on the studies of targeted therapeutic treatments for sleep disorders in children who suffer from HI. 
26759211	To explore the characteristics of sleep disturbance and its related factors in patients with rheumatoid arthritis (RA).A total of 71 patients with RA in Department of Rheumatology Huaxi Hospital have completed the following questionnaires, including Pittsburgh sleeping quality index (PSQI), visual analogue scale (VAS), disease activity score in 28 joints (DAS28), health assessment questionnaire(HAQ), hospital anxiety and depression scale (HADS), fatigue severity scale (FSS) and a self-designed general status questionnaire.	The prevalence of sleep disturbance was 42.3% (30/71) in rheumatoid arthritis patients (68.4%). The scores of DAS28, VAS, PSQI, HAQ, FSS and HADS in patients with sleep disturbance were significantly higher than those in patients with good sleep, which were respectively 3.90±1.12 vs 2.92±1.92, (5.03±2.63) scores vs (2.41±1.84) scores, (10.87±2.42) scores vs (4.29±1.85) scores, 3.0(0.0,7.0) scores vs 2.0 (0.5, 4.0) scores, (39.17±14.02) scores vs (29.63±16.12) scores, (14.50±7.77) scores vs (9.49±6.57) scores (P<0.05 in all scales). According to the results of Pearson correlation analysis, PSQI had significantly positive correlation with DAS28 (r=0.462, P<0.01), VAS (r=0.556, P<0.01), HAQ (r=0.360, P<0.01), FSS (r=0.420, P<0.01) and HADS (r=0.447, P<0.01) respectively. The logistic regression analysis indicated that VAS was a predictor for poor sleep quality (P<0.01). The patients receiving biological agents had significantly (P<0.05) lower scores of DAS28 (2.86±1.39 vs 3.52±1.10), PSQI [(5.90±4.24) scores vs (8.53±3.78) scores], VAS (2.15±2.30 vs 4.05±2.46), HAQ [0.0 (0.0, 2.0) scores vs 3.0 (0.0, 6.0) scores] compared to those taking oral drugs.	High prevalence of sleep disturbance in patients with RA is noted, which indirectly influences the activity of disease, quality of life, depression, fatigue and other physical and mental health. Biological agents can partly improve the sleep disturbance and functional status.	
26758352	Importancia de los problemas de sueño en los niños con cefalea y otros trastornos del neurodesarrollo en las consultas de neuropediatria.Introduccion. Los trastornos de sueño son frecuentes en niños con trastornos neurologicos. El objetivo del estudio es conocer la opinion de los neuropediatras y su prevalencia real en España. Pacientes y metodos. Estudio transversal multicentrico (12 hospitales españoles, 15 investigadores). Se administro la encuesta Bedtime, Excesive Daytime Sleepiness, Awakenings, Regularity, Sleep-Disordered Breathing (BEARS) y se definieron tres grupos: A (2-5 años), B (6-12 años) y C (> 12 años). Asimismo, se recogio la opinion de neuropediatras de la Sociedad Española de Neuropediatria mediante una encuesta anonima. Resultados. Se recogieron 939 encuestas. Los principales motivos de consulta en los grupos B y C fueron trastorno por deficit de atencion/hiperactividad (32,4% y 30,1%, respectivamente) y cefalea (25,1% y 27,6%, respectivamente), y en el grupo A, los trastornos del neurodesarrollo (32,4%) y la epilepsia (21,4%). Al menos un area del sueño alterada se encontro en el 92,9% de niños del grupo A (n = 209; media: 3 años), en el 64,2% del grupo B (n = 534; media: 9,4 años) y en el 58,2% del grupo C (n = 196; media: 13,7 años). Se recibieron 61 encuestas respondidas por los neuropediatras (16,75% de las enviadas), quienes estimaban que los trastornos del sueño afectaban a menos de una cuarta parte de sus pacientes (24,5%), y hasta un 23% afirmo que la prevalencia era inferior al 10%. Conclusion. El 58-92% de los padres-pacientes que acuden a consultas de neuropediatria refiere tener algun aspecto del sueño alterado. Aunque la mayoria de los neuropediatras subraya la importancia de un diagnostico y tratamiento de los trastornos de sueño de los niños con trastornos neurologicos, se suele infraestimar su frecuencia e importancia.	Sleep disorders are common in children with neurological disorders. The aim of this study is to know the opinion of neuropediatricians and the prevalence of these disturbances in Spain.	Multicenter cross-sectional study (12 Spanish hospitals, 15 researchers). BEARS survey was collected in three groups: A (2-5 years), (6-12 years), and C (> 12 years). The opinion of neuropediatricians was also collected.	939 questionnaires were filled. The main results in groups B and C were ADHD (32.4% and 30.1% respectively) and headache (25.1% and 27.6% respectively), whereas in group A neurodevelopmental disorders (32.4%) and epilepsy (21.4%) were the main diagnoses. Disturbances in at least one area of sleep were found in 92% of children in group A (n = 209, mean 3 years), 64.2% in group B (n = 534, mean 9.4 years) and 58.2% in group C (n = 196, mean 13.7 years). Sixty-one surveys were answered by neuropediatricians (16.75% of the total sent), estimating that less than a quarter of the patients (24.5%) suffered. Even, up to 23% of doctors claimed that the prevalence of sleep disorders was < 10%.	58-92% of parents-patients under follow up at a neuropediatrician office in Spain have some degree of disturbed sleep. Although most neurologists emphasize the importance of an early diagnosis and treatment of sleep disorders in children with neurological disorders, its frequency is often underestimated (risk of underdiagnosis).	
26757356	Objective Sleep disturbances are one of the most common psycho-physiological issues among postmenopausal women. This study was designed to evaluate the impact of walking with a pedometer on the sleep quality of postmenopausal Iranian women. Methods This randomized, controlled trial was conducted on 112 women who were randomly assigned to two groups. The women in the intervention group (n = 56) were asked to walk with a pedometer each day for 12 weeks and to increase their walking distance by 500 steps per week. A sociodemographic instrument and the Pittsburgh Sleep Quality Index were used to collect data. Sleep quality was measured at baseline, 4, 8, and 12 weeks after intervention. The control group (n = 56) did not receive any intervention. Results After 12 weeks, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction improved to a significantly greater extent in the intervention group than in the control group (p < 0.05). The total sleep quality score was significantly higher in the intervention group than in the control group (0.64 vs. 0.98, p = 0.001). Conclusion This study showed that walking with a pedometer is an easy and cost-effective way to improve the quality of sleep among postmenopausal women. Use of this method in public health centers is recommended. 
26757318	Adolescents with cancer experience many troubling symptoms, including sleep disruptions that can affect mood and quality of life. Massage is a safe and popular intervention that has demonstrated efficacy in pediatric and adult patients with cancer. This study aimed to assess the feasibility of conducting a massage intervention to help with sleep in hospitalized adolescent oncology patients.Adolescents ages 12-21 with cancer who were expected to be hospitalized for at least four consecutive nights were recruited from the inpatient unit at Children's National Health System and randomized to either massage intervention or a waitlist control. Patients in the intervention group received one massage per night, for two or three nights. Sleep was measured with actigraphy and patient and proxy reported instruments were used to measure fatigue, mood, and anxiety.	The majority (78%) of patients approached for the study consented, and almost all patients in the intervention group (94%) received at least one massage, 69% received two, and rates of completion of instruments among adolescents were high demonstrating feasibility. There were trends toward increased night time and overall sleep in the intervention group compared with standard of care, but no differences between groups in the patient reported outcome measures. Participant and parent feedback on the intervention was positive and was the impetus for starting a clinical massage service at the hospital.	Massage for hospitalized adolescents with cancer is feasible, well received, and can potentially improve patients' sleep. A randomized multicenter efficacy study is warranted.	
26756440	We studied the impact of aging during sleep in the rat models of Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology to determine the possible different and earlier onset of age-related sleep disorder during the neurodegenerative diseases vs. healthy aging. We used the bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesioned rats as the in vivo models of functionally distinct cholinergic neuropathology, and we followed the impact of aging on sleep architecture, the electroencephalographic (EEG) microstructure and motor control across sleep/wake states. Our results have shown for the first time that the earliest signs of aging during distinct cholinergic neuropathology were expressed through a different and topographically specific EEG microstructure during rapid eye movement sleep (REM). EEG delta amplitude attenuation within the sensorimotor cortex (SMCx) during REM was the earliest sign of aging in the NB lesion. EEG sigma amplitude augmentation within the motor cortex (MCx) during REM was the earliest sign of aging in the PPT lesion. In addition, aging was differently expressed through the SMCx drive alterations, but it was commonly expressed through the MCx drive alterations during all sleep/wake states. Our study provided evidence of distinct REM sleep disorders and sleep state related cortical drives as the signs of aging onset during functionally distinct cholinergic neuropathologies (NB lesion vs. PPT lesion).
26755200	Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity. 
26753792	Sleep disturbance is frequent in opioid-dependent patients. To date, no data are available about the impact of methadone maintenance treatment on sleep disturbance. Using 1-year follow-up data from the Methaville trial, we investigated the impact of methadone initiation and other correlates on sleep disturbance in opioid-dependent patients.Sleep disturbance severity was evaluated using two items from different scales (Center for Epidemiological Studies Depression Scale for depression and Opiate Treatment Index). We assessed the effect of methadone and other correlates on sleep disturbance severity during follow-up (months 0, 6, and 12) using a mixed multinomial logistic regression model.	We included 173 patients who had 1-year follow-up data on sleep disturbance, corresponding to 445 visits. At enrolment, 60.5 % reported medium to severe sleep disturbance. This proportion remained stable during methadone treatment: 54.0 % at month 6 and 55.4 % at month 12. The final multivariate model indicated that younger patients (odds ratio (OR) [95 % CI] 0.95 [0.90-1.00]), patients with pain (OR [95 % CI] 2.45 [1.13-5.32]), patients with high or very high nicotine dependence (OR [95 % CI] 5.89 [2.41-14.39]), and patients at suicidal risk (2.50 [1.13-5.52]) had a higher risk of severe sleep disturbance. Because of collinearity between suicidal risk and attention deficit hyperactivity disorder (ADHD) symptoms, ADHD was not associated with sleep disturbance in the final model. Receiving methadone treatment had no significant effect on sleep disturbance.	Sleep disturbance is frequent among opioid-dependent patients. It can be regarded as an important signal of more complex psychiatric comorbidities such as suicidal risk and ADHD. However, sleep disturbance should not be considered an obstacle to methadone maintenance treatment (MMT) initiation or continuation.	
26751571	Sleep disturbance is increasingly recognized as a major problem for patients with schizophrenia but it is rarely the direct focus of treatment. The main recommended treatment for insomnia is cognitive behavioural therapy, which we have been evaluating for patients with current delusions and hallucinations in the context of non-affective psychosis.In this article we describe the lessons we have learned about clinical presentations of sleep problems in schizophrenia and the adaptations to intervention that we recommend for patients with current delusions and hallucinations.	Twelve factors that may particularly contribute to sleep problems in schizophrenia are identified. These include delusions and hallucinations interfering with sleep, attempts to use sleep as an escape from voices, circadian rhythm disruption, insufficient daytime activity, and fear of the bed, based upon past adverse experiences. Specific adaptations for psychological treatment related to each factor are described.	Our experience is that patients want help to improve their sleep; sleep problems in schizophrenia should be treated with evidence-based interventions, and that the interventions may have the added benefit of lessening the psychotic experiences. A treatment technique hierarchy is proposed for ease of translation to clinical practice.	
26748739	Cognitive Behavioral Social Rhythm Therapy (CBSRT) is a group psychotherapy tailored for Veterans with Posttraumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and sleep disturbances. The aims of this study were to introduce and present initial outcomes of Cognitive Behavioral Social Rhythm Therapy (CBSRT), a 12-week skills group therapy designed to improve sleep and mood by reducing chaotic or isolated lifestyles in Veterans with PTSD.Twenty-four male Veterans with at least moderate PTSD and MDD participated in this open trial. Main outcomes were the daily sleep diary for sleep disturbances, the Clinician-Administered PTSD Scale (CAPS) for PTSD, and the Hamilton Depression Rating scale for MDD.	Veterans improved on all measures (a) with large within subject effects on PTSD symptoms, MDD symptoms, and sleep quality, and (b) with 46-58% of the sample receiving clinically significant benefits on MDD and PTSD symptoms respectively. The consistency of social rhythms was associated with the average reduction in global CAPS scores over time. Only 13% of participants dropped-out of the group therapy prematurely suggesting that this new group therapy is relatively well-tolerated by Veterans.	Future research that employs a control condition is necessary to establish efficacy of CBSRT.	Data from this initial pilot study demonstrate that CBSRT may be an effective group treatment option for Veterans presenting with all three symptom complaints. These data also suggest that daily routine may be an important mechanism to consider in the treatment of PTSD symptoms comorbid with depression.	
26748678	The phenomenology and diagnosis of pediatric bipolar disorder has been controversial. We aimed to update a 2005 meta analysis of the prevalence of manic symptoms in youth, in order to determine whether the picture of pediatric mania has changed as research on pediatric bipolar disorder has grown.We conducted literature reviews in PsycINFO and PubMed; studies with the prevalence of manic symptoms in youth were included. Two raters coded each study; kappa was 0.86-1.0.	Twenty studies were meta-analyzed (N = 2,226 youths). The most common symptoms across bipolar subtypes, using a random-effects model, were: increased energy 79%, irritability 77%, mood lability 76%, distractibility 74%, goal-directed activity 72%, euphoric/elated mood 64%, pressured speech 63%, hyperactive 62%, racing thoughts 61%, poor judgment 61%, grandiosity 57%, inappropriate laughter 57%, decreased need for sleep 56%, and flight of ideas 54%. Symptom rates were heterogeneous across samples; potential predictors were explored but no clear patterns were found.	Debate continues about the definitions of pediatric bipolar disorder; the results of this meta-analysis suggest that there is significant heterogeneity of symptom prevalence between studies, and that symptoms vary widely across individuals. Understanding the roots of this heterogeneity could broaden understanding of the complex clinical presentation of pediatric mania, and aid in diagnosis.	
26748465	Salivary samples were collected over a 24-hr period from one group of six juvenile (7-12 years) and one group of three adult (24-25 years) African elephant females, Loxodonta africana, and the cortisol concentration was measured in unextracted samples by EIA. Samples were collected during May, June, and November 2012 (n = 147) using cotton swabs at 4-hr intervals from 20:00 to 20:00 of the next day (seven samples per animal in each trial). The animals are kept under standard zoo management: the herd is maintained in their indoor enclosures until 10:00 and then released into the outdoor enclosures until 21:00-21:30 (May/June) and 18:30-19:00 (November). No adult elephant bull was present at the zoo during this time. The results demonstrate a clear diurnal pattern of cortisol secretion with the lowest concentration observed at 20:00 (2.03 ± 0.08 ng/ml saliva) and the peak concentrations at 08:00 (5.26 ± 0.35 ng/ml saliva). Although the cortisol values were higher in the adult cows compared to the juvenile cows in the May-June period, the differences were not significant. However, the values obtained in November from the juvenile group were significantly higher (P < 0.05) than the concentrations measured in this group in June. In conclusion, salivary cortisol in zoo elephants follows a circadian rhythm (sleep-wake cycle) adapted to daily zoo husbandry routines.

26747207	Good sleep is necessary for optimal health, especially for mental health. Insomnia, sleep deprivation will make your ability to learn and memory impaired. Nevertheless, the underlying pathophysiological mechanism of sleep disorders-induced cognitive decline is still largely unknown. In this study, the sleep deprivation of animal model was induced by chronical sleep interruption (CSI), the behavioral tests, biochemical index determinations, and a liquid chromatography-mass spectrometry (LC-MS) based serum metabolic profiling analysis were performed to explore the effects of CSI on cognitive function and the underlying mechanisms. After 14-days CSI, the cognitive function of the mice was evaluated by new objects preference (NOP) task and temporal order judgment (TOJ) task. Serum corticosterone (CORT), and brain Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT) levels were determined by ELISA kits. Data were analyzed by Principal Component Analysis (PCA), Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA), and Student's t-test. We found that the cognitive function of the mice was significantly affected by CSI. Besides, levels of CORT and MDA were higher, and SOD and CAT were lower in CSI mice than those of control. Obvious body weight loss of CSI mice was also observed. Thirteen potential serum biomarkers including choline, valine, uric acid, allantoic acid, carnitines, and retinoids were identified. Affected metabolic pathways involve metabolism of purine, retinoid, lipids, and amino acid. These results showed that CSI can damage the cognitive performance notably. The cognitive decline may ascribe to excessive oxidative stress and a series of disturbed metabolic pathways. 
26746576	The aim of this study is to evaluate the sleep quality of stroke patients, to present the influencing factors, and thus to provide more effective rehabilitation in hospitals' inpatient clinics.Twenty-three stroke patients who received inpatient treatment at Bolu Physical Therapy and Rehabilitation Hospital were retrospectively evaluated in the study. Educational background, occupation, body mass index, symptom duration, etiology, dominant hemisphere, affected hemisphere, comorbid diseases, and Brunnstrom recovery stages (9), Pittsburgh Sleep Quality Index (PSQI) score, Beck Depression Inventory (BDI) score, and Functional Independence Measure score were assessed.	In multivariate linear regression analysis, we found that BDI score (P = .030) and comorbid diseases (P = .040) had the highest effect on change in PSQI.	Depression and comorbid diseases were the most effective factors on poststroke sleep disorder in patients who underwent neurological rehabilitation and they should be managed to increase the efficacy of the neurological rehabilitation.	
26745869	The increased rates of cardiovascular morbidity and mortality in patients with psoriasis are not adequately explained by traditional risk factors. Whether concomitant sleep disorders (SDs) modify the risk of cardiovascular disease (CVD) in patients with psoriasis remains unknown.Using the Taiwan National Health Insurance Research Database (NHIRD), we conducted a cohort study to investigate the association between concomitant SDs and CVD risk in patients with psoriasis. Data from 99,628 adults who received a psoriasis diagnosis during the period from 2004 to 2010 were analyzed. Cox proportional hazards regression analysis models were used to compare the risks of ischemic heart disease (IHD) and stroke between patients with and without SDs.	Psoriasis patients with a concomitant SD had significantly higher risks of IHD (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 1.22-1.28) and stroke (aHR, 1.24; 95% CI, 1.16-1.33) as compared with psoriasis patients without SDs. All psoriasis patient subgroups, including those with mild and severe psoriasis and those with and without arthritis, had increased HRs for IHD and stroke. The increases in IHD and stroke risks conferred by SDs were proportional to the dose of hypnotics used. The effect of SDs on the risks of IHD and stroke was greater in young adults than in middle-aged and older adults.	The risks of IHD and stroke were higher for psoriasis patients with SDs than for those without SDs. Clinicians should carefully evaluate CVD risk, particularly in young patients with psoriasis.	
26745752	Sleep debt--together with circadian misalignment--is considered a central factor for adverse health outcomes associated with shift work. Here, we describe in detail sleep-wake behavior in a fast-forward rotating 12-h shift schedule, which involves at least 24 hours off after each shift and thus allows examining the role of immediate recovery after shift-specific sleep debt. Thirty-five participants at two chemical plants in Germany were chronotyped using the Munich ChronoType Questionnaire for Shift-Workers (MCTQ(Shift)) and wore actimeters throughout the two-week study period. From these actimetry recordings, we computed sleep and nap duration, social jetlag (a measure of circadian misalignment), and the daily timing of activity and sleep (center of gravity and mid-sleep, respectively). We observed that the long off-work periods between each shift create a fast alternation between shortened (mean ± standard deviation, 5h 17min ± 56min) and extended (8h 25min ± 72min) sleep episodes resulting in immanent reductions of sleep debt. Additionally, extensive napping of early chronotypes (up to 3 hours before the night shift) statistically compensated short sleep durations after the night shift. Partial rank correlations showed chronotype-dependent patterns of sleep and activity that were similar to those previously described in 8-h schedules; however, sleep before the day shift did not differ between chronotypes. Our findings indicate that schedules preventing a build-up of chronic sleep debt may reduce detrimental effects of shift work irrespective of shift duration. Prospective studies are needed to further elucidate the relationship between sleep, the circadian system, and health and safety hazards.
26745517	Recent research suggests that sleep disturbance may be a transdiagnostic process, and there is increasing interest in examining how sleep disturbance may contribute to anxiety and related disorders. The current review summarizes and synthesizes the extant research assessing sleep in anxiety and related disorders. The findings suggest that sleep disturbance exacerbates symptom severity in the majority of anxiety and related disorders. However, the nature of sleep disturbance often varies as a function of objective versus subjective assessment. Although sleep disturbance is a correlate of most anxiety and related disorders, a causal role for sleep disturbance is less clear. A model of potential mechanisms by which sleep disturbance may confer risk for the development of anxiety and related disorders is discussed. Future research integrating findings from basic sleep research with current knowledge of anxiety and related disorders may facilitate the development of novel treatments for comorbid sleep disturbance and clinical anxiety. 
26744783	This study explored whether short sleep duration and sleep quality mediate the relationship between age and depressive symptoms. For comparison, we also explored whether depressive symptoms mediate the relationship between age and short sleep duration and sleep quality. The sample comprised 741 adolescents (63.5% female, mean age 15.78 years, range 11.92-19.67 years) in grades 7-12 from 11 secondary schools in metropolitan Melbourne, Australia. Students completed the Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale (CES-D). Path analyses suggested that short sleep duration significantly mediated the relationship between age and depressive symptoms. Poor sleep quality also significantly mediated this relationship when sleep quality was defined by subjective judgement, but not sleep disturbance, sleep efficiency, or sleep onset latency. Depressive symptoms significantly mediated the relationship between age and short sleep duration and sleep quality (subjective judgement, sleep disturbance, sleep efficiency, and sleep onset latency). These findings suggest that the population-wide increase in depressive symptoms across adolescence is partially mediated by sleep-related developmental changes. They also highlight the importance of examining specific sleep problems when investigating the relationship between sleep and mood in this age group.
26743832	Mechanisms of fatigue reported during radiotherapy are poorly defined but may include inflammatory cytokines and/or sleep disturbances. This prospective, longitudinal, phase II study assessed fatigue, sleep, and serum cytokine levels during radiotherapy for early-stage prostate cancer (PCa).Twenty-eight men undergoing radiotherapy for early-stage PCa wore an Actiwatch Score to record fatigue level, sleep time, onset latency, efficiency and wake after sleep onset. Serum levels of IL-1α, IL-1β, TNF-α, IL-6, IL-8, IL-10 and VEGF were measured weekly during radiotherapy. Patient reported quality of life (QOL) metrics were collected before and after treatment. Linear mixed effects models examined trajectories across treatment weeks.	Fatigue increased across treatment weeks (P<.01), and fatigue was associated with decreased patient-reported QOL. Sleep efficiency increased across treatment weeks (rate of change over time=.29, P=.03), and sleep onset latency decreased (rate of change over time=.86, P=.06). IL-6 tended to increase during treatment (P=0.09), but none of the cytokine levels or sleep variables were significantly related to fatigue trajectories.	Despite increased sleep efficiency across treatment weeks, fatigue significantly increased. Although IL-6 increased during the course of radiotherapy, cytokines levels were not associated with fatigue scores or sleep disturbance. Further studies are needed to define the mechanisms for fatigue during radiotherapy.	
26742676	In 2004, in Genoa (Italy), the Italian Dementia Research Association (SINDem) was born. The first congress of this new scientific society took place in Rome in 2006. SINDem soon recognized the importance to investigate sleep problems in cognitive decline and created a national "sleep study group "composed by neurologists and sleep specialists. In 2012, The SINDem study group, in close relationship with the Italian Association of sleep medicine (AIMS), published the study "Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients ", confirming the high prevalence of sleep disturbances in a wide Italian population of persons with cognitive decline. The study was supported by a grant from the Italian Minister of Health and was conducted with the fundamental contribution of the Italian National Research Center (CNR). In 2014, the same group published the paper "Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review". The recommendations are wide and directed to professionals (neurologists but not exclusively) to try to establish uniform levels of care, promote collaborative studies into areas of uncertainty, and define the qualitative characteristics of Dementia Reference Centers about sleep disturbances. 
26742674	Menopause in the female life cycle is a special period due to important hormonal, physical and psychological changes. Sleep disruption represents a common complaint for midlife and menopausal women, related to primary sleep disorders, including insomnia, sleep disordered breathing, restless legs syndrome (RLS), mood and anxiety disorder, other medical illness, hormonal-related vasomotor symptoms, and aging per se. Aims of our study were to evaluate the prevalence of sleep disorders in a sample of pre and post menopausal women, and to investigate the relationship between sleep and other medical disorders, and life habits. Among workers in the six participant centers, we enrolled 334 women, aged between 40 and 60 years, that completed a questionnaire that included screening on menarche, menstrual cycle, fertility, parity, menopause, life habits, personal medical and sleep history and related treatment, and self-administered scales for sleep quality (PSQI), excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)], mood disorder [Beck Depression Inventory (BDI)], Berlin Questionnaire for sleep disordered breathing (SDB), IRLS diagnostic interview and Rating Scale. Menopausal and perimenopausal women showed an increased prevalence of poor sleep, high risk of SDB, and mood disorder; menopausal women also reported increased RLS severity. Mood disorder had a significant impact on night sleep measures and excessive daytime sleepiness, as well as on RLS severity, and had a greater prevalence in hypertensive women. Sleep disturbances are frequent in menopausal women. Their aetiology is unclear, but probably multifactorial, and many factors contribute to the sleep disruption. Our data suggest the importance of correctly investigate and address sleep problems associated with menopause, through sleep history, and a sleep study could be obtained if clinically warranted. Pharmacological and behavioural treatment strategies should then be aimed at improving sleep and life quality in perimenopausal and menopausal women. 
26742668	Sleep disorders in children can compromise quality of life of both children and families and chronic sleep deprivations is associated with poorer developmental outcome, overweight and behavioral disturbances. Clinicians should incorporate questions about sleep into their routine health assessment, and the assessment of insomnia should follow a medical approach primary and secondary contributing factors should be assessed, as well as maladaptive behaviors related to sleep. A careful examination of sleep/wake schedule, abnormal movements or behavior during sleep, and daytime consequences of sleep disruption or deprivation is mandatory. Sleeping environment, and bedtime routines should be examined to identify behavioral issues related to sleep. Polysomnography is not routinely indicated for children with insomnia, but actigraphy can give an objective estimation of sleep parameters. The Authors propose a new classification of pediatric insomnia, based on both genetic and clinical aspects, and suggest specific treatment options, including sleep hygiene, behavioral strategies and pharmacological treatment. 
26741881	Orexins/hypocretins are orexigenic peptides implicated in the regulation of feeding behavior and the sleep/wake cycle. Little is known about the functioning of these peptides in anorexia nervosa (AN). The aims of the current study were to evaluate the extent to which orexin-A might be linked to sleep and treatment outcome in AN.Fasting plasma orexin-A concentrations were measured in 48 females with AN at the start of a day hospital treatment and in 98 normal-eater/healthy-weight controls. The Pittsburgh Sleep Quality Index was administered at the beginning of the treatment as a measure of sleep quality. Other psychopathological variables were evaluated with the Symptom Checklist-Revised (SCL90R) and the Eating Disorder Inventory-2 (EDI). Patients were assessed at the start and end of treatment by means of commonly used diagnostic criteria and clinical questionnaires.	The AN patients presented more sleep disturbances and poorer overall sleep quality than did the healthy controls (p=.026) but there were no global differences between groups in plasma orexin-A concentrations (p=.071). In the AN sample, orexin-A concentrations were associated with greater sleep disturbances (|r|=.30), sleep inefficiency (|r|=.22) and poorer overall sleep (|r|=.22). Structural Equation Modeling (SEM) showed that both elevated orexin-A concentrations and inadequate sleep predicted poorer treatment outcome.	Plasma orexin-A concentrations contribute to poor sleep quality in AN, and both of these variables are associated with therapy response.	
26739718	To describe the home environment in terms of housing conditions and their association with child health in a disadvantaged immigrant population.A cross-sectional observational study.	Enrolment took place during 2010-2011 in Rosengård, Malmö, Sweden.	Children aged 0-13 years in 2 study neighbourhoods were recruited from local health records and from schools. 359 children participated, with a participation rate of 40%. Data on health, lifestyle and apartment characteristics from questionnaire-led interviews with the mothers of the children were obtained together with data from home inspections carried out by trained health communicators.	Logistic regression analysis was used to estimate ORs for various health outcomes, adjusted for demographic information and lifestyle factors.	The housing conditions were very poor, especially in one of the study neighbourhoods where 67% of the apartments had been sanitised of cockroaches, 27% were infested with cockroaches and 40% had a visible mould. The association between housing conditions and health was mostly inconclusive, but there were statistically significant associations between current asthma and dampness (OR=4.1, 95% CI 1.7 to 9.9), between asthma medication and dampness (OR=2.8, 95% CI 1.2 to 6.4), and between mould and headache (OR=4.2, 95% CI 1.2 to 14.8). The presence of cockroaches was associated with emergency care visits, with colds, with headache and with difficulty falling asleep, and worse general health was associated with mould and presence of cockroaches.	The associations between dampness and asthma, and the association between mould and headache, are in line with current knowledge. The presence of cockroaches seemed to be associated with various outcomes, including those related to mental well-being, which is less described in the literature. The results of the present study are hypothesis generating and provide strong incentives for future studies in this study population.	
26737516	Polysomnography is a comprehensive modality for diagnosing sleep apnea (SA), but it is expensive and not widely available. Several technologies have been developed for portable diagnosis of SA in the home, most of which lack the ability to detect sleep status. Wrist actigraphy (accelerometry) has been adopted to cover this limitation. However, head actigraphy has not been systematically evaluated for this purpose. Therefore, the aim of this study was to evaluate the ability of head actigraphy to detect sleep/wake status. We obtained full overnight 3-axis head accelerometry data from 75 sleep apnea patient recordings. These were split into training and validation groups (2:1). Data were preprocessed and 5 features were extracted. Different feature combinations were fed into 3 different classifiers, namely support vector machine, logistic regression, and random forests, each of which was trained and validated on a different subgroup. The random forest algorithm yielded the highest performance, with an area under the receiver operating characteristic (ROC) curve of 0.81 for detection of sleep status. This shows that this technique has a very good performance in detecting sleep status in SA patients despite the specificities in this population, such as respiration related movements. 
26737221	Long term continuous patient monitoring is required in many health systems for monitoring and analytical diagnosing purposes. Most of monitoring systems had shortcomings related to their functionality or patient comfortably. Non-contact continuous monitoring systems have been developed to address some of these shortcomings. One of such systems is non-contact physiological vital signs assessments for chronic heart failure (CHF) patients. This paper presents a novel automated estimation algorithm for the non-contact physiological vital signs assessments for CHF patients based on a patented novel non-contact biomotion sensor. A database consists of twenty CHF patients with New York Heart Association (NYHA) heart failure Classification Class II & III, whose underwent full Polysomnography (PSG) analysis for the diagnosis of sleep apnea, disordered sleep, or both, were selected for the study. The patients mean age is 68.89 years, with mean body weight of 86.87 kg, mean BMI of 28.83 (obesity) and mean recorded sleep duration of 7.78 hours. The propose algorithm analyze the non-contact biomotion signals and estimate the patients' respiratory and heart rates. The outputs of the algorithm are compared with gold-standard PSG recordings. Across all twenty patients' recordings, the respiratory rate estimation median accuracy achieved 92.4689% with median error of ± 1.2398 breaths per minute. The heart rate estimation median accuracy achieved 88.0654% with median error of ± 7.9338 beats per minute. Due to the good performance of the propose novel automated estimation algorithm, the patented novel non-contact biomotion sensor can be an excellent tool for long term continuous sleep monitoring for CHF patients in the home environment in an ultra-convenient fashion.
26736747	This paper presents a conformable wireless patch and its mobile application for physical activity, spO2 and pCO2 recording associated to digital biomarkers that aim at providing the clinicians with a reliable computer-aided diagnosis tool for rapid and continuous monitoring of sleep respiratory disorders. Each part of the system is described and results are presented and discussed. The reflectance sp02 sensor has been tested in vivo on several body sites and several subjects then compared to a reference device. The electrochemical tcpO2 sensor has been validated in vitro. Based on these physiological parameters, the proposed algorithms to automatically identifying sleep respiratory events are compared to a reference index. 
26736731	The aim of this study is the evaluation of the autonomic regulations during depressive stages in bipolar patients in order to test new quantitative and objective measures to detect such events. A sensorized T-shirt was used to record ECG signal and body movements during the night, from which HRV data and sleep macrostructure were estimated and analyzed. 9 out of 20 features extracted resulted to be significant (p<;0.05) in discriminating among depressive and non-depressive states. Such features are representation of HRV dynamics in both linear and non-linear domain and parameters linked to sleep modulations. 
26736277	In previous work, respiratory spectral features have been successfully used for sleep/wake detection. They are usually extracted from several frequency bands. However, these traditional bands with fixed frequency boundaries might not be the most appropriate to optimize the sleep and wake separation. This is caused by the between-subject variability in physiology, or more specifically, in respiration during sleep. Since the optimal boundaries may relate to mean respiratory frequency over the entire night. Therefore, we propose to adapt these boundaries for each subject in terms of his/her mean respiratory frequency. The adaptive boundaries were considered as those being able to maximize the separation between sleep and wake states by means of their mean power spectral density (PSD) curves overnight. Linear regression models were used to address the association between the adaptive boundaries and mean respiratory frequency based on training data. This was then in turn used to estimate the adaptive boundaries of each test subject. Experiments were conducted on the data from 15 healthy subjects using a linear discriminant classifier with a leave-one-subject-out cross-validation. We reveal that the spectral boundary adaptation can help improve the performance of sleep/wake detection when actigraphy is absent. 
26735553	Increasing evidence suggests that circadian and sleep parameters influence cognitive function with aging.To evaluate observational studies of sleep duration and cognition in older adults.	A systematic review of OVID Medline and PsycINFO through September 2015, and review of bibliographies from studies identified.	English-language articles reporting observational studies of sleep duration and cognitive function in older populations.	Data extraction by 2 authors using predefined categories of desired information.	Thirty-two studies met our inclusion criteria, with nearly two-thirds published in the past 4 years. One-third of studies indicated that extreme sleep durations were associated with worse cognition in older adults. More studies favored an association with long vs. short sleep durations (35 vs. 26% of studies, respectively). Four studies found that greater changes in sleep duration over time were related to lower cognition. Study design and analytic methods were very heterogeneous across studies; therefore, meta-analysis was not undertaken.	We reviewed English-language manuscripts only, with a qualitative summary of studies identified.	Observational studies of sleep duration and cognitive function in older adults have produced mixed results, with more studies suggesting that long (rather than short) sleep durations are related to worse cognition. Studies more consistently indicate that greater changes in sleep duration are associated with poor cognition. Future studies should be prospectively designed, with objective sleep assessment and longer follow-up periods; intervention studies are also needed to identify strategies for promoting cognitive health with aging.	

26735330	The present study examined (a) whether sleep related problems (SRPs) improved following cognitive-behavioral therapy (CBT) for youth with anxiety disorders, (b) whether variables that may link anxiety and SRPs (e.g., pre-sleep arousal, family accommodation, sleep hygiene) changed during treatment, and (c) whether such changes predicted SRPs at posttreatment. Youth were diagnosed with anxiety at pretreatment and received weekly CBT that targeted their principal anxiety diagnosis at one of two specialty clinics (N=69 completers, Mage=10.86). Results indicated that parent-reported SRPs improved from pre- to post-treatment and that treatment responders with regard to anxiety yielded greater SRP improvements than nonresponders. Parent report of bedtime resistance and sleep anxiety showed significant improvements. Youth reported lower rates of SRPs compared to their parents and did not demonstrate pre- to post-treatment changes in SRPs. Pre-sleep arousal and family accommodation decreased over treatment but did not predict lower SRPs at posttreatment. Higher accommodation was correlated with greater SRPs. Sleep hygiene evidenced no change and did not mediate links between accommodation and posttreatment SRPs. 
26734348	Vision and hearing impairments have long been recognised as modifiable risk factors for delirium.[1,2,3] Delirium in critically ill patients is a frequent complication (reported as high as 60% to 80% of intensive care patients), and is associated with a three-fold increase in mortality and prolonged hospital stay.[1] Guidelines by the UK Clinical Pharmacy Association recommend minimising risk factors to prevent delirium, rather than to treat it with pharmacological agents which may themselves cause delirium.[4] To address risk factors is a measure of multi-system management, such as sleep-wake cycle correction, orientation and use of vision and hearing aids, etc.[5] We designed an audit to survey the prevalence and availability of vision and hearing aids use in the intensive care unit (ICU) of one university hospital. The baseline data demonstrated a high level of prevalence and low level of availability of vision /hearing aid use. We implemented changes to the ICU Innovian assessment system, which serves to remind nursing staff performing daily checks on delirium reduction measures. This has improved practice in promoting vision and hearing aids use in ICU as shown by re-audit at six month. Further amendments to the Innovian risk assessments have increased the rate of assessment to 100% and vision aid use to near 100%. 

26732069	Sleep enuresis (SE) is the second most common sleep complaint in childhood. It has been associated with bladder hyperactivity, excessive urine production and deeper sleep. Several sleep disorders have been described in association with SE like parasomnias and sleep apnea. The aim of this study was to analyze the presence of sleep disturbances in children with SE through the use of Sleep Disturbance Scale for Children (SDSC) compared to normal children matched for age and sex.A questionnaire evaluation was performed in 76 enuretic and 112 normal children through the Sleep Disturbance Scale for Children (SDSC) validated for Portuguese language. The Scale is grouped into six subscales: Disorders in Initiating and Maintaining Sleep (DIMS), Sleep Breathing Disorders (SBD), Disorders of Arousal (DA), Sleep-Wake Transition Disorders (SWTD), Disorders Of Excessive Somnolence (DOES), and Nocturnal Hyperhidrosis (SHY). Children with renal and neurological problems were excluded from both groups.	Enuretics scored higher in several of the subscales (SBD, DOA, SWTD) and also in the total scale scores while scored low in the DIMS subscale. No differences were found for the DOES and SHY subscales.	Enuretic children showed a high comorbidity with other sleep disturbances like sleep disordered breathing and parasomnias. The novel finding of this study is that we found a decreased incidence of DIMS that is consistent with the parental perception of a more deep sleep and a high arousal threshold in SE.	
26731865	Demographic changes observed in recent decades around the world lead to the aging of societies at a rapid rate. The increasing number of elder people is a result of extending the average length of human life. Elder people are struggling with many problems--loneli- ness, disability or financial problems. The problem can also be addiction, usually suspected in young people. The aim of the study was to evaluate the prevalence of addiction--smoking, drinking alcohol, use of medicines and drugs, watching television or using the Internet--in the elderly. Additional objective was to assess the problem of sleep disorders and the purchase of OTC drugs, dietary supplements and vitamin preparations in this population. Examined group consisted of 104 people aged over 65 years, of whom only 23 were smokers and 86 were consumers of various alcohols. None of the respondents confirmed any contact with drugs and the use of addiction treatment. Only 4 respondents did not watch any TV programs and 37 did not use the Internet (nor themselves nor with the help of others). 94 respondents used drugs and non-prescription preparations. 57 responders did not experienced sleep disorders.
26731556	Sleep disorders in individuals with developmental difficulties continue to be a significant challenge for families, carers, and therapists with a major impact on individuals and carers alike. This review is designed to update the reader on recent developments in this area.A systematic search identified a variety of studies illustrating advances in the regulation of circadian rhythm and sleep disturbance in neurodevelopmental disorders. Specific advances are likely to lead in some disorders to targeted therapies. There is strong evidence that behavioural and sleep hygiene measures should be first line therapy; however, studies are still limited in this area. Nonpharmacological measures such as exercise, sensory interventions, and behavioural are reported. Behavioural regulation and sleep hygiene demonstrate the best evidence for improved sleep parameters in individuals with neurodisability.	Although the mainstay of management of children with sleep problems and neurodevelopmental disability is similar to that of typically developing children, there is emerging evidence of behavioural strategies being successful in large-scale trials and the promise of more targeted therapies for more specific resistant disorders.	
26730643	Recovery is essential for high athletic performance, and therefore especially sleep has been identified as a crucial source for physical and psychological well-being. However, due to early-morning trainings, which are general practice in many sports, athletes are likely to experience sleep restrictions. Therefore, this study investigated the sleep-wake patterns of 55 junior national rowers (17.7 ± 0.6 years) via sleep logs and actigraphy during a four-week training camp. Recovery and stress ratings were obtained every morning with the Short Recovery and Stress Scale on a 7-point Likert-type scale ranging from 0 (does not apply at all) to 6 (fully applies). The first training session was scheduled for 6:30 h every day. With two to four training sessions per day, the training load was considerably increased from athletes' home training. Objective sleep measures (n = 14) revealed less total sleep time (TST) in the first two weeks (409.6 ± 19.1 and 416.0 ± 16.3 min), while training volume and intensity were higher. In the second half of the camp, less training sessions were implemented, more afternoons were training free and TSTs were longer (436.3 ± 15.8 and 456.9 ± 25.7 min). A single occasion of 1.5-h delayed bedtime and usual early morning training (6:30 h) resulted in reduced ratings of Overall Recovery (OR) (M = 3.3 ± 1.3) and greater Negative Emotional State (NES) (M = 1.3 ± 1.2, p < .05), which returned to baseline on the next day. Following an extended night due to the only training-free day, sleep-offset times were shifted from ~5:30 to ~8:00 h, and each recovery and stress score improved (p < .01). Moreover, subjective ratings of the first six days were summarised as a baseline score to generate reference data as well as to explore the association between sleep and recovery. Intercorrelations of these sleep parameters emphasised the relationship between restful sleep and falling asleep quickly (r = .34, p < .05) as well as few awakenings (r = .35, p < .05). Overall, the findings highlight the impact of sleep on subjective recovery measures in the setting of a training camp. Providing the opportunity of extended sleep (and a day off) seems the most simple and effective strategy to enhance recovery and stress-related ratings.
26729376	It appears that not only depression, but also low life satisfaction (LS), is related to sleep disorder in the general population. We evaluate whether the prevalence of sleep disorder attributable to depressed mood is greater among participants with low LS.Analysis of cross-sectional data from 3880 cohort members from the German Heinz Nixdorf Recall study (2006-2008) aged 51-81 years. Standard mood (Center for Epidemiological Studies Depression scale (CES-D) for Depressive symptoms and a single-item life satisfaction measure) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) measures were conducted as part of the survey. Multiple imputation was used to deal with missing data in outcome, exposures or covariates. Relative excess risk for interaction (RERI) and its 95% CIs were estimated using adjusted prevalence ORs. Owing to the study size, the precision of the measures of additive interaction is relatively low.	We observed an association between depressed mood (5-units increase in CES-D score) (POR=1.7 (95% CI 1.6 to 1.8)) and sleep disorder, and between low LS (not very satisfied vs very satisfied) (POR=1.5 (1.1 to 2.2)) and sleep disorder. Also, we observed a synergistic effect between lower level of LS (not very satisfied) and depressed mood (score ≥ 16) on prevalence of sleep disorders (RERI=3.7 (-0.2 to 7.1)). Furthermore, these findings were corroborated in sensitivity analysis carried out with the complete case data set and in sex-specific analyses (RERI=5.5 (-0.4 to 11.3), and RERI=2.4 (-2.5 to 7.4) for men and women, respectively).	Both depressed mood and LS are notably associated with sleep quality, and these relationships are best captured by considering their joint effects. Depression and LS need to be taken into consideration when analysing sleep quality.	
26727258	Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling. 
26727118	Sleep duration is associated with obesity and cardiometabolic disease. It is unclear, though, how these relationship differs across age groups.Data from 2007 to 2008 National Health and Nutrition Examination Survey (NHANES) were used, including respondents aged 16+ with complete data (N = 5,607). Sleep duration and age were evaluated by self-report, and body mass index (BMI) was assessed objectively. Sleep duration was evaluated continuously and categorically [very short (≤4 h), short (5-6 h), and long (≥9 h) versus average (7-8 h)]. Age was also evaluated continuously and categorically [adolescent (16-17 years), young adult (18-29 years), early middle age (30-49 years), late middle age (50-64 years), and older adult (≥65 years)].	There was a significant interaction with age for both continuous (Pinteraction  = 0.014) and categorical (Pinteraction  = 0.035) sleep duration. A pseudo-linear relationship was seen among the youngest respondents, with the highest BMI associated with the shortest sleepers and the lowest BMI associated with the longest sleepers. This relationship became U-shaped in middle-age, and less of a relationship was seen among the oldest respondents.	These findings may provide insights for clinical recommendations and could help to guide mechanistic research regarding the sleep-obesity relationship.	
26726076	Sleep disturbance in chronic pain is common, occurring in two-thirds of patients. There is a complex relationship between chronic pain and sleep; pain can disrupt sleep and poor sleep can exaggerate pain intensity. This may have an impact on both depressive symptoms and attention to pain. This study aims to evaluate the relationship between chronic pain and sleep, and the role of mood and attention.Chronic pain patients, recruited from a secondary care outpatient clinic, completed self-report measures of pain, sleep, depressive symptoms and attention to pain. Hierarchical regression and structural equation modelling were used to explore the relationships between these measures. Participants (n = 221) were aged between 20 and 84 (mean = 52) years.	The majority of participants were found to be 'poor sleepers' (86%) with increased pain severity, depressive symptoms and attention to pain. Both analytical approaches indicated that sleep disturbance is indirectly associated with increased pain severity Instead the relationship shared by sleep disturbance and pain severity was further associated with depressive symptoms and attention to pain.	Our results indicate that sleep disturbance may contribute to clinical pain severity indirectly though changes in mood and attention. Prospective studies exploring lagged associations between these constructs could have critical information relevant to the treatment of chronic pain.	
26725468	Occupational exposure to solvents may lead to neurotoxicity and sleep disturbances. We aimed to investigate the association of occupational exposure to petroleum-derived hydrocarbons with neurotoxicity and sleep disturbance symptoms.We included male workers handling/distributing petroleum products (exposed, n = 250) and electricians (non-exposed, n = 250) from two companies in Tlemcen (Algeria). Neurotoxicity was evaluated with the Q-16 questionnaire, and sleep disturbances with the Epworth and the Berlin questionnaires. Multivariable Poisson regression models with robust error variances were applied obtaining risk ratios (RR) and their 95% confidence interval (CI).	Overall, the prevalence of reported neurotoxicity and sleep disturbance symptoms was higher in exposed than in non-exposed workers. Significant adjusted associations were observed for neurotoxicity, snoring, and excessive sleepiness (RR = 2.2, CI: 1.7-2.8; RR = 1.4; CI: 1.1-1.7; RR = 1.3, CI: 1.2-1.5, respectively). No significant associations were observed with the Epworth score.	Our questionnaire-based cross-sectional study suggests that exposure to petroleum-derived hydrocarbons is associated with self-reported sleep disturbances and neurotoxicity symptoms.	
26724432	Sleep complaints are common among older adults, and poor sleep has been found to predict chronic diseases and mortality. Many studies suggest that social participation benefits healthy aging. We examined the relationships between older adults' social participation and their sleep using two waves (2005-2006, 2010-2011) of data from the National Social Life, Health, and Aging Project (NSHAP). The NSHAP recorded older adults' social participation (including religious attendance, volunteer work, and attendance at meetings of organized groups) over five years, and included self-reported sleep duration in both waves and, in the second wave, measures of insomnia symptoms and measures of sleep patterns and rhythms using actigraphy for a subsample. Cross-sectional analysis of the second wave indicates that those reporting higher levels of social participation had better actigraphic sleep but not better self-reported sleep. However, longitudinal analysis suggests that change in social participation was not associated with actigraphic or self-reported sleep characteristics in the second wave data. Further analysis using fixed-effects model showed no association between change in social participation and change in self-reported sleep duration. Thus, although older adults with greater social participation slept better, we did not find that increasing social participation improved sleep. These findings imply that a self-selection process may at work; or if social participation does affect sleep, the causal effect may be over a much shorter time frame than five years. 
26724401	This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. 
26724295	Intensive care unit survivors often have diminished health-related quality of life.To describe health-related quality of life of former intensive care patients and identify associated factors 6 months after hospital discharge.	Six months after discharge, 193 patients from an intensive care unit completed the Short Form-36 Health Survey; measures of sleep; Intensive Care Experience Questionnaire; Depression, Anxiety and Stress Scales; and Posttraumatic Stress Disorder Checklist. Norm-based scores were calculated for the Short Form-36. Bivariate associations with Short Form-36 scores were tested by using the Pearson correlation. Multiple linear regression was used to identify independent associations with health-related quality of life.	All scores on the Short Form-36 (physical component summary, 41.8; mental component summary, 48.2) were less than population norms. Bivariate associations with health-related quality of life (P < .05) were scores on the Acute Physiology and Chronic Health Evaluation II, hospital length of stay, awareness of surroundings and frightening experiences, depression, anxiety, stress, posttraumatic symptoms, and sleep quality at 2 and 6 months. In linear regression, scores on the Acute Physiology and Chronic Health Evaluation II, hospital length of stay, and sleep quality at 6 months were independently associated with Short Form-36 physical summary scores (P < .001); depression and stress were independently associated with mental summary scores (P < .001).	Sleep, depression, and stress are potential targets for interventions to improve health-related quality of life and improve recovery.	
26723977	Non-motor symptoms (NMS) are gaining increasing relevance in the management of Parkinson's disease (PD), but little is known about their progression, especially among patients with different ages.A total of 117 PD patients who were divided into four age groups (<50, 50-60, 60-70, and >70years old) were included to assess NMS at baseline and follow-up visit (21.6±5.6months). The frequency and severity of NMS were assessed using the Non-Motor Symptom Scale (NMSS).	After adjusting for confounding factors, patients at the last visit had significantly higher frequency of "Difficulty falling asleep" item (p=0.034) and "Urinary" domain (p=0.017), and higher total NMSS score (p=0.011) as well as scores for "Sleep/fatigue" (p=0.013) and "Sexual dysfunction" (p=0.014) domains and scores for "Fatigue" (p=0.004), "Lack of motivation" (p=0.033), "Interest in sex" (p=0.014) and "Problems having sex" (p=0.031) items than patients at baseline. The frequency changes of each NMS among four age groups exhibited an anfractuous result, while the annual severity changes of each NMS were not significant different among four age groups. Multinomial logistic regression model indicated that age had no correlation with the changes of NMS frequency and severity.	The severity of NMS in PD tends to become progressively worse with the course of the disease. Age is not related to the progression of NMS in PD.	
26723880	Using knockout (KO) mice lacking the histamine (HA)-synthesizing enzyme (histidine decarboxylase, HDC), we have previously shown the importance of histaminergic neurons in maintaining wakefulness (W) under behavioral challenges. Since the central actions of HA are mediated by several receptor subtypes, it remains to be determined which one(s) could be responsible for such a role. We have therefore compared the cortical-EEG, sleep and W under baseline conditions or behavioral/pharmacological stimuli in littermate wild-type (WT) and H1-receptor KO (H1-/-) mice. We found that H1-/- mice shared several characteristics with HDC KO mice, i.e. 1) a decrease in W after lights-off despite its normal baseline daily amount; 2) a decreased EEG slow wave sleep (SWS)/W power ratio; 3) inability to maintain W in response to behavioral challenges demonstrated by a decreased sleep latency when facing various stimuli. These effects were mediated by central H1-receptors. Indeed, in WT mice, injection of triprolidine, a brain-penetrating H1-receptor antagonist increased SWS, whereas ciproxifan (H3-receptor antagonist/inverse agonist) elicited W; all these injections had no effect in H1-/- mice. Finally, H1-/- mice showed markedly greater changes in EEG power (notably in the 0.8-5 Hz band) and sleep-wake cycle than in WT mice after application of a cholinergic antagonist or an indirect agonist, i.e., scopolamine or physostigmine. Hence, the role of HA in wake-promotion is largely ensured by H1-receptors. An upregulated cholinergic system may account for a quasi-normal daily amount of W in HDC or H1-receptor KO mice and likely constitutes a major compensatory mechanism when the brain is facing deficiency of an activating system. This article is part of the Special Issue entitled 'Histamine Receptors'. 
26723014	Fatigue impairs the quality of life (QOL) of epilepsy patients, but few studies have investigated this issue and no systematic analysis of the predictors of fatigue in epilepsy patients has been performed. Thus, we investigated the degree and predictors of fatigue in epilepsy patients.We enrolled 270 consecutive adult patients with epilepsy and categorized them into three subgroups: uncontrolled epilepsy (UCE), well-controlled epilepsy (WCE), and poorly controlled epilepsy (PCE). All subjects were asked to complete the Korean versions of the Fatigue Severity Scale (K-FSS), the Neurological Disorders Depression Inventory for Epilepsy (K-NDDI-E), the Generalized Anxiety Disorder-7 (K-GAD-7) scale, and the short forms of the Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment (PROMIS-SRI) and Sleep Disturbance (PROMIS-SD) scales. Additionally, 200 normal control subjects who completed the K-FSS, K-NDDI-E, and K-GAD-7 measures were included. The K-FSS scores of the epilepsy subgroups and the control group were compared, and stepwise multiple regression analysis was performed to identify predictors of high scores on the K-FSS among epilepsy patients.	The K-FSS, K-NDDI-E, and K-GAD-7 scores were higher in the epilepsy patients than in the controls. The K-FSS scores of the UCE subgroup, but not of the PCE and WCE subgroups, were higher than those of the control group. K-FSS scores of epilepsy patients were predicted by PROMIS-SRI and K-NDDI-E scores.	Fatigue was more severe in epilepsy patients than in healthy controls without epilepsy, especially when seizures were not controlled. Sleep-related impairments and depression aggravated fatigue in epilepsy patients.	
26721620	Narcolepsy is a neurological disorder that afflicts 1 in 2000 individuals and is characterized by excessive daytime sleepiness and cataplexy-a sudden loss of muscle tone triggered by positive emotions. Features of narcolepsy include dysregulation of arousal state boundaries as well as autonomic and metabolic disturbances. Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in narcolepsy. The cause of Hcrt neurodegeneration is unknown but thought to be related to autoimmune processes. Current treatments for narcolepsy are symptomatic, including wake-promoting therapeutics that increase presynaptic dopamine release and anticataplectic agents that activate monoaminergic neurotransmission. Sodium oxybate is the only medication approved by the US Food and Drug Administration that alleviates both sleep/wake disturbances and cataplexy. Development of therapeutics for narcolepsy has been challenged by historical misunderstanding of the disease, its many disparate symptoms and, until recently, its unknown etiology. Animal models have been essential to elucidating the neuropathology underlying narcolepsy. These models have also aided understanding the neurobiology of the Hcrt system, mechanisms of cataplexy, and the pharmacology of narcolepsy medications. Transgenic rodent models will be critical in the development of novel therapeutics for the treatment of narcolepsy, particularly efforts directed to overcome challenges in the development of hypocretin replacement therapy.
26721132	To compare the clinical effective differences between shallow needling and medication for the sleep disorder of schizophrenia.Ninety-six patients with the sleep disorder of schizophrenia were randomly divided into a shallow needling group and a medication group, 48 cases in each one (one case dropping in the shallow needling group and two cases dropping in the medication group). The same dose paliperidone tablets were adopted in the two groups. In the shallow needling group, the main acupoints were Baihui (GV 20), Shangenxue (Extra) and Ezhongxian (MS 1), and the acupoints based on syndrome differentiation were selected. The shallow needling manipulation was used once a day, 5 times a week. In the medication group, 3 mg eszopiclone tablets were prescribed orally before sleep once every night. The patients were treated for 6 weeks in the two groups. Sleep condition was evaluated by Pittsburgh sleep quality index (PSQI) before and after treatment, and the clinical efficacy and the adverse reaction were assessed by positive and negative symptoms scale (PANSS) and treatment emergent symptom scale (TESS) before and after 2-week, 4-week and 6-week treatment. The clinical effects between the two groups were compared.	After treatment in the two groups, both the total scores and the each factor score of the PSQI and the PANSS were apparently decreased (P<0. 05, P<0. 01). As for the PSQI scale, after treatment the daytime dysfunctional score of the shallow needling group was reduced more obviously than that of the medication group (P<0. 05), and the falling asleep time in the medication group was declined more markedly compared with that in the shallow needling group (P<0. 05). Regarding the PANSS, the improvement of the pathological factor in the shallow needling group was better than that in the medication group after treatment (P<0. 05), and the improvement of the positive factor in the medication group was superior to that in the shallow needling group after treatment (P<0. 05). The total scores and each factor score of the PSQI and the PANSS were not statistically different between the two groups after treatment (P>0. 05). At the end of the 6th week, the curative and effective rate was 63. 9% (30/47) and the total effective rate was 95. 8% (45/47) in the shallow needling group;the curative and effective rate was 58. 7% (27/46) and the total effective rate was 91. 3% (42/46) in the medication group. The difference of the effect was not statistically significant between the two groups (P>0. 05). The scores of TESS in the shallow needling group were lower than those in the medication group (P<0. 01, P<0. 05).	The effect of shallow needling for assisting the sleeping disorder of schizophrenia is reliable and it is similar with the efficacy of eszopiclone. Also, the shallow needling can improve the daytime dysfunction and the pathological factor apparently without adverse reaction and pain. Its safety is obviously better than that of eszopiclone.	
26720316	The aim of this study was to assess the impact of screening and teaching interventions for sleep-wake disturbances in parents of childhood patients with epilepsy.This was a prospective, descriptive study using convenience sampling. After informed consent was obtained from eligible parents who agreed to participate, study questionnaires were administered. All parents were provided with an individualized teaching intervention. Study tools were readministered 8-12 weeks later to evaluate if the individualized teaching intervention altered or improved sleep-wake disturbances.	The t value for the paired t test of the Epworth Sleepiness Scale prescore and postscore was 0.000 with a two-tailed probability value of 1.000, and the t value for the paired t test of the Pittsburgh Sleep Quality Index prescore and postscore was 0.713 with a two-tailed probability value of .492, indicating no significant difference between pre and post Epworth Sleepiness Scale or Pittsburgh Sleep Quality Index scores.	A sleep hygiene teaching intervention for parents of children with epilepsy was not effective in this setting of an inner-city epilepsy monitoring unit in changing postintervention scores on measures of both nighttime sleep quality and daytime sleepiness. These results must be interpreted with caution secondary to the small number included in the initial phase of this study. A larger number of participants will be needed to verify these findings. If the results remain consistent with a larger number, studies evaluating variables of cause may be helpful to determine more effective interventions.	
26719309	Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia. 
26718349	Approximately, five million people in the United States live with the residual effects of brain injury. The causes of acquired brain injury can be categorized as traumatic brain injury or non-traumatic brain injury. There are currently no treatments shown to consistently enhance recovery from disorders of consciousness (DOC). Sporadic recovery from DOC after the administration of various pharmacological agents has been described in several case reports. Increase in arousal after zolpidem administration is seen in patients with vegetative state or minimally conscious state for treatment of restlessness and disturbances of their sleep-wake cycle. The use of zolpidem could be reasonable in select patients with neurologic injury but promising integrity of brain structures, such as intact deep and superficial gray matter structures and white matter connections. 
28490834	The airship Italia, commanded by General Umberto Nobile, crashed during its return flight from the North Pole in 1928. The cause of the accident was never satisfactorily explained. We present evidence that the crash may have been fatigue-related. Nobile's memoirs indicate that at the time of the crash he had been awake for at least 72 h. Sleep deprivation impairs multiple aspects of cognitive functioning necessary for exploration missions. Just prior to the crash, Nobile made three command errors, all of which are of types associated with inadequate sleep. First, he ordered a release of lift gas when he should have restarted engines (an example of incorrect data synthesis, with deterioration of divergent thinking); second, he inappropriately ordered the ship above the cloud layer (a deficiency in the assessment of relative risks); and third, he remained above the cloud layer for a prolonged period of time (examples of attention to secondary problems, and calculation problems). We argue that as a result of these three errors, which would not be expected from such an experienced commander, there was no longer enough static lift to maintain level flight when the ship went below the cloud layer. Applying Circadian Performance Simulation Software to the sleep-wake patterns described by Nobile in his memoirs, we found that the predicted performance for someone awake as long as he had been is extremely low. This supports the historical evidence that human fatigue contributed to the crash of the Italia.
26716836	We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.Case-crossover design.	Elderly enrollees (n = 6010) in Taiwan's National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.	After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.	Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.	
26715971	Sleep hygiene is important for sleep quality and optimal performance during the day. However, it is not always possible to follow sleep hygiene requirements. In multiday relay events, athletes have to sleep immediately after physical exertion and sometimes against their biological clock.In this pilot study we investigated the effect of having to sleep at an abnormal circadian time on sleep duration.	Eight runners and two cyclists performing a 500 km relay race were followed. They were divided into two groups that took turns in running and resting. Each group ran four times for approximately five hours while the other group slept. As a result, sleep times varied between normal and abnormal times. All athletes wore actigraphs to record the duration and onset of sleep.	Linear mixed model analyses showed that athletes slept on average 43 minutes longer when they slept during usual (night) times than during abnormal (day) times. In general, sleep duration decreased during the race with on average 18 minutes per period.	This pilot study shows that, even under extreme violation of sleep hygiene rules, there still is an apparent effect of circadian rhythm on sleep duration in relay race athletes.	
26715475	This study aims to explore the prevalence of depression and anxiety in left-behind children, and to identify patterns of parents' migration and relative factors associated with depression and anxiety risk in this population.A cross-sectional survey using a school-based sample was conducted in Puyang, Hebei, North China in December 2012.	2283 students aged 10-18 years.	Parental migration status, depression and anxiety disorder.	61.2% of participants were left-behind children. The prevalence rate of depression among left-behind children with both parents migrating (14.2%) was higher than that of children with one parent migrating (11.7%) and no parent migrating (12.6%). The prevalence rate of anxiety disorder for children with no parent migrating (25.1%) was higher than that for children living with one or neither parent (22.2% and 22.0%). The risk factors for depression were low-level social support (OR=3.46, 95% CI 2.00 to 6.01), average academic performance (OR=2.37, 95% CI 1.7 to 3.3) and low academic performance (OR=3.01, 95% CI 1.92 to 4.72), staying up late (OR=1.67, 95% CI 1.17 to 2.39), having difficulty falling asleep (OR=2.04, 95% CI 1.48 to 2.82) and being an only child (OR=1.73, 95% CI 1.04 to 2.89). The factors associated with anxiety disorder were being female (OR=2.09, 95% CI 1.64 to 2.66), being in high school (OR=1.8, 95% CI 1.38 to 2.36), physical abuse (OR=1.5, 95% CI 1.04 to 2.15), having difficulty falling asleep (OR=1.67, 95% CI 1.33 to 2.10) and low-level social support (OR=2.17, 95% CI 1.44 to 3.28) and middle-level social support (OR=1.82, 95% CI 1.3 to 2.56).	Parents' migration was not associated with depression and anxiety in rural children aged 10-18 years, but academic performance at school, sleep problems and lack of social support were associated with depression and anxiety.	
26715405	Prazosin is increasingly being used off-label to treat nightmares in patients with posttraumatic stress disorder. The literature about the psychiatric adverse effects of prazosin is very limited. We present a case in which low-dose prazosin was associated with nightmares and sleep disturbances in an elderly patient without previously diagnosed mental illness or coexisting environmental risk factors for nightmares. Insomnia and hallucinations are listed as some of the rare side effects of prazosin by the manufacturer. Prazosin could be associated with rare psychiatric adverse effects and sleep disturbances. Particular attention is required in identifying these adverse effects, which can be difficult to distinguish from other drug-related side effects in the elderly particularly because they are often using multiple medications.
26715389	The short-term effects of benzodiazepines on memory are well established and are suspected in the long term. Eleven studies have been published so far concerning benzodiazepine use and the risk of dementia disorders; nine of these studies concluded these drugs have a deleterious effect, one found a protective effect, and one (the most recently published) observed no effect. The positive association found in some studies could be due to a reverse causation bias since the main indications for benzodiazepines (e.g. sleep disorders, anxiety) can also be prodromes of dementia disorders. This bias is less likely for treatments started more than 10 years before the diagnosis. Among others, three mechanisms could underlie the potential influence of benzodiazepines on the development of dementia disorders. First, benzodiazepines can decrease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) and γ-secretase activity and slow down the accumulation of Aβ oligomers in the brain. This potential positive effect has never been confirmed; the same is true for the prevention of excitotoxicity through benzodiazepine anti-glutamatergic action. Second, since astrocytes located in the area of amyloid plaques could have gamma-aminobutyric acid (GABA)-secreting activity, patients with pre-dementia lesions could be at increased risk of presenting with more pronounced deleterious cognitive effects of benzodiazepines. Finally, owing to the neural compensation and cognitive reserve concepts, some subjects could cope with initial lesions by using/developing alternative networks. By lowering the brain activation level, benzodiazepines could limit this capacity. In conclusion, it is essential that animal studies explore the mechanistic hypotheses of this association found by most of the pharmacoepidemiological studies conducted on this topic.
26715223	We examined the association of objectively and subjectively measured sleep disturbances with depression, and explored if race/ethnicity, socioeconomic status, and sex modified these associations.We used data from the cross-sectional Multi-Ethnic Study of Atherosclerosis Sleep Study. Participants included 1,784 adults (ages 54-93 y), 36.8% non-Hispanic Whites, 28.0% African Americans, 23.7% Hispanics, 11.5% Chinese, and 46.0% males. Sleep was assessed with actigraphy, polysomnography, and self-report. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. We used relative risk regression to evaluate the association of sleep measures and depression (CES-D score ≥ 16) adjusting for site, sociodemographics, and behavioral and medical risk factors.	Overall, 14.5% had depression, 29.3% had insomnia symptoms, 14.1% had excessive daytime sleepiness (EDS), 15.1% had apnea-hypopnea index (AHI) ≥ 30, and 30.4% experienced short sleep (< 6 h). Depression was associated with short sleep duration (adjusted prevalence ratio [PR] = 1.47, 95% confidence interval [CI] = 1.11, 1.94), < 10% rapid eye movement [REM] sleep (PR = 1.57, 95% CI = 1.08, 2.27), ≥ 25% REM sleep (PR = 1.42, 95% CI = 1.03, 1.95), insomnia (PR = 1.83, 95% CI = 1.39, 2.40), excessive daytime sleepiness (EDS) (PR = 1.61, 95% CI = 1.19, 2.18), and AHI > 15 + EDS (PR = 1.55, 95% CI = 1.01, 2.39). Short sleep duration was associated with depression among those with high school education or beyond, but not among those with less education. Insomnia was more strongly associated with depression among men than women.	Sleep disturbances are associated with depression among middle-aged and older adults; these associations may be modified by education and sex. Future research should further test these hypotheses, evaluate whether early detection or treatment of sleep disturbances ameliorate depression, and explore subpopulation differences.	
26715160	Isoflavones comprise a class of phytoestrogens that resemble human estrogen in chemical structure, and have weak estrogenic effects. Because estrogen modulates sleep duration and quality, we hypothesized that isoflavones would have a beneficial effect on sleep status in a way similar to estrogen. We conducted a cross-sectional study to investigate the relationship between daily isoflavone intake and sleep status in Japanese subjects.Our study included 1076 Japanese adults aged 20-78 years. Daily isoflavone intake was assessed using a brief self-administered diet history questionnaire, and sleep was evaluated using a self-reported questionnaire.	The prevalence of regular sleep duration (7-8 h/day) and sufficient sleep quality were 13.3% and 56.2%, respectively. After adjusting for potential confounding factors, the odds ratios (95% CIs) for optimal sleep duration (7-8 h) when higher isoflavone intakes (Q2-Q4) were compared with low isoflavone intake (Q1) were Q2: 0.94 (0.53-1.56); Q3: 1.28 (0.73-2.24); and Q4: 1.84 (1.06-3.18) (p for trend = 0.013). In the final adjusted model, sufficient sleep quality across categories of isoflavone intake was Q1: 1.00 (reference); Q2: 1.30 (0.91-1.84); Q3: 1.48 (1.03-2.12); and Q4: 1.78 (1.22-2.60); (p for trend = 0.002).	Higher daily isoflavone intake was positively associated with optimal sleep duration and quality in a Japanese population. This finding suggests that daily isoflavone intake may have a potentially beneficial effect on sleep status.	
26713010	The aim of this study was to assess the effect of sodium valproic acid (SVA) on the sleep quality of patients with juvenile myoclonic epilepsy (JME).Standardized sleep questionnaires viz. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were administered to 30 drug-naïve patients with JME (male:female (M:F) = 14:16; age: 21 ± 3.7 years) and the changes following SVA monotherapy was analyzed using t- and chi-squared tests.	The mean age at onset of seizures and diagnosis was 15.43 ± 3.8 and 21 ± 5.1, years respectively. All had myoclonic jerks with mean duration of 5.23 ± 2.7 years, aggravated by sleep deprivation (23, 76.7%) and sleep-wake transition (29, 96.7%). Twenty-seven (90%) had generalized tonic-clonic seizures (GTCS), majority (70%) on awakening from sleep. Seizures were controlled in 25 patients (83.33%) with SVA monotherapy. Abnormal ESS was noted in five (16.66%) drug naïve patients compared to six (20%) patients while on SVA (P = 0.782). Mean ESS remained unchanged before and after SVA therapy (6.27 ± 4.4 vs 6.97 ± 4.7, P = 0.262). On the other hand, only four (13.3%) patients had abnormal PSQI scores at follow-up after initiation of SVA, as compared to 14 (46.7%) subjects in the drug naïve state (P = 0.037). Further, we also found significant reduction in mean PSQI scores after initiating SVA monotherapy (6.7 ± 5.6 vs 2.7 ± 2.84, P £ 0.0001).	This study showed that the mean PSQI as well as the number of patients with abnormal PSQI significantly reduced after initiating SVA therapy, suggesting a significant improvement in night-time sleep quality with SVA treatment. However, SVA therapy did not alter ESS.	
26711603	To explore the association between retinopathy and sleep disorder in patients with type 2 diabetes mellitus (T2DM).A total of 440 patients with T2DM treated from July 2011 to July 2013 in Metabolic Disease Hospital of Tianjin Medical University were divided into 2 groups according to Pittsburgh Sleep Quality Index: non-sleep disorder group (258 cases) and sleep disorder group (182 cases). Biochemical parameters including hepatorenal function, blood lipids, glycosylated hemoglobin (HbA1c), fructosamine and hemorrheology were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inteR-group differences of α-cell and β-cell function after fasting and glucose-load management. The logistic regression analysis was performed to identify the factors relevant to retinopathy.	The ratio of retinopathy was 42.9% in sleep disorder group, which was higher compared to those in non-sleep disorder group (32.6%), P=0.027. The levels of fasting plasma glucose, postprandial blood glucose, HbA1c, fructosamine, systolic blood pressure, diastolic blood pressure and the indicators of hemorrheology (plasma viscosity, erythrocyte aggregation index, erythrocyte rigidity index, fibrinogen) were significantly higher in patients with sleep disorder compared to those without sleep disorder, while the erythrocyte defomation index was significantly lower in sleep disorder group (all P<0.05). The levels of glucagon and glucagon/insulin ratio at each time point as well as area under curve of glucagon were significantly higher in sleep disorder group (all P<0.05). The levels of fasting insulin, homeostasis model assessment for insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorder compared to those without sleep disorder, while insulin sensitivity index was lower in patients with sleep disorder (all P<0.05). Logistic regression analysis showed that retinopathy was positively related to HbA1c (OR: 1.744-3.249), fibrinogen (OR: 1.687-2.998), systolic blood pressure (OR: 1.152-2.013), HOMA-IR (OR: 1.006-1.389) and sleep disorder (OR: 1.144-2.426), and negatively related to insulin sensitivity index (OR: 0.107-0.784) (all P<0.05).	Sleep disorders may be associated with retinopathy through multiple mechanisms in patients with T2DM.	
26710946	To explore the association between sleep disorder and osteoporosis in elderly female patients with type 2 diabetes mellitus (T2DM).A total of 536 elderly female T2DM patients from July 2011 to July 2014 were divided into two groups of patients without sleep disorder and those with sleep disorder based upon the Pittsburgh Sleep Quality Index. The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines (L2-L4) were measured by dual-energy X-ray absorptiometry. Biochemical indicators were detected in two groups. Oral glucose tolerance and insulin releasing tests were performed. We compared the differences of bone mineral density and β-cell function after fasting and glucose-load. The logistic regression analyses were performed between sleep disorder and osteoporosis and other indicators.	The levels of high sensitivity C-reactive protein (hs-CRP), HbA1c, cortisol (COR), adrenocorticotropic hormone (ACTH), fasting insulin (FINS) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) were significantly higher in patients with sleep disorder compared to those without sleep disorder [(3.5 ± 1.1) vs (2.6 ± 0.9) mg/L, (8.0 ± 1.9)% vs (7.3 ± 1.6)%, (512 ± 88) vs (436 ± 76) nmol/L, (6.4 ± 2.3) vs (5.1 ± 2.0) pmol/L, (13.4 ± 4.3) vs (12.4 ± 4.0) mU/L, 4.7 ± 0.8 vs 3.8 ± 0.8, all P < 0.05]. Insulin sensitivity index (ISI) was lower in patients with sleep disorder than that in patients without sleep disorder (-4.2 ± 0.5 vs -4.0 ± 0.4, P < 0.05). The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines (L2-L4) were significantly lower and the prevalence rate of osteoporosis was significantly higher in patients with sleep disorder compared to those in patients without sleep disorder (all P < 0.05). Logistic regression analysis showed that sleep disorder was positively correlated with HOMA-IR, HbA1c, COR and ACTH (all P < 0.05) and negatively with ISI (P < 0.05). Logistic regression analysis showed that osteoporosis was positively correlated with postmenopausal duration, HbA1c, COR, ACTH and sleep disorder (all P < 0.05) and negatively with ISI (P < 0.05).	Sleep disorder causes osteoporosis through various mechanisms in elderly female T2DM patients. Improving sleep disorder may help to reduce the prevalence of osteoporosis.	
26710440	Sleep quality is closely related to human health. It is very important to correctly discriminate the sleep stages for evaluating sleep quality, diagnosing and analyzing the sleep-related disorders. Polysomnography (PSG) signals are commonly used to record and analyze sleep stages. Effective feature extraction and representation is one of the most important steps to improve the performance of sleep stage classification. In this work, a collaborative representation (CR) algorithm was adopted to re-represent the original extracted features from electroencephalogram sig- nal, and then the kernel entropy component analysis (KECA) algorithm was further used to reduce the feature dimension of CR-feature. To evaluate the performance of CR-KECA, we compared the original feature, CR feature and readied CR feature (CR-PCA) after principal component analysis (PCA). The experimental results of sleep stage classification indicated that the CR-KECA method achieved the best performance compared with the original feature, CR feature, and CR-PCA feature with the classification accuracy of 68.74 +/- 0.46%, sensitivity of 68.76 +/- 0.43% and specificity of 92.19 +/- 0.11%. Moreover, CR algorithm had low computational complexity, and the feature dimension after KECA was much smaller, which made CR-KECA algorithm suitable for the analysis of large-scale sleep data.
26710181	Central serous chorioretinopathy (CSC) is a common retina disease and has a relative high recurrence rate, etiology, and pathogenesis of which remains ambiguous. The systematic review and meta-analysis aimed to measure risk factors for CSC in a quantitative method, providing some precautions and interventions on this disease and preventing further recurrences.A comprehensive literature review relating to risk factors for CSC through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and VIP databases was conducted before March 2015. Odds ratio (OR) with 95% confidence interval (CI) was calculated after data combination to assess the associations between risk factors and CSC.	A total of 9839 patients in 17 studies were included and risk factors with significant differences found between CSC and control groups were listed as follows: hypertension (OR = 1.7; 95% CI: 1.28-2.25), Helicobacter pylori (H. pylori) infection (OR = 3.12; 95% CI: 1.81-5.40), steroid usage (OR = 4.29; 95% CI: 2.01-9.15), sleeping disturbance (OR = 1.90; 95% CI: 1.28-1.83), autoimmune disease (OR=3.44; 95% CI: 1.90-6.26), psychopharmacologic medication use (OR = 2.69; 95% CI: 1.63-4.45), and Type-A behavior (OR = 2.53; 95% CI: 1.08-5.96).	The authors concluded that hypertension, H. pylori infection, steroid usage, sleeping disturbance, autoimmune disease, psychopharmacologic medication use, and Type-A behavior were possible risk factors relating to the occurrence of CSC.	
26709878	Although mounting evidence suggests that sleep and epilepsy are reciprocal and seizures influence circadian rhythms, sleep-wake pattern and seizure control have not been widely researched. This study aimed to investigate the association of sleep-wake pattern, sleep quality, and chronotype with seizures in patients with epilepsy (PWE).160 consecutive PWE (aged 20-49 years, focal epilepsy, FE: generalized epilepsy, GE=127:33) and 130 age-gender matched healthy controls (HC) were enrolled. All subjects completed a sleep diary for more than 2 weeks, Pittsburgh Sleep Quality Index (PSQI), Epworth sleepiness scale (ESS), and the Morningness-Eveningness questionnaire (MEQ). Detailed seizure history was reviewed for the last 1 year.	Sleep-wake patterns on workdays were different between PWE and HC (p<0.001), although PSQI, ESS, and MEQ did not differ. Social jetlag (difference of mid-sleep time between workdays and free days) was more evident in PWE (1.4h) than HC (0.7h, p<0.001). GE showed lower MEQ, later mid-sleep time on both workdays and free days, and larger social jetlag than FE. Higher seizure frequency was positively correlated with higher PSQI and ESS after adjusting for age, gender, and number of antiepileptic drugs (p<0.05). PWE with lower MEQ presented worse sleep quality.	Contrary to HC, PWE maintained sleep-wake patterns more regularly during workdays and free days. GE patients reported more eveningness-preference; however, their sleep quality was not worse than FE. Although sleep quality may affect seizure frequency, sleep-wake patterns and chronotype were not related to seizures in PWE.	
26709584	Following traumatic brain injury, both sleep dysfunction and cognitive impairment are common. Unfortunately, little is known regarding the potential associations between these 2 symptoms during acute recovery. This study sought to prospectively examine the relationship between ratings of sleep dysfunction and serial cognitive assessments among traumatic brain injury acute neurorehabilitation admissions.Participants were consecutive admissions to a free-standing rehabilitation hospital following moderate to severe traumatic brain injury (Median Emergency Department Glasgow Coma Scale = 7). Participants were assessed for sleep-wake cycle disturbance (SWCD) and cognitive functioning at admission and with subsequent weekly examinations. Participants were grouped on the basis of presence (SWCD+) or absence (SWCD-) of sleep dysfunction for each examination; groups were equivalent on demographic and injury variables. Individual Growth Curve modeling was used to examine course of Cognitive Test for Delirium performance across examinations.	Individual Growth Curve modeling revealed a significant interaction between examination number (ie, time) and SWCD group (β = -4.03, P < .001) on total Cognitive Test for Delirium score. The SWCD+ ratings on later examinations were predicted to result in lower Cognitive Test for Delirium scores and greater cognitive impairment over time.	This study has implications for improving neurorehabilitation treatment, as targeting sleep dysfunction for early intervention may facilitate cognitive recovery.	
26707017	According to recent findings, short sleep duration is associated with overweight in children. However, primary prevention efforts aimed at achieving adequate sleep among children are scarce. Therefore, the 'Identification and prevention of Dietary-induced and lifestyle-induced health EFfects In Children and infantS' (IDEFICS) study implemented a multilevel intervention that included sleep duration as a key behavioural target. The aim of this study is to evaluate sleep duration among children participating in the IDEFICS study.The IDEFICS nocturnal sleep intervention was included as part of stress reduction educational messages aimed at parents and children. Sleep was assessed by a parental 24-h recall (only weekdays; n = 8,543) and by a diary (weekdays and weekends separately; n = 4,150). Mixed linear models tested the intervention effect on sleep duration change between baseline when children were 2-9.9 years of age (2007/2008) and follow-up (2009/2010). Logistic mix models were used to study the intervention effect on the presence of TV in the children's bedroom (one of the intervention messages; n = 8,668). Additionally, parents provided qualitative data regarding exposure to the intervention.	About 51.1% of the parents in the intervention regions reported awareness of the sleep intervention. A small intervention effect was seen on weeknight sleep duration in that the decrease in sleep duration over 2 years was smaller in the intervention (15 min) as compared with control regions (19 min) (p = 0.044). There was no overall intervention effect on weekend sleep duration or on the presence of a TV in the bedroom. A small significant time effect between baseline and follow-up was found on bedroom TV presence depending on self-reported intervention exposure (3% increase in TV presence in exposed versus 6.6% increase in non-exposed). Children without a TV in the bedroom had longer nocturnal sleep duration.	The sleep component of the intervention did not lead to clinically relevant changes in sleep duration. Future interventions aimed at young children's sleep duration could benefit from more specific and intense messaging than that found in the IDEFICS intervention. Future research should use objective measures of sleep duration as well as intermediate outcomes (sleep knowledge, sleep environment and sleep practices).	
26705224	Sleep-related movement disorders (SRMD) are sleep disorders. As poor sleep quality is associated with cognitive impairment, we hypothesized that SRMD patients were exposed to a great risk for developing dementia.The present study was aimed to retrospectively examine the association of SRMD and dementia risk.A retrospective longitudinal study was conducted using the data obtained from the Longitudinal Health Insurance Database (LHID) in Taiwan. The study cohort enrolled 604 patients with SRMD who were initially diagnosed and 2416 patients who were randomly selected and age/gender matched with the study group. SRMD, dementia, and other confounding factors were defined according to International Classification of Diseases Clinical Modification Codes. Cox proportional-hazards regressions were employed to examine adjusted hazard ratios (HR) after adjusting with confounding factors.Our data revealed that patients with SRMD had a 3.952 times (95% CI = 1.124-4.767) higher risk to develop all-cause dementia compared with individuals without SRMD. The results showed that SRMD patients aged 45 to 64 exhibited highest risk of developing all-cause dementia (HR: 5.320, 95% CI = 1.770-5.991), followed by patients age ≥65 (HR: 4.123, 95% CI = 2.066-6.972) and <45 (HR: 3.170, 95% CI = 1.050-4.128), respectively. Females with SRMD were at greater risk to develop all-cause dementia (HR: 4.372, 95% CI = 1.175-5.624). The impact of SRMD on dementia risk was progressively increased by various follow-up time intervals (<1 year, 1-2 years, and ≥2 years).The results suggest that SRMD is linked to an increased risk for dementia with gender-dependent and time-dependent characteristics.
26704990	During the second half of the 1st year, periods of increased sleep disruption have been documented alongside overall improvement in sleep-wake regulation. The objective of the present research was to test if pulling-to-stand (PTS), a milestone typically achieved during the latter part of the 1st year, co-occurs with a period of disrupted sleep. In a longitudinal design, 20 healthy infants were followed-up, from 7 to 11-12 months, at 3-week intervals. Each measurement consisted of filmed motor observations and sleep recordings (actigraphy), both conducted at home. It was found that among early achievers of PTS (by 8 months), the milestone was time-linked to a period of disrupted sleep. The results point to the significance of timing in the interplay between domains of development, and highlight the importance of considering both chronological and developmental metrics in studying changes in sleep-wake regulation. 
26704637	Over the last thirty years, a growing number of studies showed that astrocytes play a pivotal role in the energy support to synapses. More precisely, astrocytes adjust energy production to neuronal energy needs through different mechanisms grouped under the term "neurometabolic coupling" (NMC). In this review we describe these mechanisms of coupling and how they involve astrocytes. From a physiological point of view, these mechanisms of coupling are particularly important to ensure normal synaptic functioning when neurons undergo rapid and repetitive changes in the firing rate such as during the sleep/wake transitions. Investigations into brain energy metabolism during the sleep/wake cycle have been mainly focused on glucose (Gluc) consumption and on glycogen metabolism. However, the recent development of substrate-specific biosensors allowed measurements of the variation in extracellular levels of glutamate, Gluc and lactate (Lac) with a time resolution compatible with sleep stage duration. Together with gene expression data these experiments allowed to better define the variations of energy metabolite regulation across the sleep/wake cycle. The aim of this review is to bring into perspective the role of astrocytes and NMC in the regulation of the sleep/wake cycle. The data reviewed also suggest an important role of the astrocytic network. In addition, the role of astrocytes in NMC mechanisms is consistent with the "local and use dependent" sleep hypothesis. 
26704256	Background and Objectives The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI. 
26702789	This report evaluates the scientific literature on caffeine with respect to potential central nervous system (CNS) effects, specifically effects on sleep, anxiety, and aggression/risk-taking. Caffeine has been the subject of more scientific safety studies than any other food ingredient. It is important, therefore, to evaluate new studies in the context of this large existing body of knowledge. The safety of caffeine can best be described in a narrative form, and is not usefully expressed in terms of a "bright line" numerical value like an "acceptable daily intake" (ADI). Caffeine intake has been associated with a range of reversible physiological effects, in a few studies at levels of less than 100 mg in sensitive individuals. It is also clear that many people can tolerate much greater levels - perhaps up to 600-800 mg/day or more - without experiencing such effects. The reasons for this type of variability in response are described in this report. Based on all the available evidence, there is no reason to believe that experiencing such effects from caffeine intake has any significant or lasting effect on health. The point at which caffeine intake may cause harm to the CNS is not readily identifiable, in part because data on the effects of daily intakes greater than 600 mg is limited. Effects of caffeine on risk-taking and aggressive behavior in young people have received considerable publicity, yet are the most difficult to study because of ethical concerns and limitations in the ability to design appropriate studies. At present, the weight of available evidence does not support these concerns, yet this should not preclude ongoing careful monitoring of the scientific literature. 
26701930	Sleep is fundamental to normal physiological and cognitive function. Sleep promotion strategies have been used extensively in clinical settings, as a treatment for various ailments (ie, insomnia). However, sleep problems are prevalent outside these realms, with 56% of American, 31% of Western European and 29% of Japanese people suffering from sleep problems the previous year. The global public health concern over sleep has increased the demand for sleep promotion interventions, but the efficacy of these strategies is unclear in otherwise healthy and athletic populations. One possibility is due to the presentation and analysis of grouped data, despite sleep naturally being a highly variable and inherent trait. We argue the case for (1) presenting sleep data at the individual level and (2) individualising sleep promotion interventions. 
26701140	Duchenne muscular dystrophy (DMD) is the second most common hereditary genetic disease in humans and has elevated mortality. DMD is an X-linked, life-limiting progressive muscle-wasting disease found predominantly in boys and young men. One of the main treatments for patients with DMD is corticosteroids. However, long-term use may cause major side effects such as obesity, a reduction in vitamin D, and osteoporosis. Sleep-disordered breathing is a common condition among patients with DMD, especially obstructive sleep apnea (OSA). In children, OSA is associated with obesity and a reduction of vitamin D concentration. In this article we aim to explore the interrelationship that exists between corticosteroids, obesity, OSA, and the risk of osteoporosis. Our main hypothesis is that factors such as nutrition and sleep are related to obesity and OSA, respectively. In addition, the chronic use of corticosteroids, obesity, and OSA are factors that can reduce serum levels of vitamin D, triggering osteoporosis. Thus, these factors play a key role in affecting the quality of life for patients with DMD and intervention based on these aspects may improve survival. 


26700500	To assess the impact of endometriosis of the posterior cul-de-sac on quality of sleep, average daytime sleepiness and insomnia.This age-matched case-control study was conducted in a tertiary referral centre for the diagnosis and treatment of endometriosis between May 2012 and December 2013. It included 145 women with endometriosis of the posterior cul-de-sac (cases; group E) and 145 patients referred to our Institution because of routine gynaecologic consultations (controls; group C). This study investigated whether sleep is impaired in patients with endometriosis of the posterior cul-de-sac. Sleep quality, daytime sleepiness and insomnia were assessed using the following self-administered questionnaires: the Pittsburgh Sleep Quality Index, the Epworth sleepiness scale and the Insomnia Severity Index, respectively. The primary objective of the study was to evaluate sleep quality in the two study groups. Secondary outcomes of the study were to assess average daytime sleepiness and insomnia in the two study groups.	The prevalence of poor sleep quality was significantly higher in group E (64.8%) than in group C (15.1%; p<0.001). The prevalence of excessive daytime sleepiness was significantly higher in group E (23.4%) than in group C (12.9%; p=0.033). Patients of group E experienced subthreshold insomnia (29.0%) and moderate clinical insomnia (16.6%) significantly more frequently than patients in group C (24.4% and 5.0%; p=0.002).	A substantial proportion of women with endometriosis of the posterior cul-de-sac experiences poor sleep quality, excessive daytime sleepiness and insomnia.	
26697921	Despite the perceived importance of sleep for athletes, little is known regarding athlete sleep quality, their prevalence of daytime sleepiness or risk factors for obstructive sleep apnoea (OSA) such as snoring and witnessed apnoeic episodes. The purpose of the present study was to characterise normative sleep quality among highly trained team sport athletes.175 elite or highly trained rugby sevens, rugby union and cricket athletes completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS) and Quality of Life questionnaires and an OSA risk factor screen.	On average, athletes reported 7.9 ± 1.3 h of sleep per night. The average PSQI score was 5.9 ± 2.6, and 50% of athletes were found to be poor sleepers (PSQI > 5). Daytime sleepiness was prevalent throughout the population (average global score of 8.5) and clinically significant (ESS score of ≥10) in 28% of athletes. OSA may be an important clinical consideration within athletic populations, as a considerable number of athletes (38%) defined themselves as snorers and 8% reported having a witnessed apnoeic episode. The relationship between self-rated sleep quality and actual PSQI score was strong (Pearson correlation of 0.4 ± 0.1, 90% confidence limits).	These findings suggest that this cohort of team sport athletes suffer a preponderance of poor sleep quality, with associated high levels of daytime sleepiness. Athletes should receive education about how to improve sleep wake schedules, extend total sleep time and improve sleep quality.	
26697846	Thalamic injury has been implicated in the development of continuous spike-wave during slow-wave sleep (CSWS) in children with epilepsy. We studied thalamic abnormalities in children with CSWS using F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging.Twenty-three patients (12 male; mean age 9 years) with CSWS and normal thalami on brain magnetic resonance imaging (MRI) underwent FDG-PET. Thalamic glucose metabolism, represented by standardized uptake value normalized to whole brain (nSUV, RT for right thalamus and LT for left thalamus), and its asymmetry--absolute asymmetry index (AAI): ¦(RT-LT)¦*100/[(RT+LT)/2]--was calculated. These values were compared with those from 10 normal healthy controls (five female; mean age 11.1 years).	Thalamic glucose metabolism was abnormal in 18 patients (78.3%). Thalamic nSUV was decreased (n = 6) or increased (n = 1) bilaterally in seven children without any asymmetry. Abnormal thalamic symmetry [AAI = 3.7-31.5% (0.8-3.3% in controls)] was seen in 11 children. Of these, six children had a unilateral thalamic metabolic abnormality (increased metabolism, n = 3 and decreased metabolism, n = 3), whereas 5 of 14 children had abnormal asymmetry index with bilaterally normal (n = 4) or increased (n = 1) thalamic metabolism. No clear association of thalamic metabolic abnormalities was seen with the stage of evolution of CSWS (prodromal, acute, or residual) or with the cortical FDG abnormalities.	Functional thalamic abnormalities, both unilateral and bilateral, are frequently seen in patients with CSWS. FDG-PET is a sensitive and quantifiable modality to detect these changes.	
26695400	Patients with postural tachycardia syndrome (POTS) often describe symptoms of fatigue, sleepiness, and lack of refreshing sleep. We aimed to provide further objective measures of sleep in patients with POTS.POTS patients (n = 18) were selected based on autonomic testing and evaluation at our center. Controls (n = 16) of similar age, gender, and BMI were selected from new patients referred to the Stanford Sleep Disorders Clinic for any sleep-related complaint. All patients underwent polysomnography and completed several sleep questionnaires and a 2-week sleep diary.	POTS patients and control subjects were of similar age (27 ± 10.2 vs. 29 ± 5.4 years, p = 0.92) and Body Mass Index (21 ± 3.8 vs. 24 ± 4.1, p = 0.14). The majority of subjects in both groups were females (72 % POTS vs. 81 % controls). POTS patients scored higher on subjective fatigue scales but not sleepiness scales. POTS patients scored in the normal range on the BDI and the "evening" category on the MEQ. Their sleep diaries were not different from controls. With the exception of mild OSA, slightly reduced %REM and prolonged REM latency, their PSG data were normal and no different from controls.	It is unlikely that the sleep-related complaints of POTS patients are the result of a primary sleep disorder unique to POTS. We propose that a combination of factors such as body fatigue, chronic pain, and other somatic symptoms common in POTS patients might be the underlying reason for sleep-related symptoms in POTS.	


26691833	During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity. 
26690783	To explore the direct measure of EEG amplitude (range EEG, rEEG) for detection of interburst intervals (IBIs) and bursts in neonates.Previously described 177 two-channel EEG recordings 3-6h long from 26 preterm infants (median gestational age of 26 weeks) at 23-38 weeks post-menstrual age (PMA) without major abnormalities were used to test four definitions of IBI detection algorithms with various settings of the parameters.	As the basis for all four algorithms we developed the aggregation of rEEG signal over the channels by taking its maximum, and method of EEG trace selection at different phases of sleep-wake cycle (with different degree of discontinuity). The two less restrictive algorithms - with one and two amplitude thresholds - turned to be the most promising definitions. There were enough IBI detections for analysis, with no substantial difference in mean and maximum values of intervals. The longest IBI were measured at the location of greater discontinuity. Values of bursts and IBI indices as well as association with PMA were close to the published normative values derived manually.	rEEG as a direct measure of EEG amplitude can be used for detection of bursts and IBI.	The automatic measurement of IBI based on rEEG provides a basis for improvements in neonatal brain monitoring.	
26690161	The rapid developments of sensor devices that can actively monitor human activities have given rise to a new field called wireless body area network (BAN). A BAN can manage devices in, on and around the human body. Major requirements of such a network are energy efficiency, long lifetime, low delay, security, etc. Traffic in a BAN can be scheduled (normal) or event-driven (emergency). Traditional media access control (MAC) protocols use duty cycling to improve performance. A sleep-wake up cycle is employed to save energy. However, this mechanism lacks features to handle emergency traffic in a prompt and immediate manner. To deliver an emergency packet, a node has to wait until the receiver is awake. It also suffers from overheads, such as idle listening, overhearing and control packet handshakes. An external radio-triggered wake up mechanism is proposed to handle prompt communication. It can reduce the overheads and improve the performance through an on-demand scheme. In this work, we present a simple-to-implement on-demand packet transmission scheme by taking into considerations the requirements of a BAN. The major concern is handling the event-based emergency traffic. The performance analysis of the proposed scheme is presented. The results showed significant improvements in the overall performance of a BAN compared to state-of-the-art protocols in terms of energy consumption, delay and lifetime. 
26689303	Despite the success of empirically supported treatments for posttraumatic stress disorder (PTSD), sleep impairment frequently remains refractory after treatment. This single-site, randomized controlled trial examined the effectiveness of sleep-directed hypnosis as a complement to an empirically supported psychotherapy for PTSD (cognitive processing therapy [CPT]).Participants completed either 3 weeks of hypnosis (n = 52) or a symptom monitoring control condition (n = 56) before beginning standard CPT. Multilevel modeling was used to investigate differential patterns of change to determine whether hypnosis resulted in improvements in sleep, PTSD, and depression. An intervening variable approach was then used to determine whether improvements in sleep achieved during hypnosis augmented change in PTSD and depression during CPT.	After the initial phase of treatment (hypnosis or symptom monitoring), the hypnosis condition showed significantly greater improvement than the control condition in sleep and depression, but not PTSD. After CPT, both conditions demonstrated significant improvement in sleep and PTSD; however, the hypnosis condition demonstrated greater improvement in depressive symptoms. As sleep improved, there were corresponding improvements in PTSD and depression, with a stronger relationship between sleep and PTSD.	Hypnosis was effective in improving sleep impairment, but those improvements did not augment gains in PTSD recovery during the trauma-focused intervention. (PsycINFO Database Record	
26688115	The locus coeruleus-norepinephine (LC-NE) system is implicated in mediating several aspects of arousal. Alterations in LC neuronal discharge is associated with distinct changes in behavior, cognition, sensory processing and regulation of the sleep-wake cycle. Changes in LC output and subsequent release of NE in target brain regions help adjust arousal state to respond appropriately to environmental conditions and behavioral circumstances. One way in which LC activity is controlled is through release of endogenous neuropeptides. Based on the sleep-wake cycle and environmental cues specific neuropeptide afferent systems are activated, innervating the LC. These neuropeptides include: corticotropin releasing factor (CRF), orexin (ORX), endogenous opioids, substance P (SP), melanin-concentrating hormone (MCH), neuropeptide Y (NPY) and somatostatin (SS). This review summarizes studies examining the neuroanatomical projections of these neuropeptides, their receptors in the LC, the actions on LC neurons and downstream NE release, as well as the behavioral and cognitive effects associated individual neuropeptide-mediated innervation of the LC. Finally, the relationship between individual neuropeptides, the LC-NE system and various clinical disorders is discussed, providing evidence for possible therapeutic targets for treatment of several arousal- and stress-related disorders. This article is part of a Special Issue entitled SI: Noradrenergic System. 
26687029	Refractory globus is not rare in clinical practice, but little research about it.To investigate the clinical-psychological characteristics of patients with refractory globus.	Six hundred and nineteen globus patients were divided into the refractory globus group (n=149) and the non-refractory globus group (n=470). All subjects completed the following questionnaires: demographic characteristics, medical information, Hamilton Rating Scale of Anxiety/Depression, Pittsburgh Sleep Quality Index, Glasgow Edinburgh Throat Scale, and 36-item Short Form Health Survey.	No significantly differences were found in demographic characteristics between the two groups, but the refractory globus group had longer disease duration and more serious symptoms. Sought healthcare more frequently but still had poorer quality of life than did the non-refractory globus group. Compared with the non-refractory globus group, the refractory globus group also had higher percentages of anxiety, depression, and sleep disorders. Positive correlations were observed between the severity of globus symptoms and HAMA, HAMD, and PSQI scores.	Refractory globus is not rare in clinical practice and should receive more attention from patients and doctors because of its severe symptoms, long disease duration, poor quality of life, and accompanied by psychological disorders and sleep disorders.	
26686679	Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome caused by a heterozygous mutation or deletion of the ZEB2 gene. It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. The current study investigated sleep disturbance in people with MWS. In a series of unstructured interviews focused on development and behaviors in MWS, family members frequently reported sleep disturbance, particularly early-morning waking and frequent night waking. The Sleep Disturbance Scale for Children (SDSC) was therefore administered to a sample of 35 individuals with MWS, along with the Developmental Behaviour Checklist (DBC) to measure behavioral and emotional disturbance. A high level of sleep disturbance was found in the MWS sample, with 53% scoring in the borderline range and 44% in the clinical disorder range for at least one subscale of the SDSC. Scores were highest for the Sleep-wake transition disorders subscale, with 91% of participants reaching at least the borderline disorder range. A significant positive association was found between total scores on the SDSC and the DBC Total Behaviour Problem Score. These results suggest that sleep disorders should be screened for in people with MWS, and where appropriate, referrals to sleep specialists made for management of sleep problems.
26686390	Alterations in rapid eye movement sleep (REM) have been suggested as valid translational efficacy markers: activation of the metabotropic glutamate receptor 2 (mGluR2) was shown to increase REM latency and to decrease REM duration. The present paper addresses the effects on vigilance states of the mGluR2 positive allosteric modulator (PAM) JNJ-40411813 at different circadian times in rats and after afternoon dosing in humans. Due to its dual mGluR2 PAM/serotonin 2A (5-HT2A) receptor antagonism in rodents, mGlu2R specificity of effects was studied in wild-type (WT) and mGluR2 (-/-) mice. 5-HT2A receptor occupancy was determined in humans using positron emission tomography (PET). Tolerance development was examined in rats after chronic dosing. EEG oscillations and network connectivity were assessed using multi-channel EEG. In rats, JNJ-40411813 increased deep sleep time and latency of REM onset but reduced REM time when administered 2 h after 'lights on' (CT2): this was sustained after chronic dosing. At CT5 similar effects were elicited, at CT10 only deep sleep was enhanced. Withdrawal resulted in baseline values, while re-administration reinstated drug effects. Parieto-occipital cortical slow theta and gamma oscillations were correlated with low locomotion. The specificity of functional response was confirmed in WT but not mGluR2 (-/-) mice. A double-blind, placebo-controlled polysomnographic study in healthy, elderly subjects showed that 500 mg of JNJ-40411813 consistently increased deep sleep time, but had no effect on REM parameters. This deep sleep effect was not explained by 5-HT2A receptor binding, as in the PET study even 700 mg only marginally displaced the tracer. JNJ-40411813 elicited comparable functional responses in rodents and men if circadian time of dosing was taken into account. These findings underscore the translational potential of sleep mechanisms in evaluating mGluR2 therapeutics when administered at the appropriate circadian time.

26683422	Parkinson's disease is characterized by motor and non-motor clinical features. The latter may present as pre-motor symptoms several years before the motor onset.To analyze the association between pre-motor symptoms load and its lead-time in relation to the motor onset and time to diagnosis.	A cross-sectional study was carried including subjects with Parkinson's disease from five different movement disorders clinics in Mexico. A structured questionnaire was applied to assess the presence of six self-perceived pre-motor symptoms (hyposmia, depression, anxiety, constipation, pain and sleep disorders).	Overall frequency of pre-motor symptoms was 76.2% . Among the most prevalent symptoms were depression (38%), sleep disorders (37%) and anxiety (36.6%). The lead time to motor onset was greater for constipation (9.2 ± 17.89 years) and pain (8.66 ± 13.36 years). Patients with more than two pre-motor symptoms had a later age at motor onset when compared to patients without pre-motor symptoms (52.04 ± 13.11 vs 56.55 ± 12.97 years, p = 0.037). Late onset patients had a higher frequency of pre-motor symptoms (79% vs 65% in early onset, p = 0.002) and a higher load (1.75 ± 1.37 vs 1.44 ± 1.38, p = 0.033) in comparison to those with early onset. Female subjects reported a higher number of pre-motor symptoms (1.91 ± 1.43 versus 1.48 ± 1.29, p ≤ 0.001). PIGD patients reported a greater frequency of pain (8%) compared to tremor (1%, p = 0.0064) and bradykinetic-rigid (0.61%, p = 0.0061). Anxiety lead-time was greater in tremor-dominant (10.83 ± 15.77 years) compared to bradykinetic-rigid patients (3.48 ± 12.56, p = 0.014).	Pre-motor symptoms load is associated to a later motor onset of PD. Pre-motor symptoms are more frequent in subjects with late onset Parkinson's disease. Female subjects report a higher number of pre-motor symptoms, depression and anxiety being the most common.	
26683236	Sleep and pain are thought to be bidirectional related on a daily basis in adolescents with chronic pain complaints. In addition, sleep problems have been shown to predict the long-term onset of musculoskeletal pain in middle-aged adults. Yet, the long-term effects of sleep problems on pain duration and different types of pain severity in emerging adults (age: 18-25) are unknown. This study investigated the cross-sectional and longitudinal relationship between sleep problems and chronic pain, and musculoskeletal pain, headache, and abdominal pain severity in a general population of emerging adults. We studied whether these relationships were moderated by sex and whether symptoms of anxiety and depression, fatigue, or physical inactivity mediated these effects. Data of participants from the longitudinal Dutch TRacking Adolescents' Individual Lives Survey were used. Follow-up data were collected in 1753 participants who participated in the fourth (N = 1668, mean age: 19.0 years [SD = 0.6]) and/or fifth (N = 1501, mean age: 22.3 years [SD = 0.6]) assessment wave. Autoregressive cross-lagged models were used for analyses. Sleep problems were associated with chronic pain, musculoskeletal pain, headache and abdominal pain severity, and predicted chronic pain and an increase in musculoskeletal pain severity at 3 years of follow-up. This prospective effect was stronger in females than in males and was mediated by fatigue but not by symptoms of anxiety and depression or physical inactivity. Only abdominal pain had a small long-term effect on sleep problems. Our results suggest that sleep problems may be an additional target for treatment in female emerging adults with musculoskeletal pain complaints.
26683234	The purposes of this study, in oncology outpatients receiving chemotherapy (n = 926), were to: describe the occurrence of different types of pain (ie, no pain, only noncancer pain [NCP], only cancer pain [CP], or both CP and NCP) and evaluate for differences in demographic, clinical, and symptom characteristics, and quality of life (QOL) among the 4 groups. Patients completed self-report questionnaires on demographic and symptom characteristics and QOL. Patients who had pain were asked to indicate if it was or was not related to their cancer or its treatment. Medical records were reviewed for information on cancer and its treatments. In this study, 72.5% of the patients reported pain. Of the 671 who reported pain, 21.5% reported only NCP, 37.0% only CP, and 41.5% both CP and NCP. Across the 3 pain groups, worst pain scores were in the moderate to severe range. Compared with the no pain group, patients with both CP and NCP were significantly younger, more likely to be female, have a higher level of comorbidity, and a poorer functional status. In addition, these patients reported: higher levels of depression, anxiety, fatigue, and sleep disturbance; lower levels of energy and attentional function; and poorer QOL. Patients with only NCP were significantly older than the other 3 groups. The most common comorbidities in the NCP group were back pain, hypertension, osteoarthritis, and depression. Unrelieved CP and NCP continue to be significant problems. Oncology outpatients need to be assessed for both CP and NCP conditions.
26681411	The sleep of people with dementia living in long-term care is known to be disturbed. This pre-post controlled pilot study examined the effects of a person-centered dementia care intervention on sleep in assisted living residents with dementia. The three-month intervention included in-class staff training plus supervision and support in practice. The sleep-wake patterns were measured using actigraphy for three consecutive days at baseline and postintervention. Sixteen residents from the intervention and six from the control groups completed the study. The intervention group had significantly more nighttime sleep at posttest. After adjusting for baseline, the intervention group exhibited significantly less daytime sleep and more nighttime sleep. Person-centered dementia care may be effective for improving sleep of residents with dementia.
26679739	This study examined the role of sleep problems and sleep duration on stress-related HPA axis reactivity among urban, low income adolescents. A total of 84 adolescents (M age 13.36 years; 50% male; 95% African American) and their parents provided information on adolescents' sleep problems and sleep quantity. Adolescents completed a standardized social stress test in the laboratory (the Trier Social Stress Test; TSST). Saliva samples collected before and after the TSST yielded measures of cortisol pre-test, 15 min post-test, and 55 min post-test, as well as overall cortisol secretion and its increase (AUCG and AUCI). More sleep problems and longer sleep duration predicted higher cortisol reactivity to the TSST, particularly among females. Self-reports of sleep were more consistently related to stress-related cortisol reactivity than parent reports. Sleep problems and longer sleep duration may place adolescents at risk for HPA axis hyper-reactivity to stress, contributing to academic, behavioral and health problems.
26678684	Sleep impairment is highly prevalent in patients with chronic rhinosinusitis (CRS). Although endoscopic sinus surgery (ESS) has been shown to improve overall patient-reported sleep quality, the postoperative impact on individual sleep symptoms remains unclear.Patients with medically-recalcitrant CRS who elected to undergo ESS were prospectively enrolled into a multi-institutional, observational cohort study. Sleep-related symptom severity and treatment outcomes were assessed using the sleep domain questions within the 22-item Sino-Nasal Outcome Test (SNOT-22).	A total of 334 participants met criteria and were followed postoperatively for an average of 14.5 ± 4.9 months (mean ± standard deviation [SD]). Mean SNOT-22 sleep domain scores improved from 13.7 ± 6.8 to 7.7 ± 6.6 (p < 0.001). Significant mean relative improvements were reported for "difficulty falling asleep" (45%; p < 0.001), "waking up at night" (40%; p < 0.001), "lack of a good night's sleep" (43%; p < 0.001), "waking up tired" (40%; p < 0.001), and "fatigue" (42%; p < 0.001) scores. A total of 66% of study participants reported postoperative improvement in "lack of a good night's sleep," "waking up tired," and "fatigue"; 62% reported improvement in "waking up at night"; and 58% reported improvement in "difficulty falling asleep."	Patients with CRS report significant and sustained improvements following ESS in common sleep-related symptoms as assessed by the SNOT-22 sleep domain. Despite these significant improvements, some degree of persistent postoperative sleep impairment was reported. Further study is necessary to determine what factors are associated with continued sleep dysfunction after sinus surgery.	
26678051	Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock system in humans and other mammals. In order to evaluate the extent of epigenetic differences associated with diurnal preference, we examined genome-wide patterns of DNA methylation in DNA from monozygotic (MZ) twin-pairs discordant for diurnal preference. MZ twins were selected from a longitudinal twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. Fifteen pairs of MZ twins were identified in which one member scored considerably higher on the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) than the other. Genome-wide DNA methylation patterns were assessed in twins' buccal cell DNA using the Illumina Infinium HumanMethylation450 BeadChips. Quality control and data pre-processing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. Our data indicate that DNA methylation differences are detectable in MZ twins discordant for diurnal preference. Moreover, downstream gene ontology (GO) enrichment analysis on the top-ranked diurnal preference associated DMPs revealed significant enrichment of pathways that have been previously associated with circadian rhythm regulation, including cell adhesion processes and calcium ion binding. 
26677208	Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer.We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer.	In 1987, 2% of men reported sleeping ≤5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15-8.10).	We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes.	We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men.	
26674980	Irritable bowel syndrome (IBS) represents a great challenge to public health, particularly among medical students. The aim of the study was to determine the global prevalence and risk factors of IBS among medical students.Data were obtained through searches in PubMed, Ovid, the Cochrane database, Embase, Google scholar, Institute for Scientific Information (ISI) "Web of Science," and Medline from 1990 to June 2015. The search terms included "Irritable Bowel Syndrome" and "Medical students" and "prevalence, risk factors". More than 100 articles were reviewed, scrutinized, and critically appraised for the eligibility criteria, and the relevant articles were selected.	Sixteen studies were identified, and the prevalence of IBS among medical students ranged from 9.3% to 35.5%. The relatively high prevalence among medical students may be attributed to their special stressful learning environment. Some studies found that female gender, family history of IBS, psychiatric stress, anxiety, depression, infections, dietary factors, and sleep disorders were associated with IBS.	A relatively high prevalence of IBS was prevalent among medical students. Annual screening of IBS and introduction of stress management courses are recommended.	
26673225	Prolonged psychological stress is a risk factor for illness and constitutes an increasing public health challenge creating a need to develop public interventions specifically targeting stress and promoting mental health. The present randomized controlled trial evaluated health effects of a novel program: Relaxation-Response-based Mental Health Promotion (RR-MHP).The multimodal, meditation-based course was publicly entitled "Open and Calm" (OC) because it consistently trained relaxed and receptive ("Open") attention, and consciously non-intervening ("Calm") witnessing, in two standardized formats (individual or group) over nine weeks. Seventy-two participants who complained to their general practitioner about reduced daily functioning due to prolonged stress or who responded to an online health survey on stress were randomly assigned to OC formats or treatment as usual, involving e.g., unstandardized consultations with their general practitioner. Outcomes included perceived stress, depressive symptoms, quality of life, sleep disturbances, mental health, salivary cortisol, and visual perception. Control variables comprised a genetic stress-resiliency factor (serotonergic transporter genotype; 5-HTTLPR), demographics, personality, self-reported inattentiveness, and course format.	Intent-to-treat analyses showed significantly larger improvements in OC than in controls on all outcomes. Treatment effects on self-reported outcomes were sustained after 3 months and were not related to age, gender, education, or course format. The dropout rate was only 6 %.	The standardized OC program reduced stress and improved mental health for a period of 3 months. Further testing of the OC program for public mental health promotion and reduction of stress-related illnesses is therefore warranted. A larger implementation is in progress.	
26672680	Children with autism spectrum disorder (ASD) often suffer from sleep problems that in turn correlate with behavioral problems. However, in Japan, there have been few studies of sleep problems in children with ASD.This study compared sleep problems in preschoolers from the community and preschoolers with ASD in Japan, and examined whether sleep problems were related to problematic behaviors in ASD preschoolers.	Sleep problems were assessed in 965 community and 193 ASD preschoolers using the Japanese Sleep Questionnaire for Preschoolers, which was developed to assess sleep problems in Japanese preschoolers. Behavioral problems were assessed in 107 ASD preschoolers using the Child Behavior Checklist.	Compared with community preschoolers, ASD preschoolers experienced significantly more sleep problems, including obstructive sleep apnea and parasomnias. ASD preschoolers with sleep problems exhibited more behavioral problems than those without sleep problems. The severity of sleep problems, especially insomnia, was significantly correlated with behavioral problems in ASD preschoolers.	The present study suggests that sleep problems, especially obstructive sleep apnea, are more common in ASD preschoolers than in community preschoolers. The study also shows that sleep problems, especially insomnia, are related to problematic behavior in ASD preschoolers.	
26669814	Sleep disturbance is often described as sleeping poorly, difficulty falling asleep and maintaining sleep, and waking early. Currently, most studies examining sleep disturbance have focused on negative psychological variables; however, few studies have combined both negative and positive psychosocial factors to assess sleep. The aim of this study was to investigate the prevalence of sleep disturbance and psychosocial correlates in Chinese community-dwelling adults. A total of 1471 adults, between 18 and 60 years old, from eight selected community settings in Jinan, China, were surveyed using the Pittsburgh Sleep Quality Index, Perceived Stress Scale, 10-item Connor-Davidson Resilience Scale and Multidimensional Scale of Perceived Social Support and provided sociodemographic information. We found that the prevalence of sleep disturbance was 33.9%. After adjusting for age, employment status and physical co-morbidity, perceived stress was significantly associated with sleep disturbance [odds ratio (OR) = 1.14, p < 0.001], while resilience and social support were associated with a low likelihood of sleep disturbance (OR = 0.90, p < 0.001; OR = 0.97, p < 0.001). Furthermore, regression analysis showed that the interaction between perceived stress and resilience was significant (p < 0.05). Resilience buffered the negative impact of perceived stress on sleep disturbance. Given the close relationship between sleep disturbance and psychosocial correlates, the development of effective intervention programmes to improve sleep quality in this population should be considered. Copyright © 2015 John Wiley & Sons, Ltd.
26668381	An increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption. 
26668142	Studies have reported the presence of sleep disorders in approximately 50-70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS) and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels).We used the Berlin questionnaire (BQ) for OSAS, the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI) to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels.	The study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively), and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001). These results showed that HbA1c levels were related to sleep disorders.	Sleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control.	
26667741	Introducción: el sueno participa en diversas funciones biologicas y fisiologicas, asociando su restriccion con menor rendimiento en el deporte; sin embargo, se desconoce la cantidad y calidad del sueno en deportistas paralimpicos. Objetivo: determinar la calidad del sueno, el insomnio y la somnolencia diurna en deportistas paralimpicos de elite chilenos. Material y métodos: estudio descriptivo transversal. La muestra incluyo 33 deportistas paralimpicos (24,2% mujeres), quienes practicaban natacion, tenis de mesa, futbol 5, powerlifting y tenis silla. Las variables estudiadas se midieron a traves de dos encuestas de sueno: el Cuestionario de Insomnio y el Indice de Calidad del Sueno de Pittsburgh. Resultados: los deportistas paralimpicos chilenos duermen 6,9 } 1,4 horas, un 27,7% presenta somnolencia diurna excesiva y el 69,6% insomnio (Encuesta de insomnio ≥7), mientras que el 78,7% exhibe una mala calidad del sueno. La edad mostro una correlacion positiva con latencia al sueno (r=0,417*), el insomnio con latencia al sueno (r=0,462**), el puntaje de Pittsburgh se correlaciono negativamente con la cantidad de sueno (r= -0,323) y latencia al sueno se correlaciona positivamente con el puntaje de Pittsburgh (r=0,603**). Conclusión: los deportistas paralimpicos chilenos presentan una baja calidad del sueno, insomnio y somnolencia diurna excesiva, situacion que podria influir negativamente sobre el rendimiento deportivo.the sleep takes part in diverse biological and physiological functions, associating his restriction, with minor performance in the sport, nevertheless the quantity and quality of sleep is not known in paralympic athletes.	to determine the sleep quality, insomnia and excessive daytime sleepiness in Chilean paralympic athletes.	descriptive transverse Study, the sample included 33 paralympic athletes (24.2% women), those who were practicing swimming, tennis of table, football 5, powerlifting and tennis chair. The studied variables measured up across two surveys of dream: the Questionnaire of Insomnia and the Pittsburgh Sleep Quality Index.	the paralympic athletes sleep were 6.9 } 1.4 hours, 27.7% presents daytime sleepiness, 69.6 % insomnia (Survey of insomnia =7), whereas 78.7 % exhibits a bad sleep quality. The age showed a positive correlation with latency to the sleep (r=0.417 *), the insomnia with latency to the sleep (r=0.462 **), the Pittsburg score was correlated negatively by the sleep duration (r =-0.323) and latency to the sleep is correlated positively by the Pittsburgh score (r=0.603 **).	the chilean paralympic athletes, present a low sleep quality, insomnia and excessive daytime sleepiness, situation that might influence negatively the sports performance.	
26666401	We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy. 

26664825	Sleep disturbances are common in patients with Parkinson's disease (PD) and are even more prevalent in patients with behavioural addictions, such as pathological gambling, compulsive sexual behaviour, compulsive buying, binge eating, punding, and the compulsive use of dopamine replacement therapy. An overview of the relationship between these impulse control disorders and sleep disturbances is given and potential underlying mechanisms and treatment strategies are covered. 
26662127	Depression leads to disturbances in physiological rhythms, which result in disturbances in circadian sleep-wake cycles, hormonal secretion patterns and fluctuations in mood, all of which can be objectively measured. These disturbances, which are associated with depression, can be also used to define depression. Beyond these "transversal" time-related symptoms, there are the "longitudinal" time-related symptoms, since depression evolves over a long period of time, with a profound impact on a person's life and is often associated with long-term psychosocial consequences (Mendlewicz, 2010). The circadian rhythm reflects an approximate 24-hour cycle in the biochemical, physiological and behavioral processes of living entities, which crucially influences human well-being and health. Increasing evidence from clinical and neurobiological research suggests that disrupted temporal organization impairs behavior, cognition, mood, sleep and social activity and may be implicated in mental disorders. It has been proposed that circadian malfunction is a major core feature of mood disorders, depression in particular. In depressed patients, circadian rhythms and homeostatic processes are disrupted, thereby affecting mood, sleep, activity and a variety of biological functions such as hormone secretion and body temperature (Hajak & Landgrebe, 2010). Sleep difficulties are among the most current symptoms in depressed patients. Insomnia is often the reason why depressed patients seek help and relief of sleep disturbance may encourage compliance with antidepressant treatment. Apart from the discomfort that sleep problems produce, they may lead to exhaustion, poor functioning and they are associated with an increase in suicide risk (Wilson et al., 2013). 

26658273	G-protein-coupled receptor (GPCR) agonists are known to induce both cellular adaptations resulting in tolerance to therapeutic effects and withdrawal symptoms upon treatment discontinuation. Glutamate neurotransmission is an integral part of sleep-wake mechanisms, which processes have translational relevance for central activity and target engagement. Here, we investigated the efficacy and tolerance potential of the metabotropic glutamate receptors (mGluR2/3) agonist LY354740 versus mGluR2 positive allosteric modulator (PAM) JNJ-42153605 on sleep-wake organisation in rats. In vitro, the selectivity and potency of JNJ-42153605 were characterized. In vivo, effects on sleep measures were investigated in rats after once daily oral repeated treatment for 7 days, withdrawal and consecutive re-administration of LY354740 (1-10 mg/kg) and JNJ-42153605 (3-30 mg/kg). JNJ-42153605 showed high affinity, potency and selectivity at mGluR2. Binding site analyses and knowledge-based docking confirmed the specificity of JNJ-42153605 at the mGluR2 allosteric binding site. Acute LY354740 and JNJ-42153605 dose-dependently decreased rapid eye movement (REM) sleep time and prolonged its onset latency. Sub chronic effects of LY354740 on REM sleep measures disappeared from day 3 onwards, whereas those of JNJ-42153605 were maintained after repeated exposure. LY354740 attenuated REM sleep homeostatic recovery, while this was preserved after JNJ-42153605 administration. JNJ-42153605 enhanced sleep continuity and efficiency, suggesting its potential as an add-on medication for impaired sleep quality during early stages of treatment. Abrupt cessation of JNJ-42153605 did not induce withdrawal phenomena and sleep disturbances, while the initial drug effect was fully reinstated after re-administration. Collectively, long-term treatment with JNJ-42153605 did not induce tolerance phenomena to its primary functional effects on sleep measures, nor adverse effects at withdrawal, while it promoted homeostatic recovery sleep. From the translational perspective, the present rodent findings suggest that mGluR2 positive allosteric modulation has therapeutic potential based on its superior long term efficacy over agonists in psychiatric disorders, particularly of those commonly occurring with REM sleep overdrive. 
26655281	While intervening sleep promotes the consolidation of memory, it is well established that cognitive interference from competing stimuli can impede memory retention. The current study examined changes in motor skill learning across periods of wakefulness with and without competing stimuli, and periods of sleep with and without disruption from external stimuli. A napping study design was adopted where participants (N=44) either had (1) a 30min nap composed of Non-Rapid Eye Movement (NREM) sleep, (2) 30min NREM nap fragmented by audio tone induced arousals, (3) 45min of quiet wakefulness, or (4) 45min of active wakefulness. Measures of subjective sleepiness (KSS), alertness (PVT) and motor skill learning (Sequential Finger Tapping Task, SFTT) were completed in the morning and evening to assess performance pre- and post-nap or wakefulness. Following a practice session, change in motor skill performance was measured over a 10min post training rest interval, as well as following a 7h morning to evening interval comprising one of the four study conditions. A significant offline enhancement in motor task performance (13-23%) was observed following 10min of rest in all conditions. Following the long delay with the intervening nap/wake condition, there were no further offline gains or losses in performance in any sleep (uninterrupted/fragmented) or wake (quiet/active) condition. The current findings suggest that after controlling for offline gains in performance that occur after a brief rest and likely to due to the dissipation of fatigue, the subsequent effect of an intervening sleep or wake period on motor skill consolidation is not significant. Consistent with this null result, the impact of disrupting the sleep episode or manipulating activity during intervening wake also appears to be negligible. 
26654911	Personnel working on North Sea oil/gas installations are exposed to remote and potentially hazardous environments, and to extended work schedules (typically, 14×12h shifts). Moreover, overtime (additional to the standard 84-h week) is not uncommon among offshore personnel. Evidence from onshore research suggests that long work hours and adverse environmental characteristics are associated with sleep impairments, and consequently with health and safety risks, including accidents and injuries. However, little is known about the extent to which long hours and a demanding work environment combine synergistically in relation to sleep. The present study sought to address this issue, using survey data collected from offshore day-shift personnel (N=551). The multivariate analysis examined the additive and interactive effects of overtime and measures of the psychosocial/physical work environment (job demands, job control, supervisor support, and physical stressors) as predictors of sleep outcomes during offshore work weeks. Control variables, including age and sleep during leave weeks, were also included in the analysis model. Sleep duration and quality were significantly impaired among those who worked overtime (54% of the participants) relative to those who worked only 12-h shifts. A linear relationship was found between long overtime hours and short sleep duration; personnel who worked >33h/week overtime reported <6h/day sleep. Significant interactions were also found; sleep duration was negatively related to job demands, and positively related to supervisor support, only among personnel who worked overtime. Poor sleep quality was predicted by the additive effects of overtime, low support and an adverse physical environment. These findings highlight the need to further examine the potential health and safety consequences of impaired sleep associated with high overtime rates offshore, and to identify the extent to which adverse effects of overtime can be mitigated by favourable physical and psychosocial work environment characteristics.
26654880	Exposure to artificial light at night (ALAN) has become increasing common, especially in developed countries. We investigated the effect of dALAN exposure during sleep in healthy young male subjects. A total of 30 healthy young male volunteers from 21 to 29 years old were recruited for the study. They were randomly divided into two groups depending on light intensity (Group A: 5 lux and Group B: 10 lux). After a quality control process, 23 healthy subjects were included in the study (Group A: 11 subjects, Group B: 12 subjects). Subjects underwent an NPSG session with no light (Night 1) followed by an NPSG session randomly assigned to two different dim light conditions (5 or 10 lux, dom λ: 501.4 nm) for a whole night (Night 2). We found significant sleep structural differences between Nights 1 and 2, but no difference between Groups A and B. Exposure to dALAN during sleep was significantly associated with increased wake time after sleep onset (WASO; F = 7.273, p = 0.014), increased Stage N1 (F = 4.524, p = 0.045), decreased Stage N2 (F = 9.49, p = 0.006), increased Stage R (F = 6.698, p = 0.017) and non-significantly decreased REM density (F = 4.102, p = 0.056). We found that dALAN during sleep affects sleep structure. Exposure to dALAN during sleep increases the frequency of arousals, amount of shallow sleep and amount of REM sleep. This suggests adverse effects of dALAN during sleep on sleep quality and suggests the need to avoid exposure to dALAN during sleep.
26654569	This cross-sectional population study examined associations of sleep duration and morning-evening type with sociodemographic and cardiometabolic disease in adults participating in the UK Biobank study (N = 439 933). Multivariable Poisson regression models of sleep duration and morning-evening type with a robust error variance were generated to estimate adjusted prevalence ratios and their 95% confidence intervals. All models were adjusted for sex, race, college attendance, employment status and age. Twenty five percent of the sample reported short sleep; 27% were morning, 64% intermediate and 9% evening type. Black ethnicity emerged as most strongly associated with sleep behavior. Short sleep was twice as prevalent, and morning versus intermediate type was 1.4 times more prevalent in Black than White participants. The greater prevalence of short sleep and morning type among Blacks suggests that sleep-based approaches to improving cardiometabolic outcomes may require a more multidimensional approach that encompasses adequate sleep and circadian alignment in this population.
26653408	The menopausal transition, or perimenopause, is associated with profound reproductive and hormonal changes. These changes have been well chronicled and matched with concomitant symptoms. The pattern of appearance of menopausal symptoms and their natural history have become increasingly clear thanks to the conduct of several long-term, longitudinal cohort studies that have examined many aspects of women's biology and psychology through this time of life. Menopausal symptoms are highly prevalent; they are sufficiently bothersome to drive almost 90% of women to seek out their healthcare provider for advice on how to cope. (1) The classic symptom of menopause is the hot flash, which is experienced by most women, and is moderately to severely problematic for about 1/3 of women. While most women will have an experience of hot flashes limited to just a year or two, others will experience them for a decade or more, and a small proportion of women will never be free of them. Poor sleep becomes more common in perimenopausal women not only in association with the menopausal transition but also in relation to aging. Depressed mood and increased anxiety also increase during the transition, with an abrupt rise in prevalence as women approach the later stages of the menopausal transition and have longer bouts of amenorrhea. These common symptoms often interact with one another such that depressed women tend to experience worse hot flashes along with worse sleep. As women enter the latter stages of the transition, vaginal dryness and dyspareunia also become more likely, affecting about 1/3 of the population. Unlike hot flashes, mood issues, and sleep, vaginal symptoms will not go away without treatment. Clinical approaches to these problems often involve hormone therapy, which can be safely given to most perimenopausal women on a short-term basis. Therapeutic strategies that are nonhormonal and behavioral can also be deployed. 
26652080	Academic burnout leads to creation of a series of negative and scattered thoughts, loss of hope and emotional and physical exhaustion in carrying out activities. Two factors that affect academic burnout are sleep quality and social intimacy. This study was conducted in order to investigate the relationship between sleep quality and social intimacy, and academic burn-out in the students of Tabriz University of Medical Sciences.This study was descriptive and correlational. The population of this study consisted of the students in Tabriz University of Medical Sciences and 196 medical students were selected. They completed Berso et al. Academic Burnout Questionnaire, Pittsburgh Sleep Quality Index (PSQI) and Miller Social Intimacy Scale (MSIS). The validity of the questionnaires confirmed by experts' views. Their reliability were obtained as 77%, 64% and 85% for academic burnout, sleep quality and social intimacy questionnaires respectively by calculating the internal consistency (Cronbach's alpha). For data analysis, descriptive statistics and Pearson correlation test, Regression, cluster analysis and t-test were used.	The results showed that there was a positive and significant relationship between sleep quality and academic burnout at the level p<0.05 (r=0.38). There was a negative and significant relationship between social intimacy and academic burnout at the level p<0.05 (r= -0.40). Also, the regression results showed that sleep quality and social intimacy were able to predict 37% and 39% of academic burnout respectively. Moreover, the students were divided into two clusters of individuals with high social intimacy and individuals with low social intimacy. No significant difference was found between the two types in terms of the variable of academic burn-out.	Based on the research results, it can be stated that the variables of sleep quality and social intimacy are the predictor factors of academic burn-out.	
26652002	Robust sleep/wake rhythms are important for health and cognitive function. Unfortunately, many people are living in an environment where their circadian system is challenged by inappropriate meal- or work-times. Here we scheduled food access to the sleep time and examined the impact on learning and memory in mice. Under these conditions, we demonstrate that the molecular clock in the master pacemaker, the suprachiasmatic nucleus (SCN), is unaltered while the molecular clock in the hippocampus is synchronized by the timing of food availability. This chronic circadian misalignment causes reduced hippocampal long term potentiation and total CREB expression. Importantly this mis-timed feeding resulted in dramatic deficits in hippocampal-dependent learning and memory. Our findings suggest that the timing of meals have far-reaching effects on hippocampal physiology and learned behaviour. 
26651090	In 2010, American youth aged 8 to 18 spent an average of 7.5 hours daily using entertainment media, an increase of more than an hour compared with 2005. Increase in media use is associated with multiple negative outcomes, including decreased sleep time and increased tiredness, but little research has examined whether media use is associated with poorer sleep efficiency when the individual is actually asleep.This study assessed relations between adolescent media use and sleep efficiency. Fifty-five adolescents (mean age = 14.89 years; SD = 0.62; 53% African-American and 47% white) completed self-report measures concerning their media use. Sleep quality was measured by actigraphy for 1 week, and both sleep offset and sleep efficiency were extracted from actigraphy data.	Sleep efficiency was negatively correlated to daily time spent text messaging (r(52) = -0.29; p < .05), media use after bed (r(52) = -0.32; p < .05), and number of nighttime awakenings by mobile phones (r(52) = -0.33; p < .05). Decreased sleep efficiency was related to sleeping later in the morning, presumably to make up for lost sleep at night (r(52) = -0.33; p < .05). In a regression model, media use accounted for 30% of the variance in sleep efficiency (adjusted R = 0.30; F(6,44) = 3.74; p < .01).	Media use after bed, awakenings by a mobile phone at night, and sleep offset associated with adolescents' sleep efficiency. Results support the incorporation of media use habits into adolescent sleep health education and sleep dysfunction interventions. Parental education about the effects of media use on sleep could also mitigate negative effects.	
26650949	Critically ill patients suffer from anxiety, stress, pain, sleep disturbance and delirium. The updated version of the German evidence and consensus based guideline "Analgesia, Sedation and Delirium management in Intensive Care - DAS 2015" contributes an improved therapeutic management and is aimed to improve clinical outcome based on the current state of evidence. The task force members were representatives from 17 national medical societies therefore have consented following guiding principle in common: "Patients in intensive care shall be awake, alert and free of pain, anxiety and delirium, to be able to participate in the healing process actively." 

26650922	The purpose of this descriptive study was to examine the associations of sleep hygiene and actigraphy measures of sleep with self-reported sleep quality in 197 pregnant women in northern Taiwan. Third-trimester pregnant women completed the Sleep Hygiene Practice Scale (SHPS) and the Pittsburgh Sleep Quality Index (PSQI) as well as the Center for Epidemiologic Studies-Depression Scale (CES-D), and wore an actigraph for 7 consecutive days. Student's t-test was used to compare the SHPS scores and means as well as variability of actigraphy sleep variables between poor sleepers (i.e., PSQI global score >5) and good sleepers (i.e., PSQI global score ≤5). Compared to good sleepers, poor sleepers reported significantly worse sleep hygiene, with higher SHPS scores and higher sleep schedule, arousal-related behavior, and sleep environment subscale scores. Poor sleepers had significantly greater intra-individual variability of sleep onset latency, total nighttime sleep, and wake after sleep onset than good sleepers. In stepwise linear regression, older maternal age (p = .01), fewer employment hours per week (p = .01), higher CES-D total score (p < .01), and higher SHPS arousal-related behavior subscale scores (p < .01) predicted self-reported global sleep quality. Findings support avoiding physically, physiologically, emotionally, or cognitively arousing activities before bedtime as a target for sleep-hygiene intervention in women during pregnancy.
26650246	The relationship between hypertension and sleep-related movement disorders has been hypothesized for humans, but the causes and mechanisms have not been elucidated. We investigated whether an alteration in blood pressure (BP) induced by physical exercise and/or an angiotensin-converting enzyme inhibitor (enalapril) could affect locomotor activity in spontaneously hypertensive rats, with emphasis on the dopaminergic system. We used SHR and normotensive Wistar rats distributed into 4 groups for each strain: control, physical exercise, enalapril and physical exercise+enalapril. Physical exercise was performed on a treadmill, and enalapril was administered by gavage, both for 8weeks. During this period, locomotor activity was evaluated in an open field test, and BP was evaluated by tail plethysmography. Dopaminergic receptors, dopamine transporter and tyrosine hydroxylase levels at the striatum were evaluated by Western blotting. The control group of spontaneously hypertensive rats showed higher BP, increased activity in the open field test and lower levels of D2 receptors and tyrosine hydroxylase compared with all other groups throughout the experimental period. In general, physical exercise and enalapril attenuated these alterations. This study suggested the existence of comorbidity between hypertension and sleep-related movement disorders in spontaneously hypertensive rats. Physical exercise and enalapril conferred protection for both hypertension and the observed behavioral changes. In addition, these treatments led to changes in dopaminergic signaling in the striatal region (i.e., D2 receptor, TH and DAT). 
26648878	Modern life, with its many distractions, is seeing sleep quantity and quality decline during adolescence. This is a concern as research persuasively demonstrates the negative impact of reduced sleep on academic achievement, both in terms of learning and behavior.This study examined the relationship between sleep and school functioning in adolescence, with a focus on environmental factors that might mediate this relationship.	Forty-seven adolescents took part. Sleep was measured using the School Sleep Habits Survey (SSHS) and a sleep diary. School records of year grade point averages provided a measure of academic achievement. Raven's Standard Progressive Matrices gave a measure of general cognitive processing. Environmental sleep factors falling into three groups, namely, stimulant consumption, media use and exercise, were measured using a self-report questionnaire.	An average of 7.08 h of sleep was reported. Correlations revealed that Total sleep time (TST) and bedtimes on weekdays were strongly associated with academic achievement. Morning/eveningness and sleep/wake behavior problems had a strong relationship with performance on the Ravens. Stimulant consumption and media use before bed revealed strong relationships with TST and bedtimes on weekdays. Crucially, mediation analyses confirmed that both caffeine consumption and electronic media use before bedtime were negatively associated with academic performance, via the mediating pathway by affecting sleep. Exercise was not associated with any of the sleep variables, but was associated with better academic performance.	The current findings highlight that, now more than ever, parents, schools and policy makers must be aware of the negative effects of caffeinated substances marketed to students, and electronic media use on their sleep habits. Our findings suggest that targeting caffeine consumption and electronic media use before bed may represent effective routes in alleviating modern teenage sleep debt, and in turn enhancing academic performance.	
26647380	Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a regulatory, effect on standard measures of sleep. Study output is limited by small sample size and because only evening melatonin profiles were assessed. 

26644317	Posttraumatic stress disorder (PTSD) is a disorder with significant sleep morbidity and limited treatment options. Prazosin may constitute a novel management approach and has been tested recently in a number of trials. We conducted a meta-analysis to examine the effectiveness of prazosin for nightmares and other sleep disturbances in adults with PTSD.A systematic review of databases for randomized, double-blind, placebo-controlled trials of adults diagnosed with PTSD and reporting sleep disturbances that were treated with prazosin was conducted in January 2015. No limitations were placed on language or year of publication.	Six randomized controlled trials of prazosin for sleep disturbances in patients with PTSD were included (sample n=240). We found that prazosin was statistically significantly more effective than placebo in improving sleep quality [g=0.987, 95% confidence interval (CI): 0.324-1.651] and in reducing overall PTSD symptoms (g=0.699, 95% CI: 0.139-1.260) and sleep disturbances in particular (g=0.799, 95% CI: 0.391-1.234).	Prazosin showed medium-to-large and statistically significant effects on PTSD symptoms in general and sleep disturbances in particular. While promising, results should be interpreted with caution given the limited total number of participants and the limitations induced by the majority of participants being male and noncivilian.	
26644155	Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders encountered in clinical practice. Whilst dementia has long been synonymous with AD, it is becoming more widely accepted as part of the clinical spectrum in PD (PDD). Neuropsychiatric complications, including psychosis, mood and anxiety disorders, and sleep disorders also frequently co-exist with cognitive dysfunctions in AD and PDD patients. The incidence of such symptoms is often a significant source of disability, and may aggravate pre-existing cognitive deficits. Management of AD and PDD involves both pharmacological and non-pharmacological measures. Although research on pharmacological therapies for AD and PDD has so far had some success in terms of developing symptomatic treatments, the benefits are often marginal and non-sustained. These shortcomings have led to the investigation of non-pharmacological and novel treatments for both AD and PD. Furthermore, in light of the diverse constellation of other neuropsychiatric, physical, and behavioural symptoms that often occur in AD and PD, consideration needs to be given to the potential side effects of pharmacological treatments where improving one symptom may lead to the worsening of another, rendering the clinical management of these patients challenging. Therefore, the present article will critically review the evidence for both pharmacological and non-pharmacological treatments for cognitive impairment in AD and PD patients. Treatment options for other concomitant neuropsychiatric and behavioural symptoms, as well as novel treatment strategies will also be discussed. 
26644120	To use wrist-actrigrphy to collect objective measures of sleep and to characterise actigraphy-measured sleep patterns among children with disabilities. We also assessed the extent to which, if at all, caregivers' education is associated with children's sleep disturbances.Cross-sectional study.	A rehabilitation centre in the Patagonia region, Chile.	This study was conducted among 125 children aged 6-12 years with disabilities (boys: 55.2%) and their primary caregivers in Chile. Children wore ActiSleep monitors for 7 days. A general linear model was fitted to generate least-square means and SEs of sleep efficiency (proportion of the sleep period spent asleep) across caregivers' education levels adjusting for children's age, sex, disability type, caregiver-child relationship and caregivers' age. Multivariable logistic regression analyses were conducted to estimate ORs and 95% CIs of longer sleep latency (≥ 30 min) and longer wake after sleep onset (WASO) (≥ 90 min) (a measure of sleep fragmentation) in relation to caregivers' educational attainment.	Median sleep latency was 27.3 min, WASO 88.1 min and sleep duration 8.0 h. Mean sleep efficiency was 80.0%. Caregivers' education was positively and significantly associated with children's sleep efficiency (p trend<0.001). Adjusted mean sleep efficiency was 75.7% (SE=1.4) among children of caregivers <high school education, and 81.9% (SE=1.0) among children of caregivers >high school education. Compared to children whose caregivers had >high school, children of caregivers with <high school had higher odds of longer sleep latency (OR=3.27; 95% CI 1.12 to 9.61) and longer WASO (OR=5.95; 95% CI 1.91 to 18.53). Associations were consistent across disability types.	Children with disabilities experience difficulties initiating sleep (prolonged sleep latency) and maintaining sleep (long WASO, low sleep efficiency). Among children with disabilities, lower level of caregivers' education is associated with more sleep disturbances.	

26641863	Recent work in unobtrusive sleep/wake classification has shown that cardiac and respiratory features can help improve classification performance. Nevertheless, actigraphy remains the single most discriminative modality for this task. Unfortunately, it requires the use of dedicated devices in addition to the sensors used to measure electrocardiogram (ECG) or respiratory effort. This paper proposes a method to estimate actigraphy from the body movement artifacts present in the ECG and respiratory inductance plethysmography (RIP) based on the time-frequency analysis of those signals. Using a continuous wavelet transform to analyze RIP, and ECG and RIP combined, it provides a surrogate measure of actigraphy with moderate correlation (for ECG+RIP, ρ = 0.74, p  <  0.001) and agreement (mean bias ratio of 0.94 and 95% agreement ratios of 0.11 and 8.45) with reference actigraphy. More important, it can be used as a replacement of actigraphy in sleep/wake classification: after cross-validation with a data set comprising polysomnographic (PSG) recordings of 15 healthy subjects and 25 insomniacs annotated by an external sleep technician, it achieves a statistically non-inferior classification performance when used together with respiratory features (average κ of 0.64 for 15 healthy subjects, and 0.50 for a dataset with 40 healthy and insomniac subjects), and when used together with respiratory and cardiac features (average κ of 0.66 for 15 healthy subjects, and 0.56 for 40 healthy and insomniac subjects). Since this method eliminates the need for a dedicated actigraphy device, it reduces the number of sensors needed for sleep/wake classification to a single sensor when using respiratory features, and to two sensors when using respiratory and cardiac features without any loss in performance. It offers a major benefit in terms of comfort for long-term home monitoring and is immediately applicable for legacy ECG and RIP monitoring devices already used in clinical practice and which do not have an accelerometer built-in.
26641104	The inter-relationship between arousal events and body and/or limb movements during sleep may significantly impact the performance and clinical interpretation of actigraphy. As such, the objective of this study was to quantify the temporal association between arousals and body/limb movement. From this, we aim to determine whether actigraphy can predict arousal events in children, and identify the impact of arousal-related movements on estimates of sleep/wake periods. Thirty otherwise healthy children (5-16 years, median 9 years, 21 male) with suspected sleep apnoea were studied using full polysomnography and customised raw tri-axial accelerometry measured at the left fingertip, left wrist, upper thorax, left ankle and left great toe. Raw data were synchronised to within 0.1 s of the polysomnogram. Movements were then identified using a custom algorithm. On average 67.5% of arousals were associated with wrist movement. Arousals associated with movement were longer than those without movement (mean duration: 12.2 s versus 7.9 s respectively, p  <  0.01); movements during wake and arousal were longer than other sleep movements (wrist duration: 6.26 s and 9.89 s versus 2.35 s respectively, p  <  0.01); and the movement index (movements/h) did not predict apnoea-hypopnoea index (ρ  =  -0.11). Movements associated with arousals are likely to unavoidably contribute to actigraphy's poor sensitivity for wake. However, as sleep-related movements tend to be shorter than those during wake or arousal, incorporating movement duration into the actigraphy scoring algorithm may improve sleep staging performance. Although actigraphy-based measurements cannot reliably predict all arousal events, actigraphy can likely identify longer events that may have the greatest impact on sleep quality. 
26636259	Workplace bullying is a potent stressor that may increase sleep problems. Since physical fitness improves resilience to stress, it seems plausible that recreational physical activities may moderate the association between bullying and sleep. The study aimed to examine prospectively whether (i) bullying increases the risk of sleep problems, and (ii) the association between bullying and sleep problems is moderated by leisure-time physical activity (LTPA).The study sample comprised a cohort of public and private sector employees, who were enrolled into the Work Bullying and Harassment (WBH) cohort (N=3278) or the Psychosocial Risk Factors for Stress and Mental Disease (PRISME) cohort (N=4455). We measured workplace bullying using one question that was preceded by a definition of bullying. We used the Karolinska sleep questionnaire to assess sleep problems. The number of hours per week spent on LTPA estimated the degree of physical activity.	Workplace bullying at baseline (T1) was associated with awakening problems and lack of restful sleep at follow-up (T2) but not with overall sleep problems and disturbed sleep. T1-LTPA did not moderate the association between T1-workplace bullying and T2-sleep problems.	We found support that workplace bullying is related to development of T2-sleep problems, but this association seems not to be modified by LTPA.	
26635329	Octogenarians with aortic stenosis are an increasing population of patients admitted for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). Although adequate sleep is important after illness and surgery, it has scarcely been studied in the immediate postoperative phase.To determine and compare the nature of self-reported sleep and insomnia, and recorded sleep-wake patterns in octogenarians during the in-hospital postoperative phase after SAVR or TAVI.	A prospective cohort design was used that included octogenarian patients undergoing SAVR or TAVI at a regional university hospital. Self-reports were used to document sleep and insomnia, and actigraphy was used to record sleep-wake patterns. Data were collected at baseline preoperatively, and then daily for the first five postoperative days.	SAVR patients experienced the most insomnia on postoperative nights later in recovery, while TAVI patients experienced the most insomnia on postoperative nights early in recovery. The median total sleep time, as measured by actigraphy, was 6.4 h, and the median sleep efficiency was 79% for the five postoperative nights, but no differences were found between SAVR and TAVI patients on this parameter. All patients slept more during daytime than at night, with SAVR patients having significantly more total sleep hours for all five days than TAVI patients (p < 0.01).	Octogenarians with aortic stenosis had disturbed self-reported sleep, increased insomnia, and disturbed sleep-wake patterns postoperatively, resulting in more daytime sleep and inactivity. In patients undergoing SAVR or TAVI, sleep evolves differently during the in-hospital postoperative phase.	
26632431	The aging process is often associated with more or less prominent shifts of the entrained phases of behavioral and physiological rhythms at earlier clock hours, but the oscillatory mechanisms underlying these shifts have to be determined. The analysis of self-reports on home sleep times and self-scorings of sleepiness provided by 130 participants of sleep deprivation experiments revealed the difference between intro-individual (age-related) and inter-individual (gender- and chronotype-related) variation in phase angle between sleep timing and timing of nocturnal rise of sleepiness. A heterochronity of age-related changes in phase characteristics of the circadian rhythms was suggested for explaining this difference. In particular, a rhythm's strength might determine the rate of age-related decline of its entrainment mechanism. In the case of a weak circadian rhythm, such as the homeostatic process underlying oscillations of slow wave activity in the sleep-wake cycle, a decline of the rhythm's strength might be already pronounced in middle aged adults. In contrast, a similar decline might occur much later in the cases of the homeostatic processes underlying stronger rhythms, such as the fluctuations of alertness-sleepiness, body temperature, melatonin secretion, etc. Moreover, the strength of a strong rhythm might become weaker earlier than that of the circadian pacemaker and, especially, earlier than decline of its ability to entrain to the light-dark cycle. Such sequence of changes in the circadian entrainment mechanisms might explain a general tendency to produce advance rather than delay shifts of entrained phases of circadian rhythms with progression of age from middle adulthood to elderly. 
26632429	In the article authors discuss the current data on sleep changes with aging focusing on the influence of age-related degenerative changes in orexin-containing and pacemaker brain areas. Pathophysiological mechanisms of sleep disturbances in Parkinson's and Alzheimer's diseases have much in common with normal age neurophysiological changes. Maintenance of the sleep-promoting systems function could positively modify the course of these diseases. 
26632428	Increased blood pressure and reduced robustness of circadian rhythms are frequently reported in elderly subjects. The present study was aimed to investigate whether such changes can be reversed by daily melatonin ingestion. 97 normotensive and hypertensive volunteers of both genders and 63 to 91 years old participated. They lived in the Tyumen Elderly Veteran House on a self-chosen sleep-wake regimen to suit their personal convenience. The experiment lasted for three weeks. After one control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen(TM)) each day at 22:30 h for two weeks. The other 34 subjects were placebo-treated. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured using semi-automated devices at 03:00, 08:00, 11:00, 14:00, 17:00, 23:00 h each day of the first and the third week. Specially trained personnel made the measurements, taking care not to disturb subjects' sleep. Rhythm characteristics were estimated by means of single and population-mean cosinor analyses. Bingham test was used to compare rhythm parameters between groups and investigated physiologic variables. The 24-h HR rhythm was monophasic as described in other studies for young subjects though with a steeper increase in the morning. The daily SBP and DBP rhythms were bimodal. In reference to previously reported data of younger subjects, mean blood pressure of our cohort was elevated, particularly the nocturnal fall was less pronounced. Also, the overall SBP variability was higher as was the percentage of the 12-h component. Both values and also the SBP and DBP levels were reduced during melatonin treatment. The hypotensive effect of melatonin was most pronounced between 3:00 and 8:00 in the morning, i.e. at the time of the highest risk of adverse cardiovascular events, and in subjects with highest BP values before treatment. Moreover, the morning increase of HR was gentler what could have been of additional benefit. Melatonin has a direct hypotensive effect. Also, it stabilizes the internal temporal order enhancing the circadian component and the synchronization between rhythms of different physiological functions. This may further improve health and welfare of elderly subjects and particularly of those with hypertension. Taken together our data show the usefulness of melatonin for adjuvant medication.
26631234	The debilitating nature of migraine and challenges associated with treatment-refractory migraine have a profound impact on patients. With the need for alternatives to pharmacologic agents, vagus nerve stimulation has demonstrated efficacy in treatment-refractory primary headache disorders. We investigated the use of cervical non-invasive vagus nerve stimulation (nVNS) for the acute treatment and prevention of migraine attacks in treatment-refractory episodic and chronic migraine (EM and CM) and evaluated the impact of nVNS on migraine-associated sleep disturbance, disability, and depressive symptoms.Twenty patients with treatment-refractory migraine were enrolled in this 3-month, open-label, prospective observational study. Patients administered nVNS prophylactically twice daily at prespecified times and acutely as adjunctive therapy for migraine attacks. Pain intensity (visual analogue scale [VAS]); number of headache days per month and number of migraine attacks per month; number of acutely treated attacks and time to achieve pain relief; sleep quality (Pittsburgh Sleep Quality Index [PSQI]); migraine disability assessment (MIDAS); depressive symptoms (Beck Depression Inventory(®) [BDI]); and adverse events (AEs) were evaluated.	Of the 20 enrolled patients, 10 patients each had been diagnosed with EM and CM. Prophylaxis with nVNS was associated with significant overall reductions in patient-perceived pain intensity (mean VAS scores at baseline vs 3 months: 7.75 ± 0.64 vs 4.05 ± 0.76; 95 % CI: 3.3, 4.1; p < 0.0001), mean number of headache days per month (baseline vs 3 months: 14.7 ± 4.1 vs 8.9 ± 3.66; 95 % CI: 3.3, 8.3; p < 0.0001), and mean number of migraine attacks per month (baseline vs 3 months: 7.3 ± 3.85 vs 4.45 ± 2.48; 95 % CI: 0.8, 4.9; p < 0.01). For acutely treated migraine attacks, a reduction in mean time (minutes) to achieve pain relief (baseline vs 3 months: 84.5 ± 39.1 vs 52.75 ± 16.42; 95 % CI: 12.6, 51.0; p < 0.002) was noted. Significant improvements, more evident in patients with EM, were noted in MIDAS and BDI scores along with a trend toward improvement in PSQI daytime dysfunction subscore (p = 0.07). No severe or serious AEs occurred.	In this study, treatment with nVNS was safe and provided clinically meaningful decreases in the frequency, intensity, and duration of migraine attacks in patients with treatment-refractory migraine. Improvements in migraine-associated disability, depression, and sleep quality were also noted.	
26630494	The purpose of this study is to clarify the effects of chronic powder diet feeding on sleep patterns and other physiological/anatomical changes in mice. C57BL/6 male mice were divided into two groups from weaning: a group fed with solid food (SD) and a group fed with powder food (PD), and sleep and physiological and anatomical changes were compared between the groups. PD exhibited less cranial bone structure development and a significant weight gain. Furthermore, these PD mice showed reduced number of neurogenesis in the hippocampus. Sleep analysis showed that PD induced attenuated diurnal sleep/wake rhythm, characterized by increased sleep during active period and decreased sleep during rest period. With food deprivation (FD), PD showed less enhancement of wake/locomotor activity compared to SD, indicating reduced food-seeking behavior during FD. These results suggest that powder feeding in mice results in a cluster of detrimental symptoms caused by abnormal energy metabolism and anatomical/neurological changes. 
26629892	This study compares sleep disturbances in Thai children aged 5-12 years with attention-deficit hyperactivity disorder (ADHD) and typically developing children using the Children's Sleep Habits Questionnaire (CSHQ)-Thai version. Fifty-five children with ADHD and 110 typically developing children were enrolled. Their parents completed the CSHQ, the ADHD rating scales, and the Strengths and Difficulties Questionnaire (SDQ). Children with ADHD had significantly higher scores in all subscales of the CSHQ compared to controls. Among children with ADHD, children with higher SDQ scores (> 15) appeared to have more sleep disturbances than those with relatively lower SDQ scores. Moreover, fewer sleep-related behavioral problems were observed in the medication treated group, which is particularly new to the field and for some perhaps not unexpected clinically. 
26629755	The term encephalopathy encompasses a wide variety of complex syndromes caused by a large number of different toxic, metabolic, infectious, and degenerative derangements. Acute encephalopathy typically presents with a fluctuating course involving alteration of mental status or confusion and decreased (or rarely increased) motor activity. There usually are lethargy, cognitive impairment, altered memory and mental processing of information, and disturbed sleep-wake cycles. Encephalopathy mainly occurs in the elderly and is frequently encountered in intensive care units and postoperatively. Despite new diagnostic procedures and advances in intensive medical care, acute encephalopathy constitutes a significant cause of morbidity and mortality in hospitalized patients. EEG enables rapid bedside electrophysiological monitoring providing dynamic real-time information on neocortical brain activity and dysfunction. Hence, EEG complements clinical and neuroimaging assessments of encephalopathic patients. Progressive slowing of EEG background activity with increasing cerebral compromise, the emergence of episodic electrographic transients, seizures, and decreased EEG reactivity to external stimuli provide important diagnostic and prognostic information. The aim of this review was to provide a comprehensive overview of the current evidence for the diagnostic and prognostic value of EEG in adult intensive care unit patients with acute nonhypoxic encephalopathy. 

26627637	Sleep duration holds considerable importance as an indicator of mental/physical health. The objective of this study was to investigate the association between sleep duration, mental health, and chronic disease prevalence in Koreans.Of 31,596 subjects eligible for the Korean National Health and Nutrition Examination Survey V (2010-2012), 17,638 participants who answered items on sleep duration (aged ≥ 19 yrs) were analyzed in a cross-sectional study. Association between sleep duration, mental health, and chronic disease prevalence was assessed using logistic regression, and adjusted for various socioeconomic and lifestyle characteristics.	Short or long sleep duration showed correlations with mental health, and items of significance showed gender-specific patterns. Women displayed significant associations with stress and depressive symptoms, and men with stress, thoughts of suicide, and psychiatric counseling. While stress was related with short sleep duration in both genders, depressive symptoms showed a relationship with long duration in men, and short duration in women. Prevalence of any chronic disease was associated with ≤ 6 h sleep when adjusted for factors including mental health, and among chronic diseases, cancer and osteoarthritis showed associations with short sleep duration, while diabetes and dyslipidemia were associated with normal sleep duration.	Mental health problems were associated with sleep duration with gender-specific patterns. Associations with osteoarthritis, cancer, diabetes, dyslipidemia and abnormal sleep duration persisted after adjustment for mental health.	
26619899	Sleep disturbance is common in children with autism, resulting in a great need for effective treatments. To evaluate treatments for sleep disturbance in this population, it is critical to understand the relationship between measures of sleep captured by parent report and objective measures. The Children's Sleep Habits Questionnaire (CSHQ) and actigraphy-measured data from 80 children with autism and sleep-onset delay were evaluated. Reported problems with sleep-onset delay were concurrent with sleep duration problems in 66% of children, night wakings in 72% of children, and bedtime resistance in 66% of children; 38% of children were reported to have problems with all CSHQ insomnia domains. Actigraphy-measured sleep duration was correlated with estimates using CSHQ-reported bed and wake times. 
26619760	This article documents the longitudinal and reciprocal relations among behavioral sleep problems and emotional and attentional self-regulation in a population sample of 4,109 children participating in Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC)-Infant Cohort. Maternal reports of children's sleep problems and self-regulation were collected at five time-points from infancy to 8-9 years of age. Longitudinal structural equation modeling supported a developmental cascade model in which sleep problems have a persistent negative effect on emotional regulation, which in turn contributes to ongoing sleep problems and poorer attentional regulation in children over time. Findings suggest that sleep behaviors are a key target for interventions that aim to improve children's self-regulatory capacities.
26618404	The diagnosis of Disorders of Consciousness (DOC) is still challenging. Indeed, ~ 40% of patients in vegetative state (VS) are misdiagnosed, suggesting the need of more appropriate diagnostic tools. Emerging data are showing that EEG, including sleep structure evaluation and multimodal evoked potential recording could be helpful in DOC diagnosis. Moreover, pain perception evaluation could further increase diagnosis accuracy in such individuals.Fourteen individuals with DOC, due to severe brain injury, were enrolled and admitted to the Intensive Neurorehabilitation Unit of the Research Institute. All patients were evaluated by means of the Coma Recovery Scale-Revised, a 24(hh)-polysomnography and a Laser Evoked Potential (LEP) paradigm.	Clinically-defined patients in Minimally Consciousness State showed a more preserved sleep structure, physiologic hypnic figures and preserved REM/NREM sleep distribution than subjects in VS. LEP showed increased latencies and reduced amplitudes and were also detectable in patients with more structured sleep.	The data support previous findings concerning the importance of sleep study in DOC diagnosis, with more specific neurophysiological paradigms. Interestingly, the findings shed some light on the possible correlations among global brain connectivity, sleep structure and pain perception, which are related to the activity of the wide thalamo-cortical and cortico-cortical networks underlying consciousness.	
26618213	To examine the prevalence of poor sleep quality in adults with pediatric-onset spinal cord injury (SCI) and to assess the clinical correlates.Participants completed interviews that included demographic information and standardized measures of sleep (Pittsburgh Sleep Quality Index), physical (12-item Short-Form Health Survey, Version 2), mental (Beck Anxiety Inventory and Patient Health Questionnaire), and psychosocial well-being (Satisfaction With Life Scale). The study included 177 individuals between the ages of 19 and 50 years (M = 33.5 years, SD = 7.1) who sustained a, SCI prior to age 19 (M = 13.5 years, SD = 4.6) and had been injured for at least 1 year (M = 19.5 years, SD = 8. 2). Participants were recruited from 1 of 3 pediatric SCI programs in the United States and were predominantly male (62%) and White (84%).	Sleep difficulties were fairly common, with half of participants self-reporting poor sleep quality within the last month (n = 91 [51.4%]). Both increased age (r = .20, p = .008) and tetraplegia, F(1, 175) = 6.62, p = .011, were significantly associated with poor sleep. Activity-interfering pain (r = .57, p < .001) and general health (r = .37, p < .001) were also strongly associated with poor sleep. Even after accounting for age, injury level, and pain as control variables, sleep quality explained a small, but significant, portion of the variance in depression (R2 = .06, p < .001) and anxiety (R2 = .04, p = .005), but not life satisfaction (R2 = .02, p = .075).	These results suggest that adults with pediatric-onset SCI report more sleep difficulties than the standardization sample and that sleep is significantly associated with physical and psychological functioning. Consequently, better measures to detect and treat sleep problems among those with pediatric-onset SCI are recommended.	
26617071	Accumulating evidence indicates direct relationships between sleep abnormalities and the severity and prevalence of other symptom clusters in schizophrenia. Assessment of potential state-dependent alterations in sleep architecture and arousal relative to antipsychotic-like activity is critical for the development of novel antipsychotic drugs (APDs). Recently, we reported that VU0467154, a selective positive allosteric modulator (PAM) of the M4 muscarinic acetylcholine receptor (mAChR), exhibits robust APD-like and cognitive enhancing activity in rodents. However, the state-dependent effects of VU0467154 on sleep architecture and arousal have not been examined. Using polysomnography and quantitative electroencephalographic recordings from subcranial electrodes in rats, we evaluated the effects of VU0467154, in comparison with the atypical APD clozapine and the M1/M4-preferring mAChR agonist xanomeline. VU0467154 induced state-dependent alterations in sleep architecture and arousal including delayed Rapid Eye Movement (REM) sleep onset, increased cumulative duration of total and Non-Rapid Eye Movement (NREM) sleep, and increased arousal during waking periods. Clozapine decreased arousal during wake, increased cumulative NREM, and decreased REM sleep. In contrast, xanomeline increased time awake and arousal during wake, but reduced slow wave activity during NREM sleep. Additionally, in combination with the N-methyl-d-aspartate subtype of glutamate receptor (NMDAR) antagonist MK-801, modeling NMDAR hypofunction thought to underlie many symptoms in schizophrenia, both VU0467154 and clozapine attenuated MK-801-induced elevations in high frequency gamma power consistent with an APD-like mechanism of action. These findings suggest that selective M4 PAMs may represent a novel mechanism for treating multiple symptoms of schizophrenia, including disruptions in sleep architecture without a sedative profile. 
26617050	Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators. 
26615549	Multimorbidity research typically focuses on chronic and common diseases in patient and/or older populations. We propose a multidimensional multimorbidity score (MDMS) which incorporates chronic conditions, symptoms, and health behaviors for use in younger, presumably healthier, working populations.Cross-sectional study of 372,370 Spanish workers who underwent a standardized medical evaluation in 2006. We computed a MDMS (range 0-100) based on the sex-specific results of a multicorrespondence analysis (MCA). We then used Cox regression models to assess the predictive validity of this MDMS on incident sickness absence (SA) episodes.	Two dimensions in the MCA explained about 80% of the variability in both sexes: (1) chronic cardiovascular conditions and health behaviors, and (2) pain symptoms, in addition to sleep disturbances in women. More men than women had at least one condition (40 vs 15%) and two or more (i.e., multimorbidity) (12 vs 2%). The MDMS among those with multimorbidity ranged from 16.8 (SD 2.4) to 51.7 (SD 9.9) in men and 18.5 (SD 5.8) to 43.8 (SD 7.8) in women. We found that the greater the number of health conditions, the higher the risk of SA. A higher MDMS was also a risk factor for incident SA, even after adjusting for prior SA and other covariates. In women, this trend was less evident.	A score incorporating chronic health conditions, behaviors, and symptoms provides a more holistic approach to multimorbidity and may be useful for defining health status in working populations and for predicting key occupational outcomes.	

26613995	Traumatic brain injury (TBI) is a complex neurologic and neuropathologic process that may affect the patient's behavior permanently. Clinically, TBI is associated with a wide gamut of neurologic and psychiatric disorders, such as amnesia, cognitive decline, seizures, attention and concentration deficits, depression, manic behavior, psychosis, hostile and violent behavior, and personality alterations. Therapy and rehabilitative efforts should be designed based on the type of injury and the patient's specific needs. Gaining familiarity with the behavioral disorders outlined in this article and understanding how to identify and treat them plays a significant role in the management of patients with TBI. 
26612513	Poor sleep quality and short sleep duration have been associated with elevated risk for several cancer types; however, the relationship between sleep and cancer outcomes has not been well characterized. We assessed the association between pre-diagnostic sleep attributes and subsequent cancer survival within the Women's Health Initiative (WHI).We identified WHI participants in whom a first primary invasive cancer had been diagnosed during follow-up (n = 21,230). Participants provided information on sleep characteristics at enrollment. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between these pre-diagnostic sleep characteristics and cancer-specific survival for all cancers combined and separately for common cancers. Analyses were adjusted for age, study arm, cancer site, marital status, income, smoking, physical activity, and time to diagnosis.	No individual pre-diagnostic sleep characteristics were found to be significantly associated with cancer survival in analyses of all cancer sites combined; however, women who reported short sleep duration (≤ 6 h sleep/night) combined with frequent snoring (≥ 5 nights/w experienced significantly poorer cancer-specific survival than those who reported 7-8 h of sleep/night and no snoring (HR = 1.32, 95% CI: 1.14-1.54). Short sleep duration (HR = 1.46, 95% CI: 1.07-1.99) and frequent snoring (HR = 1.34, 95% CI: 0.98-1.85) were each associated with poorer breast cancer survival; those reporting short sleep combined with frequent snoring combined had substantially poorer breast cancer survival than those reporting neither (HR = 2.14, 95% CI: 1.47-3.13).	Short sleep duration combined with frequent snoring reported prior to cancer diagnosis may influence subsequent cancer survival, particularly breast cancer survival.	
26611950	Manifestations of narcolepsy with cataplexy (NC) include disturbed nocturnal sleep - hereunder sleep-wake instability, decreased latency to rapid eye movement (REM) sleep, and dissociated REM sleep events. In this study, we characterized the electroencephalography (EEG) of various sleep stages in NC versus controls.EEG power spectral density (PSD) was computed in 136 NC patients and 510 sex- and age-matched controls. Features reflecting differences in PSD curves were computed. A Lasso-regularized regression model was used to find an optimal feature subset, which was validated on 19 NC patients and 708 non-NC patients from a sleep clinic. Reproducible features were analyzed using receiver operating characteristic (ROC) curves.	Thirteen features were selected based on the training dataset. Three were applicable in the validation dataset, indicating that NC patients show (1) increased alpha power in REM sleep, (2) decreased sigma power in wakefulness, and (3) decreased delta power in stage N1 versus wakefulness. Sensitivity of these features ranged from 4% to 10% with specificity around 98%, and it did not vary substantially with and without treatment.	EEG spectral analysis of REM sleep, wake, and differences between N1 and wakefulness contain diagnostic features of NC. These traits may represent sleepiness and dissociated REM sleep in patients with NC. However, the features are not sufficient for differentiating NC from controls, and further analysis is needed to completely evaluate the diagnostic potential of these features.	
26611944	The aim of this study was to investigate the association between short sleep duration and cardiovascular disease (CVD) risk factors including hypertension, diabetes, obesity and lipid profile among various ethnic groups (South Asian Surinamese, African Surinamese, Ghanaians, Turks, Moroccans and the Dutch) living in the Netherlands. The contribution of social economic status (SES) and lifestyle factors were also examined to this association.A total of 12,805 participants (aged 18-70 years) from the multi-ethnic Healthy Life in an Urban Setting (HELIUS) cohort. Short sleep duration was defined as <7 h/night. The association between short sleep and CVD risk factors, along with the contribution of SES and lifestyle factors, was assessed using prevalence ratios (PRs).	Short sleep was significantly associated with obesity in four out of six ethnic groups, with the socio-demographic-adjusted PR of 1.45 (95% CI, 1.07-1.95) in the Dutch, 1.21 (1.01-1.44) in South Asian Surinamese, 1.25 (1.09-1.43) in African Surinamese and 1.16 (1.04-1.29) in Turks. Short sleep was significantly associated with diabetes in African Surinamese (1.45, 1.14-1.84), Turks (1.59, 1.26-2.02) and Moroccans (1.29, 1.02-1.63). By contrast, the associations between other cardiovascular risk factors and short sleep were not significant in most ethnic groups, with the exception of the association with hypertension in the Dutch and Turks, and dyslipidaemia in South Asian Surinamese (reduced high-density lipoprotein cholesterol and triglyceride) and Moroccans (raised total cholesterol). SES and lifestyle factors contributed little to the observed associations.	The findings indicate that short sleep is associated with obesity and diabetes in most ethnic groups. The associations for other risk factors vary between ethnic groups. Further studies are warranted to establish the potential factors that might lead to the observed differences across populations.	
26611942	Postural orthostatic tachycardia syndrome (PoTS) has been frequently associated with sleep disturbances but objective sleep data are lacking. In addition, although regional autonomic denervation has been described, less is known about autonomic nervous activity overnight in these patients.A full polysomnography and heart rate variability were performed on 37 patients diagnosed with PoTS . In addition, a multiple sleep latency test (MSLT) was conducted on a subgroup of patients with excessive daytime sleepiness.	The polysomnographic data did not show major pathological findings except the percentage spent in rapid eye movement (REM) sleep which was slightly reduced at 18.4%. The MSLT did not confirm excessive daytime sleepiness as median mean sleep latency was 14.4 min (11.8-17.5). When comparing patients with and without subjective daytime sleepiness, it was found that the latter had a reduced parasympathetic activation at night as expressed by the average high frequency [6936.5 ms(2) (6028.2-8675.5) vs. 4689.5 (3922.7-7685.2) p < 0.05].	Patients with PoTS do not exhibit polysomnographic findings consistent with relevant sleep pathologies nor objective daytime sleepiness. Subjective daytime sleepiness is associated with enhanced activation of the parasympathetic nervous system.	
26611643	The National Health Interview Survey (NHIS) was used to ascertain whether increases in inadequate sleep differentially affected black and white Americans. We tested the hypothesis that prevalence estimates of inadequate sleep were consistently greater among blacks, and that temporal changes have affected these two strata differentially.NHIS is an ongoing cross-sectional study of non-institutionalized US adults (≥18 years) providing socio-demographic, health risk, and medical factors. Sleep duration was coded as very short sleep [VSS] (<5 h), short sleep [SS] (5-6 h), or long sleep [LS] (>8 h), referenced to 7-8 h sleepers. Analyses adjusted for NHIS' complex sampling design using SAS-callable SUDAAN.	Among whites, the prevalence of VSS increased by 53% (1.5% to 2.3%) from 1977 to 2009 and the prevalence of SS increased by 32% (19.3% to 25.4 %); prevalence of LS decreased by 30% (11.2% to 7.8%). Among blacks, the prevalence of VSS increased by 21% (3.3% to 4.0%) and the prevalence of SS increased by 37% (24.6 % to 33.7%); prevalence of LS decreased by 42% (16.1% to 9.4%). Adjusted multinomial regression analysis showed that odds of reporting inadequate sleep for whites were: VSS (OR = 1.40, 95% CI = 1.13-1.74, p < 0.001), SS (OR = 1.34, 95 % CI = 1.25-1.44, p < 0.001), and LS (OR = 0.94, 95% CI = 0.85-1.05, NS). For blacks, estimates were: VSS (OR = 0.83, 95% CI = 0.60-1.40, NS), SS (OR = 1.21, 95% CI = 1.05-1.50, p < 0.001), and LS (OR = 0.84, 95% CI = 0.64-1.08, NS).	Blacks and whites are characteristically different regarding the prevalence of inadequate sleep over the years. Temporal changes in estimates of inadequate sleep seem dependent upon individuals' race/ethnicity.	
26608441	The aim of this study was to evaluate the effectiveness of improving sleep quality interventions in menopausal women with sleep disturbance.Sleep disturbances are an extensive and common problem among menopausal women. There is an increased trend in the use of non-pharmacological methods to alleviate sleep disturbances. Studies that have implemented two or more non-pharmacological strategies for menopausal women are scant.	A repeat measurement with a randomized assignment was conducted. A total of 59 menopausal women with sleep disturbance were recruited and randomly assigned to experimental (n = 29) and control (n = 30) groups. Participants in the experimental group received four 2-hour improving sleep quality activities, whereas the control group received regular greeting calls. Sleep quality was measured prior to intervention, and on the 5th and 8th weeks by using the Pittsburg's Sleep Quality Index, and Actiwatch was worn before and during the 8 weeks of intervention. Generalized estimating equation was used to analyze data.	The results revealed that subjective sleep quality had significant main effect in group and time. The findings of the objective measurement showed that participants in the experimental group had significantly shorter frequency of awakening time and increased sleep efficiency.	The improving sleep quality intervention is a healthy and cost-effective method to improve sleep quality in community-dwelling menopausal women with sleep disturbance.	
26608435	The negative effects of impaired sleep on physical and mental well-being in older adults have recently been recognized by health care professionals. However, researchers and clinicians may be unaware of reliable and valid screening and evaluation tools for evaluating sleep disorders in older adults. The purpose of this article is to present subjective and objective instruments that measure sleep quality, excessive daytime sleepiness, obstructive sleep apnea, insomnia and restless leg syndrome that are appropriate for use in adult and older adult patients. 
26608255	This study examines the hypothesis that absence epilepsy is accompanied by disturbances of rhythmic activity in EEG during sleep. Sleep-wake architecture and time-frequency parameters of EEG were analyzed during drowsiness and sleep in WAG/Rij rats with genetic predisposition to absence epilepsy. The incidence of seizures varied in a group of 10 rats, in which 5 individuals did not develop epileptic discharges in their EEG (asymptomatic rats). In contrast to asymptomatic, symptomatic subjects (1) displayed less percentage of wakefulness EEG pattern and more non-REM sleep, (2) showed higher beta and less delta EEG power in frontal cortex during non-REM sleep. Mid-frequency oscillations, such as sleep spindles and 5-9 Hz oscillations, were detected in EEG automatically and underwent time-frequency analysis by means of skeletons of wavelet surfaces. Some mid-frequency oscillations showed "complex" frequency structure, consisting of the dominant and subdominant components. "Complex" sleep spindles more frequently appeared in asymptomatic rats than in symptomatic, whereas the dominant frequency of these spindles in symptomatic rats was higher than in asymptomatic (12.7 vs 11.9 Hz). In general, low-frequency components were readily integrated in sleep spindles in asymptomatic WAG/Rij rats, and decrease in number of "complex" sleep spindles may be associated with epileptic phenotype.
26607869	Multiple tender points are common in the population and, in studies of mid-life adults, are strongly associated with high levels of psychological distress. Whether this relationship occurs in older adults is unclear. This cross-sectional study investigated whether high levels of psychological distress would be associated with a high tender point count and whether the relationship would be moderated by age. Three thousand three hundred and seventy-nine individuals were mailed a questionnaire which included the Hospital Anxiety and Depression (HAD) scale, the Pain Catastrophising Scale (PCS), the Brief Illness Perception Questionnaire (Brief IPQ), and the Pittsburgh Sleep Quality Index (PSQI). A random sample of approximately 10% of subjects who returned the questionnaire undertook a physical assessment, including a manual tender point count assessment. A total of 2385 (71%) subjects completed the questionnaire, of whom 798 (33%) were invited to take part in the physical assessment and 290 (12%) participated. Of the 290 participants the median age was 64 years (range 34-97) and 63% were female. The median HAD score was 9 (IQR 5-14) and the median number of tender points was 3 (range 0-7). Increasing HAD score was positively and significantly associated with tender point count, but this relationship was not moderated by age. In a final multivariable model, sex, HAD score and PSQI score were independent predictors of multiple tender points. Psychological distress was associated with multiple tender points independent of age. Psychological distress and trouble sleeping were important, potentially modifiable factors associated with the outcome. 
26604145	Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. 
26603409	This review looked at the effect of cataract surgery on the regulation of circadian rhythms and compared the effect of blue light-filtering and clear intraocular lenses (IOLs) on circadian rhythms. A systematic review and metaanalysis were performed, and the level of evidence was evaluated based on the principles described in the Grading of Recommendations Assessment, Development, and Evaluation system. A literature search of PubMed, Embase, and Cochrane Library databases was performed, as well as a search for unpublished trials at the U.S. National Institutes of Health Clinical Trials web site. Trials that reported the effect of cataract surgery on circadian rhythms were included. Outcomes were the Pittsburgh Sleep Quality Index (PSQI) global score, number of poor sleepers, Epworth Sleepiness Score, sleep efficiency, and mean concentration of melatonin. Cataract surgery improved regulation of circadian rhythms measured by the PSQI questionnaire, but the clinical relevance is uncertain. There was no difference between the effect of the 2 IOL types.No author has a financial or proprietary interest in any material or method mentioned.	

26600201	We are witnessing the growth of urban populations, particularly in the developing world. São Paulo, the largest city in South America, continues to grow, and this growth is dramatically effecting the environment and human health. The aim of this study was to estimate the point prevalence of chronic pain in São Paulo city dwellers and to explore the influence of aspects related to urbanicity.A two-stage cluster randomized sample included 1100 individuals of the city of Sao Paulo, representing the population proportionally in terms of gender, age and social classes in 2007. For this observational cross-sectional study, the household sample was interviewed using validated questionnaires for sociodemographic aspects, the Beck inventories for anxiety and depression, the WHOQoL-REF for quality of life, the Chalder Fatigue Scale. Musculoskeletal pain was defined as diffuse pain or pain located in the back, joints or limbs. Data regarding sleep complaints and polysomnography were obtained from the Epidemiologic Sleep Study conducted in São Paulo city in 2007.	The prevalence estimate of chronic musculoskeletal pain was approximately 27%, with a female/male ratio of approximately 2.6/1. The predictors were being in the age-range of 30-39 years, low socioeconomic and schooling levels, obesity, sedentarism, fatigue, non-restorative sleep, daytime sleepiness, poor sleep quality, poor life quality, anxiety and depression symptoms. Psychological wellbeing was the main discriminator between responders with chronic musculoskeletal pain and the controls, followed by depression for the participants with poor psychological wellbeing, and fatigue, for the remaining ones. Insomnia syndrome was the third-level discriminator for those with fatigue, whereas sleep quality for those without fatigue.	Musculoskeletal pain was frequently reported by São Paulo city dwellers and its correlates with psychological and sleep aspects are suggestive of a response to urbanicity.	

26600111	Sleep-wake cycle disturbances are prevalent in patients with medical conditions and frequently present as part of a symptom cluster. Sleep disturbances impair functioning and quality of life, decrease adherence to treatments of the primary medical condition, and increase morbidity and mortality. The pathophysiology of sleep disturbances in these patients involves alterations in immune and neuroendocrine function and shares common pathophysiologic pathways with comorbidities such as fatigue and depression. Emphasis is placed on the evaluation and management of medical and psychiatric comorbidities and other factors contributing to sleep problems. Primary treatments include cognitive-behavioral therapy and pharmacotherapy. 
26600110	The circadian system regulates the timing and expression of nearly all biological processes, most notably, the sleep-wake cycle, and disruption of this system can result in adverse effects on both physical and mental health. The circadian rhythm sleep-wake disorders (CRSWDs) consist of 5 disorders that are due primarily to pathology of the circadian clock or to a misalignment of the timing of the endogenous circadian rhythm with the environment. This article outlines the nature of these disorders, the association of many of these disorders with psychiatric illness, and available treatment options. 
26600109	This article discusses the role sleep and alertness disturbance plays in the initiation, maintenance and relapse of substance use disorders. 
26600108	Sleep disturbances are prevalent in patients with schizophrenia and play a critical role in the morbidity and mortality associated with the illness. Subjective and objective assessments of sleep in patients with schizophrenia have identified certain consistent findings. Findings related to the sleep structure abnormalities have shown correlations with important clinical aspects of the illness. Disruption of specific neurotransmitter systems and dysregulation of clock genes may play a role in the pathophysiology of schizophrenia-related sleep disturbances. Antipsychotic medications play an important role in the treatment of sleep disturbances in these patients and have an impact on their sleep structure. 
26600107	Sleep disturbance is frequently associated with generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. This article reviews recent advances in understanding the mechanisms of the sleep disturbances in these disorders and discusses the implications for developing improved treatments. 
26600106	The article provides an overview of common and differentiating self-reported and objective sleep disturbances seen in mood-disordered populations. The importance of considering sleep disturbances in the context of mood disorders is emphasized, because a large body of evidence supports the notion that sleep disturbances are a risk factor for onset, exacerbation, and relapse of mood disorders. In addition, potential mechanisms for sleep disturbance in depression, other primary sleep disorders that often occur with mood disorders, effects of antidepressant and mood-stabilizing drugs on sleep, and the adjunctive effect of treating sleep in patients with mood disorders are discussed. 
26600105	Sleep disturbances are a common presenting symptom of older-age adults to their physicians. This article explores normal changes in sleep pattern with aging and primary sleep disorders in the elderly. Behavioral factors and primary psychiatric disorders affecting sleep in this population are reviewed. Further discussion examines sleep changes associated with 2 common forms of neurocognitive disorder: Alzheimer disease and Lewy Body Dementia. Common medical illnesses in the elderly are discussed in relation to sleep symptoms. Nonpharmacological and pharmacologic treatment strategies are summarized, with emphasis placed on risk of side effects in older adults. Future targets are considered. 
26600104	Sleep deprivation and sleep disorders are commonly seen in children and adolescents. They are often undiagnosed and undertreated. A balance of circadian rhythm and homeostatic drive determine sleep quality, quantity, and timing, which changes across the developmental years. Environmental and lifestyle factors can affect sleep quality and quantity and lead to sleep deprivation. A comprehensive assessment of sleep disorders includes parental report, children's self-report, and school functioning. Diagnostic tools are used in diagnosing and treating sleep disorders. 
26600100	Cortical electroencephalographic activity arises from corticothalamocortical interactions, modulated by wake-promoting monoaminergic and cholinergic input. These wake-promoting systems are regulated by hypothalamic hypocretin/orexins, while GABAergic sleep-promoting nuclei are found in the preoptic area, brainstem and lateral hypothalamus. Although pontine acetylcholine is critical for REM sleep, hypothalamic melanin-concentrating hormone/GABAergic cells may "gate" REM sleep. Daily sleep-wake rhythms arise from interactions between a hypothalamic circadian pacemaker and a sleep homeostat whose anatomical locus has yet to be conclusively defined. Control of sleep and wakefulness involves multiple systems, each of which presents vulnerability to sleep/wake dysfunction that may predispose to physical and/or neuropsychiatric disorders. 
26600099	Changes in the psychiatric diagnostic guidelines with the transition from Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV to DSM-V include acknowledgment that primary sleep disorders such as insomnia can occur in conjunction with medical and psychiatric disorders. This change in viewpoint regarding the definition of primary sleep disorders opens the way to the recognition that patients with psychiatric disorders demonstrate a high prevalence of sleep disturbances, with complaints of insomnia and excessive daytime sleepiness being especially commonly reported. Recent investigations have pointed to a bidirectional relationship between sleep disturbances and psychiatric disorders. 
26597416	The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; P<0.001]. Even after adjusting for the comorbidities, the risk of epilepsy in the Tourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; P<0.001), indicating that the increased risk was not associated with comorbidities. This population-based retrospective cohort study provides the first and strong evidence that Tourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted.
26597124	The fact that the pedunculopontine nucleus (PPN) is part of the reticular activating system places it in a unique position to modulate sensory input and fight-or-flight responses. Arousing stimuli simultaneously activate ascending projections of the PPN to the intralaminar thalamus to trigger cortical high-frequency activity and arousal, as well as descending projections to reticulospinal systems to alter posture and locomotion. As such, the PPN has become a target for deep brain stimulation for the treatment of Parkinson's disease, modulating gait, posture, and higher functions. This article describes the latest discoveries on PPN physiology and the role of the PPN in a number of disorders. It has now been determined that high-frequency activity during waking and REM sleep is controlled by two different intracellular pathways and two calcium channels in PPN cells. Moreover, there are three different PPN cell types that have one or both calcium channels and may be active during waking only, REM sleep only, or both. Based on the new discoveries, novel mechanisms are proposed for insomnia as a waking disorder. In addition, neuronal calcium sensor protein-1 (NCS-1), which is over expressed in schizophrenia and bipolar disorder, may be responsible for the dysregulation in gamma band activity in at least some patients with these diseases. Recent results suggest that NCS-1 modulates PPN gamma band activity and that lithium acts to reduce the effects of over expressed NCS-1, accounting for its effectiveness in bipolar disorder. 
26594740	Sensory over-responsivity (SOR) is a type of sensory modulation disorder in which heightened sensitivity to non-noxious sensations interrupts daily life. In this preliminary study within a larger investigation, we used infants with sleep/feeding difficulties as a proxy for later development of SOR. We tested evidence for construct validity and internal reliability of preand perinatal factors that, together, could predict infant sleep/feeding difficulties. We obtained retrospective data on 360 mother-infant dyads on 38 pre- and perinatal variables and linked the data with infant referral for sleep/feeding difficulties. We analyzed the data with Rasch analysis to examine evidence for a unidimensional construct. Our results show good evidence for a construct comprising 18 of the 38 pre- and perinatal variables examined. This construct may represent a step toward early identification of SOR and provide therapists with evidence to support the use of pre- and perinatal information as predictors of infant sleep/feeding difficulties.
26593889	Bruxism is a rhythmic masticatory muscle activity, characterized by teeth grinding and clenching. This is a phenomenon mainly regulated by the central nervous system and peripherally influenced. It has two circadian manifestations, during sleep (sleep bruxism) and awake states (awake bruxism). Bruxism is much more than just tooth wearing. It is currently linked to orofacial pain; headaches; sleep disorders; sleep breathing disorders, such as apnea and hypopnea sleep syndrome; behavior disorders, or those associated with the use of medications. It is also influenced by psycho-social and behavior factors, which means that oromandibular parafunctional activities, temporomandibular disorders, malocclusion, high levels of anxiety and stress, among others, may precipitate the occurrence of bruxism. Nowadays, its etiology is multifactorial. The dentist and the pediatrician are responsible for its early detection, diagnosis, management, and prevention of its possible consequences on the patients. The aim of this review is to update the concepts of this disease and to make health professionals aware of its early detection and its timely management. 
26593639	The safety of autologous bone marrow mononuclear cells (ABMNC) intraspinal infusion in amyotrophic lateral sclerosis (ALS) patients was evaluated considering breathing and sleep patterns. Patients between 20 and 65 years old were eligible if they had definite ALS, spinal onset, a disease duration between 6 and 36 months, FVC>50%, and a below 90% oxygen saturation (T90) <2% of sleep time. The transplant was performed 6 months after enrollment. ABMNC were infused at thoracic 3-4 level. Eleven patients were included. The REM sleep decreased slightly one year after the cell transplant but not significantly. There were no differences in apnea-hipopnea index, mean oxygen saturation and nadir desaturation evolution. An increase of T90 was observed 180 and 360 days after injection (2.95±1.51% and 4.30±4.10% respectively), although it was not statistically significant. The central drive determined by occlusion pressure (P01) and inspiratory flow showed non-significant differences after one year. Intramedullary injection of ABMNC did not worsen the cortico medullar diaphragmatic pathways. 
26593225	To simultaneously investigate the prevalence of and impact that the poststroke complications of daytime sleepiness, poor sleep quality, depression, and fatigue may be having upon deficits of sustained attention, as assessed using the Psychomotor Vigilance Task (PVT).Twenty-two patients with stroke (mean age: 68.23 ± 12.17 years) and 20 healthy control participants (mean age: 68.1 ± 9.5 years) completed subjective measures of daytime sleepiness, sleep quality, fatigue, and depression and an objective measure of sustained attention as assessed using the PVT.	Patients with stroke compared to controls showed heightened levels of fatigue (p = .001, η(2) = .29) and depression (p = .002, η(2) = .23), plus greater deficits of sustained attention as reflected by poorer performance across all PVT outcome measures including: slower mean reaction times (p = .002, η(2) = .22); increased number of lapses (p = .002, η(2) = .24); and greater variability in reaction time (RT) responses (p = .016, η(2) = .15). Reaction time distribution analysis suggested that daytime sleepiness and sleep quality had little influence across PVT performance; however, depressive symptomology was associated with longer RT responses, indicative of inattention, and fatigue impacted upon the entire distribution of PVT responses.	PVT performance illustrated significant deficits across the domain of sustained attention for patients with stroke in comparison to healthy controls, in terms of inattention as well as slower sensory-motor speed. The common poststroke complications of depressive symptomology and fatigue appear to be associated with these deficits in sustained attention, warranting further investigation.	

26589880	Delirium is a palliative care emergency where patients experience changes in perception, awareness, and behavior. Common features include changes in the sleep-wake cycle, emotional lability, delusional thinking, and language and thought disorders. Delirium results from neurotransmitter imbalances involving several neurotransmitters such as dopamine, glutamate, norepinephrine, acetylcholine, gamma-aminobutyric acid, and serotonin. Untreated delirium causes significant morbidity and mortality. Nonpharmacologic and pharmacologic approaches treat delirium. Current pharmacologic management of delirium involves using agents such as haloperidol or second-generation antipsychotics. Third-generation atypical antipsychotic drugs have emerged as a potential choice for delirium management. Aripiprazole is a third-generation antipsychotic with a dopamine receptor-binding profile distinct from other second-generation antipsychotics. Aripiprazole acts as partial agonist at dopamine D2 and 5-hydroxytryptamine (5-HT)1A receptors, stabilizing the dopamine receptor leading to improvement in symptoms. The article reviews the pharmacology, pharmacodynamics, metabolism, and evidence of clinical efficacy for this new antipsychotic agent. This article explores possible roles in palliative care.
26589468	To facilitate the performance comparison of new methods for sleep patterns analysis, datasets with quality content, publicly-available, are very important and useful. We introduce an open-access comprehensive sleep dataset, called ISRUC-Sleep. The data were obtained from human adults, including healthy subjects, subjects with sleep disorders, and subjects under the effect of sleep medication. Each recording was randomly selected between PSG recordings that were acquired by the Sleep Medicine Centre of the Hospital of Coimbra University (CHUC). The dataset comprises three groups of data: (1) data concerning 100 subjects, with one recording session per subject; (2) data gathered from 8 subjects; two recording sessions were performed per subject, and (3) data collected from one recording session related to 10 healthy subjects. The polysomnography (PSG) recordings, associated with each subject, were visually scored by two human experts. Comparing the existing sleep-related public datasets, ISRUC-Sleep provides data of a reasonable number of subjects with different characteristics such as: data useful for studies involving changes in the PSG signals over time; and data of healthy subjects useful for studies involving comparison of healthy subjects with the patients, suffering from sleep disorders. This dataset was created aiming to complement existing datasets by providing easy-to-apply data collection with some characteristics not covered yet. ISRUC-Sleep can be useful for analysis of new contributions: (i) in biomedical signal processing; (ii) in development of ASSC methods; and (iii) on sleep physiology studies. To evaluate and compare new contributions, which use this dataset as a benchmark, results of applying a subject-independent automatic sleep stage classification (ASSC) method on ISRUC-Sleep dataset are presented. 
26588182	Features of an individual's sleep/wake patterns across multiple days are governed by two dimensions, the mean and the intraindividual variability (IIV). The existing literature focuses on the means, while the nature and correlates of sleep/wake IIV are not well understood. A systematic search of records in five major databases from inception to November 2014 identified 53 peer-reviewed empirical publications that examined correlates of sleep/wake IIV in adults. Overall, this literature appeared unsystematic and post hoc, with under-developed theoretical frameworks and inconsistent methodologies. Correlates most consistently associated with greater IIV in one or more aspects of sleep/wake patterns were: younger age, non-White race/ethnicity, living alone, physical health conditions, higher body mass index, weight gain, bipolar and unipolar depression symptomatology, stress, and evening chronotype; symptoms of insomnia and poor sleep were associated with higher sleep/wake IIV, which was reduced following sleep interventions. The effects of experimentally reduced sleep/wake IIV on daytime functioning were inconclusive. In extending current understanding of sleep/wake patterns beyond the mean values, IIV should be incorporated as an additional dimension when sleep is examined across multiple days. Theoretical and methodological shortcomings in the existing literature, and opportunities for future research are discussed. 
26585523	Over the decades, pharmaceutical treatments, particularly dopaminergic (DAergic) drugs have been considered as the main therapy against motor symptoms of Parkinson's disease (PD). It is proposed that DAergic drugs in combination with other medications, such as monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, anticholinergics and other newly developed non-DAergic drugs can make a better control of motor symptoms or alleviate levodopa-induced motor complications. Moreover, non-motor symptoms of PD, such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances caused by intrinsic PD pathology or drug-induced side effects, are gaining increasing attention and urgently need to be taken care of due to their impact on quality of life. Currently, neuroprotective therapies have been investigated extensively in pre-clinical studies, and some of them have been subjected to clinical trials. Furthermore, non-pharmaceutical treatments, including deep brain stimulation (DBS), gene therapy, cell replacement therapy and some complementary managements, such as Tai chi, Yoga, traditional herbs and molecular targeted therapies have also been considered as effective alternative therapies to classical pharmaceutics. This review will provide us updated information regarding the current drugs and non-drugs therapies for PD. 
26585071	Using a population-based cohort study, we investigated whether sleep disorders (SDs) increase the risk of systemic lupus erythematosus (SLE).We identified patients with SDs and a control cohort from 1998-2001 by using the Taiwan Longitudinal Health Insurance Database 2000. Two controls for each patient with an SD were selected and randomly frequency-matched according to age, gender, and index year. The follow-up person-years were estimated for the patients from the index date to SLE diagnosis, loss to follow-up, or the end of 31 December 2011. We used the Cox proportional hazards models to evaluate how SDs influence the risk of SLE after adjustments for demographic factors and comorbidities.	A total of 144,396 subjects (48,132 SD cases and 96,264 controls) were followed for 1,477,055 person-years. The patients with SDs displayed higher incidence density rate of developing SLE than did the controls (1.03 vs. 0.46 per 10,000 person-years). After adjustment for covariates, the patients with SDs exhibited a 2.20-fold higher adjusted hazard ratio (aHR) of developing SLE than the controls (95% confidence interval (CI) = 1.44-3.36). Women exhibited a greater prevalence of SDs and SLE compared to men. Patients with SDs aged 49 years and younger exhibited a significantly increased risk of SLE compared to the controls (aHR=2.30, 95% CI = 1.33-3.98). Patients with SDs living in urban areas exhibited a significantly increased risk of SLE.	This large population-based cohort study revealed that SDs increase the risk of SLE development.	
26583109	The aim of the present study was to assess the prevalence of insomnia in chronic tinnitus and the association of tinnitus distress and sleep disturbance.We retrospectively analysed data of 182 patients with chronic tinnitus who completed the Tinnitus Questionnaire (TQ) and the Regensburg Insomnia Scale (RIS). Descriptive comparisons with the validation sample of the RIS including exclusively patients with primary/psychophysiological insomnia, correlation analyses of the RIS with TQ scales, and principal component analyses (PCA) in the tinnitus sample were performed. TQ total score was corrected for the TQ sleep items.	Prevalence of insomnia was high in tinnitus patients (76%) and tinnitus distress correlated with sleep disturbance (r = 0.558). TQ sleep subscore correlated with the RIS sum score (r = 0.690). PCA with all TQ and RIS items showed one sleep factor consisting of all RIS and the TQ sleep items. PCA with only TQ sleep and RIS items showed sleep- and tinnitus-specific factors. The sleep factors (only RIS items) were sleep depth and fearful focusing. The TQ sleep items represented tinnitus-related sleep problems.	Chronic tinnitus and primary insomnia are highly related and might share similar psychological and neurophysiological mechanisms leading to impaired sleep quality.	
26581913	Sexual dysfunction is a common experience in women with fibromyalgia. However, the physiopathology of this association is unclear. We aimed to evaluate whether sleep disturbance has an influence on sexual function in women with fibromyalgia. Fifty-four sexually active premenopausal women with fibromyalgia were enrolled in the study. The following questionnaires were used: the Female Sexual Function Index (FSFI), the Pittsburgh Sleep Quality Index (PSQI), the Fibromyalgia Impact Questionnaire (FIQ) and the Beck Depression Inventory (BDI). Appropriate statistical analyses were used by using SPSS 18. The mean FSFI score was 25.344 ± 6.52 and showed no correlation with age, body mass index, BDI or duration of fibromyalgia. However, a positive correlation between sexual dysfunction and low sleep quality was found (r=0.43; P=0.001). In addition, the median FSFI score was 29.2 (27.2-32.4) in patients with higher sleep quality (PSQI⩽5), whereas it was 21.4 (18.9-25.3) in patients with lower sleep quality (PSQI>5) (P<0.001). There was a positive correlation between sexual dysfunction and symptoms of fibromyalgia as indicated by a higher FIQ score (r=0.37; P=0.006). Sexual dysfunction in female patients with fibromyalgia may be due to low sleep quality. Treatment of the sleep disorder may improve female sexual function.
26581727	The schedules that Americans live by are not consistent with healthy sleep patterns. In addition, poor access to educational and treatment aids for sleep leaves people engaging in behavior that is harmful to sleep and forgoing treatment for sleep disorders. This has created a sleep crisis that is a public health issue with broad implications for cognitive outcomes, mental health, physical health, work performance, and safety. New public policies should be formulated to address these issues. We draw from the scientific literature to recommend the following: establishing national standards for middle and high school start times that are later in the day, stronger regulation of work hours and schedules, eliminating daylight saving time, educating the public regarding the impact of electronic media on sleep, and improving access to ambulatory in-home diagnostic testing for sleep disorders. 
26581301	To determine the frequency and relative importance of the most life-affecting symptoms in myotonic dystrophy type 2 (DM2) and to identify the factors that have the strongest association with these symptoms.We conducted a cross-sectional study of adult patients with DM2 from a National Registry of DM2 Patients to assess the prevalence and relative importance of 310 symptoms and 21 symptomatic themes. Participant responses were compared by age categories, sex, educational attainment, employment status, and duration of symptoms.	The symptomatic themes with the highest prevalence in DM2 were the inability to do activities (94.4%), limitations with mobility or walking (89.2%), hip, thigh, or knee weakness (89.2%), fatigue (89.2%), and myotonia (82.6%). Participants identified the inability to do activities and fatigue as the symptomatic themes that have the greatest overall effect on their lives. Unemployment, a longer duration of symptoms, and less education were associated with a higher average prevalence of all symptomatic themes (p < 0.01). Unemployment, a longer duration of symptoms, sex, and increased age were associated with a higher average effect of all symptomatic themes among patients with DM2 (p < 0.01).	The lives of patients with DM2 are affected by a variety of symptoms. These symptoms have different levels of significance and prevalence in this population and vary across DM2 subgroups in different demographic categories.	
26578964	Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects. 
26578474	Bipolar disorder is a disabling disease that involves a significant economic costs to the health system, making it is essential to investigate possible early predictors such as changes in sleep-wake cycle in high-risk populations.To review the available literature on alterations in the sleep-wake cycle and circadian rhythm in patients with bipolar disorder and their first degree relatives.	A literature search was performed in the data bases, Access Medicine, ClinicalKey, EMBASE, JAMA, Lilacs, OVID, Oxford Journals, ScienceDirect, SciELO, APA y PsycNET. Articles in both English and Spanish were reviewed, without limits by study type.	Actigraphy is a non-invasive, useful method for assessing sleep-wake cycle disturbances in the active phases of bipolar disorder, and during euthymia periods. Actigraphy showed good sensitivity to predict true sleep, but low specificity, compared with polysomnography. Although studies in bipolar offspring and relatives are scarce, they show sleep changes similar to bipolar patients.	Actigraphy may be a good screening tool of sleep/wake cycle in patients with bipolar disorders, because it is economic, non-invasive and sensitive. Longitudinal studies are required to evaluate its potential use as a risk marker.	
26578413	Quality of sleep and excessive daytime sleepiness (EDS) affect cognitive ability and performance of medical students. This study attempts to determine the prevalence of EDS, sleep quality, and assess their association with poor academic performance in this population.A descriptive, observational study was conducted on a random sample of 217 medical students from the Universidad Tecnológica de Pereira, who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Epworth sleepiness scale. Sociodemographic, clinic and academic variables were also measured. Multivariate analyses for poor academic performance were performed.	The included students had a mean age of 21.7±3.3 years, of whom 59.4% were men. Almost half (49.8%) had EDS criteria, and 79.3% were poor sleepers (PSQI ≥ 5), while 43.3% had poor academic performance during the last semester. The bivariate analysis showed that having used tobacco or alcohol until intoxicated, fairly bad subjective sleep quality, sleep efficiency < 65%, and being a poor sleeper were associated with increased risk of low performance. Sleep efficiency < 65% was statistically associated with poor academic performance (P=.024; OR = 4.23; 95% CI, 1.12-15.42) in the multivariate analysis.	A poor sleep quality determined by low efficiency was related to poor academic achievement at the end of semester in medical students.	
26577848	Whether sleep problems of menopausal women are associated with vasomotor symptoms and/or changes in estrogen levels associated with menopause or age-related changes in sleep architecture is unclear. This study aimed to determine if poor sleep in middle-aged women is correlated with menopause. This study recruited women seeking care for the first time at the menopause outpatient department of our hospital. Inclusion criteria were an age ≥40 years, not taking any medications for menopausal symptoms, and no sleeping problems or depression. Patients were assessed with the Pittsburgh Sleep Quality Index (PSQI), modified Kupperman Index (KI), and Menopause Rating Scale (MRS). A PSQI score of <7 indicated no sleep disorder and ≥7 indicated a sleep disorder. Blood specimens were analyzed for follicle-stimulating hormone and estradiol levels. A total of 244 women were included in the study; 103 (42.2%) were identified as having a sleep disorder and 141 as not having one. In addition, 156 (64%) women were postmenopausal and 88 (36%) were not menopausal. Follicle-stimulating hormone and estradiol levels were similar between the groups. Patients with a sleep disorder had a significantly higher total modified KI score and total MRS score (both, P<0.001) compared with those without a sleep disorder. Correlations of the PSQI total score with the KI and MRS were similar in menopausal and non-menopausal women. These results do not support that menopause per se specifically contributes to sleep problems. 

26576055	Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD.Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters.	In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019).	In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models.	
26574980	Introdução: Avaliar a privação do sono e seus efeitos sobre os jovens médicos relativamente à capacidade de concentração e desempenho psicomotor. Material e Métodos: Dezoito médicos, com idades entre 26 - 33 anos, divididos em dois grupos: grupo sem privação de sono (sem trabalho nocturno) e grupo com privação de sono (no mínimo 12 horas de trabalho nocturno / semana). Aplicámos o Índice de Qualidade de Sono de Pittsburgh para rastrear a presença de patologia do sono e a Escala de Sonolência Epworth para avaliar subjectivamente a sonolência diurna; usamos actigrafia e o diário de sono para avaliar a higiene do sono e os ciclos de sono-vigília. Para demonstrar os efeitos da privação do sono, foi aplicado o teste de Toulouse-Piéron (teste de concentração) e uma bateria de trêstestes de tempo de reação após o período de trabalho nocturno. Resultados: O grupo com privação de sono apresentou maior sonolência diurna na Escala de Sonolência Epworth (p < 0,05) e durante a semana a privação de sono foi maior (p < 0,010). A duração média do sono durante o período de trabalho nocturno foi de 184,2 minutos para o grupo com privação de sono e 397,7 minutos para grupo sem privação de sono (p < 0,001). No teste Toulouse-Piéron o grupo com privação de sono apresentou maior número de omissões (p < 0,05) com um pior resultado no índice de concentração (p < 0,05). Os testes psicomotores que avaliaram a resposta a estímulos simples revelaram maior latência na resposta (p < 0,05) e mais erros (p < 0,05) no grupo com privação de sono; no teste de reacção a instrução o e grupo com privação de sono apresentou pior índice de perfeição (p < 0,05); no teste de movimentos finos não houve diferença estatisticamente significativa entre os grupos. Discussão: A privação de sono aguda resultante do trabalho nocturno em profissões médicas está associada a uma diminuição da atenção e concentração e no atraso de resposta a estímulos. Isto pode comprometer o atendimento ao paciente, bem como a saúde e a qualidade de vida do próprio médico. Conclusão: Ã essencial estudar os efeitos da privação aguda de sono sobre a capacidade cognitiva e de desempenho dos profissionais de saúde.To evaluate sleep deprivation and its effects on young physicians in relation to concentration capacity and psychomotor performance.	Eighteen physicians aged 26 - 33 years were divided into 2 groups: non-sleep deprived group (with no night work) and sleep deprived group (minimum 12 hour of night work/week). We applied Pittsburgh Sleep Quality Index to screen the presence of sleep pathology and Epworth Sleepiness Scale to evaluate subjective daytime sleepiness; we used actigraphy and sleep diary to assess sleep hygiene and standard sleep-wake cycles. To demonstrate the effects of sleep deprivation, we applied Toulouse-Piéron's test (concentration test) and a battery of three reaction time tasks after the night duty.	Sleep deprived group had higher daytime sleepiness on Epworth Sleepiness Scale (p < 0.05) and during week sleep deprivation was higher (p < 0.010). The mean duration of sleep during the period of night duty was 184.2 minutes to sleep deprived group and 397.7 minutes to non-sleep deprived group (p < 0.001). In the Toulouse-Piéron's test, the sleep deprived group had more omissions (p < 0.05) with a poorer result in concentration (p < 0.05). Psychomotor tests that evaluated response to simple stimuli revealed longer response latency (p < 0.05) and more errors (p < 0.05) in Sleep deprived group; in reaction to instruction test the sleep deprived group showed worse perfection index (p < 0.05); in the fine movements test there was no statistically significant difference between the groups.	Acute sleep deprivation resulting from nocturnal work in medical professions is associated with a reduction in attention and concentration and delayed response to stimuli. This may compromise patient care as well as the physician's health and quality of life.	It is essential to study the effects of acute sleep deprivation on the cognitive abilities and performance of health professionals.	

26574119	The aim of this study was to compare the quantity/quality of sleep obtained by people living on split and consolidated sleep-wake schedules. The study had a between-groups design, with 13 participants in a consolidated condition (all males, mean age of 22.5yr) and 16 participants in a split condition (all males, mean age of 22.6yr). Both conditions employed forced desynchrony protocols with the activity:rest ratio set at 2:1, but the consolidated condition had one sleep-wake cycle every 28h (9.33+18.67), while the split condition had one sleep-wake cycle every 14h (4.67+9.33). Sleep was assessed using polysomnography. Participants in the split and consolidated conditions obtained 4.0h of sleep per 14h and 7.6h of sleep per 28h, respectively. Some differences between the groups indicated that sleep quality was lower in the split condition than the consolidated condition: the split sleeps had longer sleep onset latency (9.7 vs. 4.3min), more arousals (7.4 vs. 5.7 per hour in bed), and a greater percentage of stage 1 sleep (4.1% vs. 3.1%), than the consolidated sleeps. Other differences between the groups indicated that sleep quality was higher in the split condition than the consolidated condition: the split sleeps had a lower percentage of wake after sleep onset sleep (11.7% vs. 17.6%), and a greater percentage of slow wave sleep (30.2% vs. 23.8%), than the consolidated sleeps. These results indicate that the split schedule was not particularly harmful, and may have actually been beneficial, to sleep. Split work-rest schedules can be socially disruptive, but their use may be warranted in work settings where shiftworkers are separated from their normal family/social lives (e.g., fly-in fly-out mining) or where the need for family/social time is secondary to the task (e.g., emergency response to natural disasters).
26572090	ACh is an important modulator of breathing, including at the level of the retrotrapezoid nucleus (RTN), where evidence suggests that ACh is essential for the maintenance of breathing. Despite this potentially important physiological role, little is known about the mechanisms responsible for the cholinergic control of RTN function. In the present study, we show at the cellular level that ACh increases RTN chemoreceptor activity by a CO2/H(+) independent mechanism involving M1/M3 receptor-mediated inositol 1,4,5-trisphosphate/Ca(+2) signalling and downstream inhibition of KCNQ channels. These results dispel the theory that ACh is required for RTN chemoreception by showing that ACh, similar to serotonin and other modulators, controls the activity of RTN chemoreceptors without interfering with the mechanisms by which these cells sense H(+). By identifying the mechanisms by which wake-on neurotransmitters such as ACh modulate RTN chemoreception, the results of the present study provide a framework for understanding the molecular basis of the sleep-wake state-dependent control of breathing.ACh has long been considered important for the CO2/H(+)-dependent drive to breathe produced by chemosensitive neurons in the retrotrapezoid nucleus (RTN). However, despite this potentially important physiological role, almost nothing is known about the mechanisms responsible for the cholinergic control of RTN function. In the present study, we used slice-patch electrophysiology and pharmacological tools to characterize the effects of ACh on baseline activity and CO2/H(+)-sensitivity of RTN chemoreceptors, as well as to dissect the signalling pathway by which ACh activates these neurons. We found that ACh activates RTN chemoreceptors in a dose-dependent manner (EC50 = 1.2 μm). The firing response of RTN chemoreceptors to ACh was mimicked by a muscarinic receptor agonist (oxotremorine; 1 μm), and blunted by M1- (pirezenpine; 2 μm) and M3- (diphenyl-acetoxy-N-methyl-piperidine; 100 nm) receptor blockers, but not by a nicotinic-receptor blocker (mecamylamine; 10 μm). Furthermore, pirenzepine, diphenyl-acetoxy-N-methyl-piperidine and mecamylamine had no measurable effect on the CO2/H(+)-sensitivity of RTN chemoreceptors. The effects of ACh on RTN chemoreceptor activity were also blunted by inhibition of inositol 1,4,5-trisphosphate receptors with 2-aminoethoxydiphenyl borate (100 μm), depletion of intracellular Ca(2+) stores with thapsigargin (10 μm), inhibition of casein kinase 2 (4,5,6,7-tetrabromobenzotriazole; 10 μm) and blockade of KCNQ channels (XE991; 10 μm). These results show that ACh activates RTN chemoreceptors by a CO2/H(+) independent mechanism involving M1/M3 receptor-mediated inositol 1,4,5-trisphosphate/Ca(+2) signalling and downstream inhibition of KCNQ channels. Identifying the components of the signalling pathway coupling muscarinic receptor activation to changes in chemoreceptor activity may provide new potential therapeutic targets for the treatment of respiratory control disorders.	
26569624	Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD.To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD.	This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat.	Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks.	The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels.	After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, -13.7 to -4.6; P < .001), from a mean (SD) of 49.1 (24.3) to 40.2 (20.9). Moreover, the sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo (95% CI, -38.6 to -4.2; P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency (r = -0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study.	Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD.	
26569536	Caregiving for allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients carries a significant psychological burden, yet it remains unclear whether Allo-HSCT caregivers demonstrate disruptions to stress systems, such as the hypothalamic-pituitary-adrenal axis. Greater intraindividual cortisol variability (ICV) has been observed in psychiatric disorders; however, there is a knowledge gap evaluating ICV in caregivers. We predicted that greater ICV would be related to poorer mental health in Allo-HSCT caregivers.Allo-HSCT caregivers (n = 140) collected saliva for 3 consecutive days at 4 time points/d. Psychological variables included sleep quality and a summary composite score of overall mental health.	Regression analyses demonstrated that greater ICV was significantly related to poorer overall mental health (β = 0.25, p = .009), whereas poorer sleep did not reach significance (β = 0.16, p = .069). No significant relationships emerged for the cortisol area under the curve, diurnal decline, or awakening response.	Results extend prior work examining ICV as a unique marker that is possibly more sensitive than other widely applied measures of hypothalamic-pituitary-adrenal axis dysregulation to a distressed population of caregivers.	
26569414	Wrist-worn accelerometers are increasingly being used for the assessment of physical activity in population studies, but little is known about their value for sleep assessment. We developed a novel method of assessing sleep duration using data from 4,094 Whitehall II Study (United Kingdom, 2012-2013) participants aged 60-83 who wore the accelerometer for 9 consecutive days, filled in a sleep log and reported sleep duration via questionnaire. Our sleep detection algorithm defined (nocturnal) sleep as a period of sustained inactivity, itself detected as the absence of change in arm angle greater than 5 degrees for 5 minutes or more, during a period recorded as sleep by the participant in their sleep log. The resulting estimate of sleep duration had a moderate (but similar to previous findings) agreement with questionnaire based measures for time in bed, defined as the difference between sleep onset and waking time (kappa = 0.32, 95%CI:0.29,0.34) and total sleep duration (kappa = 0.39, 0.36,0.42). This estimate was lower for time in bed for women, depressed participants, those reporting more insomnia symptoms, and on weekend days. No such group differences were found for total sleep duration. Our algorithm was validated against data from a polysomnography study on 28 persons which found a longer time window and lower angle threshold to have better sensitivity to wakefulness, while the reverse was true for sensitivity to sleep. The novelty of our method is the use of a generic algorithm that will allow comparison between studies rather than a "count" based, device specific method. 
26568127	Jet lag and shift work disorder are circadian rhythm sleep-wake disorders resulting from behaviorally altering the sleep-wake schedule in relation to the external environment. Not everyone who experiences trans-meridian travel or performs shift work has a disorder. The prevalence of jet lag disorder is unclear, approximately 5%-10% of shift workers have shift work disorder. Treatment aims to realign the internal circadian clock with the external environment. Behavioral therapies include sleep hygiene and management of the light-dark and sleep schedule. Pharmacologic agents are used to treat insomnia and excessive sleepiness, and melatonin is used to facilitate sleep and circadian realignment. 
26568126	Irregular sleep-wake rhythm disorder is a circadian rhythm disorder characterized by multiple bouts of sleep within a 24-hour period. Patients present with symptoms of insomnia, including difficulty either falling or staying asleep, and daytime excessive sleepiness. The disorder is seen in a variety of individuals, ranging from children with neurodevelopmental disorders, to patients with psychiatric disorders, and most commonly in older adults with neurodegenerative disorders. Treatment of irregular sleep-wake rhythm disorder requires a multimodal approach aimed at strengthening circadian synchronizing agents, such as daytime exposure to bright light, and structured social and physical activities. In addition, melatonin may be useful in some patients. 
26568125	Non-24-hour sleep-wake rhythm disorder (N24SWD) is a cyclic debilitating circadian rhythm sleep disorder characterized by an inability to sleep on a 24-hour schedule. Individuals isolated from a 24-hour light-dark cycle exhibit sleep-wake cycles different from 24 hours. Relatively rare in sighted patients, it may be associated with delayed sleep-wake rhythm disorder or psychiatric disorders. It is more common in totally blind individuals owing to the lack of light information reaching the circadian pacemaker in the hypothalamus. We review the clinical characteristics of patients with N24SWD, discuss the biological mechanisms that may underlie its development, and describe treatment strategies. 
26568123	Circadian rhythms have a major role in physiology and behavior. Circadian disruption has negative consequences for physiologic homeostasis at molecular, cellular, organ-system, and whole-organism levels. The onset of many cerebrovascular insults shows circadian temporal trends. Impaired sleep-wake cycle, the most robust output rhythms of the circadian system, is significantly affected by neurodegenerative disorders, may precede them by decades, and may also affect their progression. Emerging evidence suggests that circadian disruption may be a risk factor for these neurologic disorders. This article discusses the implications of circadian rhythms in brain disorders, with an emphasis on cerebrovascular and neurodegenerative disorders. 
26568120	Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. This article reviews key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep. 
26567994	Uraemic pruritus is a distressing symptom that has a negative impact on the quality of life for dialysis patients. The pathophysiology of pruritus in peritoneal dialysis (PD) patients is still poorly understood. The present study aims to investigate the prevalence and related risk factors of pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients.In total, 362 CAPD cases were investigated from January 2012 to April 2013. Pruritus was assessed by visual analogue scale.	The prevalence of severe pruritus and mild to moderate pruritus was 12.7% and 52.5%, respectively. The patients with severe pruritus had the longest duration of PD (p<0.001), Pittsburgh Sleep Quality Index (PSQI) score (p<0.001), Beck Depression Inventory (BDI) score (p=0.003), intact parathyroid hormone (iPTH) level (p=0.009), and the lowest Medical Outcomes Short Form 36 Health Survey, Physical Component Score (SF-36 PCS) (p<0.001) among the three groups. The patients with mild to moderate pruritus had a significantly higher iPTH level (p=0.004) compared with the patients without pruritus. A multivariate logistic regression for pruritus showed that higher PSQI score [odds ratio (OR)=1.305, p=0.001], higher BDI score (OR=1.429, p=0.002), longer vintage (OR=1.039, p=0.004), and higher iPTH level (OR=1.317, p=0.014) were independently associated with pruritus.	The prevalence of uraemic pruritus was 65.2% in CAPD patients. Sleep disorder, depression, longer vintage, and a higher iPTH level were independent associated factors for pruritus in CAPD patients.	
26564388	Polysomnography (PSG) is the gold standard for the assessment of sleep, yet the extensive apparatus required for monitoring with PSG can be difficult to tolerate, particularly in children. Clinical populations, such as those with anxiety or tactile sensitivity, may have even greater difficulty tolerating the PSG equipment. This study evaluated an innovative protocol for obtaining full PSG in individuals diagnosed autism spectrum disorders (ASD) or developmental delay (DD), as well as typically developing controls (TD). The primary aim was to assess whether this protocol was equally successful for obtaining PSG between these groups.One hundred sixty-one individuals were recruited for participation; 93 with a diagnosis of ASD, 23 with a diagnosis of DD, and 45 TD. The participants and families were instructed on a procedure of systematic desensitization to the ambulatory PSG equipment; PSG was performed in the home of the participant.	PSG was successfully attained in 144 (89.4%) participants. There was no difference in completion rate by diagnosis (p = 0.1), though younger age (p = 0.018) and duration of desensitization (p = 0.024) did predict PSG failure. Further, it was found that individuals with ASD took longer to desensitize to the equipment (16.08 d), than those with DD (8.04 d) or TD (0.98 d).	Systematic desensitization to PSG equipment, in combination with PSG completed in the home, allows for individuals with ASD to be equally successful in completing PSG, though they do take longer to acclimate to the equipment.	
26564384	Sleep disturbances are frequently reported following traumatic brain injury (TBI); however, the exact disturbances remain unclear. This meta-analysis aimed to characterize sleep disturbance in community dwelling patients with TBI as compared to controls.Two investigators independently conducted a systematic search of multiple electronic databases from inception to May 27, 2015. Studies were selected if they compared sleep in community dwelling individuals with TBI relative to a control population without head injury. Data were pooled in meta-analysis with outcomes expressed as the standard mean difference (SMD) and 95% confidence interval (CI). The primary outcomes were derived from polysomnography and secondary outcomes were derived from subjective sleep measures.	Sixteen studies were included, combining 637 TBI patients and 567 controls, all of whom were community dwelling. Pooled polysomnography data revealed that TBI patients had poorer sleep efficiency (SMD = -0.47, CI: -0.89, -0.06), shorter total sleep duration (SMD = -0.37, CI: -0.59, -0.16), and greater wake after sleep onset time (SMD = 0.60, CI: 0.33, 0.87). Although sleep architecture was similar between the groups, a trend suggested that TBI patients may spend less time in REM sleep (SMD = -0.22, CI: -0.45, 0.01). Consistent with polysomnographic derangement, TBI patients reported greater subjective sleepiness and poorer perceived sleep quality.	The evidence suggests that TBI is associated with widespread objective and subjective sleep deficits. The present results highlight the need for physicians to monitor and address sleep deficits following TBI.	

26564126	This study tested the hypothesis that Regulators of G protein Signaling (RGS) proteins contribute to the regulation of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and to sleep disruption caused by volatile anesthetics.The three groups used in this study included wild-type (WT; n = 7) mice and knock-in mice that were heterozygous (+/GS; n = 7) or homozygous (GS/GS; n = 7) for an RGS-insensitive allele that causes prolonged Gαi2 signaling. Mice were implanted with electrodes for recording sleep and conditioned for 1 week or more to sleep in the laboratory. Using within and between groups designs, 24-h recordings of wakefulness, NREM sleep, and REM sleep were compared across three interventions: (1) baseline (control) and after 3 h of being anesthetized with (2) isoflurane or (3) sevoflurane.	Baseline recordings during the light phase revealed that relative to WT mice, homozygous RGS-insensitive (GS/GS) mice exhibit significantly increased wakefulness and decreased NREM and REM sleep. During the dark phase, these state-specific differences remained significant but reversed direction of change. After cessation of isoflurane and sevoflurane anesthesia there was a long-lasting and significant disruption of sleep and wakefulness. The durations of average episodes of wakefulness, NREM sleep, and REM sleep were significantly altered as a function of genotype and isoflurane and sevoflurane anesthesia.	RGS proteins and Gαi2 play a significant role in regulating states of wakefulness, NREM sleep, and REM sleep. Genotype-specific differences demonstrate that RGS proteins modulate sleep disruption caused by isoflurane and sevoflurane anesthesia. The results also support the conclusion that isoflurane and sevoflurane anesthesia do not satisfy the homeostatic drive for sleep.	
26564124	The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep.EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline.	Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain.	Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context.	
26564123	Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.	RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).	RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.	
26563802	Sleep deprivation due to shift work is related to perturbation of the sleep/wake cycle, associated with the modified activity/rest pattern. This may cause a significant disruption of circadian rhythms of biologic functions, driven by the body clock located in the suprachiasmatic nuclei of the hypothalamus. Shift and night workers have to change sleep times and strategies according to their duty periods; consequently, both sleep length and quality can be considerably affected depending on the variable start and finish times on different shifts. About 10% of night and rotating shift workers, aged between 18 and 65 years, have been estimated to have a diagnosable "shift-work sleep disorder," according to the International Classification of Sleep Disorders, version 2 (ICSD-2). In the long run, this may lead to persistent and severe disturbances of sleep, chronic fatigue and psychoneurotic syndromes, besides being a risk or aggravating factor for accidents, gastrointestinal, cardiovascular, and reproductive disorders, as well as, probably, for cancer. Preventive and corrective actions deal with the organization of shift schedules according to ergonomic criteria, careful health surveillance, appropriate education and training on effective countermeasures, in particular, sleep hygiene and napping. 
26563408	We aimed to investigate the frequency of restless legs syndrome (RLS) and the associations between RLS and quality of sleep and life in patients with ankylosing spondylitis (AS). One hundred and eight AS patients and 64 controls were included in this study. Demographics, clinical, and laboratory data were recorded. The presence of RLS was determined with face-to-face interview by an experienced neurologist based on the International RLS Study Group criteria. RLS severity was evaluated using International RLS Study Group rating scale. Sleep quality and insomnia severity were assessed by Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI), respectively. Disease-related quality of life was evaluated by AS quality of life questionnaire (ASQoL). The frequency of RLS was significantly higher in AS patients than in controls (36.4 vs. 14.0 %, p = 0.004). RLS severity score for AS patients was significantly higher than that for controls (p = 0.03). The AS patients had higher scores in the subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication domains of PSQI, and also total PSQI and ISI than controls (p < 0.05, for all). ASQoL scores were higher in AS patients with RLS compared to those without RLS (p < 0.001). RLS severity was observed to be independently associated with total PSQI, ISI and ASQoL (p < 0.05, for all). As RLS may adversely affect the sleep and quality of life in AS patients, clinicians should be aware of RLS for early diagnosis and management in AS patients. 


26559748	Although sleep impairment is reported by patients with chronic rhinosinusitis, the associated factors have not been well studied. Therefore, we determined the associated risk factors for sleep impairment in patients with chronic rhinosinusitis (CRS).This study was a prospective cohort study. A total of 572 adult patients (171 women, 401 men; mean age, 49.0 years; range, 18-64 years) who completed a questionnaire, had a clinical examination, and underwent endoscopic sinus surgery were analyzed using stepwise multiple linear regression.	With regard to subjective symptoms, nasal obstruction (beta coef., 0.27; p<0.001), anterior nasal drainage (beta coef., 0.13; p=0.004), facial pain/pressure (beta coef., 0.09; p=0.048), headache (beta coef., 0.10; p=0.010), and cough (beta coef., 0.14; p<0.001) were predictors of an increased risk of sleep impairment of CRS (adjusted R(2), 0.240; p=0.048). In the matter of background parameters, total polyp score (polyp grading system) (beta coef., 0.16; p<0.001) and allergic rhinitis (beta coef., 0.09; p=0.034) were predictors of an increased risk of sleep impairment of CRS (adjusted R(2), 0.029; p=0.034).	These results suggest that sleep impairment in these patients is caused by the various mechanisms associated with nasal symptoms themselves, CRS and allergic rhinitis. However, the specific pathophysiology has not been clarified yet; further studies are expected to elucidate that of sleep impairment in patients with CRS.	
26559219	Health sciences suffer from insomnia: experts too often concentrate their efforts on the wake state. Fortunately enough, some of them have taken the road towards the "Dark Third of Life": sleep. This article gives an historical account of the development of the first Canadian sleep disorders laboratory and clinic specifically and selectively designed for children and adolescents with a psychiatric diagnosis. It then stresses the importance of sleep in children bearing a psychiatric diagnosis and summarizes therapeutic strategies.Data-on-file and selective review of literature.	An innovative scheme matching sleep psychologists and psychiatrists with expertise in neurodevelopmental disorders led to the creation of a sleep research laboratory on mental health disorders. The initial research projects on the sleep and dreams of patients with schizophrenia and persons with autism are summarized. The Sleep Disorders Clinic for Children and Adolescents was then created at the Hôpital Rivière-des-Prairies, leading to much needed activities focused on youth. Indeed, sleep disorders show a high prevalence in children with a psychiatric diagnosis and the literature shows that these children have an increased sensitivity for diurnal effects of poor sleep. The main sleep-relevant issues at stake are reviewed, including the high frequency of sleep disorders in pedopsychiatric patients. Clinical challenges are described and the operating mode of the Sleep Disorders Clinic is illustrated.	Sleep disorders and their effects on daytime functioning need to be assessed in children with a psychiatric diagnosis in order to generate a full clinical picture. Appropriate tools and know-how are readily available in order to achieve this goal.	
26558838	During the dog-sled race, the Finnmarkslop (FL), which lasts up to 7 days, participants get little sleep and what they get is fragmented; concerns have been raised about proper sleep recovery. The aim of this study was to examine awareness of sleep deprivation by FL participants and post-race sleep recovery after completion of the race.A total of 55 participants responded to an online survey 1 week and 1 month after the race; this measured the following factors: their awareness of sleep loss and possible strategies for recovery; their sleep-wake patterns using a Pittsburgh Sleep Questionnaire Index; and possible changes in respondents' sleep-wake patterns compared with their regular routines.	During the FL, participants slept about 3-4 hours a day. Many were not aware of the accumulated sleep debt and did not engage in strategies to make up the loss. Insufficient levels of sleep and impoverished sleep quality were observed after the race, especially among those who were engaged in the FL for a longer period. Alertness levels were affected 1 week after the race.	Among participants in the FL, the lack of awareness of sleep debt and insufficient sleep recovery could lead to health consequences. Those engaged in the race for longer should be more cautious during the recovery process because of possible sleep problems occurring after the race. Educational campaigns and easy access to professional support should be provided for participants in this type of sporting event.	
26558357	The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation.

26554324	Sleep disturbances have been noted not only during affective episodes in bipolar disorder, but also between affective episodes. The goal of this study was to assess and identify determinants of sleep quality in patients with bipolar I disorder.This cross-sectional study enrolled patients with bipolar disorder who were currently in remission. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Mood symptoms were evaluated using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (Ham-D). Adherence was assessed using the Medication Adherence Rating Scale.	The mean age in the sample (N=103) was 37.4 years; 44.7% of the sample were men. On the basis of PSQI scores, 41 patients (39.8%) were poor sleepers. Poor sleepers had significantly higher Ham-D scores (mean score of 1.8 vs. 0.9, P=0.012) and higher rates of medication nonadherence (36.6% vs. 11.3%, P=0.002). The relationship between Ham-D scores and sleep quality did not remain significant when the sleep-related items on the Ham-D were removed. Logistic regression analysis suggested that medication nonadherence was the only independent predictor of poor sleep quality in this study.	A significant proportion of patients with bipolar disorder who are in remission have sleep problems that seem to be independent of core symptoms of depression.	

26553088	Sleep problems are common in childhood, but there are limited studies regarding that in Iranian children and awareness of the sleep problems and their complication in Iranian parents. We arranged this study in which parents of children attending for a sick visit or routine growth control to assess whether sleep problems are under-reported at general pediatric visits. In a cross-sectional study from April 2010 to April 2011 in 301 children aged 2-14 years old attending to pediatric clinics were enrolled. To investigate the general orientation of parents about their child sleep problem we asked them a global question at first regarding sleep of their child. After that, the Persian version of BEARS questionnaire was completed by them. Only 30 (9.9%) parents reported sleep problems in their children in response to primary global question but by collecting the data from BEARS questionnaire it was revealed 45.18% (136/301) of children had one or more of sleep disorders at all. As mentioned 136 (45.18%) children had slept problems of which the most frequent complaint (15.28%) was related to bedtime problems. The second complaint (11.96%) was awakening during the night children. A significant association between sleep problems and child gender was not found. Co-sleeping with parents was found in 55.48% of all children in this study. Despite the high prevalence and adverse effects of sleep disorders, the present study suggests that parents underreport sleep problems at consultation. We suggest children should be assessed for sleep disorders in monitoring and health screening visits.
26553086	Professional firefighting is among the most demanding jobs. Prior studies have showed the notable prevalence of poor sleep quality among professional firefighters that may result in catastrophes. The aim of this study was in field confirmation of zolpidem usage (10 mg/PO/bed time) for short term management of poor sleeps quality among professional firefighters. In a double-blind, randomized, placebo-controlled crossover clinical trial among professional firefighters, 27 poor sleepers were assigned randomly to one of the two groups. Two 14 days experimental periods were separated by a 14-day washout phase. Sleep quality was assessed using the Persian version of Pittsburgh Sleep Quality Index (PSQI). Six of the 27 enrolled voluntaries dropped out. Two rare side effects of zolpidem occurred in the study. A significant improvement of the PSQI score was detected in zolpidem period versus placebo in both groups (7.14 ± 3.02 vs 12.38 ± 2.51, P<0.001) although zolpidem had no significant effect on time of waking up (6.76 ± 1.21 vs.6.64 ± 1.27, P=0.89). Zolpidem significantly improved all components of PSQI (Subjective sleep quality, Sleep latency, Sleep duration, Habitual sleep efficiency, Sleep disturbances and Daytime dysfunction) in the current study except the use of sleep medication. Sleep onset latency was the component of PSQI with the greatest degree of abnormality among firefighters in a previous study. Interestingly, sleep latency was the component of PSQI with the most treatment effect of zolpidem in the current study. Zolpidem can be used asa part of treatment regimens in short time management of poor sleep quality among professional firefighters.
26551998	Sleep disturbances (SDs) are common in patients with all forms of dementia. However, most studies focus on Alzheimer's disease (AD) and less is known about the prevalence and characteristics of SD in dementia with Lewy bodies (DLB).The aims of this cross-sectional study were: (1) to examine the frequency of SD in DLB versus AD; (2) to compare patients with and without SD with regard to relevant clinical variables, and (3) to investigate the associations between SD and medication use.	Patients with a first-time diagnosis of probable or possible DLB or AD were selected from the Dementia Study of Western Norway and recruited from clinics for old age psychiatry from 2010 until the end of 2013.	In all, 123 (55.7%) subjects with dementia suffered from at least one SD. Insomnia was present in 77 (34.8%), and 34 (20.7%) patients had probable REM-sleep behaviour disorder (RBD). All SDs were also significantly more frequent in patients with DLB than in AD, and DLB patients also more often had several co-occurring SDs. The presence of any SD was associated with more neuropsychiatric symptoms, higher morbidity, more parkinsonian symptoms and excessive daytime sleepiness. Antiparkinsonian medication was used more often in RBD, restless leg syndrome (RLS) and periodic limb movements, and benzodiazepines were also common in RLS.	Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB.	
26549869	This study compared the impact of split and consolidated sleep/wake schedules on subjective sleepiness during the biological day and biological night. This was achieved using a between-group design involving two forced desynchrony protocols: consolidated sleep/wake and split sleep/wake. Both protocols included 7×28-h days with 9.33h in bed and 18.67h of wake each day. While the consolidated sleep/wake protocol had 1×9.33-h sleep opportunity and 1×18.67-h wake period each day, the split sleep/wake protocol had 2×4.67-h sleep opportunities and 2×9.33-h wake periods each day. For both protocols, subjective sleepiness was measured using the Karolinska Sleepiness Scale every 2.5h during wake. A total of 29 healthy adult males participated, with 13 in the consolidated sleep/wake group (mean age=22.5 yrs) and 16 in the split sleep/wake group (mean age=22.6 yrs). On average, subjective sleepiness during wake periods of the split condition was significantly higher than that during the first half of wake periods of the consolidated condition, but was similar to the level during the second half. These findings were observed for wake periods that occurred during both the biological day and biological night. Previous data have shown that cognitive impairment at night is lower for split schedules than consolidated schedules, but the current data indicate that feelings of sleepiness are greater for split schedules than consolidated schedules for at least half of the time awake. Thus, it should be explained to people operating split sleep/wake schedules that although they may perform well, they are likely to feel sleepy.
26549635	Children with atopic dermatitis (AD) experience significant sleep disruption, and clinically, the disease is noted to worsen in a circadian manner at night. Epidemiologic findings highlight many negative consequences of AD, such as impaired linear growth, which is uniquely related to disturbed sleep. Clinical guidelines currently recommend assessing sleep in patients with AD as a crucial parameter of disease control with appropriate treatment. In this review we describe our current understanding of the roles of sleep cycles and circadian rhythms in the nighttime exacerbation of AD (nocturnal eczema). We present a schematic to explain the mechanism of nocturnal eczema. Treatment options for sleep disturbance and future directions for research are discussed in the context of AD. 
26549253	Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration.
26549156	Morningness-eveningness (M-E) is typically considered to be a trait-like construct. However, M-E could plausibly shift in concert with changes in circadian or homeostatic processes. We examined M-E changes across three studies employing behavioral or pharmacological sleep treatments. Baseline and posttreatment M-E scores were strongly correlated across all three samples. M-E showed small but systematic changes toward morningness in sleep-disturbed military veterans receiving behavioral interventions. No systematic M-E changes were observed in the two pharmacological studies (sleep-disturbed military veterans and adults with primary insomnia, respectively). In the behavioral study, M-E changes correlated with changes in depression, positive affect, and sleep quality. M-E changes also correlated with changes in positive affect in the adult insomnia group. M-E appears to exhibit state-like aspects in addition to trait-like aspects. 
26549008	Sleep-wake and circadian rhythm disturbances are common in remitted bipolar disorder. These disturbances include difficulty initiating and maintaining sleep, daytime sleepiness, sleep irregularity, and a circadian tendency toward eveningness. To date, few studies have examined the impact of eveningness on impairments in remitted bipolar disorder. Ninety-eight adults diagnosed with bipolar disorder I, II, or not otherwise specified were evaluated. Hierarchical linear regression analyses showed that eveningness was associated with greater sleep-wake disturbances, more unhealthy dietary habits, worse quality of life, more impaired interpersonal relationships, and more dysfunctional sleep-related cognitions and behaviors, controlling for age, gender, and years of education. Targeted intervention on dysfunctional sleep-related cognitions and behaviors may reverse eveningness and improve functioning in bipolar disorder. 
26548618	Prior research has provided evidence that in children sleep and behavior are related. We aimed to determine the association between naturalistic daily variations in sleep and behavioral functioning. African American children, 5.4±1.7years old, living on the south side of Chicago participated in a repeated measures study to assess this sleep-behavior link. Data was obtained from three separate two-week periods of 24-hour actigraphy and the parental version of the Behavioral Assessment System for Children. Canonical correlations analyses were applied to investigate the relation between individual changes in sleep and behavior. After 1-month, weekday average sleep duration primarily related to internalizing behaviors, while within-child variability of sleep related to behavioral changes which may involve internalizing and externalizing symptoms. Week-weekend differences in sleep associated with maladaptive social skills. Over a 6-week period, sleep onset latency and sleep offset latency related to behavioral symptoms and maladaptive skills. Over a period of 3-months, sleep associated with symptomatic behaviors while the adverse impact of within-child variability of sleep attenuated. Alternatively, the week-weekend differences in bedtime, wake-up time, wake after sleep onset and sleep onset latency in particular related to internalizing and externalizing behavior problems. Findings showed that poor sleep related to dysfunctional behaviors. While maladaptive at the beginning, they may develop into symptomatic behaviors with potentially internalizing characteristics. As time goes on, individual changes in sleep onset and offset might be important clinical markers of a chronic 'social dysregulation'. Continued sufficient and regular sleep may improve daytime and nighttime behavioral regulation in early childhood. 
26547512	Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diagnosed with BP at intake (BP/OB; n = 47), offspring of parents with BP without BP at intake (non-BP/OB; n = 386), and offspring of matched control parents who did not have BP (controls; n = 301). We also examined the association of baseline sleep parameters with subsequent development of BP among the non-BP/OB group.Pittsburgh Bipolar Offspring Study youth (ages 6-18 years) and their parents completed assessments every two years pertaining to the child's sleep and circadian phenotypes and current psychopathology. Mixed-effects models examined differences in baseline sleep and circadian variables among the three groups.	BP/OB offspring who were in a mood episode differed significantly on sleep parameters from the non-BP/OB and the offspring of controls, such as having inadequate sleep. Mixed logistic regression procedures showed that baseline sleep and circadian variables, such as frequent waking during the night, significantly predicted the development of BP among non-BP/OB over longitudinal follow-up.	While lifetime diagnostic status accounted for differences among the groups in sleep and circadian disturbances, psychopathology explained the differences even further. Additionally, sleep disturbance may be a prognostic indicator of the development of BP in high-risk youth. Future studies are required to further disentangle whether sleep and circadian disruption are state or trait features of BP.	
26547298	Up to 50% of people living with HIV have some neurocognitive impairment. We examined associations of sleep and fatigue with self-reported cognitive problems in 268 adults living with HIV. Multivariate regression was used to examine associations between cognitive problems, self-reported sleep quality, actigraphy-measured total sleep time and wake after sleep onset, and fatigue severity. Poorer self-reported sleep quality (p < .001), short or long total sleep time (<7 or >8 vs. 7-8 hours, p = .015), and greater fatigue (p < .001) were associated with lower self-reported cognitive function scores after controlling for demographic and clinical characteristics. However, objective measure of wake after sleep onset was unrelated to self-reported cognitive function scores. Findings suggest that assessing and treating poor sleep and complaints about fatigue would be areas for intervention that could have a greater impact on improving cognition function than interventions that target only cognitive problems.
26546242	This study examined associations among anxiety, depressive symptoms, and sleep duration in a sample of middle-aged couples using the actor-partner interaction model with dyadic data. Self-report measures were completed independently by both partners as part of the health histories obtained during their annual preventive medical examinations in 2011 and 2012. Results showed that husbands' anxiety and depressive symptoms had a stronger effect on their wives' anxiety and depression than the other way around, but this was not moderated by one's own sleep duration. For both wives and husbands, higher levels of depressive symptoms and anxiety predicted shorter sleep duration for their partner 1 year later, although the effect of husbands' mental health on their wives' was again stronger. The findings suggest that sleep problems might better be treated as a couple-level phenomenon than an individual one, particularly for women.
26542934	Biological rhythms are widespread, allowing organisms to temporally organize their behavior and metabolism in advantageous ways. Such proper timing of molecular and cellular events is critical to their development and health. This is best understood in the case of the circadian clock that orchestrates the daily sleep/wake cycle of organisms. Temporal rhythms can also be used for spatial organization, if information from an oscillating system can be recorded within the tissue in a manner that leaves a permanent periodic pattern. One example of this is the "segmentation clock" used by the vertebrate embryo to rhythmically and sequentially subdivide its elongating body axis. The segmentation clock moves with the elongation of the embryo, such that its period sets the segment length as the tissue grows outward. Although the study of this system is still relatively young compared to the circadian clock, outlines of molecular, cellular, and tissue-level regulatory mechanisms of timing have emerged. The question remains, however, is it truly a clock? Here we seek to introduce the segmentation clock to a wider audience of chronobiologists, focusing on the role and control of timing in the system. We compare and contrast the segmentation clock with the circadian clock, and propose that the segmentation clock is actually an oscillatory ruler, with a primary function to measure embryonic space. 

26540080	Neuropsychiatric symptoms (NPS) are being increasingly recognized as common serious problems in Alzheimer's disease (AD). However, published data on the prevalence of NPS in persons with AD are conflicting. This meta-analysis aimed to estimate the prevalence of NPS in persons with AD.Studies published from 1964 to September 30, 2014, were identified from PubMed and Embase database, reference lists and conference abstracts. We calculated prevalence rates and conducted meta-regression analysis with random-effects model, according to study characteristics, population demographics or condition information.	We identified 48 eligible articles, which provided data for 12 NPS reported in Neuropsychiatric Inventory (NPI). The most frequent NPS was apathy, with an overall prevalence of 49% (95% CI 41-57%), followed by depression, aggression, anxiety and sleep disorder, the pooled prevalence estimates of which were 42% (95% CI 37-46%), 40% (95% CI 33-46%), 39% (95% CI 32-46%) and 39% (95% CI 30-47%), respectively. The less prevalent NPS were irritability (36%, 31-41%), appetite disorder (34%, 27-41%), aberrant motor behavior (32%, 25-38%), delusion (31%, 27-35%), disinhibition (17%, 12-21%) and hallucination (16%, 13-18%). Least common was euphoria, with an overall prevalence of 7% (95% CI 5-9%).	Several aspects, such as the quality of included studies were not always optimal and there was significant heterogeneity of prevalence estimate across studies.	NPS were observed to be highly prevalent in AD patients. Disease duration, age, education level, population origin and the severity of cognitive impairment had influence on the prevalence of some NPS.	
26539760	To investigate the links between group-level affective organizational commitment (AOC) and individual-level psychological well-being, self-reported sickness absence, and sleep disturbances.A total of 5085 care workers from 301 workgroups in the Danish eldercare services participated in both waves of the study (T1 [2005] and T2 [2006]). The three outcomes were analyzed using linear multilevel regression analysis, multilevel Poisson regression analysis, and multilevel logistic regression analysis, respectively.	Group-level AOC (T1) significantly predicted individual-level psychological well-being, self-reported sickness absence, and sleep disturbances (T2). The association between group-level AOC (T1) and psychological well-being (T2) was fully mediated by individual-level AOC (T1), and the associations between group-level AOC (T1) and self-reported sickness absence and sleep disturbances (T2) were partially mediated by individual-level AOC (T1).	Group-level AOC is an important predictor of employee well-being in contemporary health care organizations.	
26539086	The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH) and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc.) and long-term behavioral changes (such as reward seeking and addiction, stress response, etc.) in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation) and long-term changes (such as cocaine seeking) in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological, behavioral, and mental health implications of these findings will be discussed. 
26535746	The airport of Bogotá lies within the city and its expansion could produce an increase in adverse effects on the health of the inhabitants of Fontibón and Engativá districts due to the noise it generates.To determine the prevalence of sleep disturbances and associated factors among residents of Fontibón exposed to this noise.	A cross-sectional study design was used, involving a sample of 205 people aged 18 to 65, selected by means of stratified random sampling. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Descriptive statistics were carried out, as well as correlation tests between the different scales.	A total of 60% of the residents reported poor quality sleep (PSQI>5), with a mean PSQI of 7.19 (SD=3.931), and the following pathological interruptions were found: subjective sleep quality, 27%; sleep latency, 39%; sleep duration, 33%; habitual sleep efficiency, 37%; sleep alterations, 30%; diurnal dysfunction, 40%, and use of sleeping medication, 5%. According to the Epworth Sleepiness Scale (ESS>10), 28% of residents reported daytime somnolence. Regarding the prevalence of poor quality sleep according to the Pittsburgh Sleep Quality Index, 17% of those who reported not being able to sleep because of noise associated this with air traffic. A correlation was observed between the index and the scale ( r =0.329, CI 95%: 0.20-0.44).	Inhabitants of the district reported poor sleep quality due to exposure to noise, airport operations being one of the main generating sources. Noise mitigation strategies in the district need to be reviewed and the public health implications of the El Dorado Airport expansion should be considered.	
26530228	Olanzapine is an atypical antipsychotic drug that inhibits serotonergic, dopaminergic, alpha-1 adrenergic, histaminic, and muscarinic receptors. Several phase I and II trials have been published documenting the use of olanzapine in controlling chemotherapy-induced nausea and vomiting (CINV). This review aims to summarize all phase I and II trials that reported on olanzapine for the prophylaxis of CINV.A literature search was conducted in Ovid MEDLINE from 1946 to July week 1 2015, Embase Classic and Embase from 1947 to 2015 week 28, and the Cochrane Central Register of Controlled Trials up until June 2015. Phase I and II trials reporting on olanzapine for the prophylaxis for CINV were included if they reported on at least one of four primary endpoints: complete response (CR), complete control (CC), no nausea, and no emesis. Other endpoints of interest included the safety of olanzapine as measured by the M.D. Anderson Symptom Inventory.	Across the seven included studies, there were a total of 201 patients. The CR across four studies was 97.2, 83.1, and 82.8 % for the acute, delayed, and overall phases, respectively. The CC for acute, delayed, and overall phases was 92.5, 87.5, and 82.5 %, respectively. The overall no nausea rate was 92.7, 71.8, and 70.6 % for the acute, delayed, and overall phases, respectively. The overall no emesis rates for the acute, delayed, and overall phases were 100, 94.5, and 90.4 %, respectively. Fatigue, drowsiness, and disturbed sleep were common side effects.	Olanzapine is efficacious and safe when used as a prophylaxis for CINV.	
26529175	To determine whether respiratory support via heated humidified high flow nasal cannulae (HHHFNC) results in infants <32weeks gestation spending a greater proportion of time in sleep compared to those receiving nasal continuous positive airway pressure (NCPAP).A subgroup of infants enrolled in a randomized controlled trial to compare HHHFNC or NCPAP post-extubation had sleep and wake activity measured by actigraphy for 72hours post-extubation. Activity diaries were completed contemporaneously to record episodes of infant handling. Actigraphy data were downloaded with known periods of handling excluded from the analysis.	28 infants with mean gestation of 28.3weeks (SD 2) and birth weight 1074g (SD 371) were studied. Infants receiving HHHFNC spent a lesser proportion of time in sleep 59.8% (SD 18.5) than those on NCPAP 82.2% (SD 23.8) p=0.004. Infants receiving HHHFNC had a lower sleep efficiency and higher mean activity score than those on NCPAP (p=0.003, p=0.002, respectively).	Infants receiving HHHFNC had a higher mean activity score and spent less time in sleep than those allocated NCPAP. Further study of sleep wake activity in preterm infants receiving respiratory support is required as this may impact on neurodevelopmental outcomes.	
26528146	Up to the present time cerebral cortex was considered as substrate for realization of the highest psychical functions including consciousness. Cortical sensory areas were regarded as structures specialized for processing of information coming from one particular modality (visual, auditory, somatosensory, and so on). However, studies of cortical activity in sleep-wake cycle demonstrated that during sleep the same neurons in the same cortical areas switch to processing of signals coming from the various visceral systems. After awakening these visceral responses disappear and the neurons return to processing of the information coming from the exteroreceptors. These observations indicate that most likely cortical areas are universal processors, which perform particular operations with incoming information independent of its origin. During wakefulness, results of the information processing on the cortical level should be directed to structures connected with organization of behavior and consciousness, while during sleep cortical outputs should be redirected to structures performing integration of the visceral information. Thus, results of sleep studies indicate that current brain paradigm should be changed. 
26527070	Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players in the regulation and maintenance of sleep-wake-dependent changes in neuronal activity and the sleep-wake continuum. Dysregulation of these neurochemical systems leads to sleep-wake disorders. Most currently available pharmacological treatments are symptomatic rather than causal, and their beneficial and adverse effects are often variable and in part genetically determined. To evaluate opportunities for evidence-based personalized medicine with present and future sleep-wake therapeutics, we review here the impact of known genetic variants affecting exposure of and sensitivity to drugs targeting the neurochemistry of sleep-wake regulation and the pathophysiology of sleep-wake disturbances. Many functional polymorphisms modify drug response phenotypes relevant for sleep. To corroborate the importance of these and newly identified variants for personalized sleep-wake therapy, human sleep pharmacogenetics should be complemented with pharmacogenomic investigations, research about sleep-wake-dependent pharmacological actions, and studies in mice lacking specific genes. These strategies, together with future knowledge about epigenetic mechanisms affecting sleep-wake physiology and treatment outcomes, may lead to potent and safe novel therapies for the increasing number of sleep-disordered patients (e.g., in aged populations). 
26526372	Sleep is thought to be controlled by two main processes: a circadian clock that primarily regulates sleep timing and a homeostatic mechanism that detects and responds to sleep need. Whereas abundant experimental evidence suggests that sleep need increases with time spent awake, the contributions of different brain arousal systems have not been assessed independently of each other to determine whether certain neural circuits, rather than waking per se, selectively contribute to sleep homeostasis. Using the fruit fly, Drosophila melanogaster, we found that sustained thermogenetic activation of three independent neurotransmitter systems promoted nighttime wakefulness. However, only sleep deprivation resulting from activation of cholinergic neurons was sufficient to elicit subsequent homeostatic recovery sleep, as assessed by multiple behavioral criteria. In contrast, sleep deprivation resulting from activation of octopaminergic neurons suppressed homeostatic recovery sleep, indicating that wakefulness can be dissociated from accrual of sleep need. Neurons that promote sleep homeostasis were found to innervate the central brain and motor control regions of the thoracic ganglion. Blocking activity of these neurons suppressed recovery sleep but did not alter baseline sleep, further differentiating between neural control of sleep homeostasis and daily fluctuations in the sleep/wake cycle. Importantly, selective activation of wake-promoting neurons without engaging the sleep homeostat impaired subsequent short-term memory, thus providing evidence that neural circuits that regulate sleep homeostasis are important for behavioral plasticity. Together, our data suggest a neural circuit model involving distinct populations of wake-promoting neurons, some of which are involved in homeostatic control of sleep and cognition.
26526314	In this longitudinal two-wave study, bidirectional relations between work-related stress and sleep quality were examined. Moreover, it was investigated whether perseverative cognition is a potential underlying mechanism in this association, related to both work-related stress and sleep quality.A randomly selected sample of Dutch employees received an online survey in 2012 and 2013. Of all invited employees, 877 participated in both waves. Structural equation modeling was performed to analyze the data.	We found evidence for reversed relations between work-related stress and sleep quality. Specifically, when controlling for perseverative cognition, work-related stress was not directly related to subsequent sleep quality, but low sleep quality was associated with an increase in work-related stress over time. Moreover, negative bidirectional associations over time were found between perseverative cognition and sleep quality, and positive bidirectional associations were found between work-related stress and perseverative cognition. Lastly, a mediation analysis showed that perseverative cognition fully mediated the relationship between work-related stress and sleep quality.	The study findings suggest that perseverative cognition could be an important underlying mechanism in the association between work-related stress and sleep quality. The bidirectionality of the studied relationships could be an indication of a vicious cycle, in which work-related stress, perseverative cognition, and sleep quality mutually influence each other over time.	
26525812	Цель исследования - оценка информированности врачей разного профиля об актуальности проблемы инсомнических расстройств, методах их диагностики и лечения. Материал и методы. Было проведено анкетирование 90 врачей различных терапевтических специальностей в лечебно-профилактических учреждениях Казани. Результаты. Установлено, что основными причинами нарушений сна врачи называют стрессовые факторы (20%), депрессию (13%), неврозы (13%), хронические заболевания (13%), астению (10%), болевой синдром (10%). Большие различия были выявлены при анализе назначений, которые делают врачи при расстройствах сна. Заключение. Полученные данные свидетельствуют о том, что врачи плохо осведомлены о проблемах нарушений сна, имеют лишь приблизительное представление о методах его исследования и соответствующих лечебных препаратах, а также последовательности их использования для устранения расстройств сна.To assessdoctor's knowledge on the relevance of the problem of sleep disorders, methods of their diagnosis and treatment.	The survey was conducted among90physicians of different the rapeuticspecialties of Kazan medical institutions.	The doctors believe that main causes of sleep disorders are stressors (20%), depression (13%), neurosis (13%), chronic diseases (13%), asthenia (10%), pain (10%). An analysis of treatment prescribed to patients with sleep disorders revealed large differences.	Physicians are not well informed about the problems of sleep disorders, have a small idea of the methods of sleepresearch and drugs for their treatment as well as of a sequence of operations that should be used to resolve this problem.	
26524839	Insomnia is one of the most common complaints of psychiatric patients. Educational approaches for mental health always recommend early detection and intervention for insomnia. However, too much emphasis on insomnia may lead to overdiagnosis and overtreatment. Psychiatrists are often accused of overprescribing hypnotics to patients with sleep disturbance. This drug is difficult to discontinue due to factors associated with both patients and prescribers. In order to prevent the unneccessary administration of hypnotics, clinicians should evaluate both the sleep quality and daytime activities of patients. A sleep diary may help this process. Clinicians should prescribe hypnotics only when a patient's sleep disturbance is neither a part of the symptoms of major psychiatric disorders nor sleep-wake schedule disorders, and is not a consequence of inadequate lifestyle behavior. The reasonable goal of hypnotic treatment should be set in advance, and then pharmacological and psychosocial interventions for insomnia should be initiated.
26523766	A real-time fitting system is developed and used to fit the predictions of an established physiologically-based neural field model to electroencephalographic spectra, yielding a trajectory in a physiological parameter space that parametrizes intracortical, intrathalamic, and corticothalamic feedbacks as the arousal state evolves continuously over time. This avoids traditional sleep/wake staging (e.g., using Rechtschaffen-Kales stages), which is fundamentally limited because it forces classification of continuous dynamics into a few discrete categories that are neither physiologically informative nor individualized. The classification is also subject to substantial interobserver disagreement because traditional staging relies in part on subjective evaluations. The fitting routine objectively and robustly tracks arousal parameters over the course of a full night of sleep, and runs in real-time on a desktop computer. The system developed here supersedes discrete staging systems by representing arousal states in terms of physiology, and provides an objective measure of arousal state which solves the problem of interobserver disagreement. Discrete stages from traditional schemes can be expressed in terms of model parameters for backward compatibility with prior studies. 
26522742	This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time.
26522276	Baseline sleep duration has a U-shaped relationship with type 2 diabetes, but little research examines the associated changes. We examined long-term changes in sleep duration and concomitant changes in diet, physical activity, weight and subsequent diabetes.The cohort includes 59,031 women aged 55-83 years in the Nurses' Health Study without diabetes in 2000. Change in sleep duration is the difference between self-reported 24 h sleep duration in 1986 and 2000. Diet, physical activity and covariates were updated every 2-4 years. Self-reported diabetes was confirmed via validated questionnaires. Cox regression models were adjusted for 1986 sleep duration and 1986 values of diabetes risk factors, including BMI, and subsequently for change in covariates from 1986 to 2000.	We documented 3,513 incident diabetes cases through to 2012. Compared with no change, decreases in sleep duration were adversely associated with changes in diet quality and physical activity, while increases were associated with greater weight gain. After adjustment for 1986 covariates, HRs (95% CI) for ≤ -2, > -2 to < 0, > 0 to < 2 and ≥ 2 h/day changes in sleep duration (vs no change) were 1.09 (0.93, 1.28), 1.10 (1.001, 1.12), 1.09 (1.00, 1.18) and 1.30 (1.14, 1.46), respectively. Additional adjustment for diet and physical activity did not appreciably alter the results. Increases in sleep duration ≥ 2 h/day remained adversely associated with diabetes (HR [95% CI]: 1.15 [1.01, 1.30]) after adjustment for change in covariates, including BMI.	Increases in sleep duration among middle-aged and older women were modestly associated with risk of diabetes; changes in diet, physical activity and BMI did not explain associations.	
26521875	The endogenous circadian clock drives robust oscillations in physiology and behavior, such as hormone secretions and sleep/wake cycles, with a period of about 24 h. We are rarely aware of this internal clock system because it is usually synchronized with environmental light-dark cycles. However, travelling rapidly across multiple time zones in a jet airplane suddenly makes us aware of the desynchrony between the body clock and external time, causing sleep disturbances and gastrointestinal problems. Although jet lag is recognized as a chronobiological problem, its specific molecular and neural mechanisms are poorly understood. To address this issue, we identified genes highly expressed in the suprachiasmatic nucleus of the anterior hypothalamus (SCN), the mammalian master clock that controls rhythmic behavior, then analyzed the behavior of knock-out mice for these genes under jet lag condition. We found that the circadian rhythms of locomotor activity and clock gene expression rapidly re-entrained to phase-shifted light-dark cycles in mice genetically deficient in V1a and V1b receptors. Real-time imaging of cellular rhythms in the SCN suggested that interneuronal communication through V1a and V1b confers on the SCN an intrinsic resistance to external perturbation, enhancing the robustness of the SCN clockwork. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice accelerated their recovery from jet lag symptoms, suggesting vasopressin signaling as a potential pharmaceutical intervention for the management of circadian rhythm misalignment.
26521721	Sleep problems, including sleep apnoea and behavioural sleep disturbances, are common among adults with Down syndrome (DS). Despite a preliminary understanding of potential medical and behavioural comorbidities of these sleep problems among children with DS, little is known about comorbid conditions associated with these sleep problems among adults with DS. Understanding causes and sequelae of sleep problems in this ageing population is essential to providing quality health screening and treatment. The current study examines the physical health problems, mental health conditions, functional abilities and behavioural problems associated with sleep apnoea and behavioural sleep disturbances among adults with DS.Family caregivers participated in clinical interviews and completed questionnaires, providing reports regarding 75 adults with DS. Caregivers reported on sleep problems, physical and mental health conditions, daily living skills and behaviours regarding their ageing family member with DS.	Sleep apnoea was associated with more common other respiratory concerns, and more frequent visits to physicians, but not with some expected medical comorbidities (cardiac). Behavioural sleep disturbances (delayed sleep onset, night-time awakenings and morning awakenings) were associated with poorer health, more frequent overnight hospital and emergency department visits, more common cardiac conditions, less common thyroid condition, more common mental health conditions (anxiety, depression and dementia) and a higher rate of daytime behaviour problems.	The study findings suggest that there are differential correlates for the various sleep problems in adults with DS, which warrant attention when screening for medical and mental health comorbidities, assessing behavioural problems and in treatment planning for ageing adults with DS.	
26521571	To compare the difference of clinical efficacy on sleeping disorder in the children with encephalopathy between the combined therapy of acupuncture at head points and seed-pressure at ear points and the simple acupuncture at head points.Thirty cases of sleeping disorder induced by encephalopathy werei randomized into an observation group and a control group, 15 cases in each one. In the observation group, the combined therapy of acupuncture at head points and seed-pressure at ear points was adopted. The head points in cluded Sishencong (EX-HN 1), Shenting (GV 24) and Benshen (GB 13). The ear points were the positive reactive sites in the cymba and cavum conchae. In the control group, acupuncture was applied simply to the acupoints on the head. The treatment was given once on every Tuesday and Friday a week separately, 30 min each time. Totally, 16 treatments were required. Children's sleeping habit questionnaire (CSHQ) was used to observe the sleep improvements and the efficacy in the patients of the two groups.	In the observation group, the results of sleep resistance, sleep anxiety, night sleep wake, parasomnias, sleep dyspnea, daytime somnolence and the total score after treatment were all improved apparently as compared with those before treatment (all P<0. 05). In the control group, the results of night sleep wake, parasomnias, daytime somnolence and the total score after treatment were improved apparently than those before treatment (all P<0. 05). In the observation group, the results of sleep resistance, sleep dyspnea and the total score after treatment were better than those in the control group (all P<0. 05) and the scores of sleep anxiety and daytime somnolence in the control group were better than those in the observation group after treatment (both P<0. 05).	The combined therapy of acupuncture at head points and seed-pressure at the positive reactive sites in the cymba and cavum conchae achieves the superior efficacy on sleep resistance and sleep dyspnea as compared with the simple acupuncture. The efficacy of simple acupuncture is more satisfactory on sleep anxiety and daytime somnolence.	
26521484	Parkinson disease (PD) is a common neurodegenerative disease characterized by classical motor symptoms, including static tremor, bradykinesia, rigidity and postural and gait abnormalities. Besides, recent studies have found a variety of non-motor symptoms, including neuropsychiatric symptoms, sleep disorders, abnormal sensory and autonomic dysfunctions, etc. PD with pure apathy, referring to apathy without dementia and depression, is correlated with motor symptoms and other non-motor symptoms, and greatly reduces the activity of daily living and the quality of life for PD patients. The pathogenesis of PD with pure apathy involves the mechanisms of neuroanatomy, neuropathology, neurological biochemistry and neuroinflammation. This paper will introduce the clinical features and pathogenic mechanisms of PD with pure apathy.
26521253	Reduced sleep quality has been linked to obesity; however, no studies have assessed the impact of gastrointestinal (GI) symptoms on sleep quality among obese individuals. This study aims to determine the role of gastrointestinal symptoms on sleep among obese individuals in a community-based sample.A validated questionnaire was sent to 5000 randomly selected subjects in Western Sydney, Australia. Assessed were five GI symptoms that might wake individuals from sleep (abdominal pain, diarrhea, chest pain, acid regurgitation, and heartburn). Sleep quality was measured using the validated Pittsburgh Sleep Quality Index (PSQI). Additional measures included socioeconomic status (SES) and body mass index (BMI).	The response rate was 60 %. There were 647 (25.13 %) obese individuals. Prevalence estimates for general quality of sleep were reported as very good (18.51 %), fairly good (53.19 %), fairly bad (20.68 %), and very bad (7.62 %). Obese individuals reported less hours of actual sleep than nonobese individuals (OR = 0.87; 95 % CI 0.81-0.94). Quality of sleep was worse for obese compared to nonobese individuals (OR = 1.25; 95 % CI 1.12-1.40). Univariate analysis found that all GI symptoms were more likely to wake obese people from their sleep; however, only two GI symptoms (chest pain: OR = 1.60; 95 % CI 1.25-2.04) and (acid regurgitation: OR = 1.27; 95 % CI 1.05-1.53) were independent predictors of sleep disturbance.	Gastrointestinal symptoms did not predict waking in nonobese individuals. Chest pain and acid regurgitation are major GI symptoms associated with waking obese individuals from sleep. Overall, obese individuals have a worse quality of sleep compared to nonobese individuals.	
26520846	Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's α: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients. 
26519752	Sleep plays an important role in memory processing. However, its role in anesthesia-induced cognitive dysfunction was not revealed. Our study sought to investigate the connection between the cognition decline and sleep-wake rhythm disorders after long-term isoflurane anesthesia in mice. Also, we examined the effect of exogenous melatonin pretreatment on both cognitive function and circadian rhythm. Furthermore, we discussed whether NR2B (N-methyl-D-aspartate receptor 2B subunit)-CREB (cAMP-response element binding protein) signaling pathway was involved in this course.2-month-old male C57/BL-6J mice were submitted to long-term anesthesia using 1% isoflurane from CT (Circadian Time) 14 to CT20. Melatonin pretreatment were conducted before anesthesia for 7 Days. Intellicage for mice and Mini-Mitter were applied to monitor spatial memory and gross motor activity which can reflect cognition and sleep-wake rhythm. Messenger RNA and protein expression of right hippocampus NR2B and CREB were examined by RT-PCR and Western blot.	6h isoflurane anesthesia led to impaired spatial memory from Day 3 to Day 10 in mice accompanied by the disruption of sleep-wake rhythm. Meanwhile, the hippocampus CREB and NR2B expression declined in step. Melatonin pretreatment ameliorated disturbed sleep-wake cycle, improved isoflurane-induced cognitive dysfunction, and reversed the down-regulation of CREB and NR2B expression.	Our data demonstrate that sleep-wake rhythm is involved in the isoflurane-induced cognition impairment and pretreatment of melatonin has a positive effect on circadian normalization and cognition reversal. Also, NR2B-CREB signaling pathway has a critical role in this process. This study provides us a new strategy for anesthesia-induced cognitive dysfunction therapy.	
26519636	Sleep disturbance in bipolar disorder (BD) is common during and between mood episodes. In recovered (euthymic at least two months) BD patients, we assessed sleep compared to controls and its relationships with residual mood symptoms and mood episode recurrence.Recovered Stanford University BD Clinic patients diagnosed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and monitored with the STEP-BD Clinical Monitoring Form (CMF) for >1 year and healthy controls completed the Pittsburgh Sleep Quality Index (PSQI). PSQI parameters were compared in BD patients versus controls, and the most robustly differentiating PSQI parameter was assessed in relationship to residual mood symptoms, and time to mood episode recurrence in BD patients.	Eighty nine recovered BD patients compared to 56 healthy controls had significantly worse PSQI global score, more sleep medication use, longer sleep latency, and worse daytime dysfunction. PSQI global score had the greatest BD patient versus control effect size, and among BD patients, correlated significantly with residual mood symptoms and predicted earlier mood episode recurrence, even after covarying for residual mood symptoms.	Use of subjective (PSQI) rather objective (polysomnography) sleep metric. Statistical power limited by small sample size. Potential psychotropic medication confound. Northern California tertiary BD clinic referral sample.	Further research is needed to confirm that in recovered BD patients, poor sleep quality correlates with residual mood symptoms, and independently predicts mood episode recurrence. If confirmed, these observations suggest potential mood benefit for focusing on sleep quality in interventions for recovered BD patients.	
26519492	Obstructive Sleep Apnea (OSA) is the most commonly undiagnosed sleep disorder and is gaining more recognition in dentistry. Dental hygienists are at a pivotal position to discuss risks, characteristics, medical referrals and treatment options for OSA, as well as detect if an individual has OSA through questionnaires and other tools that can be done during an examination. Dental hygienists need to receive appropriate education about OSA and should be well versed in their knowledge to educate patients. The purpose of this literature review is to identify the role of the dental hygienist in detecting the risk of OSA and gain knowledge on the topic in order to educate patients.
26518707	One of the goals of the American Academy of Sleep Medicine (AASM) is to provide clear, evidence-based recommendations in our clinical practice guidelines. Periodically, the AASM will assess and update the process by which these guidelines are developed so that it is in line with the standards currently being used for guideline development. The AASM is now taking the next step forward by fully adopting GRADE (Grading of Recommendation Assessment, Development and Evaluation) as the methodology used for evaluating evidence and forming clinical practice guidelines recommendations. Starting this year, AASM recommendations will be based on the following four interdependent domains: 1. quality of evidence; 2. balance of desirable and undesirable consequences; 3. patients' values and preferences; and 4. resource use (when known). AASM strengths of recommendations will be dichotomized into two categories: "Strong" and "Weak," either for or against a patient-care strategy. In an effort to provide clarity and transparency, all AASM recommendations will be actionable statements that include the specific patient population for which the patient-care strategy is recommended, and clearly define the comparator against which the patient-care strategy was evaluated. In some recommendations, the comparator will be an alternative patient-care strategy (e.g., a "gold standard" or previously available alternative), while in other recommendations the comparator will be a placebo or no treatment; this is determined by the availability of evidence, and analyses decisions made by the AASM task force. Implementation of the complete GRADE criteria by the AASM allows us the best path forward towards continuing to provide high quality clinical practice guidelines.
26518701	Sound level meter is the gold standard approach for snoring evaluation. Using this approach, it was established that snoring intensity (in dB) is higher for men and is associated with increased apnea-hypopnea index (AHI). In this study, we performed a systematic analysis of breathing and snoring sound characteristics using an algorithm designed to detect and analyze breathing and snoring sounds. The effect of sex, sleep stages, and AHI on snoring characteristics was explored.We consecutively recruited 121 subjects referred for diagnosis of obstructive sleep apnea. A whole night audio signal was recorded using noncontact ambient microphone during polysomnography. A large number (> 290,000) of breathing and snoring (> 50 dB) events were analyzed. Breathing sound events were detected using a signal-processing algorithm that discriminates between breathing and nonbreathing (noise events) sounds.	Snoring index (events/h, SI) was 23% higher for men (p = 0.04), and in both sexes SI gradually declined by 50% across sleep time (p < 0.01) independent of AHI. SI was higher in slow wave sleep (p < 0.03) compared to S2 and rapid eye movement sleep; men have higher SI in all sleep stages than women (p < 0.05). Snoring intensity was similar in both genders in all sleep stages and independent of AHI. For both sexes, no correlation was found between AHI and snoring intensity (r = 0.1, p = 0.291).	This audio analysis approach enables systematic detection and analysis of breathing and snoring sounds from a full night recording. Snoring intensity is similar in both sexes and was not affected by AHI.	
26518595	Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells.HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles.	HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10(-4)), C*04:01 (OR = 1.34 [1.10-1.63] P = 3.23*10(-3)), and B*35:01 (OR = 1.46 [1.13-1.89] P = 3.64*10(-3)) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr(9) (OR = 1.32 [1.15-1.52] P = 6.95*10(-5)) and HLA-C-Ser(11) (OR = 1.34 [1.15-1.57] P = 2.43*10(-4)).	Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.	
26518594	Historically, mathematical models of human neurobehavioral performance developed on data from one sleep study were limited to predicting performance in similar studies, restricting their practical utility. We recently developed a unified model of performance (UMP) to predict the effects of the continuum of sleep loss-from chronic sleep restriction (CSR) to total sleep deprivation (TSD) challenges-and validated it using data from two studies of one laboratory. Here, we significantly extended this effort by validating the UMP predictions across a wide range of sleep/wake schedules from different studies and laboratories.We developed the UMP on psychomotor vigilance task (PVT) lapse data from one study encompassing four different CSR conditions (7 d of 3, 5, 7, and 9 h of sleep/night), and predicted performance in five other studies (from four laboratories), including different combinations of TSD (40 to 88 h), CSR (2 to 6 h of sleep/night), control (8 to 10 h of sleep/night), and nap (nocturnal and diurnal) schedules.	The UMP accurately predicted PVT performance trends across 14 different sleep/wake conditions, yielding average prediction errors between 7% and 36%, with the predictions lying within 2 standard errors of the measured data 87% of the time. In addition, the UMP accurately predicted performance impairment (average error of 15%) for schedules (TSD and naps) not used in model development.	The unified model of performance can be used as a tool to help design sleep/wake schedules to optimize the extent and duration of neurobehavioral performance and to accelerate recovery after sleep loss.	
26518593	To investigate the association between self-reported and objective measures of sleep and wind turbine noise (WTN) exposure.The Community Noise and Health Study, a cross-sectional epidemiological study, included an in-house computer-assisted interview and sleep pattern monitoring over a 7 d period. Outdoor WTN levels were calculated following international standards for conditions that typically approximate the highest long-term average levels at each dwelling. Study data were collected between May and September 2013 from adults, aged 18-79 y (606 males, 632 females) randomly selected from each household and living between 0.25 and 11.22 kilometers from operational wind turbines in two Canadian provinces. Self-reported sleep quality over the past 30 d was assessed using the Pittsburgh Sleep Quality Index. Additional questions assessed the prevalence of diagnosed sleep disorders and the magnitude of sleep disturbance over the previous year. Objective measures for sleep latency, sleep efficiency, total sleep time, rate of awakening bouts, and wake duration after sleep onset were recorded using the wrist worn Actiwatch2® from a subsample of 654 participants (289 males, 365 females) for a total of 3,772 sleep nights.	Participant response rate for the interview was 78.9%. Outdoor WTN levels reached 46 dB(A) with an arithmetic mean of 35.6 and a standard deviation of 7.4. Self-reported and objectively measured sleep outcomes consistently revealed no apparent pattern or statistically significant relationship to WTN levels. However, sleep was significantly influenced by other factors, including, but not limited to, the use of sleep medication, other health conditions (including sleep disorders), caffeine consumption, and annoyance with blinking lights on wind turbines.	Study results do not support an association between exposure to outdoor WTN up to 46 dB(A) and an increase in the prevalence of disturbed sleep. Conclusions are based on WTN levels averaged over 1 y and, in some cases, may be strengthened with an analysis that examines sleep quality in relation to WTN levels calculated during the precise sleep period time.	
26517583	To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS).Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires.	The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom.	Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research.	
26514204	Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents. 

26512775	Provide evidence-based recent data on oral micronized progesterone (OMP) and progestins in menopausal hormonal therapy (MHT).Medroxyprogesterone acetate (MPA) increases breast cancer acting through the glucocorticoid receptor; progestins in MHT increase thrombosis more than oral estrogens; MPA, but not OMP or other progestins, increase monocyte cell endothelium adhesion; MPA and estradiol (E2)/MPA have negative brain effects, whereas E2/progesterone (P4) has neuroregenerative brain effects. The 'window of opportunity' cardiovascular disease hypothesis is not supported by a randomized controlled trial showing that transdermal estradiol with sequential OMP in early menopause does not prevent increased carotid intimal media thickness; P4 in the cardiac electrical system opposes E2 effects and prevents sudden death/long QT syndrome; transdermal estradiol/OMP does not increase venous thromboembolism in observational data. P4 decreases breast cell proliferation and improves prognosis through P4 receptor alteration of estrogen receptor α genetic effects; OMP with conjugated equine estrogen (CEE)/estrogen (E)/E2 does not increase breast cancer in two prospective cohorts, one population-based. Endometrial cancer is increased in MHT of CEE/E/E2+cyclic OMP at 200 mg/day.	New data show CEE/E/E2+MPA/P mechanisms for negative breast cancer, venous thromboembolism, cardiovascular system, and brain effects. OMP/P4 counterbalances CEE/E/E2-related negative effects on breast cancer and long QT syndrome. OMP effectively treats vasomotor symptoms and sleep disturbances, and could safely be used alone for symptomatic menopause.	
26512752	Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep-wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72 h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep-wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep-wake behavior patterns. 
26512051	(1) To compare sleep (nighttime sleep duration and sleep efficiency) and sleep fragmentation (movement and fragmentation index), as measured by actigraphy, and symptoms (pain and fatigue) in 8- to 14-year-old children with polyarticular and extended oligoarticular juvenile idiopathic arthritis (JIA) and (2) to examine the associations between sleep fragmentation (movement and fragmentation index) and the calcium-binding protein biomarkers S100A12 and myeloid-related protein (MRP8/14).Participants included 40 children with extended oligoarticular (n = 15) or polyarticular (n = 25) JIA and their parents. Serum protein samples were obtained during routine rheumatology clinic visits. Children completed the PedsQL Multidimensional Fatigue Scale and daily pain and sleep diaries and wore actigraphy monitors for 9 consecutive days. Parents completed the Children's Sleep Habits Questionnaire (CSHQ).	Of the 40 children, 68% scored above the CSHQ clinical cutoff score for sleep disturbances. Mean nighttime sleep duration was 7.5 hr, and mean sleep efficiency was 85.3%. Group differences were not found for nighttime sleep duration, sleep efficiency, movement and fragmentation index, or S100A12 and MRP8/14 protein concentrations. In a stepwise regression, medications, joint count, and movement and fragmentation index explained 21% of the variance in MRP8/14 concentration.	Decreased nighttime sleep duration, poor sleep efficiency, and fragmented sleep were observed in our sample, regardless of JIA category. Sleep fragmentation was a significant predictor of MRP8/14 protein concentration. Additional research is needed to understand the interrelations among sleep fragmentation, effects of medication, and S100A12 and MRP8/14 protein biomarkers in JIA.	
26507124	Past research has consistently found that evening-types typically report poorer academic adjustment and higher levels of substance use compared to morning-types. An important development within the morningness-eveningness and psychosocial adjustment literature has been the hypothesis that social jetlag (i.e. the asynchrony between an individual's "biological" and "social" clocks) is one factor that may explain why evening-types are at a greater risk for negative psychosocial adjustment. Yet, only a handful of studies have assessed social jetlag. Furthermore, the few studies that have assessed social jetlag have done so only with concurrent data, and thus have not been able to determine the direction of effects among morningness-eveningness, social jetlag and psychosocial adjustment. To address this important gap in the literature, the present 3-year longitudinal study employed the use of a cross-lagged auto-regressive model to specifically examine the predictive role of perceived morningness-eveningness and social jetlag on two important indices of psychosocial adjustment among university students: academic adjustment and substance use. We also assessed whether there would be an indirect effect between perceived morningness-eveningness and psychosocial adjustment through social jetlag. Participants were 942 (71.5% female; M = 19 years, SD = 0.90) undergraduates at a mid-sized university in Southern Ontario, Canada, who completed a survey at three assessments, each one year apart, beginning in first-year university. Measures were demographics (age, gender and parental education), sleep problems, perceived morningness-eveningness, social jetlag, academic adjustment and substance use. As hypothesized, results of path analyses indicated that a greater perceived eveningness preference significantly predicted higher social jetlag, poorer academic adjustment and higher substance use over time. In contrast, we found no support for social jetlag as a predictor of academic adjustment and substance use, indicating that social jetlag did not explain the link between perceived morningness-eveningness and negative psychosocial adjustment. An important finding was the significant predictive effect of higher substance use on social jetlag over time. Results of the present study highlight the importance of employing a longitudinal framework within which to specifically determine the direction of effects among the study variables in order to validate proposed theoretical models that aim to guide our understanding of how perceived morningness-eveningness, social jetlag, academic adjustment and substance use relate to each other. 

26501968	The aim of this study was to evaluate the presence of degenerative bone changes of the temporomandibular joint (TMJ) in individuals suffering from sleep bruxism (SB), associating these characteristics with the quality of sleep. For this, we followed the International Classification of Sleep Disorders for the diagnosis of SB, in addition to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for the classification of TMD and cone beam computed tomography. It was found that 97.7% of the individuals with bruxism had at least 1 RDC/TMD group III diagnosis, 75.6% of the subjects considered their sleep quality as poor, and the largest group (23%) had centric bruxism. There was no significant association between the pattern of sleep quality (P = 0.36), the type of SB (P = 0.277), and the presence of degenerative changes of the TMJ. Regardless of the quality of sleep and the type of bruxism presented, the prevalence of degenerative bone disorders was high (67%) among women with a mean age of 46 years and a clinical diagnosis of SB. 
26499809	The transition from wakefulness into sleep is accompanied by modified activity in the brain's thalamocortical network. Sleep-related decreases in thalamocortical functional connectivity (FC) have previously been reported, but the extent to which these changes differ between thalamocortical pathways, and patterns of intra-thalamic FC during sleep remain untested. To non-invasively investigate thalamocortical and intra-thalamic FC as a function of sleep stage we recorded simultaneous EEG-fMRI data in 13 healthy participants during their descent into light sleep. Visual scoring of EEG data permitted sleep staging. We derived a functional thalamic parcellation during wakefulness by computing seed-based FC, measured between thalamic voxels and a set of pre-defined cortical regions. Sleep differentially affected FC between these distinct thalamic subdivisions and their associated cortical projections, with significant increases in FC during sleep restricted to sensorimotor connections. In contrast, intra-thalamic FC, both within and between functional thalamic subdivisions, showed significant increases with advancement into sleep. This work demonstrates the complexity and state-specific nature of functional thalamic relationships--both with the cortex and internally--over the sleep/wake cycle, and further highlights the importance of a thalamocortical focus in the study of sleep mechanisms.
26498239	Behavioral sleep problems are ideally measured using a combination of objective and subjective measures. However, this is not always feasible. Thus, a global subjective measure has been used to assess sleep problems in children with attention deficit hyperactivity disorder (ADHD), yet it is unclear how this relates to more detailed multidimensional measures of sleep problems. In children with ADHD, parent report of a global measure of sleep problem severity (classified no/mild versus moderate/severe) is compared with the following: (1) a 7-Day Sleep Log and (2) the validated Children's Sleep Habits Questionnaire (CSHQ).This study recruited 392 children with ADHD (aged 5-13 years) from 50 pediatric practices across Victoria, Australia. All caregivers completed the CSHQ, and 257 children prospectively completed the 7-Day Sleep Logs.	Sleep log data identified distinct sleep patterns according to parent-reported sleep problem severity; children with moderate/severe sleep problems slept 30 min less per day, took longer to fall asleep, and experienced more night awakenings. This pattern was also repeated across the CSHQ, where children with moderate/severe sleep problems experienced more problematic sleep symptoms across all domains (effect sizes: 0.5-1.1; all p < 0.001).	A subjective, global measure of sleep problem severity appears to be a useful tool for the initial assessment of sleep problems in children with ADHD when more extensive measures are not feasible, as it is reflective of well-established multidimensional measures. However, further research is required to determine its validity.	
26497901	The present study aims to explore the extent to which gender, epilepsy severity and illness perceptions predict fatigue and sleep problems in youngsters with epilepsy.Structured interviews were conducted in 100 young patients (Mage = 13,9, SD = 2.21; 41% girls) and data were analyzed by means of multiple hierarchical regression analyses.	Most patients (91%) were well controlled by anti-epileptics; 3% had infrequent seizures and 6% were pharmacoresistant. At a multivariate level it appeared that youngsters with epilepsy who believe that they have less personal control over their illness and who feel that the illness has a high emotional impact on their lives reported higher levels of fatigue. In addition, more sleep problems were reported by youngsters who think they have less personal control over the disease, who believe that treatment controls epilepsy and report that the disease has a high emotional impact on their lives.	Given the importance of illness perceptions, it is suggested that they are targets for future interventions that aim to reduce fatigue and sleep problems in youngsters with epilepsy.	
26496476	Slow wave activity (SWA) generation depends on cortico-thalamo-cortical loops that are disrupted in patients with chronic Disorders of Consciousness (DOC), including the Unresponsive Wakefulness Syndrome (UWS) and the Minimally Conscious State (MCS). We hypothesized that the modulation of SWA by means of a repetitive transcranial magnetic stimulation (rTMS) could reveal residual patterns of connectivity, thus supporting the DOC clinical differential diagnosis. We enrolled 10 DOC individuals who underwent a 24hh polysomnography followed by a real or sham 5Hz-rTMS over left primary motor area, and a second polysomnographic recording. A preserved sleep-wake cycle, a standard temporal progression of sleep stages, and a SWA perturbation were found in all of the MCS patients and in none of the UWS individuals, only following the real-rTMS. In conclusion, our combined approach may improve the differential diagnosis between MCS patients, who show a partial preservation of cortical plasticity, and UWS individuals, who lack such properties. 
26496458	The aim of this paper was to provide an overview of the literature on clinically significant burnout, focusing on its assessment, associations with sleep disturbances, cognitive impairments, as well as neurobiological and physiological correlates. Fifty-nine English language articles and six book chapters were included. The results indicate that exhaustion disorder (ED), as described in the Swedish version of the International Classification of Diseases, seems to be the most valid clinical equivalent of burnout. The data supports the notion that sleep impairments are causative and maintaining factors for this condition. Patients with clinical burnout/ED suffer from cognitive impairments in the areas of memory and executive functioning. The studies on neuro-biological mechanisms have reported functional uncoupling of networks relating the limbic system to the pre-frontal cortex, and decreased volumes of structures within the basal ganglia. Although there is a growing body of literature on the physiological correlates of clinical burnout/ED, there is to date no biomarker for this condition. More studies on the role of sleep disturbances, cognitive impairments, and neurobiological and physiological correlates in clinical burnout/ED are warranted. 
26494569	Cognitive, affective, and behavioural disturbances are commonly reported following thalamic strokes. Conversely, sleep disorders are rarely reported in this context.Herein, we report the cases of two young patients admitted for an ischemic stroke located in the territories of the left pre-mammillary and paramedian arteries. Together with aphasia, memory complaint, impaired attention and executive functions, they reported lucid dreams with catastrophic content or conflicting situations.	Lucid dreams are an atypical presentation in thalamic strokes. These cases enlarge the clinical spectrum of sleep-wake disturbances potentially observed after an acute cerebrovascular event.	
26494526	The poor sleep quality is one of the major risk factors of somatic, psychiatric and social disorders and conditions as well as the major predictors of quality of employees' performance. The previous studies in Iran had neglected the impacts of social factors including social networks and ties on adults sleep quality. Thus, the aim of the current research was to determine the relationship between social networks and adult employees' sleep quality. This study was conducted with a correlational and descriptive design. Data were collected from 360 participants (183 males and 177 females) who were employed in Yazd public organizations in June and July of 2014. These samples were selected based on random sampling method. In addition, the measuring tools were the Pittsburgh Sleep Quality Index (PSQI) and Social Relations Inventory (SRI). Based on the results, the prevalence rate of sleep disorder among Iranian adult employees was 63.1% (total PSQI>5). And, after controlling for socio-demographic variables, there was significant difference between individuals with strong and poor social network and ties in terms of overall sleep quality (p<.01), subjective sleep quality (p<.01), habitual sleep efficiency (p<.05), and daytime dysfunction (p<.01). The results also revealed that the employees with strong social network and ties had better overall sleep quality, had the most habitual sleep efficiency, and less daytime dysfunction than employees with poor social network and ties. It can be implied that the weak social network and ties serve as a risk factor for sleep disorders or poor sleep quality for adult employees. Therefore, the social and behavioral interventions seem essential to improve the adult's quality sleep. 
26487563	Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown.This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m(2)) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups.	This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms.	
26485745	Anxiety is one of the most common psychiatric symptoms frequently associated with sleep disorders. Despite the intensive research, the role of sleep in the patomechanism of anxiety has remained unclear. The aim of the study was to investigate the anxiety-related changes in the sleep macrostructure and the impact of ageing, gender and the presence of depression.1083 patients with sleep symptoms were enrolled in the study. All patients have all night polysomnographies. The effect of anxiety, depression, aging and gender on the sleep initiation, maintenance and sleep stages respectively; were analysed in 4 different statistical approaches.	Anxiety increased the latency of sleep and REM sleep; and decreased the length of REM sleep and slow-wave sleep; while depressive symptoms were associated with reduced REM latency, slow-wave sleep and increased REM duration. The length of slow-wave sleep, REM phase decreased with ageing and the sleep was fragmented. Women had more slow-wave sleep and less REM sleep than men.	Normal order of sleep stages is essential in the cognitive processing of the brain. Changes in sleep macrostructure may have an impact in the impairment of cognitive functions of patients suffering from anxiety or depression.	
26483949	Schizophrenia is characterized by major sleep/wake disturbances including increased vigilance and arousal, decreased slow wave sleep, and increased REM sleep drive. Other arousal-related symptoms include sensory gating deficits as exemplified by decreased habituation of the blink reflex. There is also dysregulation of gamma band activity, suggestive of disturbances in a host of arousal-related mechanisms. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of the disease. Recent discoveries on the physiology of the pedunculopontine nucleus help explain many of these disorders of arousal in, and point to novel therapeutic avenues for, schizophrenia. 
26483938	Human sleep begins in stage 1 and progresses into stages 2 and 3 of Non-Rapid-Eye-Movement (NREM) sleep. These stages were defined using several arbitrarily-defined thresholds for subdivision of albeit continuous process of sleep deepening. Since recent studies indicate that stage 3 (slow wave sleep) has unique vital functions, more accurate measurement of this stage duration and continuity might be required for both research and practical purposes. However, the true neurophysiological boundary between stages 2 and 3 remains unknown. In a search for non-arbitrary threshold criteria for distinguishing the boundaries between NREM sleep stages, scores on the principal components of the electroencephalographic (EEG) spectrum were analyzed in relation to stage onsets. Eighteen young men made 12-20-minute attempts to nap during 24-hour wakefulness. Single-minute intervals of the nap EEG records were assigned relative to the minute of onsets of polysomnographically determined stages 1, 2, and 3. The analysis of within-nap time courses of principal components scores revealed that, unlike any conventional spectral EEG index, score on the 4th principal component exhibited a rather rapid rise on the boundary between stages 2 and 3. This was mostly a change from negative to positive score. Therefore, it might serve as yes-or-no criterion of stage 3 onset. Additionally, similarly rapid changes in sign of scores were exhibited by the 1st and 2nd principal components on the boundary of stages 2 and 1 and on the boundary between stage 1 and wakefulness, respectively. 
26483937	There were no validation studies on portable sleep devices under different ambient temperature, thus this study evaluated the validity of wrist Actiwatch2 (AW2) or SenseWear armband (SWA) against polysomnography (PSG) in different ambient temperatures. Nine healthy young participants (6 males, aged 23.3±4.1 y) underwent nine nights of study at ambient temperature of 17 °C, 22 °C and 29 °C in random order, after an adaptation night. They wore the AW2 and SWA while being monitored for PSG simultaneously. A linear mixed model indicated that AW2 is valid for sleep onset latency (SOL), total sleep time (TST) and sleep efficiency (SE) but significantly overestimated wake after sleep onset (WASO) at 17 °C and 22 °C. SWA is valid for WASO, TST and SE at these temperatures, but severely underestimates SOL. However, at 29 °C, SWA significantly overestimated WASO and underestimated TST and SE. Bland-Altman plots showed small biases with acceptable limits of agreement (LoA) for AW2 whereas, small biases and relatively wider LoA for most sleep variables were observed in SWA. The kappa statistic showed a moderate sleep-wake epoch agreement, with a high sensitivity but poor specificity; wake detection remains suboptimal. AW2 showed small biases for most of sleep variables at all temperature conditions, except for WASO. SWA is reliable for measures of TST, WASO and SE at 17-22 °C but not at 29 °C, and SOL approximates that of PSG only at 29 °C, thus caution is needed when monitoring sleep at different temperatures, especially in home sleep studies, in which temperature conditions are more variable. 
26483921	Circadian rhythmicity in humans has been well studied using actigraphy, a method of measuring gross motor movement. As actigraphic technology continues to evolve, it is important for data analysis to keep pace with new variables and features. Our objective is to study the behavior of two variables, interdaily stability and intradaily variability, to describe rest activity rhythm. Simulated data and actigraphy data of humans, rats, and marmosets were used in this study. We modified the method of calculation for IV and IS by modifying the time intervals of analysis. For each variable, we calculated the average value (IVm and ISm) results for each time interval. Simulated data showed that (1) synchronization analysis depends on sample size, and (2) fragmentation is independent of the amplitude of the generated noise. We were able to obtain a significant difference in the fragmentation patterns of stroke patients using an IVm variable, while the variable IV60 was not identified. Rhythmic synchronization of activity and rest was significantly higher in young than adults with Parkinson׳s when using the ISM variable; however, this difference was not seen using IS60. We propose an updated format to calculate rhythmic fragmentation, including two additional optional variables. These alternative methods of nonparametric analysis aim to more precisely detect sleep-wake cycle fragmentation and synchronization. 
26483920	The aim of the present study was to characterize the temporal patterns of sleep and wakefulness in a sample of the adult subjects from São Paulo city. All subjects filled the Morningness/Eveningness Questionnaire (MEQ) and wore an actigraph for at least three consecutive days. A total of 359 subjects were considered for the analyses. The mean age was 43±14 years, the mean body mass index was 26.7±5.7 kg/m(2), and 60% were female. The mean MEQ score was 58.0±10.7. The sleep pattern evaluated by the actigraphic analyses showed that 92% had a monophasic sleep pattern, 7% biphasic, and 1% polyphasic sleep pattern. Cluster analysis, based on time to sleep onset, sleep efficiency, sleep latency, and total sleep time, was able to identify three different groups denominated: morning type, evening type, and undefined type. Morning type subjects were more frequent, older, and had higher MEQ scores than evening type subjects. Our results showed that the actigraph objectively assessed the sleep-wake cycle and was able to discriminate between morning and evening type individuals. These findings suggest that the actigraph could be a valuable tool for assessing temporal sleep patterns, including the circadian preferences. 
26482754	Psychological and psychosocial factors have long been linked to cardiovascular disease. These psychosocial factors, including low socioeconomic status, social support/isolation, stress and distress, personality, and sleep disturbance increase risk of cardiovascular events and negatively impact quality of life. These factors may have direct effects on cardiovascular disease via immune or neuroendocrine pathways, or more indirect effects, by, for example, limiting adherence to recommended therapies and cardiac rehabilitation. Most psychosocial risk factors can be assessed relatively easily using standardised tools. Sleep disturbance, in particular, is gaining evidence for its importance and may be crucial to address. While the management of certain psychosocial risk factors is an ethical requirement for care and improves quality of life, unfortunately there is little evidence that such strategies impact on 'hard' endpoints such as recurrent myocardial infarction. A comprehensive biopsychosocial approach to management of these psychosocial factors is required to maximise the benefits patients derive from cardiac care. 



26478806	Insomnia is a highly prevalent disorder that can occur in conjunction with other medical or psychiatric conditions or can occur in the absence of a coexisting disorder. Regardless, treatment of insomnia is beneficial to the patient and may benefit comorbidities if they exist. Nonpharmacologic modalities such as sleep hygiene and stimulus controls are important mainstays of insomnia therapy, but may not be sufficient to treat the disorder. Dual orexin receptor antagonists (DORAs) are a new class of insomnia medication that target wakefulness-promoting neuropeptides to regulate the sleep-wake cycle. Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. Suvorexant has a novel mechanism of action and may represent an alternative for patients who cannot tolerate or do not receive benefit from traditional sleep agents. Suvorexant is generally effective and well tolerated, but has not been compared head to head with traditional sleep agents and being only newly available, lacks a longer-term 'real-world' experience base. 
26478564	The presence of pets in the bedroom can alter the sleep environment in ways that could affect sleep. Data were collected by questionnaire and interview from 150 consecutive patients seen at the Center for Sleep Medicine, Mayo Clinic in Arizona. Seventy-four people (49%) reported having pets, with 31 (41% of pet owners) having multiple pets. More than half of pet owners (56%) allowed their pets to sleep in the bedroom. Fifteen pet owners (20%) described their pets as disruptive, whereas 31 (41%) perceived their pets as unobtrusive or even beneficial to sleep. Health care professionals working with patients with sleep concerns should inquire about the presence of companion animals in the sleep environment to help them find solutions and optimize their sleep. 
26478197	The older patient population is growing rapidly around the world and in the USA. Almost half of seniors over age 65 who live at home are dissatisfied with their sleep, and nearly two-thirds of those residing in nursing home facilities suffer from sleep disorders. Chronic and pervasive sleep complaints and disturbances are frequently associated with excessive daytime sleepiness and may result in impaired cognition, diminished intellect, poor memory, confusion, and psychomotor retardation all of which may be misinterpreted as dementia. The key sleep disorders impacting patients with dementia include insomnia, hypersomnolence, circadian rhythm misalignment, sleep disordered breathing, motor disturbances of sleep such as periodic leg movement disorder of sleep and restless leg syndrome, and parasomnias, mostly in the form of rapid eye movement (REM) sleep behavior disorder (RBD). RBD is a pre-clinical marker for a class of neurodegenerative diseases, the "synucleinopathies", and requires formal polysomnographic evaluation. Untreated sleep disorders may exacerbate cognitive and behavioral symptoms in patients with dementia and are a source of considerable stress for bed partners and family members. When left untreated, sleep disturbances may also increase the risk of injury at night, compromise health-related quality of life, and precipitate and accelerate social and economic burdens for caregivers. 
26478195	Chronobiological therapies for mood disorders include manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance and the controlled exposure to light and darkness. Their antidepressant efficacy can overcome drug resistance and targets the core depressive symptoms including suicide, thus making them treatment options to be tried either alone or as adjunctive treatments combined with common psychopharmacological interventions. The specific pattern of mood change observed with chronobiological therapies is characterized by rapid and sustained effects, when used among themselves or combined with drugs. Effects sizes are the same reported for the most effective psychiatric treatments, but side effects are usually marginal or absent. New treatment protocols are developed to adapt them in different clinical settings. This review deals with the general principles of clinical chronobiology and the latest findings in this rapidly developing field. 
26474479	Narcolepsy type 1 is associated with loss of orexin neurons, sleep-wake derangements, cataplexy, and a wide spectrum of alterations in other physiological functions, including energy balance, cardiovascular, and respiratory control. It is unclear which narcolepsy signs are directly related to the lack of orexin neurons or are instead modulated by dysfunction of other neurotransmitter systems physiologically controlled by orexin neurons, such as the histamine system. To address this question, we tested whether some of narcolepsy signs would be detected in mice lacking histamine signaling (HDC-KO). Moreover, we studied double-mutant mice lacking both histamine signaling and orexin neurons (DM) to evaluate whether the absence of histamine signaling would modulate narcolepsy symptoms produced by orexin deficiency. Mice were instrumented with electrodes for recording the electroencephalogram and electromyogram and a telemetric arterial pressure transducer. Sleep attacks fragmenting wakefulness, cataplexy, excess rapid-eye-movement sleep (R) during the activity period, and enhanced increase of arterial pressure during R, which are hallmarks of narcolepsy in mice, did not occur in HDC-KO, whereas they were observed in DM mice. Thus, these narcolepsy signs are neither caused nor abrogated by the absence of histamine. Conversely, the lack of histamine produced obesity in HDC-KO and to a greater extent also in DM. Moreover, the regularity of breath duration during R was significantly increased in either HDC-KO or DM relative to that in congenic wild-type mice. Defects of histamine transmission may thus modulate the metabolic and respiratory phenotype of murine narcolepsy. 
26473793	Objectives To investigate sleep quality, anxiety/depression and quality-of-life in patients with xerostomia. Materials and methods This prospective, observational, cross-sectional study was conducted among a group of xerostomia patients (n = 30) compared with 30 matched control subjects. The following evaluation scales were used to assess the psychological profile of each patient: the Hospital Anxiety and Depression Scale, the Oral Health Impact Profile-14 (OHIP-14), the Xerostomia Inventory, the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Results The PSQI obtained 5.3 3 ± 1.78 for patients with xerostomia compared with 4.26 ± 1.01 for control subjects (p = 0.006); ESS obtained 5.7 ± 2.1 for test patients vs 4.4 0 ± 1 for control subjects (p = 0.010). Statistical regression analysis showed that xerostomia was significantly associated with depression (p = 0.027). Conclusions Patients with xerostomia exhibited significant decreases in sleep quality compared with control subjects. 
26472554	There are compelling reasons to study the role of steroids and sex differences in the circadian timing system. A solid history of research demonstrates the ubiquity of circadian changes that impact virtually all behavioral and biological responses. Furthermore, steroid hormones can modulate every attribute of circadian responses including the period, amplitude and phase. Finally, desynchronization of circadian rhythmicity, and either enhancing or damping amplitude of various circadian responses can produce different effects in the sexes. Studies of the neuroendocrine underpinnings of circadian timing systems and underlying sex differences have paralleled the overall development of the field as a whole. Early experimental studies established the ubiquity of circadian rhythms by cataloging daily and seasonal changes in whole organism responses. The next generation of experiments demonstrated that daily changes are not a result of environmental synchronizing cues, and are internally orchestrated, and that these differ in the sexes. This work was followed by the revelation of molecular circadian rhythms within individual cells. At present, there is a proliferation of work on the consequences of these daily oscillations in health and in disease, and awareness that these may differ in the sexes. In the present discourse we describe the paradigms used to examine circadian oscillation, to characterize how these internal timing signals are synchronized to local environmental conditions, and how hormones of gonadal and/or adrenal origin modulate circadian responses. Evidence pointing to endocrinologically and genetically mediated sex differences in circadian timing systems can be seen at many levels of the neuroendocrine and endocrine systems, from the cell, the gland and organ, and to whole animal behavior, including sleep/wake or rest/activity cycles, responses to external stimuli, and responses to drugs. We review evidence indicating that the analysis of the circadian timing system is amenable to experimental analysis at many levels of the neuraxis, and on several different time scales, rendering it especially useful for the exploration of mechanisms associated with sex differences. 
26471270	Children with neurodevelopmental disorders are at risk of sleep problems, typically difficulty getting to sleep, sleep/wake rhythm disturbances and reduced duration of sleep (insomnia). This may be associated with abnormally timed or inadequate secretion of melatonin, a naturally-occurring hormone involved in coordinating the body's sleep-wake cycle. Previously, we reviewed the use of a melatonin product licensed for primary insomnia in adults aged over 55 years. Here we review off-label and unlicensed use of melatonin in children with attention-deficit hyperactivity disorder (ADHD) or autism spectrum disorder or related neurodevelopmental disorders.
26469798	We determined whether sleep hygiene is directly related to mood and quality of life (QoL) in people with epilepsy and, if not, documented the indirect effects of sleep hygiene through sleep quality.Data were collected from 150 adults with epilepsy. The Sleep Hygiene Index (SHI), Quality of Life in Epilepsy-10 (QOLIE-10), Hospital Anxiety and Depression Scale (HADS), Sleep Problems Index-2 (SPI-2) of the Medical Outcomes Study-Sleep Scale, and Epworth Sleepiness Scale (ESS) were used. To determine the direct and indirect associations between SHI, mood, and QoL, multiple linear regression analyses and the Sobel test were performed.	Inadequate sleep hygiene behaviors were answered affirmatively by ≥15% of the participants represented by 6 out of 13 items of the SHI. A younger age was independently related to higher SHI scores (p=0.013). The higher SHI scores were directly related to lower QoL independent of sleep quality, anxiety, and depressive symptoms (p<0.05) but not independently related to anxiety and depressive symptoms. The Sobel test confirmed that the SHI scores were associated with anxiety and depressive symptoms through sleep quality (p<0.001).	Inadequate sleep hygiene is independently related to low QoL but indirectly related to anxiety and depressive symptoms through sleep quality. Patients of a younger age are at risk of poorer sleep hygiene.	
26469790	We proposed and tested a method to estimate sleep period time (SPT) using electrodermal activity (EDA) signals. Eight healthy subjects and six obstructive sleep apnea patients participated in the experiments. Each subject's EDA signals were measured at the middle and ring fingers of the dominant hand during polysomnography (PSG). For nine of the 17 participants, wrist actigraphy was also measured for a quantitative comparison of EDA- and actigraphy-based methods. Based on the training data, we observed that sleep onset was accompanied by a gradual reduction of amplitude of the EDA signals, whereas sleep offset was accompanied by a rapid increase in amplitude of EDA signals. We developed a method based on these EDA fluctuations during sleep-wake transitions, and applied it to a test dataset. The performance of the method was assessed by comparing its results with those from a physician's sleep stage scores. The mean absolute errors in the obtained values for sleep onset, offset, and period time between the proposed method, and the results of the PSG were 4.1, 3.0, and 6.1 min, respectively. Furthermore, there were no significant differences in the corresponding values between the methods. We compared these results with those obtained by applying actigraphic methods, and found that our algorithm outperformed these in terms of each estimated parameter of interest in SPT estimation. Long awakening periods were also detected based on sympathetic responses reflected in the EDA signals. The proposed method can be applied to a daily sleep monitoring system.
26468939	Sleep disturbance is considered both a behavioral symptom of and a contributor to functional difficulties in children with attention-deficit/hyperactivity disorder (ADHD). The construct of sluggish cognitive tempo (SCT) has also been linked to ADHD; however, little is known regarding the effects of sleep specifically on SCT symptoms. This study examined the association between parent-reported sleep disturbance and parent- and teacher-reported SCT, while controlling for the effects of ADHD and mood symptoms.Participants included 746 clinically referred children (65% male, age range: 5-18 years) with both parent and teacher ratings assessing symptoms of ADHD, mood symptoms (depression, anxiety), and SCT. Parents/caregivers also rated their child's sleep problems with regard to 4 core concerns: falling asleep, sleep restlessness, difficulty waking, and breathing difficulties. The SCT scale included three empirically derived subscales: sleepy/sluggish, low initiation/persistence, and daydreamy.	After accounting for age, medication status, ADHD symptoms, depressive symptoms, and anxiety, sleep problems accounted for a small but significant proportion of additional variance in the prediction of parent-reported sleepy/sluggish SCT. Difficulty waking showed the strongest associations with parent-reported SCT. There were no significant relationships found between parent-reported sleep difficulties and teacher-reported SCT.	Some elements of sluggishness and lethargy inherent to the SCT construct may be associated with sleep difficulties, even after accounting for ADHD and mood symptoms; however, these associations are not consistent across SCT subscales and sleep problem domains.	

26468189	Although the functions of sleep remain to be fully elucidated, it is clear that there are far-reaching effects of its disruption, whether by curtailment for a single night, by a few hours each night over a long period, or by disruption in sleep continuity. Epidemiological and experimental studies of these different forms of sleep disruption show deranged physiology from subcellular levels to complex affective behavior. In keeping with the multifaceted influence of sleep on health and well-being, we illustrate how the duration of sleep, its timing, and continuity can affect cellular ultrastructure, gene expression, metabolic and hormone regulation, mood, and vigilance. Recent brain imaging studies provide some clues on mechanisms underlying the most common cause of disrupted sleep (insomnia). These insights should ultimately result in adequate interventions to prevent and treat sleep disruption because of their high relevance to our most prevalent health problems.Disruption of the duration, timing, and continuity of sleep affects cellular ultrastructure, gene expression, appetite regulation, hormone production, vigilance, and reward functions.	
26466871	Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist.Between Aug 25, 2010, and July 5, 2012, we screened 391 totally blind patients for SET, of whom 84 (22%) were assigned to receive tasimelteon (n=42) or placebo (n=42). Two patients in the tasimelteon group and four in the placebo group discontinued the study before τ was measured, due to adverse events, withdrawal of consent, and a protocol deviation. Circadian entrainment occurred in eight (20%) of 40 patients in the tasimelteon group compared with one (3%) of 38 patients in the placebo group at month 1 (difference 17%, 95% CI 3·2-31·6; p=0·0171). Nine (24%) of 38 patients showed a clinical response, compared with none of 34 in the placebo group (difference 24%, 95% CI 8·4-39·0; p=0·0028). Between Sept 15, 2011, and Oct 4, 2012, we screened 58 patients for eligibility in RESET, 48 (83%) of whom had τ assessed and entered the open-label tasimelteon run-in phase. 24 (50%) patients entrained, and 20 (34%) were enrolled in the randomisation phase. Two (20%) of ten patients who were withdrawn to placebo remained entrained compared with nine (90%) of ten who continued to receive tasimelteon (difference 70%, 95% CI 26·4-100·0; p=0·0026). No deaths were reported in either study, and discontinuation rates due to adverse events were comparable between the tasimelteon (3 [6%] of 52 patients) and placebo (2 [4%] of 52 patients) treatment courses. The most common side-effects associated with tasimelteon in SET were headache (7 [17%] of 42 patients given tasimelteon vs 3 [7%] of 42 patients given placebo), elevated liver enzymes (4 [10%] vs 2 [5%]), nightmares or abnormal dreams (4 [10%] vs none), upper respiratory tract infection (3 [7%] vs none], and urinary tract infections (3 [7%] vs 1 [2%]).	Once-daily tasimelteon can entrain totally blind people with non-24; however, continued tasimelteon treatment is necessary to maintain these improvements.	Vanda Pharmaceuticals.	
26466096	Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan.We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio.	The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26-1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23-1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19-1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35-2.40, p< 0.001).	In this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.	
26465005	The fruit fly Drosophila melanogaster is a diurnal insect active during the day with consolidated sleep at night. Social interactions between pairs of flies have been shown to affect locomotor activity patterns, but effects on locomotion and sleep patterns have not been assessed for larger populations. Here, we use a commercially available locomotor activity monitor (LAM25H) system to record and analyze sleep behavior. Surprisingly, we find that same-sex populations of flies synchronize their sleep/wake activity, resulting in a population sleep pattern, which is similar but not identical to that of isolated individuals. Like individual flies, groups of flies show circadian and homeostatic regulation of sleep, as well as sexual dimorphism in sleep pattern and sensitivity to starvation and a known sleep-disrupting mutation (amnesiac). Populations of flies, however, exhibit distinct sleep characteristics from individuals. Differences in sleep appear to be due to olfaction-dependent social interactions and change with population size and sex ratio. These data support the idea that it is possible to investigate neural mechanisms underlying the effects of population behaviors on sleep by directly looking at a large number of animals in laboratory conditions. 
26461857	To examine the relationships between employees' trouble sleeping and absenteeism, work performance, and health care expenditures over a 2-year period.Utilizing the Kansas State employee wellness program (EWP) data set from 2008 to 2009, multinomial logistic regression analyses were conducted with trouble sleeping as the predictor and absenteeism, work performance, and health care costs as the outcomes.	EWP participants (N = 11,698 in 2008; 5636 followed up in 2009) who had higher levels of sleep disturbance were more likely to be absent from work (all P < 0.0005), have lower work performance ratings (all P < 0.0005), and have higher health care costs (P < 0.0005). Longitudinally, more trouble sleeping was significantly related to negative changes in all outcomes.	Employees' trouble sleeping, even at a subclinical level, negatively impacts on work attendance, work performance, and health care costs.	
26461072	Patients with chronic pain frequently experience concomitant sleep disorders. There has been controversy on whether opioids have a beneficial or deleterious effect on sleep quality, duration and efficiency. There is also concern regarding the association between chronic opioid therapy (COT) and sleep disordered breathing (SDB) and the increased risk for unintentional opioid related overdose. This article provides a narrative review of the literature on the effect of opioids on sleep disorders and discusses risk assessment and mitigation strategies.A narrative review of the current literature on the effect of prescription opioids on sleep quality and efficiency, the relationship between opioids and sleep disorders and potential risk factors in patients with chronic pain.	There is conflicting evidence regarding the benefit of opioids in improving sleep quality, duration and efficiency with several studies and reviews suggesting a beneficial effect of opioids on sleep and other studies demonstrating the opioids can cause sleep disturbance leading to hyperalgesia. There was credible evidence of a strong relationship between opioids and SDB with noted risk factors including use of methadone, high opioid dosing (>200 mg MED) and combining opioids with benzodiazepines.	Further research is required to elucidate the effect of prescription opioids on sleep quality and pain intensity and the risks associated with opioids and SDB. The risk of SDB should be routinely assessed in patients on COT.	
26460330	We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities.In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses.	Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis.	Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not over-diagnose attention-deficit/hyperactivity disorder in the adult population. Recalled childhood attention-deficit/hyperactivity disorder symptom severity was correlated with conduct disorder, oppositional defiant disorder, dysthymia and sleep disorders.	
26459685	Cardiovascular risk factors develop in childhood and adolescence. This enumerative review addresses whether sleep characteristics, including sleep duration, continuity, quality, and daytime sleepiness, are associated with cardiovascular risk factors in young people. Thirty-nine studies were identified, which examined the following risk factors: metabolic syndrome, glucose and insulin, lipids, blood pressure, and cardiovascular responses to psychological stressors. Due to the availability of other reviews, 16 longitudinal studies of obesity published in 2011 and later were also included in this report. Excluded from the review were studies of participants with suspected or diagnosed sleep disorders and reports from sleep deprivation experiments. Combining studies, evidence was strongest for obesity, followed by glucose, insulin, blood pressure (especially ambulatory blood pressure), and parasympathetic responses to psychological stressors. There was little evidence for metabolic syndrome cluster, lipids, and blood pressure responses to psychological stressors. The more positive associations were obtained for studies that incorporated objective measures of sleep and that included adolescents. The foundational evidence is almost entirely cross-sectional, except for work on obesity. In summary, available evidence suggests that the associations between sleep characteristics and cardiovascular risk vary by risk factor. It is time to conduct studies to determine antecedent and consequent relationships, and to expand risk factors to include markers of inflammation.
26459675	Marcel Proust is considered one the greatest novelists of all times. His life was characterised by a long list of diseases. We analyse an important illness suffered by Proust: insomnia. It began in childhood and continued throughout his life, worsening progressively, and leading to a complete reversal of the sleep-wake cycle in the last years of the novelist's life. Several factors may be involved in the pathogenesis of Proust's insomnia. The beginning of insomnia since childhood, its characteristics, and the lack of precipitating factors suggest a form of idiopathic insomnia. Psychological traits of his personality (severe anxiety and depression) may have played a central role in the onset of insomnia. Further factors such as asthma and intake of stimulating substances may have had an important role in the maintenance and worsening of his insomnia. This sleep disorder affected both the lifestyle and literary genius of Marcel Proust. Insomnia is the prominent figure in the first novel ("Swann's way") of Proust's masterpieces entitled "In search of lost time," in which the novelist begins his journey through involuntary memory starting from his insomnia. 
26459660	Non motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the course of disease. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent clinical and neurobiological research suggests the existence of discrete non motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers. 
26459092	We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF. The proband underwent surgery for right mesiotemporal FCD. 3-T MRIs in four individuals were unremarkable. Linkage analysis revealed peaks on chromosome 9p24 (LOD 2.43) and 10q22-25 (LOD 2.04). A novel heterozygous LGI1 mutation was identified in all affected individuals except for the proband indicating a phenocopy. Exome sequencing did not reveal variants within the chromosome 9p24 region. Closely located variants in KANK1 and a RELN variant did not segregate with the phenotype. We provide detailed description of the phenotypic spectrum within a large ADEAF family with a novel LGI1 mutation that was conspicuously absent in the proband with FCD, demonstrating that despite identical clinical symptoms, phenocopies in ADEAF families may exist. This family illustrates that rare epilepsy syndromes within a single family can have both genetic and structural etiologies.
26457552	The mammalian basal forebrain (BF) has important roles in controlling sleep and wakefulness, but the underlying neural circuit remains poorly understood. We examined the BF circuit by recording and optogenetically perturbing the activity of four genetically defined cell types across sleep-wake cycles and by comprehensively mapping their synaptic connections. Recordings from channelrhodopsin-2 (ChR2)-tagged neurons revealed that three BF cell types, cholinergic, glutamatergic and parvalbumin-positive (PV+) GABAergic neurons, were more active during wakefulness and rapid eye movement (REM) sleep (wake/REM active) than during non-REM (NREM) sleep, and activation of each cell type rapidly induced wakefulness. By contrast, activation of somatostatin-positive (SOM+) GABAergic neurons promoted NREM sleep, although only some of them were NREM active. Synaptically, the wake-promoting neurons were organized hierarchically by glutamatergic→cholinergic→PV+ neuron excitatory connections, and they all received inhibition from SOM+ neurons. Together, these findings reveal the basic organization of the BF circuit for sleep-wake control. 
26456505	Neurons that utilize melanin-concentrating hormone (MCH) as neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area. These neurons project throughout the central nervous system and play a role in sleep regulation. With the hypothesis that the MCHergic system function would be modified by the time of the day as well as by disruptions of the sleep-wake cycle, we quantified in rats the concentration of MCH in the cerebrospinal fluid (CSF), the expression of the MCH precursor (Pmch) gene in the hypothalamus, and the expression of the MCH receptor 1 (Mchr1) gene in the frontal cortex and hippocampus. These analyses were performed during paradoxical sleep deprivation (by a modified multiple platform technique), paradoxical sleep rebound and chronic sleep restriction, both at the end of the active (dark) phase (lights were turned on at Zeitgeber time zero, ZT0) and during the inactive (light) phase (ZT8). We observed that in control condition (waking and sleep ad libitum), Mchr1 gene expression was larger at ZT8 (when sleep predominates) than at ZT0, both in frontal cortex and hippocampus. In addition, compared to control, disturbances of the sleep-wake cycle produced the following effects: paradoxical sleep deprivation for 96 and 120 h reduced the expression of Mchr1 gene in frontal cortex at ZT0. Sleep rebound that followed 96 h of paradoxical sleep deprivation increased the MCH concentration in the CSF also at ZT0. Twenty-one days of sleep restriction produced a significant increment in MCH CSF levels at ZT8. Finally, sleep disruptions unveiled day/night differences in MCH CSF levels and in Pmch gene expression that were not observed in control (undisturbed) conditions. In conclusion, the time of the day and sleep disruptions produced subtle modifications in the physiology of the MCHergic system.
26455684	Psychiatric, neurologic, and medical conditions frequently coexist with sleep disorders and contribute to poor treatment outcomes when unrecognized and untreated. For patients who present with excessive daytime sleepiness (EDS) or fatigue, clinicians should screen for sleep disorders (eg, obstructive sleep apnea, narcolepsy), medical and neurologic conditions (eg, cancer, Parkinson's disease), and psychiatric disorders (eg, depression, substance abuse) to determine if they are the cause or a contributing factor to sleep symptoms. Once recognized, comorbid conditions may be targeted along with EDS or fatigue using behavioral and pharmacologic treatment strategies. 
26455403	Sleep disturbance after total knee arthroplasty (TKA) has not been studied 6 months after surgery. A prospective study was conducted on 34 primary, unilateral TKA patients preoperatively until 6 months postoperatively. Sleep quality was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Pain was measured on a visual analog scale. Sleep quality worsened from baseline during the first 6 weeks postoperatively (P = .03), but improved at 3 and 6 months (P = .003). Pain scores decreased from baseline over all time points, and there was no correlation between sleep quality and pain. The Epworth Sleepiness Scale did not change over time. This study can be used to counsel TKA patients to expect initial sleep disturbances that improve by 3 months. 
26453387	The manifestations of nocturnal movements in Parkinson's disease (PD) are protean, with major disabilities related to nocturnal hypokinesia. While it can be assessed by clinical interviews and screening instruments, these are often inaccurate and prone to recall bias. In light of advances in sensor technology, we explored the use of sensors in the study of nocturnal hypokinesia, by performing a systematic review of the professional literature on this topic. Evidence suggests that nocturnal hypokinesia exists even in patients in the early stages, and PD patients turned significantly less and with much slower speed and acceleration than controls, partly related to low nocturnal dopamine level. We conducted another systematic review to evaluate the evidence of the efficacy of dopaminergic agents in the treatment of nocturnal hypokinesia. Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms. Sensor parameters could be considered as one of the important objective outcomes in future clinical trials investigating potential drugs to treat nocturnal hypokinesia. Physicians should be aware of this technology as it can aid the clinical assessment of nocturnal hypokinesia and enhance the quality of patient care. In addition, the use of sensors currently is being considered for various aspects of research on early diagnosis, treatment, and rehabilitation of PD patients. 
26453284	The menstrual cycle is an example of a human infradian rhythm, but an altered sleep-wake cycle or a disrupted circadian rhythm can change the regularity of the menstrual cycle. In this study, we investigated whether an irregular menstrual cycle is associated with polymorphisms in the CLOCK (3111T > C) and/or PER3 (variable number tandem repeat, VNTR) genes, which are known to have an impact on the circadian rhythm. One hundred ninety-seven postmenarchal, adolescent girls from two girls' high schools in Seoul, Korea, were studied. All participants were requested to complete the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI) to assess the emotional distress that might cause menstrual irregularity. Every participant donated a blood sample from which DNA was extracted and genotyped for the CLOCK 3111T > C and PER3 VNTR polymorphisms. A significant association was found between the CLOCK 3111T > C genotype and irregular menstrual cycles. Subjects with the 3111T > C genotype had a high risk of an irregular menstrual cycle compared with 3111T/T homozygous subjects (odds ratio [OR] = 2.88; 95% confidence interval [CI]: 1.26-6.55). When multivariate logistic regression analysis was performed to adjust for age, PSS, STAI, BDI and BMI, subjects with the 3111T > C polymorphism showed a significantly increased OR for irregular menstrual cycles (OR = 3.09; 95% CI: 1.32-7.21). There was no significant association between the PER3 VNTR polymorphism and the irregularity of the menstrual cycle (p > 0.05). The results of this study suggest that the CLOCK 3111T > C polymorphism could be an independent risk factor for irregular menstrual cycles, irrespective of psychological distress and endocrine or metabolic conditions, and could be used as a molecular marker for gynecological studies on this aspect.
26453178	The assessment of diurnal preference, or the preferred timing of sleep and activity, is generally based on comprehensive questionnaires such as the Horne-Östberg (HÖ). The aim of the present study was to assess the reliability of a subject's self-classification as extremely morning (Self-MM), more morning than evening (Self-M), more evening than morning (Self-E) or extremely evening (Self-EE) type, based on the last question of the HÖ (Self-ME). A convenience sample of 461 subjects [23.8 ± 4.7 years; 322 females] completed a full sleep-wake assessment, including diurnal preference (HÖ), night sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Karolinska Sleepiness Scale, KSS), and habitual sleep-wake timing (12 d sleep diaries; n = 296). Significant differences in HÖ total score were observed between Self-ME classes, with each class being significantly different from neighboring classes (p < 0.0001). Significant differences in sleep-wake timing (bed time, try to sleep and sleep onset, wake up, and get up time) were observed between Self-ME classes. Such differences were maintained when sleep-wake habits were analysed separately on work and free days, and also in a smaller group of 67 subjects who completed the Self-ME as a stand-alone rather than as part of the original questionnaire. Significant differences were observed in the time-course of subjective sleepiness by Self-ME class in both the large and the small group, with Self-MM and Self-M subjects being significantly more alert in the morning and sleepier in the evening hours compared with their Self-E and Self-EE counterparts. Finally, significant differences were observed in night sleep quality between Self-ME classes, with Self-EE/Self-E subjects sleeping worse than their Self-MM/Self-M counterparts, and averaging just over the abnormality PSQI threshold of 5. In conclusion, young, healthy adults can define their diurnal preference based on a single question (Self-ME) in a way that reflects their sleep-wake timing, their sleepiness levels over the daytime hours, and their night sleep quality. Validation of the Self-ME across the decades and in diseased populations seems worthy. 

26450397	Understanding how metabolite levels change over the 24 hour day is of crucial importance for clinical and epidemiological studies. Additionally, the association between sleep deprivation and metabolic disorders such as diabetes and obesity requires investigation into the links between sleep and metabolism. Here, we characterise time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles. Healthy male participants (n = 15) completed an in-laboratory study comprising one 24 h sleep/wake cycle prior to 24 h of continual wakefulness under highly controlled environmental conditions. Urine samples were collected over set 2-8 h intervals and analysed by (1)H NMR spectroscopy. Significant changes were observed with respect to both time of day and sleep deprivation. Of 32 identified metabolites, 7 (22%) exhibited cosine rhythmicity over at least one 24 h period; 5 exhibiting a cosine rhythm on both days. Eight metabolites significantly increased during sleep deprivation compared with sleep (taurine, formate, citrate, 3-indoxyl sulfate, carnitine, 3-hydroxyisobutyrate, TMAO and acetate) and 8 significantly decreased (dimethylamine, 4-DTA, creatinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 4-DEA, 4-hydroxyphenylacetate). These data indicate that sampling time, the presence or absence of sleep and the response to sleep deprivation are highly relevant when identifying biomarkers in urinary metabolic profiling studies. 


26447831	Oral propranolol has been shown to be safe and effective in infants with infantile hemangioma (IH). Side effects such as sleep disturbances have been associated with propranolol. The aim of this study was to evaluate the efficacy and safety of oral nadolol in a small series of patients whose propranolol therapy was discontinued due to sleep disturbances.A retrospective study of patients with IHs who were treated with oral nadolol due to propranolol-related sleep disturbances at a pediatric tertiary care center between July 2008 and March 2013. Clinical response to oral nadolol and disappearance of propranolol-related side effects were analyzed.	A total of 97 patients presenting IH received oral propranolol. Nine patients (9.3%) developed sleep disturbances. Oral propranolol was discontinued in seven patients and switched to oral nadolol, with resolution of these side effects in 5 (71%) of the cases. One patient developed sleep disturbances again after four months of oral nadolol.	The sample size was too small to draw generalizable conclusions and to draw any statistical inference as to the incidence of sleep disturbances with nadolol therapy.	The use of oral nadolol in the treatment of IH in our series of 7 patients, resolved the propranolol-related sleep disturbances in 5 (71%), while in one patient the symptoms recurred after 4 months of oral nadolol at a dose of 2 mg/kg/day. In most cases, switching beta-blockers did not compromise efficacy, and is recommended when sleep disturbance necessitates discontinuation of beta-blocker therapy of IH.	

26446246	leep problems may constitute a risk for health problems, including cardiovascular disease, depression, diabetes, poor work performance, and motor vehicle accidents. The primary purpose of this study was to assess the validity of the current Behavioral Risk Factor Surveillance System (BRFSS) sleep questions by establishing the sensitivity and specificity for detection of sleep/ wake disturbance.Repeated cross-sectional assessment of 300 community dwelling adults over the age of 18 who did not wear CPAP or oxygen during sleep. Reliability and validity testing of the BRFSS sleep questions was performed comparing to BFRSS responses to data from home sleep study, actigraphy for 14 days, Insomnia Severity Index, Epworth Sleepiness Scale, and PROMIS-57.	Only two of the five BRFSS sleep questions were found valid and reliable in determining total sleep time and excessive daytime sleepiness.	Refinement of the BRFSS questions is recommended.	
26446213	Individuals with Angelman syndrome (AS) suffer sleep disturbances that severely impair quality of life. Whether these disturbances arise from sleep or circadian clock dysfunction is currently unknown. Here, we explored the mechanistic basis for these sleep disorders in a mouse model of Angelman syndrome (Ube3a(m-/p+) mice). Genetic deletion of the maternal Ube3a allele practically eliminates UBE3A protein from the brain of Ube3a(m-/p+) mice, because the paternal allele is epigenetically silenced in most neurons. However, we found that UBE3A protein was present in many neurons of the suprachiasmatic nucleus--the site of the mammalian circadian clock--indicating that Ube3a can be expressed from both parental alleles in this brain region in adult mice. We found that while Ube3a(m-/p+) mice maintained relatively normal circadian rhythms of behavior and light-resetting, these mice exhibited consolidated locomotor activity and skipped the timed rest period (siesta) present in wild-type (Ube3a(m+/p+)) mice. Electroencephalographic analysis revealed that alterations in sleep regulation were responsible for these overt changes in activity. Specifically, Ube3a(m-/p+) mice have a markedly reduced capacity to accumulate sleep pressure, both during their active period and in response to forced sleep deprivation. Thus, our data indicate that the siesta is governed by sleep pressure, and that Ube3a is an important regulator of sleep homeostasis. These preclinical findings suggest that therapeutic interventions that target mechanisms of sleep homeostasis may improve sleep quality in individuals with AS.Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have severe sleep dysfunction that affects their cognition and presents challenges to their caregivers. Unfortunately, current treatment strategies have limited efficacy due to a poor understanding of the mechanisms underlying sleep disruptions in AS. Here we demonstrate that abnormal sleep patterns arise from a deficit in accumulation of sleep drive, uncovering the Ube3a gene as a novel genetic regulator of sleep homeostasis. Our findings encourage a re-evaluation of current treatment strategies for sleep dysfunction in AS, and suggest that interventions that promote increased sleep drive may alleviate sleep disturbances in individuals with AS.	
26446125	Narcolepsy is caused by loss of the orexin (also known as hypocretin) neurons. In addition to the orexin peptides, these neurons release additional neurotransmitters, which may produce complex effects on sleep/wake behavior. Currently, it remains unknown whether the orexin neurons promote the initiation as well as the maintenance of wakefulness, and whether the orexin neurons influence initiation or maintenance of sleep. To determine the effects of the orexin neurons on the dynamics of sleep/wake behavior, we analyzed sleep/wake architecture in a novel mouse model of acute orexin neuron loss.We used survival analysis and other statistical methods to analyze sleep/wake architecture in orexin-tTA ; TetO diphtheria toxin A mice at different stages of orexin neuron degeneration.	Progressive loss of the orexin neurons dramatically reduced survival of long wake bouts, but it also improved survival of brief wake bouts. In addition, with loss of the orexin neurons, mice were more likely to wake during the first 30 sec of nonrapid eye movement sleep and then less likely to return to sleep during the first 60 sec of wakefulness.	These findings help explain the sleepiness and fragmented sleep that are characteristic of narcolepsy. Orexin neuron loss impairs survival of long wake bouts resulting in poor maintenance of wakefulness, but this neuronal loss also fragments sleep by increasing the risk of awakening at the beginning of sleep and then reducing the likelihood of quickly returning to sleep.	
26446116	Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome.We studied sleep in mutant mice that carry a deletion of Snord116 at the orthologous locus (mouse chromosome 7) of the human PWS critical region (PWScr). In particular, we assessed EEG and temperature profiles, across 24-h, in PWScr (m+/p-) heterozygous mutants compared to wild-type littermates. High-resolution magnetic resonance imaging (MRI) was performed to explore morphoanatomical differences according to the genotype. Moreover, we complemented the mouse work by presenting two patients with a diagnosis of PWS and characterized by atypical small deletions of SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects.	By studying the mouse mutant line PWScr(m+/p-), we observed specific rapid eye movement (REM) sleep alterations including abnormal electroencephalograph (EEG) theta waves. Remarkably, we observed identical sleep/EEG defects in the two PWS cases. We report brain morphological abnormalities that are associated with the EEG alterations. In particular, mouse mutants have a bilateral reduction of the gray matter volume in the ventral hippocampus and in the septum areas, which are pivotal structures for maintaining theta rhythms throughout the brain. In PWScr(m+/p-) mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients.	Our study indicates that paternally expressed Snord116 is involved in the 24-h regulation of sleep physiological measures, suggesting that it is a candidate gene for the sleep disturbances that most individuals with PWS experience.	
26446109	To evaluate bisphenol-A (BPA) level and its relationship to sleep adequacy in a nationally representative sample of U.S. adults.A population-based cross-sectional study was conducted using 2005-2010 National Health and Nutrition Examination Survey whereby data were collected using in-person interviews, physical examination and laboratory testing. BPA level was measured in urine samples and analyzed as loge-transformed variable and in quartiles (< 0.9 ng/mL; 0.9 to < 1.9 ng/mL; 1.9 to < 3.7 ng/mL; 3.7+ ng/mL). Sleep adequacy was operationalized with three questions: "How much sleep do you usually get at night on weekdays or workdays?", "Have you ever told a doctor or other health professionals that you have trouble sleeping?" and "Have you ever been told by a doctor or other health professional that you have a sleep disorder?" Sleep duration was further categorized as (< 6 h, ≥ 6 h); (< 7 h, 7-8 h, > 8 h); (< 5 h, 5-6 h, 7-8 h, ≥ 9 h). Linear, binary, and ordinal logistic regression models were constructed.	Loge-transformed BPA level was inversely related to sleep duration defined, in hours, as a continuous variable, a dichotomous variable (≥ 6, < 6), or an ordinal variable (≥ 9, 7-8, 5-6, < 5), after adjustment for confounders. Help-seeking behavior for sleep problems and diagnosis with sleep disorders were not significantly associated with loge-transformed BPA level in fully adjusted models.	Loge-transformed BPA level may be associated with fewer hours of sleep among U.S. adults, with implications for prevention. Further research involving diverse populations are needed to confirm these study findings.	
26446107	Patients with Huntington's disease (HD) show a high prevalence of sleep disorders that typically occur prior to the onset of motoric symptoms and neurodegeneration. Our understanding of the pathophysiological alterations in premanifest HD is limited, hindering the ability to measure disease modification in response to treatment. We used a full-length knock-in HD model to determine early changes in the electroencephalogram (EEG) and sleep that may predict the onset and progression of the disease.A 10-month longitudinal study was designed to determine the effect of the HD mutation on the EEG and sleep/wake changes in heterozygous (HET) and homozygous (HOM) zQ175 mice and wild-type (WT) littermates from 8 to 48 w of age. Mice were instrumented with tethered headmounts to record EEG/electromyography signals. Telemeters were implanted to continuously measure locomotor activity (LMA) and body temperature (Tb). Sleep deprivation (SDep) was performed at 8, 12, 16, 24, 32, and 48 w of age.	The HD mutation disrupted the EEG field potential from 8-12 w in an age- and mutant huntington dose-dependent manner, prior to changes in sleep/wake states, LMA, and Tb. Prominent effects of the HD mutation on the EEG included a progressive reduction in low frequency power, a slowing of rapid eye movement peak theta frequency, and the emergence of state-dependent beta/gamma oscillations. There was no effect of genotype on the relative increase in nonrapid eye movement delta power or sleep time in response to SDep.	The expression of the Huntington's disease (HD) mutation results in complex EEG alterations that occur prior to deficits in behavioral measures and are one of the earliest phenotypes uncovered in this mouse model. Despite these EEG changes, homeostatic responses to sleep loss were preserved in HET and HOM zQ175 mice. Greater insight into the localization and response of these EEG alterations to novel therapies may enable early intervention and improve outcomes for patients with HD.	
26445706	Patients with lumbar spine disease sometimes complain of nocturnal leg cramps. We sought to investigate the effectiveness of blocking the medial branch of the deep peroneal nerve as treatment for nocturnal leg cramps after spinal surgery for lumbar spine disease.We evaluated 66 postoperative patients in this prospective comparative study of a group of patients with a nerve block (n = 41) and a control group without (n = 25). In the block group, the medial branch of the deep peroneal nerve was blocked at the distal two-thirds of the interspace between the first and second metatarsals using 5.0 mL of 1.0% lidocaine.	Two weeks after the block, the frequency of nocturnal leg cramps was reduced to less than a quarter of pretreatment baseline frequency in 61.0% of patients (n = 25) and less than half in 80.5% (n = 33). In the control group, the frequency of the leg cramps was reduced from baseline in 32.0% of patients (n = 8), and was unchanged or increased in 68.0% (n = 17) at 2 weeks. Cramp frequency was reduced to less than a quarter or less than half of baseline frequency in a significantly (P < 0.05 and P < 0.01, respectively) larger percentage of patients in the block group. The severity of each cramp was less in about two-thirds of patients (63.4%; n = 26) in the block group and was unchanged in one-third (31.7%; n = 13).	Blocking the medial branch of the peroneal nerve can be an effective, long-lasting, and simple treatment with low risk for nocturnal cramps sustained after lumbar spine surgery.	
26445645	Each year Muslims fast from dawn to sunset for 1 month (Ramadan). In Saudi Arabia, the sleep-wake cycle during Ramadan is severely disturbed and is associated with abolition of the circadian cortisol rhythm, exposing Saudis to continuously increased cortisol levels, which may influence the immune response. In addition to cortisol, sleep and fasting affect the secretion of parathyroid hormone (PTH) and hence bone metabolism.Our objective was to investigate the effect of Ramadan type fasting on secretory patterns of PTH, markers of bone metabolism, and serum immunoglobulins. Blood samples from healthy young volunteers were collected at 9 a.m. and 9 p.m. (± 1 hour) before (Shaban) and 2 weeks into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig) A, M and G were measured.	During Ramadan, evening-adjusted calcium was higher (p = 0.036) and phosphate lower (p < 0.001) than the corresponding morning value. Moreover, the Ramadan mean morning phosphate was higher and the evening level lower was than Shabaan values (p = 0.010 and p <0.001, respectively), while mean iPTH level was decreased compared with the morning value (p = 0.001), and the evening mean during Shabaan (p = 0.029). Mean IgG concentration was significantly lower during Ramadan (p = 0.003 and p = 0.021 for morning and evening, respectively).	Changes in dietary practices during Ramadan modulated PTH secretion to a pattern which might be beneficial to bone health. Combined effects of fasting and disturbed sleep led to a noted decrease in IgG level. Therefore, a possible beneficial effect of fasting on bone turnover is combined with decreased immune response.	
26444713	Association of knee and low back pain with sleep disturbance is poorly understood. We aimed to clarify the independent and combined effects of these orthopedic symptoms on sleep in a large-scale general population.Cross-sectional data about sleep and knee/low back pain were collected for 9,611 community residents (53±14 years old) by a structured questionnaire. Sleep duration less than 6 h/d was defined as short sleep. Sleep quality and the presence of knee and low back pain were evaluated by dichotomous questions. Subjects who complained about knee or low back pains were graded by tertiles of a numerical response scale (NRS) score and a Roland-Morris disability questionnaire (RDQ) score respectively. Multivariate regression analyses were performed to determine the correlates of short sleep duration and poor sleep quality.	Frequency of participants who complained of the orthopedic symptoms was as follows; knee pain, 29.0%; low back pain, 42.0% and both knee and low back pain 17.6%. Both knee and low back pain were significantly and independently associated with short sleep duration (knee pain: odds ratio (OR) = 1.19, p<0.01; low back pain: OR = 1.13, p = 0.01) and poor sleep quality (knee pain: OR = 1.22, p<0.01; low back pain; OR = 1.57, p<0.01). The group in the highest tertile of the NRS or RDQ score had the highest risk for short sleep duration and poor sleep quality except for the relationship between the highest tertile of the RDQ score and short sleep duration.(the highest tertile of the NRS: OR for short sleep duration = 1.31, p<0.01; OR for poor sleep quality = 1.47, p<0.01; the highest tertile of the RDQ: OR for short sleep duration = 1.11, p = 0.12; OR for poor sleep quality = 1.81, p<0.01) Further, coincident knee and low back pain raised the odds ratios for short sleep duration (either of knee or low back pain: OR = 1.10, p = 0.06; both knee and low back pain: OR = 1.40, p<0.01) and poor sleep quality (either of knee or low back pain: OR = 1.61, p<0.01; both knee and low back pain: OR = 2.17, p<0.01).	Knee and low back pains were independently associated with short sleep duration and poor sleep quality. Further, they additively increased the correlation with these sleep problems in the general population.	
26444951	Depression and sleep disorders are among the most prevalent nonmotor symptoms of Parkinson disease (PD). Because agomelatine acts as a MT1 and MT2 agonist and as a 5HT2c antagonist, this study was designed to assess the efficacy of agomelatine in treating depressive symptoms in PD patients, and the potential changes both in sleep quality and motor symptoms. Depressed patients with PD were treated with agomelatine for 6 months, and they were evaluated with an array of scales. Completed nocturnal video-polysomnography was performed at baseline and week 12. The efficacy analysis population included 24 patients (12 men). The mean (SD) age was 75.2 (8.3) years. The mean (SD) daily dose of agomelatine was 25.00 (10.43) mg at 24 weeks. No changes in dopamine replacement therapy were made. There was a significant decrease in the 17-item Hamilton Depression Scale score over the course of the study (P < 0.0005). The Scales for Outcomes in Parkinson disease Sleep Questionnaire showed a statistically significant improvement over time in each of its subscales: nighttime sleep (P < 0.005), last month nighttime sleep (P < 0.0005), and daytime sleepiness (P < 0.0005). Surprisingly, changes over time in the motor subscale of Unified Parkinson Disease Rating Scale were statistically significant (P < 0.0005). Periodic limb movements and awakenings measured by polysomnography improved significantly (P < 0.005 and P < 0.05, respectively). We concluded that the use of agomelatine in PD depressed patients may have a considerable therapeutic potential because of its dual action for treating both symptoms of depression and disturbed sleep given its secondary beneficial effects regarding the reduction of extrapyramidal symptoms.
26441819	Morning-type individuals experience more difficulties to maintain optimal attentional performance throughout a normal waking day than evening types. However, time-of-day modulations may differ across cognitive domains. Using functional magnetic resonance imaging (fMRI), we investigated how chronotype and time of day interact with working memory at different levels of cognitive load/complexity in a N-back paradigm (N0-, N2-, and N3-back levels). Extreme morning- and evening-type individuals underwent two fMRI sessions during N-back performance, one 1.5 h (morning) and one 10.5 h (evening) after wake-up time scheduled according to their habitual sleep-wake preference. At the behavioral level, increasing working memory load resulted in lower accuracy while chronotype and time of day only exerted a marginal impact on performance. Analyses of neuroimaging data disclosed an interaction between chronotype, time of day, and the modulation of cerebral activity by working memory load in the thalamus and in the middle frontal cortex. In the subjective evening hours, evening types exhibited higher thalamic activity than morning types at the highest working memory load condition only (N3-back). Conversely, morning-type individuals exhibited higher activity than evening-type participants in the middle frontal gyrus during the morning session in the N3-back condition. Our data emphasize interindividual differences in time-of-day preferences and underlying cerebral activity, which should be taken into account when investigating vigilance state effects in task-related brain activity. These results support the hypothesis that higher task complexity leads to a chronotype-dependent increase in thalamic and frontal brain activity, permitting stabilization of working memory performance across the day. 
26441501	Methamphetamine (MA) consumption causes disruption of many biological rhythms including the sleep-wake cycle. This circadian effect is seen shortly following MA exposure and later in life following developmental MA exposure. MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms. We analyzed and compared immunoreactivity of the immediate early gene c-Fos, a marker of neuronal activity, to assess neuronal activation 2 h following MA exposure in the light and dark phases. We used network analyses of correlation patterns derived from global brain immunoreactivity patterns of c-Fos, to infer functional connectivity between brain regions. There were five distinct patterns of neuronal activation. In several brain areas, neuronal activation following exposure to MA was stronger in the light than the dark phase, highlighting the importance of considering circadian periods of increased effects of MA in defining experimental conditions and understanding the mechanisms underlying detrimental effects of MA exposure to brain function. Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain. 
26440425	Mild traumatic brain injury (mTBI) causes transient sleep disorders and circadian dysrhythmia. One of the clock genes, PERIOD3 (PER3), regulates the circadian rhythm and contains a genetic polymorphism, namely a variable-number tandem repeat in the coding area with either four or five repeats. PER3(5) carriers are inclined to have a morning preference and associated with higher risk of bipolar disorder and diabetes. This study investigated the effects of PER3 polymorphism on sleep quality changes after mTBI.From May 2012 to May 2014, a total of 96 mTBI patients completed the baseline (1 week after mTBI) and follow-up (6 weeks after mTBI) assessments, including the Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression questionnaires. Statistics were analyzed using the Mann-Whitney U test, Wilcox signed-rank test or chi-squared test.	Among the 96 patients, 24 were heterozygous PER3(5) carriers (PER3(4/5)), and the rest of 72 were PER3(5) noncarriers (PER3(4/4)). The subscale of PSQI questionnaire results indicated that the PER3(5) allele was associated with significant sleep duration shortening, but improvement in overall sleep quality. Furthermore, analyzing patients with sleep disturbance at the baseline (PSQI >5) revealed that only the PER3(5) noncarriers exhibited a significant improvement in overall PSQI scores.	PER3(5) carriers exhibited sleep duration shortening and improved daytime function 6 weeks after mTBI compared with the baseline values. On the other hand, among poor sleepers, PER3(5) carriers did not embrace a significant improvement of overall PSQI scores as noncarriers. The underlying mechanisms and clinical significances must be investigated further.	
26439374	Adults in intensive care units (ICUs) often suffer from a lack of sleep or frequent sleep disruptions. Non-pharmacological interventions can improve the duration and quality of sleep and decrease the risk of sleep disturbance, delirium, post-traumatic stress disorder (PTSD), and the length of stay in the ICU. However, there is no clear evidence of the effectiveness and harms of different non-pharmacological interventions for sleep promotion in adults admitted to the ICU.To assess the efficacy of non-pharmacological interventions for sleep promotion in critically ill adults in the ICU.To establish whether non-pharmacological interventions are safe and clinically effective in improving sleep quality and reducing length of ICU stay in critically ill adults.To establish whether non-pharmacological interventions are cost effective.	We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 6), MEDLINE (OVID, 1950 to June 2014), EMBASE (1966 to June 2014), CINAHL (Cumulative Index to Nursing and Allied Health Literature, 1982 to June 2014), Institute for Scientific Information (ISI) Web of Science (1956 to June 2014), CAM on PubMed (1966 to June 2014), Alt HealthWatch (1997 to June 2014), PsycINFO (1967 to June 2014), the China Biological Medicine Database (CBM-disc, 1979 to June 2014), and China National Knowledge Infrastructure (CNKI Database, 1999 to June 2014). We also searched the following repositories and registries to June 2014: ProQuest Dissertations & Theses Global, the US National Institutes of Health Ongoing Trials Register (www.clinicaltrials.gov), the metaRegister of Controlled Trials (ISRCTN Register) (www.controlled-trials.com), the Chinese Clinical Trial Registry (www.chictr.org.cn), the Clinical Trials Registry-India (www.ctri.nic.in), the Grey Literature Report from the New York Academy of Medicine Library (www.greylit.org), OpenGrey (www.opengrey.eu), and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch). We handsearched critical care journals and reference lists and contacted relevant experts to identify relevant unpublished data.	We included all randomized controlled trials (RCT) and quasi-RCTs that evaluated the effects of non-pharmacological interventions for sleep promotion in critically ill adults (aged 18 years and older) during admission to critical care units or ICUs.	Two authors independently screened the search results and assessed the risk of bias in selected trials. One author extracted the data and a second checked the data for accuracy and completeness. Where possible, we combined results in meta-analyses using mean differences and standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes. We used post-test scores in this review.	We included 30 trials, with a total of 1569 participants, in this review. We included trials of ventilator mode or type, earplugs or eye masks or both, massage, relaxation interventions, foot baths, music interventions, nursing interventions, valerian acupressure, aromatherapy, and sound masking. Outcomes included objective sleep outcomes, subjective sleep quality and quantity, risk of delirium, participant satisfaction, length of ICU stay, and adverse events. Clinical heterogeneity (e.g., participant population, outcomes measured) and research design limited quantitative synthesis, and only a small number of studies were available for most interventions. The quality of the evidence for an effect of non-pharmacological interventions on any of the outcomes examined was generally low or very low. Only three trials, all of earplugs or eye masks or both, provided data suitable for two separate meta-analyses. These meta-analyses, each of two studies, showed a lower incidence of delirium during ICU stay (risk ratio 0.55, 95% confidence interval (CI) 0.38 to 0.80, P value = 0.002, two studies, 177 participants) and a positive effect of earplugs or eye masks or both on total sleep time (mean difference 2.19 hours, 95% CI 0.41 to 3.96, P value = 0.02, two studies, 116 participants); we rated the quality of the evidence for both of these results as low.There was also some low quality evidence that music (350 participants; four studies) may improve subjective sleep quality and quantity, but we could not pool the data. Similarly, there was some evidence that relaxation techniques, foot massage, acupressure, nursing or social intervention, and sound masking can provide small improvements in various subjective measures of sleep quality and quantity, but the quality of the evidence was low. The effects of non-pharmacological interventions on objective sleep outcomes were inconsistent across 16 studies (we rated the quality of the evidence as very low): the majority of studies relating to the use of earplugs and eye masks found no benefit; results from six trials of ventilator modes suggested that certain ventilator settings might offer benefits over others, although the results of the individual trials did not always agree with each other. Only one study measured length of stay in the ICU and found no significant effect of earplugs plus eye masks. No studies examined the effect of any non-pharmacological intervention on mortality, risk of post-traumatic stress disorder, or cost-effectiveness; the included studies did not clearly report adverse effects, although there was very low quality evidence that ventilator mode influenced the incidence of central apnoeas and patient-ventilator asynchronies.	The quality of existing evidence relating to the use of non-pharmacological interventions for promoting sleep in adults in the ICU was low or very low. We found some evidence that the use of earplugs or eye masks or both may have beneficial effects on sleep and the incidence of delirium in this population, although the quality of the evidence was low. Further high-quality research is needed to strengthen the evidence base.	
26439359	In rodent studies, paired box 6 (PAX6) appears to play an important role in the development of the pineal, the primary source of the circadian regulating hormone, melatonin. Pineal hypoplasia has been previously reported in patients with PAX6 haploinsufficiency (+/−); however, pineal measurement, melatonin concentrations and sleep quality have not been reported. This cross-sectional descriptive study examined pineal volume, melatonin secretion and sleep disturbance in 37 patients with PAX6+/− (age 15.3 ± 9.9 years) and 17 healthy controls (16.0 ± 7.2 years), within an inpatient setting at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, USA. Pineal volume was evaluated by magnetic resonance imaging. Diurnal serum cortisol, serum melatonin and urine 6-sulphatoxymelatonin concentrations were measured by enzyme-linked immunosorbent assay. The Child Sleep Habits Questionnaire was administered for patients <13 years old. Pineal volume was fivefold lower in PAX6+/− versus controls (mean ± SD: 25 ± 15 versus 129 ± 50 μL, P < 0.001). Midnight serum cortisol was similar in PAX6+/− versus controls (P = 0.14). Midnight serum melatonin was > twofold lower in PAX6+/− versus controls [median (25th-75 th): 28 (22-42) versus 71 (46-88) pg mL-(1), P < 0.001]. First morning void urinary 6-sulphatoxymelatonin was fourfold lower in PAX6+/− versus controls [11 (6-26) versus 45 (34-61) ng mg(-1) Cr, P = 0.001]. Child Sleep Habits Questionnaire score was higher in PAX6+/− versus controls (48 ± 6 versus 41 ± 5, P = 0.03). The current findings suggest that PAX6+/− is associated with smaller pineal size, lower melatonin secretion and greater parental report of sleep disturbances in children. Further studies are needed to explore the potential use of melatonin replacement for improving sleep quality in patients with PAX6+/−.
26438138	To explore associations between features of sleep during pregnancy and adverse outcomes for the infant.E Moe, Māmā is a cohort study in Aotearoa/New Zealand that investigates self-reported sleep and maternal health in late pregnancy and the postpartum period.	Women (N=633; 194 Māori) reported detailed information on their sleep duration, quality, disturbances, disorders (snoring, breathing pauses, twitching legs, restless legs) and daytime sleepiness between 35 and 37 weeks gestation.	Birthweight and fetal distress during labour were extracted from medical records. Associations between each sleep variable and small or large for gestational age (SGA/LGA) using customised birthweight centile or fetal distress were estimated using multinomial/logistic regression, controlling for potential confounders. Secondary analyses considered differences in associations between Māori and non-Māori women.	There was some indication that breathing pauses (a measure of sleep apnoea) were associated with both SGA (OR 2.8, 95% CI 0.9 to 9.0, p=0.08) and LGA (OR 2.0, 95% CI 0.7 to 5.7, p=0.20), with the association for LGA being stronger when only pregnancy-onset breathing pauses were considered (OR 3.5, 95% CI 1.3 to 9.6, p=0.01). There was also some evidence that pregnancy-onset leg twitching (OR 3.3, 95% CI 1.1 to 10.0, p=0.03) and frequent sleep disturbance due to feeling too hot or too cold (OR 1.7, 95% CI 0.9 to 3.6, p=0.13) were associated with higher risk of fetal distress. Other sleep measures, including snoring, were not associated with SGA, LGA or fetal distress. Many of the associations we observed were considerably stronger in Māori compared with non-Māori women.	We did not find evidence of previously reported associations between snoring and SGA. Our findings tentatively suggest that self-reported breathing pauses and leg twitching in late pregnancy are associated with infant outcomes, and highlight ethnic inequalities.	
26437972	The incidence of pelvic girdle pain (PGP) in pregnancy is wide ranged depending on definition, the utilised diagnostic means, and the design of the studies. PGP during pregnancy has negative effects on activities of daily living and causes long sick leave, which makes it a major public health issue. Our objectives were to explore the frequency of sick leave in pregnancy due to PGP, assess the relationship between different types of pain-related activities of daily living, examine physical workload, type of work in relation to sick leave, and to explore factors that make women less likely to take sick leave for PGP.All women giving birth at the maternity ward of Stavanger University Hospital, Norway, were asked to participate and complete a questionnaire on demographic features, PGP, pain-related activities of daily living, sick leave in general and for PGP, frequency of exercising before and during pregnancy. Drawings of pelvic girdle and low back area were used for the localization of pain. PGP intensity was then rated retrospectively on a numerical rating scale. Non-parametric tests, multinomial logistic regression and sequential linear regression analysis were used in the statistical analysis.	PGP is a frequent and major cause of sick leave during pregnancy among Norwegian women, which is also reflected in activities of daily living as measured with scores on all Oswestry disability index items. In the multivariate analysis of factors related to sick leave and PGP we found that work satisfaction, problems with lifting and sleeping, and pain intensity were risk factors for sick leave. In addition, women with longer education, higher work satisfaction and fewer problems with sitting, walking and standing, were less likely to take sick leave in pregnancy, despite the same pain intensity as women being on sick leave.	A coping factor in pregnant women with PGP was discovered, most likely dependant on education, associated with work situation and/or work posture, which decreases sick leave. We recommend these issues to be further examined in a prospective longitudinal study since it may have important implications for sick leave frequency during pregnancy.	

26435268	Recent evidence has suggested that sleep may facilitate language learning. This study examined variation in language ability in 29 toddlers with Down syndrome (DS) in relation to levels of sleep disruption. Toddlers with DS and poor sleep (66%, n = 19) showed greater deficits on parent-reported and objective measures of language, including vocabulary and syntax. Correlations between sleep and language were found in groups with equivalent medical and social backgrounds and after control for relevant behavioral comorbidities, including autism symptoms. These results emphasize the important role of quality sleep in all children's expressive language development, and may help increase our understanding of the etiology of language deficits in developmental disorders, potentially leading to new treatment approaches.
26434672	Emil Kraepelin is considered one of the most influential psychiatrists ever. His research on sleep, however, has received little attention to date. Therefore, Kraepelin's published work was reviewed, statements on the topic "sleep" identified, historically contextualized and compared with current knowledge. His assumptions on the "physiology of sleep" are rather speculative and not substantiated by own research. The opposite is true for his findings on the "phenomenology of sleep". For example, his results on sleep depth and sleep stages are not only in overall good agreement with current concepts, but also based on sleep studies. Of special relevance are his findings on chronotypes: Based on empirical clinical studies, neuropsychological experiments and sleep studies, Kraepelin systematically described a morning and evening disposition and intermediate types on the basis of the maximum physical capacity, cognitive ability and alertness/sleepiness during the day as well as sleeping habits. In fact, this concept is basically still valid and these aspects are being captured in morningness-eveningness scales. Our findings challenge the common notion that Nathaniel Kleitman was the first to systematically describe the morningness-eveningness dimension. Overall, we deem Kraepelin's contributions to sleep research, compiled here for the first time, well worth being acknowledged by modern sleep research. 
26431774	The goal of this study was to examine how heroin self-administration, abstinence, and extinction/reinstatement affect circadian sleep-wake cycles and the associated sleep architecture. We used electroencephalography (EEG) and electromyography (EMG) to measure sleep patterns in male Sprague-Dawley rats over 16 trials of heroin self-administration (acquisition), 14 days of abstinence, and a single day of extinction and drug-induced reinstatement. Rats self-administering heroin showed evidence of reversed (diurnal) patterns of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep throughout acquisition. During abstinence, their wake and NREM sleep patterns were immediately restored to the normal nocturnal distribution. REM patterns remained inverted for the first 3-6 days of abstinence in heroin self-administering rats. The single extinction/reinstatement test was without effect. These data suggest that heroin may have the ability to affect circadian distribution of sleep and wakefulness, either indirectly, where animals shift their sleep-wake cycle to allow for drug taking, or directly, through wake-promoting actions or actions at circadian oscillators in the brain. 
26431758	Cardiometabolic diseases, which include obesity, diabetes, hypertension, and cardiovascular disease, are associated with reduced quality of life and reduced life expectancy. Unfortunately, there are racial/ethnic and socioeconomic disparities associated with these diseases such that minority populations, such as African Americans and Hispanics, and those of lower socioeconomic status, experience a greater burden. Several reports have indicated that there are differences in sleep duration and quality that mirror the disparities in cardiometabolic disease. The goal of this paper is to review the association between sleep and cardiometabolic disease risk because of the possibility that suboptimal sleep may partially mediate the cardiometabolic disease disparities.We review both experimental studies that have restricted sleep duration or impaired sleep quality and examined biomarkers of cardiometabolic disease risk, including glucose metabolism and insulin sensitivity, appetite regulation and food intake, and immune function. We also review observational studies that have examined the association between habitual sleep duration and quality, and the prevalence or risk of obesity, diabetes, hypertension, and cardiovascular disease.	Many experimental and observational studies do support an association between suboptimal sleep and increased cardiometabolic disease risk.	
26431756	Decrements in sleep health, including insufficient sleep duration, irregular timing of sleep, poor sleep quality, and sleep/circadian disorders, are widespread in modern society and are associated with an array of disease risks and outcomes, including those contributing to health disparities (eg, cardiovascular disease, obesity and diabetes, psychiatric illness, and cancer). Recent findings have uncovered racial/ethnic and socioeconomic position differences in sleep health; however, the contribution of sleep deficiency to health disparities remains largely unexplored, and understanding the underlying causes of disparities in sleep health is only beginning to emerge. In 2011, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop, bringing together sleep and health disparities investigators, to identify research gaps and opportunities to advance sleep and health disparities science. This article provides a brief background and rationale for the workshop, and it disseminates the research recommendations and priorities resulting from the working group discussions.
26431755	Sleep represents a set of biological functions necessary for the maintenance of life. Performing these functions, though, requires that an individual engage in behaviors, which are affected by social and environmental factors. Race/ethnicity and socioeconomic position represent categories of factors that likely play a role in the experience of sleep in the community. Previous studies have suggested that racial/ethnic minorities and the socioeconomically disadvantaged may be more likely to experience sleep patterns that are associated with adverse health outcomes. It is possible that disparities in sleep represent a pathway by which larger disparities in health emerge. This review (1) contextualizes the concept of race/ethnicity in biomedical research, (2) summarizes previous studies that describe patterns of sleep attainment across race/ethnicity groups, (3) discusses several pathways by which race/ethnicity may be associated with sleep, (4) introduces the potential role of socioeconomic position in the patterning of sleep, and (5) proposes future research directions to address this issue.
26429757	Childhood abuse is associated with increased risks of adult psychiatric disorders and physical health conditions. Mounting evidence documents associations of childhood abuse with sleep disturbances in adulthood. However, to date, no study has evaluated associations of childhood abuse and sleep disturbances among pregnant women.This cross-sectional study included 634 pregnant Peruvian women. To collect information regarding socio-demographic characteristics, history of childhood abuse, and complaints of sleep disturbances, face-to-face interviews were conducted with women in early pregnancy. Ford Insomnia Response to Stress Test (FIRST-S) and the Pittsburgh Sleep Quality Index (PSQI-S), translated from English to Spanish, were used to assess stress-related sleep disturbance and sleep quality, respectively. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CIs).	Women who experienced any childhood abuse had a 1.65-fold increased odds of stress-related sleep disturbance (aOR = 1.65; 95% CI: 1.15-2.38) and 2.11-fold increased odds of poor sleep quality during early pregnancy (aOR = 2.11; 95% CI: 1.35-3.30) as compared with women who reported no abuse. Women who reported both physical and sexual abuse during childhood were more than twice as likely to suffer from stress-related sleep disturbance (aOR = 2.26; 95% CI: 1.44-3.53) and poor sleep quality (aOR = 2.43; 95% CI: 1.45-4.09) in comparison to women who reported no childhood abuse.	A history of childhood abuse is associated with increased odds of stress-related sleep disturbance and poor sleep quality during pregnancy. These findings, if replicated, should be used to inform the development of trauma-informed care for such sleep disturbances induced by childhood trauma.	
26429755	The current study aimed to determine the differences between sleep-wake habits and circadian preference in Mexican adolescents attending classes at a morning shift or an afternoon shift.The sample consisted of 568 students of a secondary school in Reynosa, northeastern Mexico, of whom 280 were boys and 288 were girls (mean age 14.08 ± 0.72 years, age range 13-16 years). In the morning shift, 287 students attend classes on a schedule from 7:30 to 13:00 and the afternoon shift, 281 students, on a schedule from 13:20 to 19:00. Students completed a general information questionnaire, the Sleep Timing Questionnaire and the Spanish version of the Morningness-Eveningness Questionnaire.	The adolescents who attended the morning shift had earlier bedtime and waking time, but shorter sleep duration than those who attended the afternoon shift. Those oriented to eveningness had later bedtime, waking time, and a shorter sleep duration than those oriented to morningness. Two interactions were found between school shift and chronotype. First, with regard to waking time during weekdays, students who attended the afternoon shift and were oriented to eveningness woke up later than those who attended the morning shift and were oriented to eveningness; during weekdays, there were no differences between the waking time of morning-type and evening-type students who attended the morning shift. Second, with regard to sleep duration on weekdays, students who attended the morning shift and were oriented to eveningness had the shortest sleep duration. Furthermore, there were no differences between sleep duration on weekdays in evening-type and morning-type students of the afternoon shift.	Adolescents who attend classes in the morning shift and are oriented to eveningness are the most sleep deprived. Those who attend the afternoon shift will have optimal sleep duration, regardless of their circadian preference.	

26429750	Poor sleep may be a risk factor for obesity. Previous studies have mainly investigated the effects of sleep duration on body mass index, but research considering overall sleep quality and other anthropometric measures is scarce. The aim of this study was to examine the association between sleep quality and different measures of obesity (general obesity, abdominal obesity, body composition) in a population-based sample of adults.The study included 753 participants aged 35-65 years from the BiDirect Study, conducted in Münster, Germany. Participants completed the Pittsburgh Sleep Quality Index (PSQI) on sleep characteristics. Weight, height, and waist circumference were measured by trained study nurses. Body composition (fat mass and fat-free mass) was assessed using bioelectrical impedance analysis. The cross-sectional relationship between sleep quality and measures of obesity was investigated using logistic regression analysis.	Among the participants, 65.3% reported good (PSQI ≤ 5) and 34.7% poor (PSQI > 5) sleep quality. We observed a significant association of poorer sleep quality assessed by the continuous PSQI score with general obesity and high body fat (for both, odds ratio = 1.07, 95% confidence interval = 1.01-1.13), adjusted for socio-demographic and lifestyle factors. Further adjustment for depressive symptoms and somatic comorbidities attenuated the relationship. The observed association was mainly driven by the PSQI components sleep latency, sleep disturbances, and daytime dysfunction.	The present study suggests that poor sleep quality may predict obesity and high body fat mass among adults. However, a causal relationship still has to be confirmed by prospective studies with objective measurements of sleep and obesity.	
26429746	There is a need for brief, psychometrically sound instruments to assess adolescent sleep, particularly for ethnic minority and economically disadvantaged adolescents. A 10-item short version of the Adolescent Sleep-Wake Scale was recently proposed based upon exploratory factor analysis with primarily Caucasian healthy adolescents from middle- to high-income families. The aim of this study was to expand the utility of the short version of the Adolescent Sleep-Wake Scale by investigating the empirical and construct validity of the measure on an ethnically diverse sample of adolescents from an economically disadvantaged community.Participants included 467 adolescents (40% African American, 35.5% Caucasian, 16.5% Latino, and 7.9% multiethnic), aged 12-18 years (mean = 15.27 years, SD = 1.96 years), who completed the Adolescent Sleep-Wake Scale. A confirmatory factor analysis (CFA) was conducted with Mplus 7 based on the three-factor solution proposed by Essner et al. (2014).	CFA indicated that the three-factor structure was a good fit for the data (χ(2) (29) = 52.053, p = 0.005, root mean square error of approximation (RMSEA) = 0.04, CFI = 0.98, TLI = 0.96, standardized root mean residuals (SRMR) = 0.03), and factor loadings for each item were >0.40. Cronbach's alphas by ethnicity indicated that the scale has acceptable reliability (0.70 ≤ α ≤ 0.90) for African American, Caucasian, and multiethnic adolescents, but not for Latino adolescents.	Our results support the use of the Adolescent Sleep-Wake Scale short form for the majority of ethnic minority and economically disadvantaged adolescents.	
26429744	This study aimed to examine the relationship between sleep problems and working memory in children aged 5-13 years with attention-deficit/hyperactivity disorder (ADHD).Children with ADHD were recruited into a randomized controlled trial from 21 paediatric practices in VIC, Australia. Cross-sectional data for intervention and control children were pooled at 6 months post randomization for the current analyses (n = 189). Children who met the Diagnostic Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for ADHD and had a parent-reported moderate/severe sleep problem that fulfilled diagnostic criteria for a behavioural sleep disorder were recruited into the study. Sleep was assessed by detailed parent (Children's Sleep Habits Questionnaire) and self-reports (Self-Sleep Report). Working memory was measured using the Working Memory Test Battery for Children (low and very low working memory defined as <25th and <10th percentiles, respectively). Analyses were adjusted for child age and gender, internalizing and externalizing comorbidities, and socio-economic status.	Self-reported sleep problem severity was associated with poorer working memory; for each standard deviation increase in self-reported sleep problems, working memory scores decreased by -3.8 points (95% confidence interval (CI): -6.7, -0.8; p = 0.01). There was some evidence that self-reported sleep problems were associated with low (p = 0.06) and very low working memory (p = 0.01). There was minimal evidence that parent-reported sleep problems were associated with poorer working memory with the exception of bedtime resistance problems.	Behavioural sleep problems and working memory are associated in children with ADHD, particularly when sleep is assessed by self-report.	
26429613	A cross-sectional survey administered to first- and second-year podiatric medical students aimed to investigate the effect of coffee intake, energy drink consumption, and perceived stress on sleep quality in medical students during their preclinical studies.Ninety-eight of 183 students contacted (53.6%) completed a questionnaire comprising standard instruments measuring sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness scale), and perceived stress (ten-item Perceived Stress Scale). Furthermore, we investigated coffee and energy drink consumption. Logistic regression was conducted to identify factors associated with poor sleep quality and the relation between sleep quality and academic performance (grade point average).	High prevalences of poor sleep quality, excessive daytime sleepiness, and perceived stress were reported. In addition, higher odds of developing poor sleep quality were associated with coffee and energy drink intake, perceived stress, and excessive daytime sleepiness. The total Pittsburgh Sleep Quality Index score was inversely correlated with grade point average.	First- and second-year podiatric medical students have poor sleep quality. Further research is needed to identify effective strategies to reduce stress and decrease coffee and energy drink intake to minimize their negative effect on sleep quality and academic performance in podiatric medical students.	

26426478	Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\wake states, feeding, stress, and reward. To elucidate the mechanism that enables these various functions and to identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified and comprehensive high-resolution imaging revealed gene-specific localization in all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are predicted to be regulated by shared transcription factors. These findings show that Hcrt neurons are heterogeneous and that integrative molecular mechanisms orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a, which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene inactivation system. The mutant kcnh4a (kcnh4a(-/-)) larvae showed reduced sleep time and consolidation, specifically during the night, suggesting that Kcnh4a regulates sleep. 
26425109	We previously published the performance evaluation of an automated electroencephalography (EEG)-based single-channel sleep-wake detection algorithm called Z-ALG used by the Zmachine(®) sleep monitoring system. The objective of this paper is to evaluate the performance of a new algorithm called Z-PLUS, which further differentiates sleep as detected by Z-ALG into Light Sleep, Deep Sleep, and Rapid Eye Movement (REM) Sleep, against laboratory polysomnography (PSG) using a consensus of expert visual scorers.Single night, in-lab PSG recordings from 99 subjects (52F/47M, 18-60 years, median age 32.7 years), including both normal sleepers and those reporting a variety of sleep complaints consistent with chronic insomnia, sleep apnea, and restless leg syndrome, as well as those taking selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor antidepressant medications, previously evaluated using Z-ALG were re-examined using Z-PLUS. EEG data collected from electrodes placed at the differential-mastoids (A1-A2) were processed by Z-ALG to determine wake and sleep, then those epochs detected as sleep were further processed by Z-PLUS to differentiate into Light Sleep, Deep Sleep, and REM. EEG data were visually scored by multiple certified polysomnographic technologists according to the Rechtschaffen and Kales criterion, and then combined using a majority-voting rule to create a PSG Consensus score file for each of the 99 subjects. Z-PLUS output was compared to the PSG Consensus score files for both epoch-by-epoch (eg, sensitivity, specificity, and kappa) and sleep stage-related statistics (eg, Latency to Deep Sleep, Latency to REM, Total Deep Sleep, and Total REM).	Sensitivities of Z-PLUS compared to the PSG Consensus were 0.84 for Light Sleep, 0.74 for Deep Sleep, and 0.72 for REM. Similarly, positive predictive values were 0.85 for Light Sleep, 0.78 for Deep Sleep, and 0.73 for REM. Overall, kappa agreement of 0.72 is indicative of substantial agreement.	This study demonstrates that Z-PLUS can automatically assess sleep stage using a single A1-A2 EEG channel when compared to the sleep stage scoring by a consensus of polysomnographic technologists. Our findings suggest that Z-PLUS may be used in conjunction with Z-ALG for single-channel EEG-based sleep staging.	
26424879	After withdrawal from cocaine, chronic cocaine users often experience persistent reduction in total sleep time, which is accompanied by increased sleep fragmentation resembling chronic insomnia. This and other sleep abnormalities have long been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here, we report that after prolonged withdrawal from cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep fragmentation. In an attempt to improve sleep after cocaine withdrawal, we applied chronic sleep restriction to the rats during their active (dark) phase of the day, which selectively decreased the fragmentation of REM sleep during their inactive (light) phase without changing NREM or the total amount of daily sleep. Animals with improved REM sleep exhibited decreased incubation of cocaine craving, a phenomenon depicting the progressive intensification of cocaine seeking after withdrawal. In contrast, experimentally increasing sleep fragmentation after cocaine self-administration expedited the development of incubation of cocaine craving. Incubation of cocaine craving is partially mediated by progressive accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals with improved REM sleep exhibited reduced accumulation of CP-AMPARs in the NAc, whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation. These results reveal a potential molecular substrate that can be engaged by sleep to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic opportunities for cocaine addiction. Significance statement: Sleep abnormalities are common symptoms in chronic drug users long after drug withdrawal. These withdrawal-associated sleep symptoms, particularly reduction in total sleep time and deteriorating sleep quality, have been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here we show in rats that the sleep pattern was persistently changed long after withdrawal from cocaine self-administration, and demonstrate that sleep interventions can bidirectionally regulate cocaine craving and seeking after withdrawal. We further demonstrate that glutamatergic synapses in the nucleus accumbens are potential neuronal targets for sleep intervention to influence cocaine craving after withdrawal. These results provide a strong rationale supporting sleep-based therapies for cocaine addiction.
26424539	Parkinson's disease (PD) is a multisystem disorder, and besides the classical motor symptoms it is now known that patients also suffer from a variety of non-motor symptoms that adversely affect quality of life (QOL). Since data on Hispanic populations on this issue are scarce, our aim was to study the association of non-motor symptoms and QOL in patients with PD. This study is a cross-sectional observational study involving patients with PD using the following instruments: Quality of Life Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part III (UPDRS part III), and Non-Motor Symptom Scale (NMSS). We included 52 patients, with a median age of 64 years. Sleep/fatigue and mood/cognitive domains were the most common non-motor symptoms. Only sleep/fatigue, mood/cognition and gastrointestinal domains were associated with worse PDQ-8 scores. After adjusting for confounding variables, NMSS scores were significantly associated with a high PDQ-8 score. Higher NMSS scores were associated with and predicted higher PDQ-8 scores. The focus of management in PD should shift to a comprehensive strategy that incorporates care of non-motor symptoms and improves QOL. 
26424155	The prevalence of dementia in Australian nursing homes is high. A large proportion of residents express themselves through agitated behaviors, with substantial interpersonal and day-to-day variance. One factor that may increase agitation is poor sleep. The current study aimed to determine if sleep influences symptoms of agitation in nursing home residents, and whether this effect differed by dementia status. As benzodiazepines are used widely as hypnotic medication, their impact was also considered.Actigraph devices worn on residents' non-dominant wrists for three days were used to obtain objective measures of sleep. Symptoms of agitation were assessed using staff responses to two standardized questionnaires - the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory - nursing home version (NPI-NH). Presence of dementia and benzodiazepine use were obtained from resident medical charts.	Forty-nine residents (mean age: 85.57 years) from four nursing homes in Tasmania were included in the study. Results indicated that residents were in bed for an average of 11.04 h and slept for 10.14 h per day. Significant relationships between sleep and verbal as well as non-aggressive agitation were found. No relationships between sleep and aggressive agitation were detected. A significant moderation effect of dementia was found, in which residents without dementia expressed verbal agitation when obtaining less sleep, but not residents with dementia. Benzodiazepine use did not result in significantly more sleep.	These results suggest that sleep could play an important role in explaining agitation, but more research is needed to explore the relationship between sleep and benzodiazepines in nursing home residents.	
26422058	The aim of this paper was to assess the relationship between pain and sleep in older adults taking depression, stress, and medical comorbidities into account.A cross-sectional analysis was performed using Einstein Aging Study, a community-based cohort study of adults aged 70 years and older. Ratings of pain intensity and interference from the Medical Outcomes Study (MOS) Short-Form 36 were used to assign individuals to low-pain versus high-pain severity. Sleep disturbance was assessed using the nine-item sleep problems index from the Medical Outcomes Study Sleep Scale. Other measures included the Geriatric Depression Scale and Perceived Stress Scale (PSS). Linear regression models were used to assess the association between pain grade and sleep disturbance adjusted for demographics, PSS, Geriatric Depression Scale, and other comorbidities.	Five hundred sixty-two eligible participants with a mean age of 78.22 years (standard deviation = 5.43) were included; 64% were women. Pain grade [β = 5.40, 95% confidence interval (CI) 2.56-8.21, p < 0.001] was associated with sleep disturbance after adjusting for demographic variables. In models including pain grade (β = 3.08, 95% CI 0.32-5.85, p = 0.03) and PSS (β = 0.57, 95% CI 0.39-0.75, p < 0.001), both were associated with sleep disturbance, although the PSS attenuated the relationship between pain and sleep by 34%. Depression, when added to previous model, was also associated with sleep (β = 2.17, 95% CI 1.48-2.85, p < 0.001) and attenuated the relationship between pain (β = 2.41, 95% CI -0.25 to 5.08, p = 0.07) and sleep by 22%. Stratified for depression, we found that pain, stress, and other medical comorbidities were significantly associated with sleep disturbance in non-depressed individuals but not individuals with depression.	Pain, stress, and medical comorbidities are associated with sleep disturbance, especially in non-depressed older adults.	
26421989	Mutations of SLC9A6 may cause an X-linked clinical syndrome first described by Christianson in 1999 in which affected males exhibited profound intellectual disability, autism, drug-resistant epilepsy, ophthalmoplegia, mild craniofacial dysmorphism, microcephaly, and ataxia.We describe a child with an SLC9A6 mutation and an electroencephalographic pattern consistent with electrographic status epilepticus of sleep.	Our patient's electrographic status epilepticus of sleep resolved after treatment with felbamate. Following treatment, he remained seizure-free but did not make significant or lasting gains in language.	Our report extends the clinical epilepsy phenotype in children with SLC9A6 mutations to include electrographic status epilepticus of sleep. In addition, felbamate was an effective treatment for electrographic status epilepticus of sleep in our patient.	
26420687	Fatigue is defined as a condition or phenomenon of decreased ability and efficiency of mental and/or physical activities, caused by excessive mental or physical activities, diseases, or syndromes. It is often accompanied by a peculiar sense of discomfort, a desire to rest, and reduced motivation, referred to as fatigue sensation. Acute fatigue is a normal condition or phenomenon that disappears after a period of rest; in contrast, chronic fatigue, lasting at least 6 months, does not disappear after ordinary rest. Chronic fatigue impairs activities and contributes to various medical conditions, such as cardiovascular disease, epileptic seizures, and death. In addition, many people complain of chronic fatigue. For example, in Japan, more than one third of the general adult population complains of chronic fatigue. It would thus be of great value to clarify the mechanisms underlying chronic fatigue and to develop efficient treatment methods to overcome it. Here, we review data primarily from behavioral, electrophysiological, and neuroimaging experiments related to neural dysfunction as well as autonomic nervous system, sleep, and circadian rhythm disorders in fatigue. These data provide new perspectives on the mechanisms underlying chronic fatigue and on overcoming it.
26420374	In a population-based sampling study conducted in community-dwelling older adults living in rural Ecuador, we aimed to assess the relation among sleep-disordered breathing, cerebral pulsatility index, and diffuse small vessel disease.Of 25 participants, 9 (36%) had moderate-to-severe sleep-disordered breathing, characterized by an apnea/hypopnea index ≥15 per hour, and 10 (40%) had moderate-to-severe white matter hyperintensities, graded according to the modified Fazekas scale. Mean (SD) pulsatility index in the middle cerebral artery was 1.18 (0.19) and positively correlated with the apnea/hypopnea index (R = .445, P = .03, [Pearson's correlation coefficient]). The middle cerebral artery pulsatility index was increased in persons with moderate-to-severe sleep-disordered breathing compared with persons who had none-to-mild sleep-disordered breathing (mean [SD] 1.11 [0.12] vs. 1.3 [0.23], P = .01). No significant differences were found in the prevalence of moderate-to-severe white matter hyperintensities across groups of sleep-disordered breathing (P = .40) or in the mean apnea/hypopnea index across groups of persons with none-to-mild or moderate-to-severe white matter hyperintensities (P = .16).	This pilot study shows that moderate-to-severe sleep-disordered breathing correlates with cerebral pulsatility, but such association might be independent of diffuse small vessel disease.	
26419612	Polysomnography studies in Parkinson's disease (PD) patients show altered sleep microstructure with decreased level of arousability, indicating impaired sleep-wake dynamics in PD. The aim of this study was to investigate dynamical aspects of sleep EEG in PD as compared to healthy controls.In this retrospective, controlled study, we applied a previously established mathematical model of sleep EEG analysis (state space model) to PD patients and age- and gender-matched healthy volunteers (N=64). Dynamical aspects of sleep were quantified by measuring the spectral variability of the sleep EEG (by means of state space velocity).	State space analysis revealed preserved global sleep-wake architecture in PD patients, but the velocity of sleep stage transitions was significantly reduced as compared to healthy controls. Correlation analysis revealed a strong association of state space velocity with arousal scores and daily dopamine agonist intake.	Quantitative analysis of spectral sleep EEG variability (state space velocity) revealed reduced sleep-wake dynamics in PD patients as compared to control subjects.	We propose state space velocity as an objective and quantitative measure for altered sleep microstructure and as a potential biomarker of sleep alterations in PD, not accessible by conventional sleep analysis.	
26419467	Pain from osteoarthritis (OA) affects millions of people worldwide, yet treatments are limited to acetaminophen, NSAIDs, physical therapy, and ultimately, surgery when there is significant disability. In recent years, our understanding of pain pathways in OA has developed considerably. Though joint damage and inflammation play a significant role in pain generation, it is now understood that both central and peripheral nervous system mechanisms exacerbate symptoms. Evolving management strategies for OA address central factors (e.g., sleep difficulties, catastrophizing, and depression) with treatments such as cognitive behavioral therapy and exercise. In addition, emerging data suggest that antibodies against peripheral signaling neuropeptides, such as nerve growth factor-1 (NGF-1), may significantly alleviate pain. However, concerns regarding potential adverse effects, such as rapidly progressive OA, still remain. A nuanced understanding is essential if we are to make headway in developing more effective treatments for OA. 
26418664	In this observational cross-sectional study, 49 subjects were assessed for sleep disorders and for ADHD symptoms. Thirty-six received an ADHD diagnosis (29: combined type (ADHD-C); 7: inattentive type). An RLS and RLS symptoms prevalence of 34.5% was found, with a higher prevalence rate in the ADHD-C subgroup, although not significantly (p = 0.066). RLS symptoms were correlated with particularly hyperactivity-impulsivity (ρ = 0.742; p: 0.000). ADHD patients with positive RLS scores reported higher scores on the ADHD-Rating scale compared with patients with negative RLS scores (Z: -2.968, p = 0.003), mainly due to higher hyperactivity-impulsivity scores (Z: -3.145; p = 0.002). Our findings show that clinicians need to be aware of RLS among adult ADHD patients, particularly those with severe hyperactivity-impulsivity symptoms. 
26417799	Sleep disorders have a proven association with psychiatric illness. Therefore, psychiatrists require appropriate training in diagnosing and treating sleep disorders. To date, there is no data available in Europe on training in sleep medicine for early career psychiatrists (ECP).To identify the availability of training in sleep medicine for psychiatric trainees across Europe and to establish how confident doctors feel in treating these conditions.	European-wide survey carried out by the European Psychiatric Association (EPA)-Early Career Psychiatrists Committees. Representatives of ECPs from each participating European country filled in a questionnaire about availability of training in sleep medicine in their country. ECPs were also invited to fill out a questionnaire at the EPA congress in Nice in 2013.	55 participants from 27 European countries responded. Only 24% had sleep medicine training mandatorily included in their national training curriculum. A majority (60%) felt that the quality of the training they received was either average or below average. 88% felt either very or fairly confident in treating insomnia. However, when asked to select the correct management options for insomnia from a provided list of six, only 19% and 33% of respondents chose the two correct options.	There is a clear gap between the level of confidence and the clinical judgements being made to treat insomnia among European ECPs. There is a definite need to improve the availability and structure of sleep medicine training for psychiatric trainees in Europe.	
26416490	It is unknown why some breast cancer survivors experience cancer-related cognitive impairments (CRCI) after cancer treatment, and modifiable risk factors for CRCI remain to be explicated. This mixed-method systematic review synthesizes quantitative and qualitative evidence for relationships between modifiable factors and CRCI in breast cancer survivors who receive chemotherapy as part of their treatment.Keyword Searches of PubMed/Medline, PsychINFO, and CINAHL were performed for January 2005 through June 2015. Studies that provided data on associations between modifiable biological, behavioral, environmental, and psychosocial factors and cognition were included.	Twenty-two quantitative studies and five qualitative studies were identified after applying inclusion and exclusion criteria yielding evidence for significant relationships among modifiable biological (inflammatory cytokines), behavioral (sleep quality, physical activity), and psychosocial (stress, distress, affect) factors and CRCI.	Many women unfortunately experience CRCI after breast cancer chemotherapy, with limited treatment options available to improve cognitive function. This review synthesizes current evidence to support the associations between modifiable factors and CRCI and can inform research to evaluate these factors prospectively. The clinical implications of these findings suggest that lifestyle factors such as physical activity, stress management, and sleep quality may be appropriate targets for behavioral interventions to improve cognitive function following breast cancer chemotherapy; however, further research is necessary.	
26416477	The orexin receptors OX1 and OX2 play important roles in the regulation of sleep-wake cycles, feeding, reward and energy homeostasis. Since these G protein-coupled receptors were deorphanised in 1998, more than 200 patents containing orexin receptor antagonists have been filed and, in 2014, suvorexant (Belsomra®) became the first of these compounds to receive approval from the FDA. Suvorexant is a dual orexin receptor antagonist (DORA) which is available for the treatment of insomnia. This review provides a historical perspective on the discovery and development of DORAs as well as selective OX1 receptor antagonists (1-SORAs) and selective OX2 receptor antagonists (2-SORAs). 2-SORAs are under clinical evaluation for their ability to modulate sleep, and 1-SORAs have shown promise for the treatment of addiction in pre-clinical animal models. Detailed medicinal chemistry case studies are presented and future opportunities for orexin receptor antagonists are considered.
26416397	Parkinson's disease (PD) has a wide range of non-motor symptoms including; constipation, sleep disturbance, deficits in vision and olfaction, mood disorders and cardiac autonomic dysfunction. Several of these non-motor symptoms can manifest prior to the onset of motor symptoms. Recognizing these pre-motor symptoms may enable early diagnosis of PD. Currently, no single pre-motor symptom is able to predict the development of PD with 100% sensitivity or specificity. Ongoing studies in several independent at-risk cohorts should reveal the potential of combinations of pre-motor symptoms and multi-stage screening strategies to identify individuals at increased risk of PD. PD progression may be governed by a prion-like spread of a-syn throughout the nervous system. Identifying individuals at the earliest stage will likely be critical to preventing the pathological progression of PD, highlighting the relevance of pre-motor symptoms in the future treatment of the disease. 
26415836	To assess trends in benzodiazepine use from 2001 to 2010 in older adults in U.S. ambulatory clinics and emergency departments (EDs).Retrospective analysis.	2001 to 2010 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS).	Individuals aged 65 and older for whom the reason for visit might prompt a physician to use a benzodiazepine (e.g., anxiety, detoxification, back sprain).	The NAMCS and NHAMCS were used to evaluate U.S. ambulatory clinic and ED visits. Encounters involving individuals aged 65 and older for whom a benzodiazepine might be prescribed were analyzed. Trends in benzodiazepine use in these visits were explored, and predictors of use were assessed using survey-weighted chi-square tests and logistic regression.	From 2001 to 2010, benzodiazepines were used in 16.6 million of 133.3 million ambulatory clinic visits and 1.9 million of 18.1 million ED visits with the selected reasons for the visits. There was no change in benzodiazepine use in either setting over the study period, although benzodiazepine use for those aged 85 and older increased from 8.9% to 19.3% in ambulatory clinics and 10.1% to 17.2% in EDs. Individuals visiting clinics with anxiety were five times as likely to receive benzodiazepines (odds ratio (OR) = 4.8), and those in EDs were twice as likely (OR = 2.3).	Despite safety concerns, benzodiazepine use in older adults in U.S. ambulatory clinics and EDs did not change from 2001 to 2010. In the oldest individuals, who are at higher risk of adverse events, a greater increase was seen than in those aged 65 to 84. Additional measures may be needed to promote alternatives to benzodiazepines.	
26414990	This study examined the effects of milnacipran on polysomnographic (PSG) measures of sleep and subjective complaints in patients with fibromyalgia and disturbed sleep.This was a single-site, double-blind, placebo-controlled, two-period crossover PSG study. Eligible subjects (aged 28-72 y) were randomized (1:1) to milnacipran (100 mg/d) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose-escalation and dose-maintenance phase, with a 2-w taper/washout between periods. In-laboratory PSGs were collected at baseline, and at the end of each treatment period. The primary endpoints were the difference in PSG-recorded wake after sleep onset (WASO), number of awakenings after sleep onset (NAASO), and sleep efficiency (SE) between 4 w of maintenance treatment with milnacipran and placebo. Other PSG measures, subject-rated sleep, fatigue, physical functioning, and pain were assessed. Post hoc analysis was performed in subjects showing at least 25% reduction in pain from baseline in the Brief Pain Inventory Score (responders).	Of 19 subjects randomized, 15 completed both periods. Subjects treated with milnacipran showed no significant improvements in WASO and NAASO, but showed reduced SE (p = 0.049). Milnacipran did not show significant improvement in other PSG parameters or subjective endpoints. Two thirds of completers met responder criteria and additionally showed a significant improvement in daily effect of pain (p = 0.043) and subjective sleep quality (p = 0.040).	The data suggest that milnacipran is not sedating in most patients with fibromyalgia and improvements in sleep are likely a result of pain improvement.	
26414986	A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.


26414983	The American Academy of Sleep Medicine's (AASM) Taskforce on Sleep Telemedicine supports telemedicine as a means of advancing patient health by improving access to the expertise of Board-Certified Sleep Medicine Specialists. However, such access improvement needs to be anchored in attention to quality and value in diagnosing and treating sleep disorders. Telemedicine is also useful to promote professionalism through patient care coordination and communication between other specialties and sleep medicine. Many of the principles and key concepts adopted here are based on U.S. industry standards, with special consideration given to the body of work by the American Telemedicine Association (http://www.americantelemed.org/), and abide by standards endorsed by the American Medical Association (http://www.ama-assn.org/). Practitioners who wish to integrate sleep telemedicine into their practice should have a clear understanding of the salient issues, key terminology, and the following recommendations from the AASM. The Taskforce recommends the following: • Clinical care standards for telemedicine services should mirror those of live office visits, including all aspects of diagnosis and treatment decisions as would be reasonably expected in traditional office-based encounters. • Clinical judgment should be exercised when determining the scope and extent of telemedicine applications in the diagnosis and treatment of specific patients and sleep disorders. • Live Interactive Telemedicine for sleep disorders, if utilized in a manner consistent with the principles outlined in this document, should be recognized and reimbursed in a manner competitive or comparable with traditional in-person visits. • Roles, expectations, and responsibilities of providers involved in the delivery of sleep telemedicine should be defined, including those at originating sites and distant sites. • The practice of telemedicine should aim to promote a care model in which sleep specialists, patients, primary care providers, and other members of the healthcare team aim to improve the value of healthcare delivery in a coordinated fashion. • Appropriate technical standards should be upheld throughout the telemedicine care delivery process, at both the originating and distant sites, and specifically meet the standards set forth by the Health Insurance Portability and Accountability Act (HIPAA). • Methods that aim to improve the utility of telemedicine exist and should be explored, including the utilization of patient presenters, local resources and providers, adjunct testing, and add-on technologies. • Quality Assurance processes should be in place for telemedicine care delivery models that aim to capture process measures, patient outcomes, and patient/provider experiences with the model(s) employed. • Time for data management, quality processes, and other aspects of care delivery related to telemedicine encounters should be recognized in value-based care delivery models. • The use of telemedicine services and its equipment should adhere to strict professional and ethical standards so as not to violate the intent of the telemedicine interaction while aiming to improve overall patient access, quality, and/or value of care. • When billing for telemedicine services, it is recommended that patients, providers, and others rendering services understand payor reimbursements, and that there be financial transparency throughout the process. • Telemedicine utilization for sleep medicine is likely to rapidly expand, as are broader telehealth applications in general; further research into the impact and outcomes of these are needed. This document serves as a resource by defining issues and terminology and explaining recommendations. However, it is not intended to supersede regulatory or credentialing recommendations and guidelines. It is intended to support and be consistent with professional and ethical standards of the profession.
26414975	This study examined the extent to which self-reported exposure to blast during deployment to Iraq and Afghanistan affects subjective and objective sleep measures in service members and veterans with and without posttraumatic stress disorder (PTSD).Seventy-one medication-free service members and veterans (mean age = 29.47 ± 5.76 years old; 85% men) completed self-report sleep measures and overnight polysomnographic studies. Four multivariate analyses of variance (MANOVAs) were conducted to examine the impact of blast exposure and PTSD on subjective sleep measures, measures of sleep continuity, non-rapid eye movement (NREM) sleep parameters, and rapid eye movement (REM) sleep parameters.	There was no significant Blast × PTSD interaction on subjective sleep measures. Rather, PTSD had a main effect on insomnia severity, sleep quality, and disruptive nocturnal behaviors. There was no significant Blast × PTSD interaction, nor were there main effects of PTSD or Blast on measures of sleep continuity and NREM sleep. A significant PTSD × Blast interaction effect was found for REM fragmentation.	The results suggest that, although persistent concussive symptoms following blast exposure are associated with sleep disturbances, self-reported blast exposure without concurrent symptoms does not appear to contribute to poor sleep quality, insomnia, and disruptive nocturnal disturbances beyond the effects of PTSD. Reduced REM sleep fragmentation may be a sensitive index of the synergetic effects of both psychological and physical insults.	
26414573	Women with ovarian cancer have a continued high symptom burden in comparison to other cancer survivors secondary to ongoing chemotherapy treatment. Prolonged or ineffective management of treatment-related symptoms can contribute to treatment noncompliance, worsening of symptoms, and reduced health-related quality of life.This review of the literature was conducted to describe experimental and quasi-experimental research addressing nonpharmacologic interventions for the treatment-related symptoms of sleep disturbance, pain, anxiety, depression, and low energy or fatigue in women with ovarian cancer and to critique the quality of interventions.	A systematic search of the literature was conducted in PubMed and yielded 136 articles. Eight articles met the inclusion criteria and were evaluated.	Nonpharmacologic interventions for treatment-related symptoms were complex, with an average of 4.4 components. Intervention delivery, setting, and exposure varied widely across studies. Only three studies contained details sufficient to replicate the intervention. Lack of clarity in intervention reporting may explain perceptions of clinically inefficacious symptom management in this context. Greater attention to reporting would facilitate better translation of interventions into practice and when addressing complex cancer symptom clusters.	
26414556	Traumatic brain injury (TBI) is a major cause of persistent disabilities such as sleep-wake disorders (SWD). Rodent studies of SWD after TBI are scarce, however, because of lack of appropriate TBI models reproducing acceleration-deceleration forces and compatible with electroencephalography/myography (EEG/EMG)-based recordings of vigilance states. We therefore adapted the Marmarou impact acceleration model to allow for compatibility with EEG-headset implantation. After implantation of EEG/EMG electrodes, we induced closed TBI by a frontal, angular hit with a weight-drop device (56 rats, weight 2500 g, fall height 25 cm). Subsequently, we tested our model's usefulness for long-term studies on a behavioral, electrophysiological, and histological level. Neurological, motor, and memory deficits were assessed with the neurological severity score, open field, and novel object recognition tests, respectively. EEG/EMG recordings were performed in both Sham (n = 7) and TBI (n = 7) rats before and 1, 7, and 28 days after trauma to evaluate sleep-wake proportions and post-traumatic implant stability. Histological assessments included hematoxylin and eosin staining for parenchymal damage and hemorrhage and amyloid precursor protein staining for diffuse axonal damage. All rats survived TBI without major neurological or motor deficits. Memory function was impaired after TBI at weeks 1, 2, and 3 and recovered at week 4. EEG implants were stable for at least 1 month and enabled qualitative and quantitative sleep analyses. Histological assessments revealed no major bleedings or necrosis but intense diffuse axonal damage after TBI. This approach fulfills major pre-conditions for experimental TBI models and offers a possibility to electrophysiologically study behavioral states before and after trauma. 
26412255	Hippocrates flagged the value of sleep for good health. Nonetheless, historically, researchers with an interest in developmental psychopathology have largely ignored a possible role for atypical sleep. Recently, however, there has been a surge of interest in this area, perhaps reflecting increased evidence that disturbed or insufficient sleep can result in poor functioning in numerous domains. This review outlines what is known about sleep in the psychiatric diagnoses most relevant to children and for which associations with sleep are beginning to be understood. While based on a comprehensive survey of the literature, the focus of the current review is on the latest science (largely from 2010). There is a description of both concurrent and longitudinal links as well as possible mechanisms underlying associations. Preliminary treatment research is also considered which suggests that treating sleep difficulties may result in improvements in behavioural areas beyond sleep quality.To maximise progress in this field, there now needs to be: (a) greater attention to the assessment of sleep in children; (b) sleep research on a wider range of psychiatric disorders; (c) a greater focus on and examination of mechanisms underlying associations; (d) a clearer consideration of developmental questions and (e) large-scale well-designed treatment studies.	While sleep problems may sometimes be missed by parents and healthcare providers; hence constituting a hidden risk for other psychopathologies - knowing about these difficulties creates unique opportunities. The current excitement in this field from experts in diverse areas including developmental psychology, clinical psychology, genetics and neuropsychology should make these opportunities a reality.	
26412074	Most depressed patients suffer from sleep abnormalities, which are one of the critical symptoms of depression. They are robust risk factors for the initiation and development of depression. Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep. REM sleep alterations include a decrease in REM sleep latency, an increase in REM sleep duration and REM sleep density with respect to depressive episodes. Emotional brain processing dependent on the normal sleep-wake regulation seems to be failed in depression, which also promotes the development of clinical depression. Also, REM sleep alterations have been considered as biomarkers of depression. The disturbances of norepinephrine and serotonin systems may contribute to REM sleep abnormalities in depression. Lastly, this review also discusses the effects of different antidepressants on REM sleep disturbances in depression. 
26411501	Twenty-seven to 80% of patients with Parkinson's Disease (PD) complain of subjective sleep dysfunction and insomnia symptoms. Our aim is to describe the prevalence and features of subjective sleep dysfunction and insomnia symptoms in patients with PD compared to other patients.Cross-sectional analysis of 636 adult PD patients compared to 143 age and sex-matched non-PD control patients consulting their general practitioners. Insomnia symptoms and other sleep features were assessed by the Pittsburgh Sleep Quality Index (PSQI), a global score > 5 defining impaired sleep. The Chi-square test or the Student's t-test were used to assess the potential clinical and demographic differences between groups and between PD patients with vs. without sleep dysfunction. Logistic regression analysis was employed to test multivariate effects.	Sleep dysfunction and insomnia symptoms were more frequent in PD patients compared to control patients (63 vs. 45%, p = 0.001). Female gender, PD duration, presence of depression and anxiety were associated with the presence of insomnia in PD. Subjective sleep efficiency, habitual sleep quality, sleep disturbance and daytime dysfunction, but not sleep latency, were reduced in PD patients compared to controls.	The prevalence of sleep dysfunction is higher in PD than in other general medical conditions. Insomnia in PD seems to affect sleep maintenance and consolidation, but not sleep onset.	
26409172	The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling.To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD.	In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy.	No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate.	A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.	
26407961	Sleeping problems and fatigue in pregnancy are often accepted as a normal part of pregnancy; however, these conditions can be linked to serious consequences for both the mother and child. Despite established links between sleeping disturbance and a wide range of pregnancy complications, little is known about the health-care utilisation of women experiencing sleeping problems and fatigue. This study addresses the existing gap in the literature by examining cross-sectional data to identify health service utilisation patterns of pregnant women experiencing sleeping problems and/or tiredness or fatigue.In 2010, a sub-study of the Australian Longitudinal Study on Women's Health was conducted as a cross-sectional survey of 2445 women who had recently given birth. Associations between reported symptoms of sleeplessness and/or tiredness or fatigue and health service utilisation were determined using logistic regression analysis.	During their pregnancy, 15.2 % of women experienced sleeping problems while 35.4 % experienced tiredness or fatigue. Women most commonly consulted with an obstetrician (n = 96) or a general practitioner (GP) (n = 74) for their tiredness or fatigue rather than a midwife (n = 56). A substantial number of women sought help from a complementary and alternative medicine (CAM) practitioner for sleeping problems (33 %) or tiredness/fatigue (28 %).	Sleeping problems and/or tiredness or fatigue is reported by a reasonable percentage of pregnant women, and women obtain assistance from conventional and CAM practitioners for their symptoms, but not all seek help. Given the serious implications of untreated sleep- and fatigue-related symptoms for mother and baby, this area of research deserves and requires more attention.	
26407540	Sleep dysfunction is extremely common in patients with schizophrenia. Recent research indicates that sleep dysfunction may contribute to psychotic experiences such as delusions and hallucinations.The review aims to evaluate the evidence for a relationship between sleep dysfunction and individual psychotic experiences, make links between the theoretical understanding of each, and highlight areas for future research.	A systematic search was conducted to identify studies investigating sleep and psychotic experiences across clinical and non-clinical populations.	66 papers were identified. This literature robustly supports the co-occurrence of sleep dysfunction and psychotic experiences, particularly insomnia with paranoia. Sleep dysfunction predicting subsequent psychotic experiences receives support from epidemiological surveys, research on the transition to psychosis, and relapse studies. There is also evidence that reducing sleep elicits psychotic experiences in non-clinical individuals, and that improving sleep in individuals with psychosis may lessen psychotic experiences. Anxiety and depression consistently arise as (partial) mediators of the sleep and psychosis relationship.	Studies are needed that: determine the types of sleep dysfunction linked to individual psychotic experiences; establish a causal connection between sleep and psychotic experiences; and assess treatments for sleep dysfunction in patients with non-affective psychotic disorders such as schizophrenia.	
26407225	Some patients with hepatitis C starting interferon-α (IFN-α) therapy experience depression, although many patients do not develop depressive symptoms. We have found that poor sleep is associated with increased depressive symptoms on average. It is unknown whether this association holds generally or is driven by a specific, distinct subgroup. This investigation first determined whether patterns of change in depressive symptoms form clinically meaningful, distinct subgroups and then tested the extent to which sleep disturbances are associated with a less favorable depression trajectory.Group-based trajectory modeling was used on 124 patients with hepatitis C who started IFN-α therapy. The Pittsburgh Sleep Quality Index (PSQI) assessed pretreatment sleep, the Beck Depression Inventory minus the sleep question assessed depression over time, and the Structured Clinical Interview for DSM-IV provided categorical diagnoses.	Three distinct subgroups were found, where each subgroup shared similar patterns of depressive symptoms over time. The groups were characterized as "nondepressed," "slow increase," and "rapid increase." The nondepressed subgroup (44.4%) experienced low depressive symptoms with little change over time. In comparison, all rapid increasers (11.3%) were diagnosed as having a mood disorder by 12 weeks of treatment. The PSQI was strongly associated with group membership, where the odds of developing a rapid increase was elevated 39% for every unit-score increase in the PSQI compared with individuals who remained nondepressed (odds ratio = 1.39, 95% confidence interval = 1.07-1.80, adjusted for depression at baseline).	Only a distinct subpopulation of people is notably vulnerable to a developing a rapid increase in depression symptoms during IFN-α therapy. This group may be identifiable by their markedly poor sleep before IFN-α therapy.	
26406786	This study analyzed cross-sectional data to examine gender differences in the association of sleep quality and daytime sleepiness with mood and functional outcomes in adults with type 2 diabetes (T2DM). Measures included demographic and clinical data as well as scales that measured subjective daytime sleepiness, sleep quality, mood disturbances, and functional outcomes. The majority of the sample (N = 116) had poor sleep quality and was subjectively sleepy. We observed in males and females significantly different associative patterns between the predictor variables of daytime sleepiness and sleep quality and the outcome variables of mood and functional outcome. There was no significant difference in daytime sleepiness or impaired sleep quality between men and women with T2DM; however, there was a difference in the expression of impaired sleep on mood and functional outcomes between genders. 
26405539	Sickness behavior is defined as states of lethargy, depression, anxiety, loss of appetite, hypersomnia, hyperalgesia, reduction of grooming and failure to concentrate that can be induced by inflammatory diseases, such as infections and cancer. Recent findings revealed that the lipopolysaccharide (LPS) injection causes lethargy as a consequence of the inhibition of hypocretin signaling. The hypocretin system maintains the vigilance state in various physiological processes. In order to investigate the sleep arousal system against sickness behavior, LPS-induced sickness behavior was examined in hypocretin-ataxin-3 transgenic mice, whose hypocretin neurons were postnatally ablated. Sleep-wake activity was determined following the administration of LPS at Zeitgeber time (ZT) 8.0 in ataxin-3 transgenic mice, and the age-, gender-matched wild-type littermates. LPS injection induced increases in non-rapid eye movement (REM) sleep in the matched wild-type littermates. In addition, a further increase in periods of sleep according to the loss of hypocretin neurons was identified in the ataxin-3 transgenic mice. A marked reduction of awakening during ZT12-ZT18 was observed as expected following LPS injection in the mouse lines. The increase in the period of non-REM sleep was not observed on the next day following LPS administration in either of the mouse lines. Complete recovery of physical activity was not observed in the matched wild-type littermates. Ataxin-3 transgenic mice recovered their physical activity to the same level as that on the first day before LPS administration. These results suggest the possibility that a faster recovery is the result of deeper resting according to the absence of hypocretin neurons, as ataxin-3 transgenic mice demonstrated more non-REM sleep.
26404757	The association between current level of suicidal ideation and physical activity was tested in a broad sample of veterans seeking care from the Veterans Health Administration. It was hypothesized that the two variables would be significantly inversely related. It was further hypothesized that the relationship would be mediated by depressive symptoms, disturbed sleep, and a measure of heart rate variability based on existing research regarding physical activity and sleep. Due to the first hypothesis not being supported, the second could not be tested. Post hoc correlation analyses did find associations between physical activity and depressive symptoms, in expected directions, and are discussed. Possible explanations for the negative findings along with recommendations for future research to continue exploring links between suicide risk and physical activity are presented. We conclude by suggesting that physical activity may have promise as a risk reduction intervention and that prospective data are more likely to yield significant results than the cross-sectional methodology employed in the current study.
26404039	The aim of this study was to investigate the effects of a cognitive behavioural intervention combined with a breathing relaxation exercise on sleep quality and heart rate variability in patients with major depression.Depression is a long-lasting illness with significant effects not only in individuals themselves, but on their family, work and social relationships as well. Cognitive behavioural therapy is considered to be an effective treatment for major depression. Breathing relaxation may improve heart rate variability, but few studies have comprehensively examined the effect of a cognitive behavioural intervention combined with relaxing breathing on patients with major depression.	An experimental research design with a repeated measure was used.	Eighty-nine participants completed this study and entered data analysed. The experimental group (n = 43) received the cognitive behavioural intervention combined with a breathing relaxation exercise for four weeks, whereas the control group (n = 46) did not. Sleep quality and heart rate variability were measured at baseline, posttest1, posttest2 and follow-up. Data were examined by chi-square tests, t-tests and generalised estimating equations.	After adjusting for age, socioeconomic status, severity of disease and psychiatric history, the quality of sleep of the experimental group improved, with the results at posttest achieving significance. Heart rate variability parameters were also significantly improved.	This study supported the hypothesis that the cognitive behavioural intervention combined with a breathing relaxation exercise could improve sleep quality and heart rate variability in patients with major depression, and the effectiveness was lasting.	The cognitive behavioural intervention combined with a breathing relaxation exercise that included muscle relaxation, deep breathing and sleep hygiene could be provided with major depression during hospitalisation. Through group practice and experience sharing, participants could modulate their heart rate variability and share feeling about good sleep as well relaxation.	
26402831	There has been insufficient evidence on whether exposure to hypnotics affects the risk of type 2 diabetes (T2DM). The aim of this study was to examine patients with nonapnea sleep disorders using zolpidem, benzodiazepines (BZDs), or a combination of both, and their risk of T2DM. This was a population-based retrospective cohort study using data from 1997 to 2011. Data from the Taiwan National Health Insurance Research Database were employed for this study. A total of 45,602 patients with nonapnea sleep disorders and use of hypnotics were identified as the study cohort. The control cohort comprised 40,799 age- and sex-matched patients. We conducted a Cox proportional hazard regression analysis to estimate the effects of hypnotics on risk of T2DM. The overall incidence of T2DM was 20.1 per 1000 person-years for patients using zolpidem, which was significantly higher than that of the control group (11.9 per 1000 person-years). Overall, patients with nonapnea sleep disorders using zolpidem had a higher risk of T2DM compared with patients not using zolpidem and the control cohort (adjusted hazard ratio [HR] = 1.41, 95% confidence interval [CI] = 1.35-1.48). We also observed a significantly higher risk of T2DM in patients with both zolpidem and BZD use (adjusted HR = 1.77, 95% CI = 1.64-1.91) than that of those without zolpidem use and BZD use. Compared with patients not using hypnotics, patients using zolpidem had a higher risk of developing T2DM; the risk was particularly pronounced in those using both zolpidem and BZDs.
26402074	Cognitive deficits are presumed to be the primary driver of functional impairment in Alzheimer's disease (AD); however, functional impairment is likely multifactorially determined.Our objective was to determine the relative contribution of neuropsychiatric symptoms in predicting ratings of functional status.	A total of 223 patients received routine neurological and neuropsychological evaluations and met criteria of probable AD dementia based on the McKhann criteria. Demographic, cognitive, and neuropsychiatric variables were entered in a hierarchical linear regression analysis to predict functional status as measured by the Functional Activities Questionnaire (FAQ).	The total model explained 29.7% of the variance (p <  0.001) in FAQ. Importantly, neuropsychiatric variables explained 12.7% of the unique variance, with apathy and sleep as significant contributors.	Two neuropsychiatric variables, apathy and changes in sleep/nighttime behaviors, predicted ratings of functional status in AD patients independent of age, global cognition, memory and executive function measures, and depressive symptoms. These results highlight the importance of neuropsychiatric symptoms in understanding and potentially treating the functional limitations so prevalent in AD.	

26400408	CEP-32215 is a new, potent, selective, and orally bioavailable inverse agonist of the histamine H3 receptor (H3R) with drug-like properties. High affinity in human (hH3R Ki = 2.0 ± 0.2 nM) and rat (rH3R Ki = 3.6 ± 0.7 nM) H3R radioligand binding assays was demonstrated. Potent functional antagonism (Kb = 0.3 ± 0.1 nM) and inverse agonism (EC50 = 0.6 ± 0.2 nM) were demonstrated in [(35)S]guanosine 5(')-O-(γ-thio)-triphosphate binding assays. Oral bioavailability and dose-related exposure was consistent among rat, dog, and monkey. After oral dosing, occupancy of H3R by CEP-32215 was estimated by the inhibition of ex vivo binding in rat cortical slices (ED50 = 0.1 mg/kg p.o.). Functional antagonism in brain was demonstrated by the inhibition of R-α-methylhistamine-induced drinking in the rat dipsogenia model (ED50 = 0.92 mg/kg). CEP-32215 significantly increased wake duration in the rat EEG model at 3-30 mg/kg p.o. Increased motor activity, sleep rebound or undesirable events (such as spike wave or seizure activity) was not observed following doses up to 100 mg/kg p.o., indicating an acceptable therapeutic index. CEP-32215 may have potential utility in the treatment of a variety of sleep disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. 
26397027	The number of informal caregivers providing assistance to adults is increasing commensurate with our aging society. Sleep disturbances are prevalent in caregivers and associated with negative physical, medical, and functional outcomes. Here, we describe the predisposing, precipitating, and perpetuating factors contributing to the development of sleep problems in caregivers, and discuss three understudied caregiving populations that have clinical importance and unique circumstances influencing sleep quality and health.There is clear evidence supporting the interaction between sleep loss, caregiving stress, and vulnerability to chronic disease. Telehealth and telemedicine sleep interventions for caregivers combined with assistive technologies targeting care-receivers have potential to be more individualized, affordable, and widely accessible than traditional in-person insomnia treatment approaches. Limited data exist describing the etiology and treatment of sleep problems in caregivers of veterans, medical patients newly discharged from the hospital, and developmentally disabled adults.	There is a growing literature describing the general determinants of sleep disturbances in caregivers, the health consequences of these disturbances, and intervention strategies for treating them. Identifying effective sleep treatments suited to more specialized caregiving situations and increasing intervention access will help caregivers continue to provide quality care while protecting their own health and well-being.	
26395305	The mild cognitive impairment (MCI) is described as an intermediate state of cognitive impairment whereby individuals present with mild clinical symptoms but with nearly normal daily living activities. These subjects do not meet the clinical criteria for dementia, yet their cognitive functioning is below what we would expect for age and education in healthy people. In the other hand, older adults are at risk for sleep disorders including obstructive sleep apnea syndrome, restless legs syndrome, REM sleep behavioral disorder and chronic insomnia, which could have an impact on cognitive functioning and are exclusion criteria for the MCI diagnosis. Moreover, REM sleep behavioral disorder represents a risk factor for the development of neurodegenerative diseases. In subjects more 65 years of age the association between chronic insomnia and cognitive changes is still debated. The main aim of this paper is to focus on identification of sleep disorders in the context of cognitive disturbances among professionals working with the elderly. 
26393492	Tasimelteon, a novel circadian regulator, is the first product for the treatment of Non-24-hour Sleep-Wake Disorder (Non-24) approved by either the FDA or the European Medicines Agency (EMA). Tasimelteon is a potent and specific melatonin (MT1 and MT2) receptor agonist with 2 - 4 times greater affinity for the MT2 receptor.Safety was assessed in two controlled and two open-label studies in blind individuals with Non-24 and in two controlled studies of primary insomnia. Periodic assessments included collection of adverse events (AEs), laboratory testing, electrocardiograms (ECGs), vital sign monitoring, physical examinations and assessment for the potential for suicide. One study included additional assessments for endocrine function.	A total of 184 blind individuals with Non-24 received tasimelteon nightly with a median exposure > 1 year. In placebo-controlled studies, 387 patients with insomnia and 42 patients with Non-24 received tasimelteon nightly for 4 - 26 weeks. The total patient years exposure for the six studies assessed here is 258.64 patient years. Discontinuations due to AEs were similar across treatment groups. Overall in the clinical studies described here, AEs attributable to tasimelteon treatment were headache, diarrhea, dry mouth, alanine aminotransferase increased, somnolence, dizziness and nightmare/abnormal dreams. There were no clinically significant differences in treatment group with ECGs, vital signs, withdrawal, endocrine function and suicidality assessments.	Long-term tasimelteon administration was safe and well-tolerated. This is supported by placebo-controlled data in both Non-24 and insomnia patients.	
26391786	Disturbed sleep is a significant health issue for pregnant women. Inadequate vitamin D intake is common among pregnant women and can affect many bodily systems. The purpose of this cross-sectional study was to test the hypothesis that serum vitamin D levels are low in pregnant women who have poor sleep quality in their last trimester.We enrolled 92 pregnant women who were admitted to the Maternity Clinic of Turgut Ozal University (Ankara, Turkey) in their last trimester. Venous blood sampling was performed to determine serum 25-hydroxyvitamin D levels. Sleep quality was measured by the Pittsburgh Sleep Questionnaire. The Student t test and Chi-square test were used to evaluate the relationships between variables. Logistic regression analysis was used to identify independent predictors of the vitamin D level.	The median score of the Pittsburgh Sleep Questionnaire was 6.2 ± 3.3 (range, 1-17). We determined that 43.5% (40) of participants had poor sleep quality. The mean number of sleep hours at night was 8.6 ± 1 hours (range, 6.30-11 hours), and the mean sleep latency was 20.3 ± 12.7 minutes (range, 5-60 minutes). Vitamin D levels were measured for 87 participants; the median serum level of 25 (OH) vitamin D was 22.9 ± 16.2 ng/mL (range, 4.9-99 ng/mL). Among all patients, we did not determine any significance between the vitamin D-deficient group and the non-vitamin D-deficient group with regard to the Pittsburgh Sleep Questionnaire Inventory (PSQI) total score and subcomponents scores of the questionnaire (p > 0.05). Among 37 patients with poor sleep quality and for whom the vitamin D level was measured, 56.8% (21) women had vitamin D deficiency, and 81% (30) women had vitamin D insufficiency. However, we did not find any significance between participants with poor sleep and participants with good sleep quality with regard to age, occupational status, relationship with her partner, prepregnancy body mass index (BMI), weight gain during pregnancy, being primiparus, length of labor, and mode of delivery. Our findings further showed that being in a low income family was associated with poor sleep quality.	Inadequate vitamin D and poor sleep quality are prevalent in pregnant women, but low levels of vitamin D are not associated with poor sleep quality. Further studies with larger sample sizes and studies that include preterm deliveries and special sleep disorders should be performed to understand this issue better.	
26391284	To compare patterns of sleep and the presence of sleep disturbances in individuals in at-risk mental states (ARMS) for psychosis and bipolar disorder (BD) with a healthy control (HC) group.This was a comparative study involving 20 individuals in ARMS for psychosis or BD, according to the Comprehensive Assessment of At-Risk Mental States, and 20 age- and sex-matched healthy controls. Quality of sleep in the previous month was assessed using the Pittsburgh Sleep Quality Index, diurnal somnolence was evaluated using The Epworth Sleepiness Scale, and chronotype was determined using the Questionnaire of Morningness/Eveningness (QME). All of the participants underwent polysomnography (PSG) during the entire night for two consecutive nights. The first night aimed to adapt the subject to the environment, and only the data from the second night were used for the analysis.	Compared with the HC group, individuals in the ARMS group reported significantly worse sleep quality, as measured by the Pittsburgh Sleep Quality Index. Both groups had scores consistent with daytime sleepiness on the Epworth Sleepiness Scale, and there were no differences with regard to chronotype between the groups, with a predominance of the indifferent type in both groups. In the PSG assessment, we observed increased Sleep Latency (SL) and increased Rapid Eye Movement Sleep Onset Latency (REMOL) in the ARMS group, compared to the HC group.	The results of this study indicated that sleep abnormalities could be found early in the course of mental diseases, even in at-risk stages, and support the further investigation of their predictive value in the transition to psychosis and BD.	
26390111	Childhood sexual abuse (CSA) is linked to negative consequences, including insomnia. Few studies have examined the enduring effects of CSA on adult insomnia. Given the relationship between sleep and poor health, a better understanding of these effects has clinical implications. We used a representative adult twin sample. Both sexes were assessed with a broad CSA variable, with a subset of females (n = 424) given additional items capturing escalating physical contact and abuse characteristics. A sum score of past-month insomnia symptoms was calculated from the Symptom Checklist-90 (shortened version). Logistic regression was used to estimate the effects of CSA, physical contact, and incident characteristics on insomnia symptoms. Of the full sample (N = 8,184), 9.8% reported CSA. CSA significantly predicted insomnia symptoms in the female sample (n = 1,407; odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.35-2.06, p < .0001) but the continuum of physical contact did not. Individually, more than 1 perpetrator and feeling forced/threatened increased sleep risk, whereas having a male perpetrator (vs. female or multiple) decreased risk. These associations did not hold when combined. In the mixed-sex sample (n = 6,777), we replicated our CSA finding (OR = 1.65, 95% CI = 1.34-2.04, p < .0001) and found that female gender (OR = 1.16, 95% CI = 1.03-1.30, p = .0125), but not the gender*CSA interaction, was significant. CSA predicts adult insomnia symptoms decades after abuse, but the small sample size for incident characteristics (n = 424) resulted in limited conclusions about associated risk.
26389988	To evaluate age-related differences in sleep-wake symptoms.Cross-sectional.	Technologist-attended, laboratory-based polysomnography (PSG).	Community-dwelling adults aged 20 to 89 (N = 201): 52 aged 18 to 39, 72 aged 40 to 59, and 77 aged 60 and older.	Medical burden (Charlson Comorbidity Index, medications, health status), PSG-defined sleep disorders (sleep-disordered breathing (SDB), sleep-associated hypoxemia, periodic limb movements in sleep (PLMS)), sleep-wake symptoms (Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), fatigue (Facit-F Scale)).	Medical burden increased significantly with age (Charlson Comorbidity Index and number of medications, P < .001; health status, P = .005). Severity of sleep disorders also increased significantly with age (SDB and hypoxemia, P < .001; PLMS, P = .008). Conversely, sleep-wake symptoms decreased with age (daytime drowsiness (ESS ≥ 10), P = .02; insomnia (ISI ≥ 8), P = .04; fatigue, P < .001). In adjusted models, a 1-year increase in age was significantly associated with a 4% decrease in the odds of having daytime drowsiness (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93-0.98). Similarly, but only in those with mild SDB, a 1-year increase in age was significantly associated with a 5% decrease in the odds of having insomnia (OR = 0.95, 95% CI = 0.92-0.99).	Older age was characterized by less-severe sleep-wake symptoms (daytime drowsiness, insomnia, fatigue), despite an age-related increase in disease severity (medical burden, sleep disorders). Because the increase in disease severity included well-established risk factors for having sleep-wake symptoms, the age-related decrease in sleep-wake symptoms may reflect a decrease in symptom awareness.	
26388955	Sleep disturbance is part of the behavioural phenotype of the rare genetic condition mucopolysaccharidosis (MPS) type III. A growing body of evidence suggests that underlying disturbance in circadian rhythm functioning may explain sleep problems within the MPS III population.Actigraphic data were recorded in eight children with MPS III over 7-10 days and compared to age-matched typically developing controls. Parameters of circadian rhythmicity and activity levels across a 24-h period were analysed.	Statistically and clinically significant differences between the two groups were noted. Analysis indicated that children with MPS III showed significantly increased fragmentation of circadian rhythm and reduced stability with external cues (zeitgebers), compared to controls. Average times of activity onset and offset were indicative of a phase delayed sleep-wake cycle for some children in the MPS III group. Children with MPS III had significantly higher activity levels during the early morning hours (midnight-6 am) compared to controls.	Results are consistent with previous research into MPS III and suggest that there is an impairment in circadian rhythm functioning in children with this condition. Implications for clinical practice and the management of sleep difficulties are discussed.	
26388508	To examine the psychometric properties of the Menopausal Symptoms Distress Affecting Sleep Quality Scale.Sleep disturbances are an extensive and common problem among menopausal women. However, no unique and specific scale has yet been developed to detect the inductive symptoms distresses that cause poor sleep quality for menopausal women.	A cross-sectional design.	The Menopausal Symptoms Distress Affecting Sleep Quality Scale was based on in-depth interviews with menopausal women and literature review. Convenience sampling was employed. One hundred and fifty three women participated in this study. Exploratory factor analysis, concurrent validity and contrasting group validity were used to examine the validity of the Menopausal Symptoms Distress Affecting Sleep Quality Scale. Cronbach's α was conducted to test the reliability. The accuracy of the scale was analysed with the receiver operating characteristic from MED CALC version 10.4.8.0 software. The scale's sensitivity, specificity, positive and negative predictive value were analysed to locate the best cut-off point.	One factor was generated by Exploratory factor analysis, and this factor explained 49·07% of total variance. In addition, the Menopausal Symptoms Distress Affecting Sleep Quality Scale had significant positive correlations with the Greene Climacteric Scale and the self-evaluation of menopausal symptoms scale. Cronbach's α of the Menopausal Symptoms Distress Affecting Sleep Quality Scale was 0·89. Moreover, the diagnostic accuracy probability of the scale's receiver operating characteristic curve was 0·85. The best cut-off point was three with a sensitivity of 76% and a specificity of 87%.	The Menopausal Symptoms Distress Affecting Sleep Quality Scale had good reliability and validity, as well as refined indicators for assessing the tool's accuracy.	The Menopausal Symptoms Distress Affecting Sleep Quality Scale is easy to use, can quickly detect the sleep conditions of menopausal women who suffer from menopausal symptom distress, and provide efficient nursing interventions to relieve menopausal symptom distresses, and then improve sleep quality.	
26388157	Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain.Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining.	In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice.	Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.	
26387894	The aims of this study were to monitor cabin crew fatigue, sleep, and performance on an ultra-long range (ULR) trip and to evaluate the appropriateness of applying data collection methods developed for flight crew to cabin crew operations under a fatigue risk management system (FRMS).Prior to, throughout, and following the ULR trip (outbound flight ULR; mean layover duration=52.6 h; inbound flight long range), 55 cabin crew (29 women; mean age 36.5 yr; 25 men; mean age 36.6 yr; one missing data) completed a sleep/duty diary and wore an actigraph. Across each flight, crewmembers rated their fatigue (Samn-Perelli Crew Status Check) and sleepiness (Karolinska Sleepiness Scale) and completed a 5-min Psychomotor Vigilance Task (PVT) at key times.	Of crewmembers approached, 73% (N=134) agreed to participate and 41% (N=55) provided data of suitable quality for analysis. In the 24 h before departure, sleep averaged 7.0 h and 40% took a preflight nap. All crewmembers slept in flight (mean total sleep time=3.6 h outbound, 2.9 h inbound). Sleepiness and fatigue were lower, and performance better, on the longer outbound flight than on the inbound flight. Post-trip, crewmembers slept more on day 1 (mean=7.9 h) compared to baseline days, but there was no difference from day 2 onwards.	The present study demonstrates that cabin crew fatigue can be managed effectively on a ULR flight and that FRMS data collection is feasible for cabin crew, but operational differences between cabin crew and flight crew need to be considered.	
26384529	Sleep is disrupted during active use of methamphetamine (MA), during withdrawal from the drug, and during abstinence from its use. However, relatively little is known about possible mediatory functions of disrupted sleep in the emergence, manifestation, and maintenance of cognitive and affective symptoms of MA abuse. We hypothesise that sleep functions as a mediator for stimulant drug effects. Specifically, we propose that objectively-measured sleep parameters can be used to explain some of the variability in the experience and presentation of memory deficits and emotion dysregulation in MA abusers. After describing how important healthy sleep is to unimpaired cognitive and affective functioning, we review literature describing how sleep is disrupted in MA abuse. Then, we provide a conceptual framework for our hypothesis by explaining the relationship between MA abuse, sleep disruption, memory deficits, emotion dysregulation, and changes in reward-related brain networks. We conclude by discussing implications of the hypothesis for research and treatment. 
26384466	Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women's Health Initiative Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention.To evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depression symptoms, cognitive functioning, and sleep quality.	This randomized controlled trial was analyzed as intent to treat.	Between 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline ≥32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type 1 diabetes, or medical conditions with predicted survival <3 years.	Goals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings, and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter.	The RAND 36-Item Health Survey was used to assess HRQoL at baseline, Year 1, and close-out (about 8 years postrandomization), and estimate differential HRQoL subscale change scores.	Mean change in HRQoL scores (Year 1 minus baseline) were compared by randomization group using linear models.	At 1 year, there was a differential change between intervention and comparison group of 1.7 units (95% CI 1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (95% CI 1.7, 2.3), vitality by 1.9 units (95% CI 1.6, 2.2), and global quality of life by 0.09 units (95% CI 0.07, 0.12). With the exception of global quality of life, these effects were significantly modified by body mass index at baseline.	DM intervention was associated with small, but significant improvements in three HRQoL subscales: general health, physical functioning, and vitality at 1 year follow-up, with the largest improvements seen in the women with the greatest baseline body mass index.	
26384115	Autism spectrum disorder (ASD), a neurodevelopmental disorder with a prevalence of 1 in 68 children, commonly presents with comorbid conditions which include sleep disorders. Sleep disorders reported in ASD include, among others, increased bedtime resistance, insomnia, parasomnia, sleep disordered breathing, morning rise problems, and daytime sleepiness. Polysomnography studies show that children with ASD have altered sleep architecture including shorter total sleep time and longer sleep latency than typically developing peers. Sleep-related problems have been shown to affect overall autism scores, social skills decits, stereotypic behavior, and cognitive performance. Additionally, problematic sleep in children with ASD has been associated with higher levels of parental stress. Underlying causes specically related to sleep disorders are not fully known. Gastrointestinal (GI) disorders are commonly associated with sleep problems in these patients. Children with ASD and GI symptoms have been found to have a higher prevalence of sleep disturbances compared with typically developing peers who do not have GI symptoms. Treatment approaches to children with sleep disorders are varied and range from lifestyle modications and behavioral interventions to drug therapies and surgical interventions. Physicians should take into account GI disorders as possible underlying causes of sleep-related problems in children with ASD. Therapeutic interventions should begin with less invasive methods before progressing to more invasive options such as pharmacotherapy and should be based on medical indications in order to provide effective care while minimizing potential adverse health effects. Evidence-based studies concerning GI and sleep disorders in children with ASD are limited and further studies are warranted. 
26382909	Common mental disorder (CMD) and sleep disturbance are two common conditions among women in late pregnancy, affecting up to 20% and 63% of women, respectively, and may adversely affect their quality of life.The aim of this study is to examine the relationship between sleep disturbance in pregnancy and persistent CMD among low-income pregnant women living in Brazil.	This was a prospective cohort study conducted with pregnant women recruited from public primary care clinics in São Paulo, Brazil. We performed a longitudinal analysis of 219 women who had CMD from the Self-Report Questionnaire during the 20-30 weeks of pregnancy. Two groups were examined: (1) those who had CMD remission in the postpartum and (2) those who had persistent CMD in the postpartum (measured once in the postpartum period). Poisson regression was used to estimate the degree of association between sleep disturbance in pregnancy and the risk for persistent CMD postpartum.	After adjusting for sociodemographic and clinical factors, sleep disturbance during pregnancy is associated with persistent CMD (RR = 1.36, 95% confidence interval: 1.01-1.84).	In this sample of low-income pregnant women living in Brazil, the presence of sleep disturbance during pregnancy was associated with persistent common mental disorder in the postpartum period. Identification of sleep disturbance in pregnant women with CMD will be important in order to recognize those women at higher risk of persistent CMD in the postpartum period.	
26382163	Adolescence is a period of dynamic change in both sleep and emotional systems, with related increases in problems controlling emotion and behavior. Youth with anxiety enter adolescence with pre-existing vulnerabilities in systems of sleep and emotion that may place them at heightened risk. This review summarizes recent research on sleep and anxiety during the transition to adolescence, and highlights emerging themes.Prospective studies support that sleep predicts anxiety symptoms in early adolescence. Notably, robust evidence for subjective sleep problems in anxious youth is not well corroborated by objective assessments. Longitudinal designs and methodology that carefully examine dimensions of anxiety and sleep may clarify inconsistencies. Preliminary evidence suggests that late childhood to early adolescence may be a sensitive period for escalating problems with sleep and anxiety. Recent advances in the neuroscience of sleep can further refine integrative mechanistic models of developmental psychopathology - the role of sleep in emotional learning and memory is provided as an example.	Sleep problems are common and prospectively predict escalating anxiety symptoms. Precision is needed regarding the nature of sleep disruption, and how and when sleep affects various aspects of developmental trajectories. This precision, along with advances in the neuroscience of sleep, may lead to developmentally informed translational interventions.	
26382160	The perinatal period introduces a myriad of changes. One important but often overlooked change is the increased risk for sleep disturbance. Although casually regarded as a consequence of pregnancy or postpartum, there is emerging evidence to suggest that women with significant sleep disturbance, characterized by insomnia symptoms and/or poor sleep quality, are more likely to report an increase in depressive symptomatology or develop postpartum depression (PPD). Significant consequences may arise as a result including issues with maternal-infant bonding, effective care for the infant and behavioral or emotional difficulties in the infant. This review discusses the relevant literature as to how disturbed sleep during pregnancy as well as in the postpartum may increase the risk for PPD.Symptoms of insomnia and poor sleep quality are independently associated with greater depressive symptoms across pregnancy and throughout postpartum. Likewise, both can negatively impact the ability to mother effectively.	The presence of insomnia or sleep disturbance during the perinatal period is a risk factor for depressive symptoms. Women with depression are at an increased risk of developing sleep disturbance thereby increasing depressive symptomatology. This bidirectional and additive relationship needs more clinical attention as both sleep disturbance and depression are noted risk factors for adverse pregnancy outcomes.	

26376909	This study aimed at exploring the cross-sectional and prospective associations between psychosocial work factors and sleep problems.The study population consisted of a national representative sample of the French working population (SIP survey). The sample sizes were 7506 and 3555 for the cross-sectional and prospective analyses. Sleep problems were defined by either sleep disturbances or insufficient sleep duration at least several times a week. Psychosocial work factors included classical (job strain model factors) and emergent factors (recognition, insecurity, role/ethical conflict, emotional demands, work-life imbalance, etc.). Occupational factors related to working time/hours and physical work environment were also included as well as covariates related to factors outside work. Statistical analyses were performed using weighted Poisson regression analysis.	In the cross-sectional analyses, psychological demands, low social support, low recognition, emotional demands, perception of danger, work-life imbalance and night work were found to be associated with sleep problems. In the prospective analyses, psychological demands and night work were predictive of sleep problems. Using a less conservative method, more factors were found to be associated with sleep problems. Dose-response associations were observed, showing that the more frequent the exposure to these factors, the higher the risk of sleep problems. No effect of repeated exposure was found on sleep problems.	Classical and emergent psychosocial work factors were associated with sleep problems. More prospective studies and prevention policies may be needed.	
26376078	Attention Deficit Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental disorder that increases accidental risk. Recent studies show that some patients with ADHD can also suffer from excessive daytime sleepiness but there are no data assessing the role of sleepiness in road safety in patients with ADHD. We conducted an epidemiological study to explore sleep complaints, inattention and driving risks among automobile drivers.From August to September 2014, 491186 regular highway users were invited to participate in an Internet survey on driving habits. 36140 drivers answered a questionnaire exploring driving risks, sleep complaints, sleepiness at the wheel, ADHD symptoms (Adult ADHD Self-Report Scale) and distraction at the wheel. 1.7% of all drivers reported inattention-related driving accidents and 0.3% sleep-related driving accidents in the previous year. 1543 drivers (4.3%) reported ADHD symptoms and were more likely to report accidents than drivers without ADHD symptoms (adjusted OR = 1.24, [1.03-1.51], p < .021). 14.2% of drivers with ADHD symptoms reported severe excessive daytime sleepiness (Epworth Sleepiness Scale >15) versus 3.2% of drivers without ADHD symptoms and 20.5% reported severe sleepiness at the wheel versus 7.3%. Drivers with ADHD symptoms reported significantly more sleep-related (adjusted OR = 1.4, [1.21-1.60], p < .0001) and inattention-related (adjusted OR = 1.9, [1.71-2.14], p<0001) near misses than drivers without ADHD symptoms. The fraction of near-misses attributable to severe sleepiness at the wheel was 4.24% for drivers without ADHD symptoms versus 10,35% for drivers with ADHD symptoms.	Our study shows that drivers with ADHD symptoms have more accidents and a higher level of sleepiness at the wheel than drivers without ADHD symptoms. Drivers with ADHD symptoms report more sleep-related and inattention-related near misses, thus confirming the clinical importance of exploring both attentional deficits and sleepiness at the wheel in these drivers. Road safety campaigns should be improved to better inform drivers of these accidental risks.	
26375410	Little is known about the effect of different lifestyle interventions on sleep disturbances among sedentary obese or overweight persons. We randomized men and women aged 35-65 to 6 months of a weight loss diet (D); or D combined with supervised exercise training D + E. Measurements were self-reported sleep disturbances, the Profile of Mood States questionnaire, BMI, total abdominal subcutaneous and visceral fat by magnetic resonance imaging, and aerobic fitness expressed as VO2peak. The groups did not differ in changes for body weight, abdominal total fat, VO2peak, and sleep disturbances. The novel finding herein is that reduced abdominal subcutaneous fat and depressive symptoms, with either D or D + E were associated with less sleep disturbances.
26375320	It has frequently been reported that exposure to artificial light at night (ALAN) may cause negative health effects, such as breast cancer, circadian phase disruption and sleep disorders. Here, we reviewed the literature assessing the effects of human exposure to ALAN in order to list the health effects of various aspects of ALAN. Several electronic databases were searched for articles, published through August 2014, related to assessing the effects of exposure to ALAN on human health; these also included the details of experiments on such exposure. A total of 85 articles were included in the review. Several observational studies showed that outdoor ALAN levels are a risk factor for breast cancer and reported that indoor light intensity and individual lighting habits were relevant to this risk. Exposure to artificial bright light during the nighttime suppresses melatonin secretion, increases sleep onset latency (SOL) and increases alertness. Circadian misalignment caused by chronic ALAN exposure may have negative effects on the psychological, cardiovascular and/or metabolic functions. ALAN also causes circadian phase disruption, which increases with longer duration of exposure and with exposure later in the evening. It has also been reported that shorter wavelengths of light preferentially disturb melatonin secretion and cause circadian phase shifts, even if the light is not bright. This literature review may be helpful to understand the health effects of ALAN exposure and suggests that it is necessary to consider various characteristics of artificial light, beyond mere intensity. 
26374931	Routine exposure to artificial light at night (ALAN) in work, home, and community settings is linked with increased risk of breast and prostate cancer (BC, PC) in normally sighted women and men, the hypothesized biological rhythm mechanisms being frequent nocturnal melatonin synthesis suppression, circadian time structure (CTS) desynchronization, and sleep/wake cycle disruption with sleep deprivation. ALAN-induced perturbation of the CTS melatonin synchronizer signal is communicated maternally at the very onset of life and after birth via breast or artificial formula feedings. Nighttime use of personal computers, mobile phones, electronic tablets, televisions, and the like--now epidemic in adolescents and adults and highly prevalent in pre-school and school-aged children--is a new source of ALAN. However, ALAN exposure occurs concomitantly with almost complete absence of daytime sunlight, whose blue-violet (446-484 nm λ) spectrum synchronizes the CTS and whose UV-B (290-315 nm λ) spectrum stimulates vitamin D synthesis. Under natural conditions and clear skies, day/night and annual cycles of UV-B irradiation drive corresponding periodicities in vitamin D synthesis and numerous bioprocesses regulated by active metabolites augment and strengthen the biological time structure. Vitamin D insufficiency and deficiency are widespread in children and adults in developed and developing countries as a consequence of inadequate sunlight exposure. Past epidemiologic studies have focused either on exposure to too little daytime UV-B or too much ALAN, respectively, on vitamin D deficiency/insufficiency or melatonin suppression in relation to risk of cancer and other, e.g., psychiatric, hypertensive, cardiac, and vascular, so-called, diseases of civilization. The observed elevated incidence of medical conditions the two are alleged to influence through many complementary bioprocesses of cells, tissues, and organs led us to examine effects of the totality of the artificial light environment in which humans reside today. Never have chronobiologic or epidemiologic investigations comprehensively researched the potentially deleterious consequences of the combination of suppressed vitamin D plus melatonin synthesis due to life in today's man-made artificial light environment, which in our opinion is long overdue.
26373981	The aim was to describe nurses' experiences of patients' sleep at an emergency hospital and their perceptions of sleep-promoting interventions.Promotion of patients' sleep during hospital care is an important intervention for the nursing profession. To promote sleep and to initiate sleep-promoting interventions, nurses need basic knowledge about sleep and its physiology. Therefore, it is of importance to explore and expand knowledge about how nurses experience patients' sleep and how they perceive working with it while providing care.	A qualitative descriptive design was used.	Data were collected from four focus groups and seven individual interviews. A total of twenty-two registered nurses participated. Data were analysed using a qualitative content analysis.	Nurses expressed a desire and an ambition to work in ways that promote patients' sleep during hospitalisation. Nurses reported that health care services and emergency hospitals were not organised according to patients' perspective and needs. Furthermore, they did not have opportunities to work effectively to promote sleep according to the patients' wishes. Several nurses stated that they did not have sufficient knowledge about sleep and that they did the best they could under prevailing circumstances. Nurses emphasised the importance of sleep for patients and that it was an area that should be given far greater priority.	The results indicate that nurses currently have insufficient knowledge about sleep and sleep-promoting interventions. These aspects of nursing is based on personal experience and common sense rather than being evidence based. Furthermore, sleep as a nursing topic needs to be developed and given more focus in order for nurses to be able to deliver high quality care at emergency hospitals.	Nurses require more knowledge and education to gain deeper understanding of sleep and to deliver evidence-based, high quality care.	
26372816	Guillain-Barré syndrome (GBS) may rarely manifest as a peripheral locked-in syndrome.Clinical and instrumental features of a fulminant form of infantile GBS were assessed.	After 2 days of rhinitis, a 6-month-old infant was intubated in the emergency room for sudden-onset respiratory failure. Neurological examination showed generalized areflexic flaccid paralysis with no detectable interaction, which resembled a coma. Brain MRI was normal. Lumbar puncture showed pleocytosis (43 cells/mm(3)) and herpes simplex virus 1 (HSV1) PCR positivity. EEG showed normal sleep-wake cycles, and EMG demonstrated nerve inexcitability. Acyclovir and immunoglobulins provided no benefit. After 1 week, lumbar puncture showed albuminocytological dissociation (protein 217 mg/dl). Plasmapheresis was then started, and progressive improvement occurred. At age 1 year, the child had recovered well with residual distal lower limb hyporeflexic weakness.	A fulminant infantile GBS variant presenting as peripheral locked-in syndrome can be associated with HSV1 infection likely due to autoimmune cross-reactivity.	
26369866	A distributed network of neurons regulates wake, non-rapid eye movement (NREM) sleep, and REM sleep. However, there are also glia in the brain, and there is growing evidence that neurons and astroglia communicate intimately to regulate behaviour. To identify the effect of optogenetic stimulation of astrocytes on sleep, the promoter for the astrocyte-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP) was used to direct the expression of channelrhodopsin-2 (ChR2) and the linked reporter gene, enhanced yellow fluorescent protein (EYFP), in astrocytes. rAAV-GFAP-ChR2 (H134R)-EYFP or rAAV-GFAP-EYFP was microinjected (750 nL) into the posterior hypothalamus (bilateral) of mice. Three weeks later baseline sleep was recorded (0 Hz) and 24 h later optogenetic stimulation applied during the first 6 h of the lights-off period. Mice with ChR2 were given 5, 10 or 30 Hz stimulation for 6 h (10-ms pulses; 1 mW; 1 min on 4 min off). At least 36 h elapsed between the stimulation periods (5, 10, 30 Hz) and although 0 Hz was always first, the order of the other three stimulation rates was randomised. In mice with ChR2 (n = 7), 10 Hz, but not 5 or 30 Hz stimulation increased both NREM and REM sleep during the 6-h period of stimulation. Delta power did not increase. In control mice (no ChR2; n = 5), 10 Hz stimulation had no effect. This study demonstrates that direct stimulation of astrocytes powerfully induces sleep during the active phase of the sleep-wake cycle and underlines the inclusion of astrocytes in network models of sleep-wake regulation. 

26368540	Delirium is an acute-onset syndrome that exacerbates patients' condition and significantly increases consequential morbidity and mortality. There is no comprehensive, cellular and tissue-level, pathophysiological theory. The melatonin hormone imbalance has been shown to be linked to circadian rhythms, sleep-wake cycle disturbances, and delirium incidence. There has been relatively little research about melatonin in delirium, and there has been no such study done in the group of elderly patients of a general medicine ward yet. The aim of our study was to compare melatonin hormone concentration in relation to the presence of delirium in elderly patients hospitalized in the general medicine ward. Blood samples were collected four times a day for two days (at 12:00, 18:00, 00:00 and 6:00), on the day when delirium was diagnosed and 72 h after the delirium resolution. Delirium was diagnosed with the Confusion Assessment Method and the criteria of the Diagnostic and Statistic Manual of Mental Disorders, 4th Revision. The mean age of 30 patients (73.3% women) was 86.5 ± 5.2 years. Delirium was diagnosed most often on the second and third day of hospitalization. A lot of predisposing and precipitating factors for delirium were identified. There was a significant difference in the melatonin hormone concentration measurement at 12:00 when patients had acute delirium and after its resolution [18.5 (13.8, 27.5) vs 12.9 (9.8, 17.8), p<0.01]. Different patterns of the melatonin hormone concentration were shown in analyses in the subgroups defined according to the patients' diagnosis of dementia. We found that the delirium recovery was, in fact, associated with the alteration of the daily profile of melatonin.
26366433	The mental health of educators is a growing problem in many countries. This study sought to identify self-reported stressful working conditions of elementary schoolteachers and the biopsychosocial consequences of those working conditions and then identify working conditions that promote well-being for teachers in the workplace. Exploratory study was done with 37 teachers. Data collection was performed using a structured interview with a questionnaire. Results show that stressful working conditions are related to inadequate salary, an excessive number of activities, and having to take work home. Biopsychosocial consequences include anxiety, stress, and sleep disorders. There was a statistically significant association between inadequate salary and anxiety (p = 0.01) and between an excessive number of activities and stress (p = 0.01). Teachers reported that a good relationship among colleagues is a working condition that promotes well-being in the workplace. The identification of stressful working conditions for teachers, the biopsychosocial consequences, and working conditions that promote well-being in the workplace are relevant to determining actions that improve the work environment and, consequently, the health of teachers. 
26365136	It is well established that sleep disorders have neuropsychological consequences in otherwise healthy people. Studies of night-time sleep problems and cognition in Parkinson's disease (PD), however, paint a mixed picture, with many reporting no relationship between sleep problems and neuropsychological performance. This review aimed to meta-analyse this research and to examine the factors underlying these mixed results. A literature search was conducted of published and unpublished studies, resulting in 16 papers that met inclusion criteria. Data were analysed in the domains of: global cognitive function; memory (general, long-term verbal recognition, long-term verbal recall); and executive function (general, shifting, updating, inhibition, generativity, fluid reasoning). There was a significant effect of sleep on global cognitive function, long-term verbal recall, long-term verbal recognition, shifting, updating, generativity, and fluid reasoning. Although there are effects on memory and executive function associated with poor sleep in PD, the effects were driven by a small number of studies. Numerous methodological issues were identified. Further studies are needed reliably to determine whether disturbed sleep impacts on cognition via mechanisms of hypoxia, hypercapnia, sleep fragmentation, chronic sleep debt or decreased REM and/or slow wave sleep in PD, as this may have important clinical implications. 
26362381	An increased propensity for seizures is associated with different stages of the sleep-wake cycle. In this study, we prospectively analyzed patients with new-onset epilepsy and investigated the clinical correlates of the yield obtained from sleep electroencephalography (EEG) recordings in patients with a normal wakefulness EEG.All patients admitted to our epilepsy unit due to unprovoked epileptic seizures and not yet treated with antiepileptic drugs were recruited consecutively for the last three years. All had a routine EEG at wakefulness (WEEG), and those with no epileptiform activity had a video-EEG recording during sleep (SEEG).	We investigated a total of 241 patients; 129 patients (53.5%) had both wakefulness and sleep EEG recordings. The patients with abnormal WEEG were older than those with normal WEEG (p = 0.005). Abnormal WEEG was detected in only 31.2% of patients with focal seizures, but in 77.3% of patients with generalized seizures (p < 0.001). WEEG was abnormal in 44.0% of patients with diurnal seizures, but in 27.5% of nocturnal seizures (p = 0.007). Abnormal WEEG was present in 75.5% of patients with a presumed genetic origin and in 59.3% of patients with structural etiology (p < 0.001). Sleep EEG detected an abnormality in 41.8% of patients with normal WEEG; of these, 82.8% were focal abnormalities. In contrast, the majority of abnormalities detected in WEEG were generalized (55.8%, p < 0.001).	Our results showed a greater likelihood of abnormal WEEG in older patients and in those with generalized epilepsy, diurnally precipitating seizures, and epilepsy of presumed genetic origin.	
26361788	Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency.
26356393	Цель исследования - оценка клинической эффективности и безопасности дивазы в лечении пациентов с хронической цереброваскулярной болезнью. Материал и методы. В основную, лечившуюся дивазой группу вошли 40 пациентов (средний возраст - 56,2±5,7 года) с астеновегетативными и вестибуло-атактическими расстройствами, развившимися на фоне хронической цереброваскулярной болезни. Выраженность симптомов заболевания оценивалась по визуальной аналоговой шкале (ВАШ). Нейропсихологический и психоэмоциональный статусы исследовались с помощью краткой шкалы оценки психического статуса (MMSE), субъективной шкалы астении (MFI-20), шкалы тревоги Гамильтона (HAM-A), анкеты балльной оценки субъективных характеристик сна, схемы исследования для выявления признаков вегетативных нарушений; были также использованы шкала качества жизни SF-36 и шкала общего клинического впечатления (CGI). Всем пациентам проводилось определение уровня фибриногена и фактора Виллебранда в плазме. Контрольную группу составили 40 больных с хронической цереброваскулярной недостаточностью, сопоставимых по возрасту, полу и тяжести неврологических проявлений с основной группой. Результаты и заключение. После терапии дивазой был отмечен достоверный регресс субъективной симптоматики. При использовании шкал выявлено достоверное улучшение со стороны астенических проявлений, тревоги, нарушений сна, вегетативных расстройств, что привело к достоверному улучшению качества жизни пациентов. У пациентов основной группы отмечены достоверное уменьшение и нормализация уровней фактора Виллебранда и фибриногена в плазме крови. Препарат хорошо переносился больными, нежелательные эффекты (аллергические реакции) были отмечены всего в 5% случаев. Таким образом, в результате проведенного исследования было продемонстрировано значимое положительное влияние дивазы на состояние больных с хронической цереброваскулярной недостаточностью, что позволяет рекомендовать этот препарат для использования в комплексной терапии этой категории больных.To evaluate the clinical efficacy and safety of divasa in the treatment of patients with cerebrovascular insufficiency.	The main group included 40 patients (mean age 56.2±5.7 years) with asthenic/autonomic and vestibular/ataxic disorders developed during chronic cerebrovascular disease. The severity of symptoms was measured with the Visual Analogue scale (VAS). Neuropsychological and psychoemotional status was assessed with MMSE, MFI-20, HAM-A, a subjective sleep questionnaire, a scheme for detection of signs of autonomic disorders. Quality of life questionnaire (SF-36) and CGI scale were used as well. The plasma levels of fibrinogen and the von Willebrand factor were determined in all patients. The control group included 40 patients with chronic cerebrovascular insufficiency matched for age, sex and severity of neurological symptoms to the main group.	The scores of asthenic symptoms, anxiety, sleep disorders and autonomic disorders were decreased significantly that led to the improvement of quality of life of patients. A significant decrease and normalization of the plasma levels of fibrinogen and the von Willebrand factor were identified in the patients of the main group. The drug was well-tolerated, side-effects (allergic reactions) were noted only in 5%.	The positive effect of divasa on patient's condition was demonstrated. The drug may be recommended for the use in complex treatment of these patients.	

26354106	An accumulating amount of evidence has linked humoral mediators of inflammation with sleep measures. Nevertheless, important details of this association, in particular the role of the complement components in the context of chronic sleep attributes, have remained largely uncharacterized.Fifty university students (age, 23.3 ± 3.8 years; BMI, 23.7 ± 2.9 kg/m(2)) completed the study. Four dichotomized sleep measures assessed by the Pittsburgh Sleep Quality Index (PSQI) were used in association analysis using binary logistic regression with complement component 3, 4, and complement factor I (CFI). The sleep measures were defined as sleep quality (good sleep/poor sleep; PSQI ≤5/PSQI >5), bedtime (early/late; before 00:00 h/after 0:00 h), sleep duration (short/normal ≤6 h/>6 h), and sleep onset latency (normal/disturbed; 0-1 score/2-3 score on the PSQI component of sleep latency).	The complement component 4 was associated with sleep quality (unadjusted, OR = 1.025, p < 0.05; adjusted for age, OR = 1.025, p < 0.05; adjusted for BMI, OR = 1.027, p < 0.05) and sleep duration (unadjusted, OR = 1.041, p < 0.01; adjusted for age, OR = 1.041, p < 0.01; adjusted for BMI, OR = 1.046, p < 0.01). CFI was associated with bedtime (unadjusted, OR = 0.737, p < 0.01; adjusted for age, OR = 0.717, p < 0.01; adjusted for BMI, OR = 0.677, p < 0.01) and with sleep duration (unadjusted, OR = 0.796, p < 0.05; adjusted for age, OR = 0.796, p < 0.05).	The findings indicate the importance of the role of complement components in the dynamics of sleep. Therefore, sleep should be assessed in conditions where complement components are affected.	
26353096	Analyzing the quality of sleep of hypertensive patients registered in the national registration system and monitoring of hypertensive patients.A cross-sectional study of quantitative and descriptive analyses with 280 hypertensive patients registered in the National Program of Hypertension and Diabetes of the Federal Government in the months from August to October 2011. Questionnaires were used which allowed for tracking sociodemographic data on hypertension and Pittsburgh Sleep Quality Index (PSQI).	The prevalence of poor sleep quality among respondents (156 hypertensive patients) and high rates of using medication for sleeping (106 hypertensive patients) was observed. Other relevant data refers to the quality of sleep among hypertensive patients using sleep medication compared to those who do not use it (p≤0.01).	Individuals with high blood pressure have a negative association with sleep quality.	
26352911	To test the hypothesis of 'horizontal epidemiology', i.e. that psychosocial difficulties (PSDs), such as sleep disturbances, emotional instability and difficulties in personal interactions, and their environmental determinants are experienced in common across neurological and psychiatric disorders, together called brain disorders.A multi-method study involving systematic literature reviews, content analysis of patient-reported outcomes and outcome instruments, clinical input and a qualitative study was carried out to generate a pool of PSD and environmental determinants relevant for nine different brain disorders, namely epilepsy, migraine, multiple sclerosis, Parkinson's disease, stroke, dementia, depression, schizophrenia and substance dependency. Information from these sources was harmonized and compiled, and after feedback from external experts, a data collection protocol including PSD and determinants common across these nine disorders was developed. This protocol was implemented as an interview in a cross-sectional study including a convenience sample of persons with one of the nine brain disorders. PSDs endorsed by at least 25% of patients with a brain disorder were considered associated with the disorder. PSD were considered common across disorders if associated to 5 out of the 9 brain disorders and if among the 5 both neurological and psychiatric conditions were represented.	The data collection protocol with 64 PSDs and 20 determinants was used to collect data from a convenience sample of 722 persons in four specialized health care facilities in Europe.	57 of the PSDs and 16 of the determinants included in the protocol were found to be experienced across brain disorders.	This is the first evidence that supports the hypothesis of horizontal epidemiology in brain disorders. This result challenges the brain disorder-specific or vertical approach in which clinical and epidemiological research about psychosocial difficulties experienced in daily life is commonly carried in neurology and psychiatry and the way in which the corresponding health care delivery is practiced in many countries of the world.	
26352702	To determine the impact of a cognitive behavioral pain management program on sleep in patients with chronic pain.Prospective nonrandomized controlled pilot study with evaluations at baseline and 12 weeks.	Out-patient multidisciplinary cognitive behavioral pain management program in a university teaching hospital.	Patients with chronic pain who fulfilled the criteria for participation in a cognitive behavioral pain management program.	Patients assigned to the intervention group (n = 24) completed a 4 week cognitive behavioral pain management program, and were compared with a waiting list control group (n = 22). Assessments for both groups occurred at baseline and two months post cognitive behavioral pain management program. Outcome measures included self-report (Pittsburgh Sleep Quality Index) and objective (actigraphy) sleep measures, pain and quality of life measures.	Both groups were comparable at baseline, and all had sleep disturbance. The Pittsburgh Sleep Quality Index correlated with only two of the seven objective sleep measures (fragmentation index r = 0.34, P = 0.02, and sleep efficiency percentage r = -0.31, P = 0.04). There was a large treatment effect for cognitive behavioral pain management program group in mean number of wake bouts (d = 0.76), where a significant group*time interaction was also found (P = 0.016), showing that the CBT-PMP group improved significantly more than controls in this sleep variable.	Patients attending a cognitive behavioral pain management program have high prevalence of sleep disturbance, and actigraphy technology was well tolerated by the patients. Preliminary analysis of the impact of a cognitive behavioral pain management program on sleep is promising, and warrants further investigation.	
26351020	Sleep and sleep-related problems play a role in a large number of human disorders and affect every field of medicine. It is estimated that 50 to 70 million Americans suffer from a chronic sleep disorder, which hinders their daily life, affects their health, and confers a significant economic burden to society. The negative public health consequences of sleep disorders are enormous and could have long-term effects, including increased risk of hypertension, diabetes, obesity, heart attack, stroke and in some cases death. Polysomnographic modalities can monitor sleep cycles to identify disrupted sleep patterns, adjust the treatments, increase therapeutic options and enhance the quality of life of recording the electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG). Although the skills acquired by medical facilitators are quite extensive, it is just as important for them to have access to an assortment of technologies and to further improve their monitoring and treatment capabilities. Computer-aided analysis is one advantageous technique that could provide quantitative indices for sleep disorder screening. Evolving evidence suggests that Parkinson's disease may be associated with rapid eye movement sleep behavior disorder (RBD). With this article, we are reviewing studies that are related to EMG signal analysis for detection of neuromuscular diseases that result from sleep movement disorders. As well, the article describes the recent progress in analysis of EMG signals using temporal analysis, frequency-domain analysis, time-frequency, and sparse representations, followed by the comparison of the recent research. 
26350606	Sleep and fatigue difficulties appear to be highly prevalent among individuals with end-stage renal disease and individuals who have received a kidney transplant. While there is some evidence of biopsychosocial factors predicting sleep disturbance in these populations, previous studies have relied on single time point retrospective measurements.The study utilized a 2-week prospective measurement approach, including one night of polysomnographic measurement, nightly sleep diaries, and self-report measures of health, sleep, and mood.	The current study demonstrates that a number of psychological and behavioral factors, including negative mood, quality of life, napping, and caffeine consumption, are related to sleep disturbance among pre- and post-kidney transplant patients. This study also found that many of these factors have different relationships with sleep disturbance when comparing pre- and post-kidney transplant patients.	These results suggest that such factors may be worthwhile areas for intervention in treating the symptoms of insomnia among pre- and post-transplant recipients. A nuanced approach to understanding sleep problems is likely warranted when conceptualizing insomnia and developing a treatment plan.	
26350604	To investigate emotion regulation difficulties in association with self-reported insomnia symptoms, nightmares, and depression symptoms in a sample of current and retired firefighters.A total of 880 current and retired United States firefighters completed a web-based survey of firefighter behavioral health. Self-report measures included the Center for Epidemiologic Studies Depression Scale, Insomnia Severity Index, PTSD Checklist, and Difficulties in Emotion Regulation Scale.	A notable portion of participants reported clinically significant depression symptoms (39.6%) and insomnia symptoms (52.7%), as well as nightmare problems (19.2%), each of which demonstrated a strong association with emotion regulation difficulties (rs = 0.56-0.80). Bootstrapped mediation analyses revealed that the indirect effects of overall emotion regulation difficulties were significant both for the relationship between insomnia and depression (95% CI: 0.385-0.566) and nightmares and depression (95% CI: 1.445-2.365). Limited access to emotion regulation strategies emerged as the strongest, significant indirect effect for both relationships (insomnia 95% CI: 0.136-0.335; nightmares 95% CI: 0.887-1.931).	Findings extend previous affective neuroscience research by providing evidence that insomnia and nightmares may influence depression symptoms specifically through the pathway of explicit emotion regulation difficulties. Sleep disturbances may impair the ability to access and leverage emotion regulation strategies effectively, thus conferring risk for negative affect and depression.	
26348500	Sleep complaints are common among caregivers and are associated with detriments in mental and physical health. Cortisol, a biomarker of the stress process, may link sleep with subsequent health changes in caregivers. The current study examines whether sleep duration is directly associated with the cortisol awakening response (CAR), or whether it is moderated by Adult Day Services (ADS) use, an intervention found previously to influence daily CAR by reducing stressor exposure.Associations were examined in caregivers (N = 158) of individuals with dementia (IWD) on days when IWDs attended ADS and days when IWDs did not attend ADS. Data were gathered over 8 consecutive days. Caregivers were primarily female (87.3%) with a mean age of 61.59. A multilevel growth curve model tested the association of an interaction of today's ADS use and last night's sleep duration with today's CAR as the outcome.	The interaction between ADS use and within-person sleep duration was significant such that when an individual sleeps longer than their average but does not use ADS, they have a smaller or blunted CAR. On the other hand when an individual sleeps longer than their average and uses ADS, they have a higher but nonsignificant CAR. Sleeping shorter than usual was associated with a dynamic rise regardless of ADS use.	Findings indicate that ADS use moderates the association between sleep duration and CAR such that longer than average sleep is associated with blunted, dysregulated cortisol patterns only on non-ADS days.	
26346413	Fatty liver is associated with alcohol habits and/or overweight/obesity. We challenged several lifestyle features associated with fatty liver and, particularly, with non-alcoholic fatty liver disease (NAFLD). Among them, sleep shortage as a result of nightlife habits and a preference for plus-size fashion were assessed. The latter consists of fashionable plus-sized clothing for actual individuals' size and reflects a frequent attitude of some social or age groups, conceivably indicating more global and widespread trend and behaviour.We studied a group of 708 non-diabetic youngsters, 458 women and 250 men, 21.72 ± 3.71 years old (range 15-35 years), referred for minor digestive ailments for clinical assessment, ultrasound detection of fatty liver and nutritional counselling. Details of personal history regarding lifestyle, food intake frequency and alcohol intake, dietary and physical exercise profile, sleep duration and clothing preferences were recorded.	The prevalence of NAFLD in this cohort of youngsters is 67/708 (9.4%). Even if it is quantitatively very low in both groups, the average alcohol intake, always below 20 g/day, is greater in NAFLD subjects (5.83 ± 4.32 g) vs. subjects with normal liver (2.02 ± 3.20 g). The number of meals/day and adherence to a Mediterranean diet profile are smaller in NAFLD subjects. By multiple regression, BMI, sedentary life, plus-sized clothing for their actual size, sleep shortage and lower frequency of daily food intake are associated with the presence of NAFLD.	Onset and continuation of fatty liver disease, beyond food and exercise quantity and quality, with their effects on obesity, may also be associated with other aspects of lifestyle.	
26346395	In the United States, approximately 60 million Americans suffer from sleep disorders and about 22 million Americans report substance dependence or use disorders annually. Sleep disturbances are common consequences of substance use disorders and are likely found in primary care as well as in specialty practices. The aim of this review was to evaluate the effects of the most frequently used substances-nicotine, alcohol, opioids, cocaine, caffeine, and cannabis-have on sleep parameters measured by polysomnography (PSG) and related clinical manifestations.We used electronic databases such as PubMED and PsycINFO to search for relevant articles. We only included studies that assessed sleep disturbances using polysomnography and reviewed the effects of these substances on six clinically relevant sleep parameters: Total sleep time, sleep onset latency, rapid-eye movement, REM latency, wake after sleep onset, and slow wave sleep.	Our review indicates that these substances have significant impact on sleep and that their effects differ during intoxication, withdrawal, and chronic use. Many of the substance-induced sleep disturbances overlap with those encountered in sleep disorders, medical, and psychiatric conditions. Sleep difficulties also increase the likelihood of substance use disorder relapse, further emphasizing the need for optimizing treatment interventions in these patients.	Our review highlights the importance of systematically screening for substance use in patients with sleep disturbances and highlights the need for further research to understand mechanisms underlying substances-induced sleep disturbances and on effective interventions addressing these conditions.	
26343602	Brain-derived neurotrophic factor (BDNF) binds to Tropomyosin-receptor-kinase B (TrkB) receptors that regulate synaptic strength and plasticity in the mammalian nervous system. 7,8-Dihydroxyflavone (DHF) is a recently identified small molecule Trk B agonist that has been reported to ameliorate depression, attenuate the fear response, improve memory consolidation, and exert neuroprotective effects. Poor and disturbed sleep remains a symptom of major depressive disorder and most current antidepressants affect sleep. Therefore, we conducted sleep/wake recordings and concomitant measurement of brain orexins, endogenous peptides that suppress sleep, in mice for this study. Baseline polysomnograph recording was performed for 24 h followed by treatment with either 5 mg/kg of DHF or vehicle at the beginning of the dark phase. Animals were sacrificed the following day, one hour after the final treatment with DHF. Orexin A and B were quantified using ELISA and radioimmunoassay, respectively. Total sleep was significantly decreased in the DHF group, 4 h after drug administration in the dark phase, when compared with vehicle-treated animals. This difference was due to a significant decrease of non-rapid eye movement sleep, but not rapid eye movement sleep. DHF increased power of alpha and sigma bands but suppressed power of gamma band during sleep in dark phase. Interestingly, hypothalamic levels of orexin A were also significantly decreased in the DHF group (97 pg/mg) when compared with the vehicle-treated group (132 pg/mg). However, no significant differences of orexin B were observed between groups. Additionally, no change was found in immobility tests. 
26343525	This study aimed to evaluate the association between perceived stress, social support, disease progression and mortality in a nationwide population-based cohort of men with prostate cancer.The study surveyed 4105 Swedish men treated for clinically localized prostate cancer regarding stress, grief, sleep habits and social support. Associations between these factors and mortality were assessed using multivariate Cox regression analysis.	Men with the highest levels of perceived stress had a statistically significantly increased rate of prostate cancer-specific mortality compared with men with low stress levels (hazard ratio 1.66, 95% confidence interval 1.05-2.63). Men with high stress levels also had a high frequency of grieving and sleep loss. They also had fewer people with whom to share their emotional problems and felt an inability to share most of their problems with partners, friends and family.	This study contributes to the growing field of psychosocial quality of life research in men with prostate cancer. The findings show a significant association between prostate cancer-specific mortality and perceived stress in patients initially diagnosed with localized, non-metastatic prostate cancer. Significant associations between perceived stress and various psychosocial factors were also seen. The findings of this study could prove useful to target interventions to improve quality of life in men with prostate cancer.	
26342649	Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during the pre- and postoperation periods and have normal pain perception presurgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. Here, we report that pre- or postexposure to rapid eye movement sleep disturbance (REMSD) for 6 hours daily for 3 consecutive days did not alter basal responses to mechanical, heat, and cold stimuli, but did delay recovery in incision-induced reductions in paw withdrawal threshold to mechanical stimulation and paw withdrawal latencies to heat and cold stimuli on the ipsilateral side of male or female rats. This short-term REMSD led to stress shown by an increase in swim immobility time, a decrease in sucrose consumption, and an increase in the level of corticosterone in serum. Blocking this stress via intrathecal RU38486 or bilateral adrenalectomy abolished REMSD-caused delay in recovery of incision-induced reductions in behavioral responses to mechanical, heat, and cold stimuli. Moreover, this short-term REMSD produced significant reductions in the levels of mu opioid receptor and kappa opioid receptor, but not Kv1.2, in the ipsilateral L4/5 spinal cord and dorsal root ganglia on day 9 after incision (but not after sham surgery).Our findings show that short-term sleep disturbance either pre- or postsurgery does not alter basal pain perception, but does exacerbate postsurgical pain hypersensitivity. The latter may be related to the reductions of mu and kappa opioid receptors in the spinal cord and dorsal root ganglia caused by REMSD plus incision. Prevention of short-term sleep disturbance may help recovery from postsurgical pain in patients.	
26342603	Poor sleep quality is common in patients with chronic heart failure (CHF). This study tested the hypothesis that adaptive servo-ventilation (ASV) therapy in CHF patients whose central sleep apnoea (CSA) was not suppressed by continuous positive airway pressure (CPAP) (CPAP-non-responders) would improve sleep quality compared to CPAP-responders receiving ongoing CPAP therapy.Eighty-two patients with CHF (65 ± 9 years, left ventricular ejection fraction 35 ± 16 %) and CSA [apnoea-hypopnoea index (AHI) ≥15/h] were retrospectively studied. Within an average of 47 days, patients were reevaluated on CPAP therapy and stratified according to their suppression of CSA: 34 were CPAP-non-responders switched to ASV therapy the following day and 48 were CPAP-responders who continued on CPAP therapy. Polysomnographic parameters were assessed in the diagnostic night and on the last night of PAP therapy (CPAP or ASV) before the patient was discharged with the final pressure settings.	Compared with the CPAP group, the ASV group had significantly greater reductions from baseline in AHI (-37 ± 15/h vs -28 ± 18/h, p = 0.02), arousal index (-12.7 ± 13.6/h vs -6.8 ± 12.5/h, p = 0.04) and sleep stage N1 (-9 ± 14 % vs -2 ± 12 %, p = 0.03). In addition, the ASV group gained significantly more rapid eye movement (REM) sleep compared with the CPAP group (+5 ± 9 % vs +1 ± 9 %, p = 0.02).	CPAP therapy is effective in reducing AHI in a significant proportion of CHF patients with reduced ejection fraction and CSA. Treatment of CSA with ASV in CHF patients reduces sleep fragmentation and improves sleep structure to a significantly greater extent than changes seen in responders to CPAP therapy.	
26341910	Sleep is strongly implicated in learning, especially in the reprocessing of recently acquired memory. Children with intellectual disability (ID) tend to have sleep-wake disturbances, which may contribute to the pathophysiology of the disease. Given that sleep is partly controlled by the circadian clock, we decided to study the rhythmic expression of genes in the hippocampus, a brain structure which plays a key role in memory in humans and rodents. By investigating the hippocampal transcriptome of adult mice, we identified 663 circadian clock controlled (CCC) genes, which we divided into four categories based on their temporal pattern of expression. In addition to the standard core clock genes, enrichment analysis identified several transcription factors among these hippocampal CCC genes, and our findings suggest that genes from one cluster regulate the expression of those in another. Interestingly, these hippocampal CCC genes were highly enriched in sleep/wakefulness-related genes. We show here that several genes in the glucocorticoid signaling pathway, which is involved in memory, show a CCC pattern of expression. However, ID genes were not enriched among these CCC genes, suggesting that sleep or learning and memory disturbances observed in patients with ID are probably not related to the circadian clock in the hippocampus. 
26341647	Unstable (cyclical alternating pattern, or CAP) sleep is associated with surges of sympathetic nervous system activity, increased blood pressure and vasoconstriction, heightened baroreflex sensitivity, and unstable heart rhythm and breathing. In susceptible persons, CAP sleep provokes clinically significant events, including hypertensive crises, sleep-disordered breathing, and cardiac arrhythmias. Here we explore the neurophysiology of CAP sleep and its impact on cardiovascular and respiratory functions. We show that: (i) an increase in neurophysiological recovery rate can explain the emergence of slow, self-sustained, hypersynchronized A1 CAP-sleep pattern and its transition to the faster A2-A3 CAP-sleep patterns; (ii) in a two-dimensional, continuous model of cardiac tissue with heterogeneous action potential duration (APD) distribution, heart rate accelerations during CAP sleep may encounter incompletely recovered electrical excitability in cell clusters with longer APD. If the interaction between short cycle length and incomplete, spatially heterogeneous repolarization persists over multiple cycles, irregularities and asymmetry of depolarization front may accumulate and ultimately lead to a conduction block, retrograde conduction, breakup of activation waves, reentrant activity, and arrhythmias; and (iii) these modeling results are consistent with the nighttime data obtained from patients with structural heart disease (N=13) that show clusters of atrial and ventricular premature beats occurring during the periods of unstable heart rhythm and respiration that accompany CAP sleep. In these patients, CAP sleep is also accompanied by delayed adaptation of QT intervals and T-wave alternans.
26341585	To examine the hypothesis that respondents with any of three specific sleep patterns would have a higher likelihood of suicidality than those without reports of these patterns in Korean adolescents.Data from the 2011-2013 Korea Youth Risk Behavior Web-based Survey were used.	191,642 subjects were included. The survey's target population was students in grades 7 through 12 in South Korea.	Sleep time.	Suicidal thoughts, plans and attempts.	The odds of suicidal thoughts in subjects with very short or long time in bed were 1.487-fold higher (95% CI 1.219 to 1.815) or 0.611-fold lower (95% CI 0.460 to 0.811), respectively, than for subjects with 7 h/day in bed; the odds were similar for suicidal plans. The odds of suicidal thoughts in subjects with early or late awakening times were 1.231-fold higher (95% CI 1.050 to 1.442) or 1.528-fold lower (95% CI 1.000 to 2.334), respectively, than for subjects with 7 h/day in bed; these odds were lower for suicidal plans and attempts. The odds of suicidal thoughts in subjects with early bedtime were 1.748-fold higher (95% CI 1.302 to 2.346), the odds of suicidal plans in people with an early bedtime were 2.494-fold higher (95% CI 1.671 to 3.722) and the odds of suicide attempts in subjects with late bedtime were 1.313-fold higher (95% CI 1.005 to 1.716) than for subjects with a bedtime of 23:00.	The sleep-related time is associated with suicide-related behaviours in Korean adolescents. Multilateral approaches are needed to identify the greatest risk factors for suicidal behaviours.	
26340651	Sleep is an emerging area of concern in children with juvenile idiopathic arthritis (JIA). Research shows the presence of poor sleep quality and related adverse outcomes in pediatric pain populations, including JIA, but few studies have examined the prospective patterns of association between sleep and associated outcomes. This prospective study evaluated the direction and magnitude of associations between subjective sleep characteristics (sleep quality, difficulty initiating sleep, and sleep duration), pain intensity, and functional limitations in children with JIA. We hypothesized that pain intensity would partially mediate the relationship between sleep and functional limitations.Children and adolescents with JIA (n=59; age range, 8 to 18 y) recruited during clinic visits, completed smartphone-based diaries for 1 month. Subjective sleep characteristics were reported each morning; pain and functioning were assessed 3 times daily.	As hypothesized, the associations between sleep quality and functional limitations and between difficulty initiating sleep and functional limitations were partially mediated by pain intensity, at any given moment (z=-3.27, P=0.001, z=2.70, P<0.05). Mediation was not detected in a model testing the association between sleep duration, pain intensity, and functional limitations (z=-0.58, P=0.56).	Results suggest that sleep is integral to understanding the momentary association between pain intensity and functioning in children with JIA.	
26337732	Artificial lighting can alter individual behaviour, with often drastic and potentially negative effects on biological rhythms, daily activity and reproduction. Whether this is caused by a disruption of sleep, an important widespread behaviour enabling animals to recover from daily stress, is unclear. We tested the hypothesis that light pollution disrupts sleep by recording individual sleep behaviour of great tits, Parus major, that were roosting in dark nest-boxes and were exposed to light-emitting diode light the following night. Their behaviour was compared to that of control birds sleeping in dark nest-boxes on both nights. Artificial lighting caused experimental birds to wake up earlier, sleep less (-5%) and spent less time in the nest-box as they left their nest-box earlier in the morning. Experimental birds did not enter the nest-box or fall asleep later than controls. Although individuals in lit nest-boxes did not wake up more often nor decreased the length of their sleep bouts, females spent a greater proportion of the night awake. Our study provides the first direct proof that light pollution has a significant impact on sleep in free-living animals, in particular in the morning, and highlights a mechanism for potential effects of light pollution on fitness. 

26337408	To investigate relationships between caregiving and subjective sleep reports among older New Zealanders.Participants were 434 carers (177 home-based) and 1747 non-carers (aged 55-72 years) who completed the 2008 Health Work and Retirement survey. Sleep outcomes (feeling worn out, tired, or dissatisfied with sleep or having a diagnosed sleep disorder) were explored by caregiving status. Logistic regression was used to investigate caregiving as an independent predictor of poor sleep health after controlling for other demographic variables.	Home-based carers were more likely to report feeling tired some/all of the time than non-carers (odds ratio 1.6, 95% confidence interval 1.1-2.2). Being Māori, a woman, younger or more socioeconomically deprived (New Zealand Deprivation Index 2006) were also significant independent predictors of poor sleep outcomes.	Carers are at increased risk of feeling tired in the daytime. Early recognition and management of underlying sleep problems are particularly important for older people providing care at home.	
26337264	To determine whether multiple subpial transection in the posterior temporal lobe has an impact on long-term outcome in children who have drug-resistant Landau-Kleffner syndrome (LKS) or other "electrical status epilepticus during sleep" (ESES)-related regression. Given the wide variability in outcomes reported in the literature, a secondary aim was to explore predictors of outcome.The current study includes a surgery group (n = 14) comprising patients who underwent multiple subpial transection of the posterior temporal lobe and a nonsurgery comparison group (n = 21) comprising patients who underwent presurgical investigations for the procedure, but who did not undergo surgery. Outcomes were assessed utilizing clinical note review as well as direct assessment and questionnaires.	The distribution of nonclassical cases was comparable between groups. There were some differences between the surgery and nonsurgery groups at presurgical investigation including laterality of discharges, level of language impairment, and age; therefore, follow-up analyses focused on change over time and predictors of outcome. There were no statistically significant differences between the groups in language, nonverbal ability, adaptive behavior, or quality of life at follow-up. There was no difference in the proportion of patients showing improvement or deterioration in language category over time for either group. Continuing seizures and an earlier age of onset were most predictive of poorer quality of life at long-term follow-up (F2,23 = 26.2, p = <0.001, R(2) = 0.714).	Both surgery and nonsurgery groups had similar proportions of classic LKS and ESES-related regression. Because no significant differences were found in the changes observed from baseline to follow-up between the two groups, it is argued that there is insufficient evidence to suggest that multiple subpial transection provides additional benefits over and above the mixed recovery often seen in LKS and related regressive epilepsies.	
26337159	Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Treatment of ESES is assumed to improve cognitive outcome. The aim of this study is to create an overview of the current evidence for different treatment regimens in children with ESES syndrome.A literature search using PubMed and Embase was performed. Articles were selected that contain original treatment data of patients with ESES syndrome. Authors were contacted for additional information. Individual patient data were collected, coded, and analyzed using logistic regression analysis. The three predefined main outcome measures were improvement in cognitive function, electroencephalography (EEG) pattern, and any improvement (cognition or EEG).	The literature search yielded 1,766 articles. After applying inclusion and exclusion criteria, 112 articles and 950 treatments in 575 patients could be analyzed. Antiepileptic drugs (AEDs, n = 495) were associated with improvement (i.e., cognition or EEG) in 49% of patients, benzodiazepines (n = 171) in 68%, and steroids (n = 166) in 81%. Surgery (n = 62) resulted in improvement in 90% of patients. In a subgroup analysis of patients who were consecutively reported (585 treatments in 282 patients), we found improvement in a smaller proportion treated with AEDs (34%), benzodiazepines (59%), and steroids (75%), whereas the improvement percentage after surgery was preserved (93%). Possible predictors of improved outcome were treatment category, normal development before ESES onset, and the absence of structural abnormalities.	Although most included studies were small and retrospective and their heterogeneity allowed analysis of only qualitative outcome data, this pooled analysis suggests superior efficacy of steroids and surgery in encephalopathy with ESES.	
26336863	Smith-Magenis syndrome is a complex neurodevelopmental disorder that includes intellectual deficiency, speech delay, behavioral disturbance and typical sleep disorders. Ninety percent of the cases are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases are linked to mutations of the same gene. Behavioral disorders often include outbursts, attention deficit/hyperactivity disorders, self-injury with onychotillomania and polyembolokoilamania (insertion of objects into body orifices), etc. Interestingly, the stronger the speech delay and sleep disorders, the more severe the behavioral issues. Sleep disturbances associate excessive daytime sleepiness with nighttime agitation. They are underpinned by an inversion of the melatonin secretion cycle. However, the combined intake of beta-blockers in the morning and melatonin in the evening may radically alleviate the circadian rhythm problems.Once sleep disorders are treated, the next challenge is finding an effective treatment for the remaining behavioral problems. Unfortunately, there is a lack of objective guidelines. A comprehensive evaluation of such disorders should include sleep disorders, potential causes of pain, neurocognitive level and environment (i.e. family and school). In any case, efforts should focus on improving communication skills, identifying and treating attention deficit/hyperactivity, aggressiveness and anxiety. Treatment of Smith-Magenis syndrome is complex and requires a multidisciplinary team including, among others, geneticists, psychiatrists, neuropediatricians/neurologists, somnologists, developmental and behavioral pediatricians, and speech and language therapists.	
26335094	Research into the sleep-wake cycle has provided new treatment targets for patients with insomnia as well as a better understanding of how medications affect sleep processes. Current insomnia medications, including benzodiazepines and nonbenzodiazepines, focus on enhancing sleep-promoting systems through broad antagonism of GABA. Other medications that promote sleep by blocking wake-promoting systems include antidepressants, antipsychotics, and antihistamines, but adverse effects and nonspecific therapeutic effects limit their use. New and emerging insomnia medications are focusing on blocking wake-promoting systems via more selective antagonism of orexin, serotonin, and norepinephrine. These medications may offer improved efficacy with fewer adverse effects. 
26334870	Hypogonadism, or low testosterone, is a common disorder. There are currently no patient-reported outcome (PRO) instruments designed to comprehensively evaluate the symptoms of hypogonadism and to detect changes in these symptoms in response to treatment.The purpose of this study was to develop a PRO instrument, the Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) and to assess its content validity.	A literature review, expert clinician input, and qualitative concept elicitation with 39 male hypogonadism patients (four focus groups: n = 25; individual interviews: n = 14; mean age 52.3 ± 14.3 years) from the USA were used to develop the draft HIS-Q. Subsequent cognitive interviews (n = 29; mean age 51.5 ± 15.4 years) were used to evaluate content validity.	Emergent discussion with participants yielded symptoms within the sexual, physical, energy, sleep, cognition, and mood domains. Low libido and tiredness were most commonly reported. The initial version of the HIS-Q includes 53 items that were consistently understood by the participants, who found the instrument to be relevant to their experiences with hypogonadism and comprehensive in the content coverage of symptoms.	The HIS-Q is a comprehensive PRO measure of hypogonadism symptom severity in males. Its design elements, including the response options and recall period, were suitable, and content validity was confirmed.	
26334341	The need to educate the future nursing workforce to increase understanding of healthy sleep practices, adverse health consequences of impaired sleep, and common sleep disorders is pressing. Unfortunately, education about sleep and sleep disorders has not been part of established undergraduate nursing curricula.This study developed a sleep education program for college nursing students and tested its effect on knowledge about sleep and sleep disorders.	With a total time commitment of 10 hours, this program included three sequential components: traditional in-classroom teaching, guided online virtual self-learning, and interactive simulation-based discussion. This innovative education program was implemented in a core course offered to senior nursing students in spring 2013, and demonstrated its effectiveness in improving knowledge about sleep and sleep disorders.	Translating into undergraduate nursing curriculum, it will lay a foundation for improving health care of patients and decreasing the health risks of nurses as care providers.	
26333784	Corticotropin releasing factor (CRF) is implicated in sleep and arousal regulation. Exogenous CRF causes sleep suppression that is associated with activation of at least two important arousal systems: pontine noradrenergic and hypothalamic orexin/hypocretin neurons. It is not known whether CRF also impacts sleep-promoting neuronal systems. We hypothesized that CRF-mediated changes in wake and sleep involve decreased activity of hypothalamic sleep-regulatory neurons localized in the preoptic area. To test this hypothesis, we examined the effects of intracerebroventricular administration of CRF on sleep-wake measures and c-Fos expression in GABAergic neurons in the median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) in different experimental conditions. Administration of CRF (0.1 nmol) during baseline rest phase led to delayed sleep onset and decreases in total amount and mean duration of non-rapid eye movement (NREM) sleep. Administration of CRF during acute sleep deprivation (SD) resulted in suppression of recovery sleep and decreased c-Fos expression in MnPN/VLPO GABAergic neurons. Compared with vehicle controls, intracerebroventricular CRF potentiated disturbances of both NREM and REM sleep in rats exposed to a species-specific psychological stressor, the dirty cage of a male conspecific. The number of MnPN/VLPO GABAergic neurons expressing c-Fos was reduced in the CRF-treated group of dirty cage-exposed rats. These findings confirm the involvement of CRF in wake-sleep cycle regulation and suggest that increased CRF signaling in the brain 1) negatively affects homeostatic responses to sleep loss, 2) exacerbates stress-induced disturbances of sleep, and 3) suppresses the activity of sleep-regulatory neurons of the MnPN and VLPO. 
26332974	Circadian clocks are biologic oscillators present in all photosensitive species that produce 24-h cycles in the transcription of rate-limiting metabolic enzymes in anticipation of the light-dark cycle. In mammals, the clock drives energetic cycles to maintain physiologic constancy during the daily switch in behavioural (sleep/wake) and nutritional (fasting/feeding) states. A molecular connection between circadian clocks and tissue metabolism was first established with the discovery that 24-h transcriptional rhythms are cell-autonomous and self-sustained in most tissues and comprise a robust temporal network throughout the body. A major window in understanding how the clock is coupled to metabolism was opened with discovery of metabolic syndrome pathologies in multi-tissue circadian mutant mice including susceptibility to diet-induced obesity and diabetes. Using conditional transgenesis and dynamic metabolic testing, we have pinpointed tissue-specific roles of the clock in energy and glucose homeostasis, with our most detailed understanding of this process in endocrine pancreas. Here, we review evidence for dynamic regulation of insulin secretion and oxidative metabolic functions by the clock transcription pathway to regulate homeostatic responses to feeding and fasting. These studies indicate that clock transcription is a determinant of tissue function and provide a reference for understanding molecular pathologies linking circadian desynchrony to metabolic disease. 
26332968	Recent advances in methods for making mammalian organs translucent have made possible whole-body fluorescent imaging with single-cell resolution. Because organ-clearing methods can be used to image the heterogeneous nature of cell populations, they are powerful tools to investigate the hierarchical organization of the cellular circadian clock, and how the clock synchronizes a variety of physiological activities. In particular, methods compatible with genetically encoded fluorescent reporters have the potential to detect circadian activity in different brain regions and the circadian-phase distribution across the whole body. In this review, we summarize the current methods and strategy for making organs translucent (removal of lipids, decolourization of haemoglobin and adjusting the refractive index of the specimen). We then discuss possible applications to circadian biology. For example, the coupling of circadian rhythms among different brain regions, brain activity in sleep-wake cycles and the role of migrating cells such as immune cells and cancer cells in chronopharmacology. 
26331760	Circadian rhythms take place with a periodicity of 24 hr, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the "central pacemaker" of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hr as manifest when an animal is placed into constant dark or "free-running" conditions. Simple measurements of an organism's activity in free-running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their homecage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are presented here including the process of entrainment, determination of tau (period length) in free-running conditions, determination of circadian periodicity in response to light disruption (e.g., jet lag studies), and evaluation of clock plasticity in non-24-hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of environmental surroundings.
26330644	Several reasons justify the need for nonpharmacological interventions for bipolar disorder (BD) in women. This review focuses on psychosocial therapies for BDs in women. The research evidence for a wide range of psychosocial interventions for the management of BDs in women has been presented. All the interventions have some common components like targeting disease management, information regarding illness, and coping skills. There also are distinctive features like cognitive restructuring and self-rated mood charts in cognitive behavior therapy, regulation of sleep/wake cycles and daily routines in interpersonal sleep regulation therapy, and communication skill training in family treatments. Many psychosocial interventions hold promise as adjunctive therapies for bipolar patients. In India, there is a considerable dearth of literature in this area due lack of skilled staff for psychosocial interventions. Future trials need to: Clarify which populations are most likely to benefit from which strategies; identify putative mechanisms of action; systematically evaluate costs, benefits, and generalizability of effects, and record adverse effects. 
26330183	Obstructive sleep apnea (OSA), a common and serious disorder in which breathing repeatedly stops during sleep, is associated with excess weight and obesity. Little is known about the co-occurrence of OSA among pregnant women from low and middle-income countries.We examined the extent to which maternal pre-pregnancy overweight or obesity status are associated with high risk for OSA, poor sleep quality, and excessive daytime sleepiness in 1032 pregnant women in Lima, Peru. The Berlin questionnaire was used to identify women at high risk for OSA. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to examine sleep quality and excessive daytime sleepiness, respectively. Multinomial logistic regression procedures were employed to estimate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for putative confounding factors.	Compared with lean women (<25 kg/m(2)), overweight women (25-29.9 kg/m(2)) had 3.69-fold higher odds of high risk for OSA (95% CI 1.82-7.50). The corresponding aOR for obese women (≥30 kg/m(2)) was 13.23 (95% CI: 6.25-28.01). Obese women, as compared with their lean counterparts had a 1.61-fold higher odds of poor sleep quality (95% CI: 1.00-2.63).	Overweight or obese pregnant women have increased odds of sleep disorders, particularly OSA. OSA screening and risk management may be indicated among pregnant women in low and middle income countries, particularly those undergoing rapid epidemiologic transitions characterized by increased prevalence of excessive adult weight gain.	
26330176	We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti-NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome.	Only two out of 27 patients were white, whereas 16 out of 27 patients were from the Pacific Islands/New Zealand Maori. The mean duration of admission was 69 days (10-224d) and 48% of patients (13/27) needed treatment in an intensive care setting. A mean of eight medications per patient was used for symptomatic management. Symptoms treated were agitation (n=25), seizures (n=24), movement disorders (n=23), sleep disruption (n=17), psychiatric symptoms (n=10), and dysautonomia (n=four). The medications used included five different benzodiazepines (n=25), seven anticonvulsants (n=25), eight sedatives and sleep medications (n=23), five antipsychotics (n=12), and five medications for movement disorders (n=10). Sedative and sleep medications other than benzodiazepines were the most effective, with a mean benefit of 67.4% per medication and a mean adverse effect-benefit ratio of 0.04 per medication. Antipsychotic drugs were used for a short duration (median 9d), and had the poorest mean benefit per medication of 35.4% and an adverse effect-benefit ratio of 2.0 per medication.	Long-acting benzodiazepines, anticonvulsants, and clonidine can treat multiple symptoms. Patients with anti-NMDAR encephalitis appear vulnerable to antipsychotic-related adverse effects. Pacific Islanders appear to have a vulnerability to anti-NMDAR encephalitis in our region.	
26329450	A scoping review is an approach to identify or map the extent of key concepts and main sources and types of evidence available on a topic. Hypnic jerks are considered a parasomnia categorized as a sleep-wake transition disorder. Although hypnic jerks are considered a benign sleep/movement disorder, some of the latest research indicates that they may be a clinical characteristic for other sleep disorders that affect health care outcomes. This article conducts a scoping review of the literature to determine the extent, range, and nature of the research activity related to hypnic jerks and identifies research gaps in the existing literature. 
26329449	Various medications and behavioral treatments for sleep-related leg cramps have been tried, but the quality of the evidence is low. Quinine seems to be effective, but dangerous. β-Agonists may be one of the more common causes of secondary leg cramps. Statins may not be implicated in leg cramps as much as has been believed. Potassium-sparing diuretics may have a higher incidence of sleep-related leg cramps than potassium-depleting diuretics. Plantar flexion of the feet may elicit most sleep-related leg cramps. More research into behavioral treatments is needed. A standardized sleep-related leg cramp questionnaire would be useful to expand research. 
26329444	Adopting prior models of sleep-wake transitions, a flip-flop switch in synchronized neurotransmitter activity is proposed to underlie restless leg syndrome onset. In this model, leg quiescence homeostasis sustained through concerted activities of several neurotransmitters in basal ganglia is perturbed and produces striatal motor activity along sensory activity associated with thalamocortical circuits (conscious urge and discomfort). This model explains the association of restless leg syndrome with a wide variety of associated pathologies emphasizing that perturbed function and imbalance may occur under different steady states of neurotransmitter levels. Likewise, this concept links various central and peripheral etiologies and integrates the augmenting and transient effects of therapeutic neuromodulators. 
26329114	Sleep problems are common across the adult life span and may exacerbate depressive symptoms and the effect of common risk factors for depressive symptoms such as life stress. We examine sleep disturbance as a moderator of the association between stressful life events and depressive symptoms across five waves (25 years) of the nationally representative, longitudinal American Changing Lives Study.The sample includes 3,597 adults aged 25 years or older who were surveyed up to five times over 25 years. Multilevel models were run to examine between- and within-person variability in sleep disturbance and life event stress as predictors of depressive symptoms, and an interaction to test sleep disturbance as a moderator is included in a second step.	Life events and sleep disturbance were associated with elevated depressive symptoms at the between- and within-person levels. A significant sleep disturbance by interaction of life events was found, indicating that when individuals experienced an above average number of life events and slept more restlessly than usual, they had a higher risk for depressive symptoms than individuals who experienced above average stress but slept well.	Sleeping restfully may allow individuals the rejuvenation needed to manage stress adaptively and reduce depressive symptom burden.	

26325012	This study investigated the effects of sleep extension on tennis serving accuracy, as well as daytime sleepiness in college varsity tennis players.Twelve (seven females and five males) healthy students on a college varsity tennis team maintained their habitual sleep-wake schedule for a one-week baseline period followed by a one-week sleep extension period. Participants were requested to sleep at least nine hours, including naps, during the sleep extension period. Serving accuracy was assessed when participants were sleep deprived (prior to the sleep extension period) and after the sleep extension period. Levels of daytime sleepiness were monitored via the Epworth Sleepiness Scale and the Stanford Sleepiness Scale, and caffeine consumption was recorded throughout the study.	Participants slept significantly more in the second week--the sleep extension week--compared with the first week--the baseline week (8.85 vs. 7.14 h; p<0.05). Following the sleep extension period, accuracy of the tennis serves improved significantly (35.7% vs. 41.8%; p<0.05), and the Epworth Sleepiness Scale and Stanford Sleepiness Scale scores declined significantly (12.15 vs. 5.67; p<0.05 and 3.56 vs. 2.67; p<0.05, respectively).	This study demonstrates that an increase in sleep of approximately 2h per night significantly increased athletic performance in college varsity tennis players.	
26322364	Рассматривается связь нарушений сна с расстройствами аутистического спектра у детей. Приводятся данные о характерных вариантах нарушений сна, в числе которых сопротивление укладыванию спать, частые ночные пробуждения ребенка, парасомнии, изменения структуры сна, прежде всего - уменьшение доли фазы быстрого сна. Обращается внимание на возможность непосредственной связи нарушений сна с патогенезом расстройств аутистического спектра. Обсуждается роль нарушений выработки нейромедиаторов и морфологических изменений структур головного мозга, характерных для расстройств аутистического спектра, в генезе нарушений сна у детей. Намечены возможные подходы к нефармакологической и фармакологической коррекции.An association between sleep disorders and autistic spectrum disorders in children is considered. Characteristic variants of sleep disorders, including resistance to going to bed, frequent night awakenings, parasomnias, changes in sleep structure, primarily, the decrease in the percentage of rapid eye movement sleep, are presented. Attention is focused on the possibility of the direct relationship between sleep disturbance and the pathogenesis of autistic spectrum disorders. A role of pathological alterations in the production of neuromediators and morphological changes in the brain structures characteristic of autistic spectrum disorders in the genesis of sleep disorders in children is discussed. Possible non-pharmacological and pharmacological approaches are suggested.	
26321393	There is emerging evidence of the beneficial role of the melatonin system in a wide range of psychiatric and neurologic disorders, including anxiety, depression, and epilepsy. Although melatoninergic drugs have chronobiotic and antioxidant properties that positively influence circadian rhythm desynchronization and neuroprotection in neurodegenerative disorders, studies examining the use of melatonin for epilepsy's comorbid psychiatric and neurological symptomatology are still limited. Preclinical and clinical findings on the beneficial effects of the melatonin system on anxiety, depression, and epilepsy suggest that melatoninergic compounds might be effective in treating comorbid behavioral complications in epilepsy beyond regulation of a disturbed sleep-wake cycle.
26321106	According to a recent national survey, tobacco use is a critical public health issue in China, with more than two-thirds of Chinese males smoking. Findings in Western populations suggest that smoking may cluster with other health-risk behaviors. To explore these relationships in Chinese male adults, we utilized baseline data from the China Seven Cities Study (CSCS).Male adults (n = 12,122) were included. Smoking status was defined as never smokers, ex-smokers, current smokers, and current heavy smokers. Logistic regression was employed to investigate the association of cigarette smoking and patterns of food consumption, physical activity, and alcohol drinking.	After controlling for age, socioeconomic status, and city residence, heavy smokers consumed significantly less vegetables, fruits, milk and other dairy products, spent significantly more time watching television, slept and exercised less, and got drunk or engaged in binge drinking more frequently compared to never, ex-, or current smokers (p < 0.05).	Findings suggest significant associations of heavy cigarette smoking with other health-risk behaviors in Chinese male adults, underscoring the need for tobacco control interventions for Chinese males.	
26319831	Introducción: estudios recientes sugieren que las mujeres con diagnóstico de diabetes gestacional tienen más probabilidad de padecer trastornos del sueño en comparación con el resto de las mujeres embarazadas. Los objetivos de este estudio fueron analizar los factores de riesgo asociados a diabetes gestacional y verificar una asociación entre padecer o no diabetes gestacional y la calidad del sueño y/o somnolencia. Material y métodos: estudio observacional de casos y controles a partir de una muestra de 130 gestantes, 46 con diabetes gestacional y 84 controles. Se realizó una valoración antropométrica, evaluando peso, estatura, índice de masa corporal (IMC) y perímetro abdominal. Se realizó una valoración sociodemográfica, evaluando edad y situación familiar y laboral, así como un estudio ginecológico, evaluando número de partos simples y múltiples, número de abortos y patología ginecológica durante los últimos tres años. Para el diagnóstico de diabetes gestacional se realizó el test de O‘Sullivan. Se midió la calidad del sueño y la somnolencia diurna. Resultados: del total de gestantes estudiadas, 46 fueron diagnosticadas de diabetes gestacional. Existen diferencias significativas (p < 0,001) en las puntuaciones del IMC entre gestantes diabéticas y no diabéticas, siendo sus valores más elevados entre las diabéticas. Existe una asociación significativa (p = 0,002) entre la existencia de antecedentes familiares de diabetes mellitus tipo 2 y padecer o no diabetes gestacional. Las gestantes diabéticas presentan un significativo empeoramiento (p < 0,001) de la calidad del sueño. Respecto a la somnolencia diurna, las gestantes diabéticas poseen una somnolencia diurna superior a la media poblacional. Conclusiones: en la población estudiada, puntuaciones elevadas en el IMC, así como antecedentes familiares de diabetes mellitus tipo 2 parecen ser factores asociados al riesgo de padecer diabetes gestacional. Las embarazadas con diabetes gestacional poseen una peor calidad del sueño y un grado de somnolencia diurna superior al de la media poblacional, reduciéndose con ello el bienestar de la madre y del feto.recent studies suggest that women with gestational diabetes are more likely to suffer sleep disorders compared to pregnant women without diabetes. The objectives of this study were to analyze the risk factors associated with gestational diabetes and to verify if exist an association between the presence or abscense of gestational diabetes and the quality of the sleep and/or daytime sleepiness.	case-controls study with a sample of 130 pregnant women, 46 of them with gestational diabetes and 84 controls. Anthropometric parameters such as weight, stature, body mass index (BMI) and abdominal perimeter were evaluated. Socio-demographic variables, including age and family situation were assessed, and a gynecological study was performed, evaluating the number of simple or multiple births, number of miscarriages and gynecological pathology during the past 3 years. The O'Sullivan test was conducted for the diagnosis of gestational diabetes. The quality of sleep and daytime sleepiness were also measured.	46 women were diagnosed of gestational diabetes. There are significant differences (p < 0.001) in BMI scores among women with gestational diabetes and controls, being the highest values in the diabetic group. There is a significant association (p = 0.002) between the existence of family history of type 2 diabetes mellitus and the presence or abscense of gestational diabetes. Women with gestational diabetes present a significant worse quality of sleep (p < 0.001), and values of daytime sleepiness higher than the general population.	high values of BMI or family history of type 2 diabetes mellitus seems to be factors associated to the risk of suffer gestational diabetes. Women with gestational diabetes have a poorer quality of sleep and a higher degree of daytime sleepiness than the general population, reducing the well-being of the mother and the fetus.	


26317888	We attempted to explore the relationship between working hours and sleep disturbance according to occupation and gender among Korean workers. Data were derived from the third Korean Working Conditions Survey, conducted in 2011 by the Korea Occupational Safety and Health Agency. From a total of 50,032 workers, 34,783 salaried contract workers were selected. Work hours were categorized as <40, 40-48 (reference), 49-60, and >60 h/week. The outcome variable was sleep disturbance, which was assessed by a single question item (During the past 12 months, have you experienced sleep disturbance or insomnia?). Multiple survey logistic regression models were performed after adjusting with age, education level, marital status, self-rated health, salary, shift work, smoking and alcohol drinking. Gender and occupation were stratified in these models. The adjusted odds ratio (OR) for sleep disturbance in male non-manual workers with long work hours (>60 h/week) was 3.017 [95% confidence interval (CI) 1.956-4.653]. In female non-manual workers who work 49-60 working hour per week, the OR was 1.525 (95% CI 1.034-2.249). Long working hours can be a risk factor for sleep disturbance in Korean workers. The association was especially prominent in male non-manual workers.
26317786	The timing, duration, and intensity of sleep are determined by the interaction between a sleep-wake-dependent homeostatic process and a sleep-wake-independent, intrinsic, clock-like circadian process. Chronotype represents individual differences in diurnal preferences, which are not only genetically determined but also influenced by social and environmental factors. Thus, the discrepancy between biological and social clocks, so-called "social jetlag", occurs. Chronotype, social jetlag, and the links between chronotype and behavioral problems are well documented in adults and adolescents. However, such studies on young children are limited. We conducted a survey of sleep and health for preschool children attending kindergarten or childcare centers in Wako, Okayama and Kurashiki cities, Japan, between May and July 2012. A total of 654 children aged 4-6 years (342 boys and 312 girls, with an average age of 4.7 years) were assessed using the Children's ChronoType Questionnaire and the Strength and Difficulties Questionnaire. Morning (M)-type, neither (N)-type and evening (E)-type accounted for 36.2%, 54.0% and 9.8% of the participants, respectively. The weekday-to-weekend differences in midsleep time--originally proposed as the concept of social jetlag--were 11, 25 and 35 min for M-, N- and E-types, respectively. There was a negative correlation between chronotype and sleep period during weekdays (p < 0.001) and a positive correlation on weekends (p < 0.001). The weekday-to-weekend difference in sleep period was 0.5 h for E-types, whereas there was no difference for M-types. Binomial logistic regression analyses were used to examine the links between chronotype and behavioral problems, adjusted for participants' sex, age, childcare programs and locations. Chronotype was significantly associated with hyperactivity/inattention: N-type (adjusted OR = 1.74, 95% CI = 1.03-2.95, p < 0.05) and E-type (adjusted OR = 2.47, 95% CI = 1.18-5.20, p < 0.05). E-type was significantly associated with conduct problems (adjusted OR = 2.11, 95% CI = 1.03-4.31, p < 0.05) and peer problems (adjusted OR = 2.75, 95% CI = 1.18-6.44, p < 0.05). The results suggest that E-type children are vulnerable to higher social jetlag and more behavioral problems. The immature adjustment function of their endogenous circadian pacemakers may not be able to correct a small but significant social jetlag to synchronize with their social clocks. Furthermore, guidance based on chronobiological evidence is required for parents, teachers and health professionals to help children achieve optimal sleep and reduce behavioral problems.
26317594	Yawning, although easily recognized, is difficult to explain. Traditional explanations stressed physiological mechanisms, but more recently, behavioral processes have received increasing attention. This is the first study to test a range of hypotheses on yawning in wild primate populations. We studied two sympatric strepsirrhine species, Lemur catta, and Propithecus verreauxi, of the Ankoba forest (24.99°S, 46.29°E, Berenty reserve) in southern Madagascar. Sexual dimorphism is lacking in both species. However, their differences in ecological and behavioral characteristics facilitate comparative tests of hypotheses on yawning. Our results show that within each species males and females yawned with similar frequencies supporting the Dimorphism Hypothesis, which predicts that low sexual dimorphism leads to little inter-sexual differences in yawning. In support of the State Changing Hypothesis yawning frequencies was linked to the sleep-wake cycle and punctuated transitions from one behavior to another. Accordingly, yawning frequencies were significantly higher in L. catta than in P. verreauxi, because L. catta has a higher basal level of activity and consequently a higher number of behavioral transitions. In agreement with the Anxiety Hypothesis, yawning increased significantly in the 10 min following predatory attacks or aggression. Our findings provide the first empirical evidence of a direct connection between anxiety and yawning in lemurs. Our results show that yawning in these two strepsirrhines occurs in different contexts, but more research will be necessary to determine if yawns are a single, unitary behavior.
26317591	Since its discovery in 1998, the orexin system, composed of two G-protein coupled receptors, orexins 1 and 2, and two neuropeptide agonists, orexins A and B, has captured the attention of the scientific community as a potential therapeutic target for the treatment of obesity, anxiety, and sleep/wake disorders. Genetic evidence in rodents, dogs, and humans was revealed between 1999 and 2000, demonstrating a causal link between dysfunction or deletion of the orexin system and narcolepsy, a disorder characterized by hypersomnolence during normal wakefulness. These findings encouraged efforts to discover agonists to treat narcolepsy and, alternatively, antagonists to treat insomnia. This perspective will focus on the discovery and development of structurally diverse orexin antagonists suitable for preclinical pharmacology studies and human clinical trials. The work described herein culminated in the 2014 FDA approval of suvorexant as a first-in-class dual orexin receptor antagonist for the treatment of insomnia.
26317268	Cortisol acts as a critical biological intermediary through which chronic stressors like shift work impact upon multiple physiological, neuro-endocrine and hormonal functions. Therefore, the cortisol awakening response (CAR) is suggested as a prime index of shift work tolerance. Repeated assessments of the CAR (calculated as MnInc) in a group of 25 young novice police officers showed that in the interval between about 4 and 14 months after transitioning from regular day work to rotating shift work, mean values began to rise from baseline to significantly higher levels at about 14 months after they commenced shift work. Visual inspection of the individual trends revealed that a subgroup of 10 subjects followed a monotonically rising trend, whereas another 14 subjects, after an initial rise from about 4-14 months, reverted to a smaller, baseline level cortisol response at about 20 months after the start of shift work. If the initial increase in the cortisol response marks the development of a chronic stress response, the subsequent reversal to baseline levels in the subgroup of 14 participants might be indicative of a process of recovery, possibly the development of shift work tolerance. 
26316356	The purpose of this study is to investigate the incidence of sleep disorders (SD), characteristic of cerebral infarction patients with different parts affected.The research selected 101 patients with a first occurrence of acute cerebral infarction as the experimental group, and 86 patients without cerebral infarction as controls. Polysomnography, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and US National Stroke Scale were assessed.	Compared with control group, the incidence of SD was higher in experimental group (P < .05), and the incidence of SD in women was more frequent in experimental group (P < .05). There was no significant difference in the types of SD patients with acute cerebral infarction. In addition, the sleep quality of cerebral infarction patients with different parts affected was different: the sleep quality of left hemisphere infarction patients was poor compared with the right one, and the sleep quality of anterior circulation patients was poor compared with posterior circulation patients. Patients with thalamus infarction had a longer sleep time and a shorter sleep latency and stage 2 of non-rapid eye movement sleep compared with non-thalamus infarction group.	The prevalence of SD was relatively high in acute cerebral infarction patients, and the detailed classification of acute cerebral infarction may provide a more effective therapeutic method and therefore relieve patients' pain and supply a better quality of sleep.	

26311481	Sleep problems in children and adolescents are a significant public health concern and may be linked to a variety of psychoemotional difficulties. This study aimed to evaluate sleep quality and associated factors in conflict-affected Georgian adolescents after 9 months of forced displacement. Thirty-three internally displaced adolescents (mean age 11.4 years) and 33 adolescents (mean age 10.8 years) from the general population completed the Epworth Sleepiness Scale and the Children's Depression Inventory (CDI). Parents completed the Children's Sleep-Wake Scale and provided information on their socioeconomic status (SES) and the adolescents' sleep behavior, academic performance, and peer social relationships. The groups differed significantly in sleep quality, peer relationships, SES, and CDI scores. In the internally displaced group, the only significant predictor of sleep quality was SES, which increased the predictive capacity of the model (demographic and psychosocial variables) by 20% in the hierarchical analyses. The most significant predictor in the non-internally displaced group was CDI. This research indicates that displacement may affect sleep quality and psychosocial functioning. The importance of family SES as a contributing factor to displaced adolescents' poor sleep quality is highlighted. An integrated approach designed to improve the psychosocial environment of internally displaced adolescents is needed for their protection. 
26311122	Information regarding sleep disturbances in the population with advanced cancer is meager.To assess the prevalence of sleep disturbances and possible correlations with associated factors in a large number of patients with advanced cancer admitted to different palliative care settings.	This was an observational study performed in different settings of palliative care. A consecutive sample of patients with advanced cancer was prospectively assessed for a period of six months. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System scores, and concomitant medical treatment were recorded. Patients were administered the Athens Insomnia Scale and the Hospital Anxiety and Depression Scale (HADS).	A total of 820 patients were surveyed. Mean age was 69.7 years (SD 12.7), and 429 patients were males. Consistent sleep disturbances (moderate to maximum) were found in 60.8% of patients. Aged patients were less likely to have sleep disturbances, whereas a poor Karnofsky level was significantly associated with sleep problems. Breast, gastrointestinal, head and neck, lung, and prostate cancers were associated with sleep problems. Patients who had a secondary school or undergraduate education had less sleep disturbances. Hormone therapy and use of opioids and corticosteroids were positively associated with sleep disturbances, and there was a positive correlation of HADS-Anxiety and HADS-Depression scores with sleep disturbances.	More than 60% of palliative care patients have relevant sleep disturbances. Several factors associated with sleep disorders have been identified and should prompt physicians to make a careful examination and subsequent treatment of these disturbances.	
26310555	To understand the infantile nocturnal sleep-wake pattern developmental trajectory with Actiwatch, which would benefit the clinical assessment of infantile sleep.This study was a longitudinal study conducted between 7 Oct, 2009-30 Oct, 2011 in 10 hospitals of 9 cities of China ( Beijing, Xi'an, Qingdao, Wuhan, Changsha, Chongqing, Huzhou, Xiamen and Liuzhou). Actiwatch was used to track the sleep-wake pattern development trajectory of healthy infants in the first year of life in the home setting. Participating infants were followed up at 10th day and 28th day during the first month, and then monthly from the second to the sixth month after birth, and then at ninth and twelve months of age respectively. Meanwhile, infantile sleep was observed continuously for about 60 hours at each visit. According to the characteristics of repeated measurement data of this study, two-level random effect model was adopted to analyze the trend of infantile nocturnal sleep-wake parameters changing with age, and the gender difference.	A total of 473 healthy infants were included in this study, among whom 246 (52.0%) were boys, and 227 (48.0%) were girls; 355 (75.1%) infants completed the whole year follow-up survey. With infants' age increasing, the latency of infants' nighttime sleep onset decreased from 66.8 minutes on 10th day to 15.5-18.7 minutes at 6-12 months of age. The number of night wakes also decreased with age, while uninterrupted sleep periods lengthened with age. On the 10th day, there were 3.0 times of nightwaking on average, and the longest continuous sleeping interval lasted for 227.6 minutes on average. At 12-month of age, infants could sleep continuously for 350.9 minutes at most on average, while the number of nightwaking decreased to 1.6 times per night on average. Generally, nighttime sleep efficiency increased from 66.3% on the 10th day to 86.3% at 12-month of age. The differences of sleep-wake patterns between boys and girls presented as boys' nocturnal longest uninterrupted sleep period was 19 minutes shorter(266.6 vs. 285.6 min), and the average nighttime sleep efficiency was 2.2% lower (74.2% vs. 76.4%) compared with girls respectively. And the differences of sleep efficiency between boys and girls reduced gradually along with the growth.	During the first 6 months after birth, infantile sleep-wake pattern undergo obvious change. The capability of sleep-onset and uninterrupted sleep improved with age, and the sleep efficiency increased.	
26307037	Non-dipping of nocturnal blood pressure (BP) is associated with target organ damage and cardiovascular disease. Obstructive sleep apnoea (OSA) is associated with incident non-dipping. However, the relationship between disordered breathing during rapid eye movement (REM) sleep and the risk of developing non-dipping has not been examined. This study investigates whether OSA during REM sleep is associated with incident non-dipping.Our sample included 269 adults enrolled in the Wisconsin Sleep Cohort Study who completed two or more 24 h ambulatory BP studies over an average of 6.6 years of follow-up. After excluding participants with prevalent non-dipping BP or antihypertensive use at baseline, there were 199 and 215 participants available for longitudinal analysis of systolic and diastolic non-dipping, respectively. OSA in REM and non-REM sleep were defined by apnoea hypopnoea index (AHI) from baseline in-laboratory polysomnograms. Systolic and diastolic non-dipping were defined by systolic and diastolic sleep/wake BP ratios >0.9. Modified Poisson regression models estimated the relative risks for the relationship between REM AHI and incident non-dipping, adjusting for non-REM AHI and other covariates.	There was a dose-response greater risk of developing systolic and diastolic non-dipping BP with greater severity of OSA in REM sleep (p-trend=0.021 for systolic and 0.024 for diastolic non-dipping). Relative to those with REM AHI<1 event/h, those with REM AHI≥15 had higher relative risk of incident systolic non-dipping (2.84, 95% CI 1.10 to 7.29) and incident diastolic non-dipping (4.27, 95% CI 1.20 to 15.13).	Our findings indicate that in a population-based sample, REM OSA is independently associated with incident non-dipping of BP.	
26306695	The mechanisms underlying the unconsciousness of general anesthesia are not completely understood. Accumulating evidence indicates the ventrolateral preoptic nucleus (VLPO) in the endogenous sleep circuits may contribute to loss of consciousness (LOC) induced by GABA-enhancing anesthetics. However, there are few studies that look into distinct sleep pathway in the sleep-wake system. In the neural pathway from VLPO to the locus coeruleus (LC), we compared the inhibition effect of propofol on the LC activity before and after VLPO lesion in vivo rats. Systemic administration of propofol (20 mg/kg, i.p.) in normal rats caused a fast and obvious inhibition of LC neurons spontaneous firing (from 0.24 ± 0.06 to 0.12 ± 0.03 Hz). The LC neuronal firing rate of VLPO lesion rats only decreased to 0.18 ± 0.05 Hz (P = 0.021 vs. non-VLPO rats) after the propofol injection, and the time to reach the maximal inhibition level was also prolonged in VLPO lesion rats (2.3 ± 0.7 vs. 5.8 ± 1.2 min, P = 0.037). Microinjections of a selective GABAA receptor antagonist (SR95531) into the LC fully reversed the inhibitory effect of propofol on the LC neuronal activity, but did not significantly affect the latency to loss of righting reflex of rats after propofol administration (3.4 ± 0.9 vs. 3.7 ± 1.2 min, P = 0.639). Our results indicated that VLPO is necessary for the propofol-induced inhibition of LC activity, but the LC may not play an important role in the propofol-induced LOC.
26306014	Sleep disorders are frequent. Economic costs and impairment of quality of life can be substantial. Usually, patients suffer from insomnia or hypersomnia. Several effective therapeutic options are available. Sleep disorders appear independently or accompany a multitude of organic and psychiatric diseases. Fatigue has to be distinguished from sleep disorders clearly. For classification, the ICSD-3, published by the American Academy of Sleep Medicine, is used. Patients should be explicitly asked for their sleep quality, for many do not report actively. Patient's history and clinical examination usually narrow the diagnosis to a large extent. Clinical diagnostics should be carried out according to the diagnostic algorithm by the German Sleep Society (DGSM). An optimal sleep hygiene and if necessary weight reduction are crucial and can prevent chronification and health consequences. In addition, assistive technology, drug therapy, behaviour therapy, and in few cases surgery are available. 

26303010	Astrocytes can mediate neurovascular coupling, modulate neuronal excitability, and promote synaptic maturation and remodeling. All these functions are likely to be modulated by the sleep/wake cycle, because brain metabolism, neuronal activity and synaptic turnover change as a function of behavioral state. Yet, little is known about the effects of sleep and wake on astrocytes.Here we show that sleep and wake strongly affect both astrocytic gene expression and ultrastructure in the mouse brain. Using translating ribosome affinity purification technology and microarrays, we find that 1.4 % of all astrocytic transcripts in the forebrain are dependent on state (three groups, sleep, wake, short sleep deprivation; six mice per group). Sleep upregulates a few select genes, like Cirp and Uba1, whereas wake upregulates many genes related to metabolism, the extracellular matrix and cytoskeleton, including Trio, Synj2 and Gem, which are involved in the elongation of peripheral astrocytic processes. Using serial block face scanning electron microscopy (three groups, sleep, short sleep deprivation, chronic sleep restriction; three mice per group, >100 spines per mouse, 3D), we find that a few hours of wake are sufficient to bring astrocytic processes closer to the synaptic cleft, while chronic sleep restriction also extends the overall astrocytic coverage of the synapse, including at the axon-spine interface, and increases the available astrocytic surface in the neuropil.	Wake-related changes likely reflect an increased need for glutamate clearance, and are consistent with an overall increase in synaptic strength when sleep is prevented. The reduced astrocytic coverage during sleep, instead, may favor glutamate spillover, thus promoting neuronal synchronization during non-rapid eye movement sleep.	
26302278	To (a) investigate fatigue and sleep patterns of children and adolescents at home and (b) examine factors associated with fatigue and sleep..Descriptive with repeated measures
.	Homes of study participants in Los Angeles and Orange, California
.	35 children and adolescents with cancer.	Data were collected using the PedsQL Multidimensional Fatigue Scale, which was completed once at home by each participant, and sleep actigraphs, which were worn for five days at home following discharge from hospitalization
.	General fatigue, cognitive fatigue, sleep-rest fatigue, sleep duration, sleep quantity, sleep efficiency, and wake after sleep onset
.	More than half of the participants had problems with fatigue at home. Significant correlations were found between sleep/rest fatigue and sleep duration. Factors that affected fatigue were age, gender, and cancer diagnosis. Adolescents had more problems with fatigue than children, and female patients had more problems with fatigue than male patients. Patients with sarcoma had more problems with fatigue than those with leukemia, lymphoma, and other cancer diagnoses. Adolescents slept less than children.	Children and adolescents with cancer have fatigue and sleep problems at home that vary by age, gender, and cancer diagnosis
.	Data from the current study support the need for nurses to provide teaching about fatigue and sleep at home in children and adolescents with cancer. Future studies are needed to examine interventions that may alleviate fatigue and improve sleep at home
.	
26299758	The objectives of this study were to compare individuals with traumatic brain injury (TBI) and healthy controls on neuropsychological tests of attention and driving simulation performance, and explore their relationships with participants' characteristics, sleep, sleepiness, and fatigue. Participants were 22 adults with moderate or severe TBI (time since injury ≥ one year) and 22 matched controls. They completed three neuropsychological tests of attention, a driving simulator task, night-time polysomnographic recordings, and subjective ratings of sleepiness and fatigue. Results showed that participants with TBI exhibited poorer performance compared to controls on measures tapping speed of information processing and sustained attention, but not on selective attention measures. On the driving simulator task, a greater variability of the vehicle lateral position was observed in the TBI group. Poorer performance on specific subsets of neuropsychological variables was associated with poorer sleep continuity in the TBI group, and with a greater increase in subjective sleepiness in both groups. No significant relationship was found between cognitive performance and fatigue. These findings add to the existing evidence that speed of information processing is still impaired several years after moderate to severe TBI. Sustained attention could also be compromised. Attention seems to be associated with sleep continuity and daytime sleepiness; this interaction needs to be explored further.

26298791	Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition.Eleven subjects with MCI (mean age 68.5 ± 7.0 years), 11 patients with mild probable Alzheimer's disease (AD; mean age 72.7 ± 5.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters.	Rapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found.	MCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration.	
26298788	Young women are at a risk of poor sleep, but the extent to which their sleep difficulties remain chronic is not known. Little is also known about the frequency of seeking health care for sleep and satisfaction with that health care. This longitudinal study investigated these issues over nine years in women who reported sleep difficulties over the preceding 12 months.Data from the Australian Longitudinal Study on Women's Health were analysed (N = 9683). Information on self-reported sleep difficulties, help seeking, and health-care satisfaction was obtained from four surveys collected from 2000 (aged 22-27 years) to 2009. Generalized estimating equations were conducted to calculate odds ratios (OR) for the likelihood of women who reported sleep difficulties in 2000 to report sleep difficulties at subsequent surveys.	The prevalence of self-reported sleep difficulties 'often' was consistent at 9.1-10.8%. Women who reported sleep difficulties 'often' in 2000 had a markedly increased risk of continued sleep difficulties 'often' over the subsequent 9 years [2003: OR (95% confidence interval, CI) = 11.07 (8.03-15.27); 2006: 12.19 (8.08-16.88); 2009: 10.70 (7.57-15.12)]. Of women who reported sleep difficulties 'often' in 2000 (N = 981), 45.1% had persistent sleep problems and 21.1% experienced relapse of symptoms. About one-third of women who reported sleep problems 'often' sought help.	Self-reported frequent sleep difficulties in non-depressed young women strongly predicted a continuation of this level of sleep difficulty over a decade, even if help is sought. Current health practice may not be breaking the ongoing chronicity of sleep difficulties in young women.	

26298783	Delayed sleep phase (DSP) in adolescence has been linked to reduced academic performance, but there are few population-based studies examining this association using validated sleep measures and objective outcomes.The youth@hordaland-survey, a large population-based study from Norway conducted in 2012, surveyed 8347 high-school students aged 16-19 years (54% girls). DSP was assessed by self-report sleep measures, and it was operationalized according to the International Classification of Sleep Disorders - Second Edition. School performance (grade point average, GPA) was obtained from official administrative registries, and it was linked individually to health data.	DSP was associated with increased odds for poor school performance. After adjusting for age and gender, DSP was associated with a threefold increased odds of poor GPA (lowest quartile) [odds ratio (OR) = 2.95; 95% confidence interval (CI): 2.03-4.30], and adjustment for sociodemographics and lifestyle factors did not, or only slightly, attenuate this association. Adjustment for nonattendance at school reduced the association substantially, and in the fully adjusted model, the effect of DSP on poor academic performance was reduced to a non-significant level. Mediation analyses confirmed both direct and significant indirect effects of DSP on school performance based on school absence, daytime sleepiness, and sleep duration.	Poor academic performance may reflect an independent effect of underlying circadian disruption, which in part could be mediated by school attendance, as well as daytime sleepiness and short sleep duration. This suggests that careful assessment of sleep is warranted in addressing educational difficulties.	
26298779	To assess sleep-associated aspects of temporomandibular disorder (TMD) with myofascial pain (MP) in the orofacial area of patients and controls.Three hundred five female patients were screened to find 44 participants fulfilling the inclusion criteria, 22 suffering from MP and 22 in a control group. Sleep quality was assessed by use of the Pittsburgh Sleep-Quality-Index (PSQI) and a validated German sleep questionnaire (SF-AR). Tooth wear was assessed and anterior temporalis muscle activity was measured at home for several nights by use of a portable electromyography (EMG) device.	22 patients (45.0 ± 13.6 years) and 22 controls (45.2 ± 9.0 years) were recruited. The PSQI sum-score was 7.5 ± 3.7 for patients and 4.4 ± 3.0 for controls (p = 0.006). The SF-AR showed that 23% of the controls and 14% of the patients were "long sleepers". The overall number of episodes in the two groups was not significantly different (4.10 ± 2.65 versus 4.57 ± 1.99 episodes per hour). However, more patients had temporalis muscle activity possibly related to SB during all four consecutive nights (p = 0.04). According to the International Classification of Sleep Disorders - Third Edition (ICSD-3) criteria, 13.6% of the controls and 71.4% of the patients (p < 0.001) showed SB.	Sleep-associated disturbances, including reduction of sleep quality and greater prevalence of SB and facial pain in the morning, occurred significantly more often among TMD patients. Additionally, SB fluctuated over the nights especially in controls. This should be taken into consideration when the prevalence of SB is assessed by use of EMG.	
26298778	The aim of this study was to determine whether there are differences in sleep between people with and without obsessive-compulsive disorder (OCD), and, if so, whether such differences are associated with comorbid depressive symptoms or other conditioning factors. We conducted a search for articles published until March 2013 in PubMed, Web of Knowledge, PsycINFO, Scopus, Trip Database, Dissertation Abstracts, and OpenSIGLE. We retrieved 9658 records, which were assessed against the inclusion and quality criteria. Six studies were included in the review and four were included in the meta-analysis. They were all cross-sectional studies with medium methodological quality. All studies except one were polysomnographic. The total sample of the meta-analysis consisted of 111 patients with OCD and 141 controls. The synthesis of results showed differences in sleep between people with and without OCD. The presence of comorbid depression was a key issue in the amount and type of differences found. Nevertheless, in order to support these results, longitudinal studies should be conducted with larger sample sizes and different age ranges. 
26295379	Sleep disturbance, pain, anxiety, depression, and low energy/fatigue, the SPADE pentad, are the most prevalent and co-occurring symptoms in the general population and clinical practice. Co-occurrence of SPADE symptoms may produce additive impairment and negatively affect treatment response, potentially undermining patients' health and functioning. The purpose of this paper is to determine: (1) prevalence and comorbidity (ie, clustering) of SPADE symptoms; (2) internal reliability and construct validity of a composite SPADE symptom score derived from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures; and (3) whether improvement in somatic symptom burden represented by a composite score predicted subsequent measures of functional status at 3 and 12 months follow-up.Secondary analysis of data from the Stepped Care to Optimize Pain care Effectiveness study, a randomized trial of a collaborative care intervention for Veterans with chronic pain.	Most patients had multiple SPADE symptoms; only 9.6% of patients were monosymptomatic. The composite PROMIS symptom score had good internal reliability (Cronbach's alpha=0.86) and construct validity and strongly correlated with multiple measures of functional status; improvement in the composite score significantly correlated with higher scores for 5 of 6 functional status outcomes. The standardized error of measurement (SEM) for the composite T-score was 2.84, suggesting a 3-point difference in an individual's composite score may be clinically meaningful.	Brief PROMIS measures may be useful in evaluating SPADE symptoms and overall symptom burden. Because symptom burden may predict functional status outcomes, better identification and management of comorbid symptoms may be warranted.	
26294978	Background and Objective. Depressive state is often associated with such physical symptoms as general weakness, fatigue, tiredness, slowness, reduced activity, low energy, and sleepiness. The involvement of the sleep-wake regulating mechanisms has been proposed as one of the plausible explanations of this association. Both physical depressive symptoms and increased physiological sleep propensity can result from disordered and insufficient sleep. In order to avoid the influence of disordered and insufficient sleep, daytime and nighttime sleepiness were tested in winter depression characterized by normal night sleep duration and architecture. Materials and Methods. A total sample consisted of 6 healthy controls and 9 patients suffered from depression in the previous winter season. Sleep latency was determined across 5 daytime and 4 nighttime 20-min attempts to nap in summer as well as in winter before and after a week of 2-hour evening treatment with bright light. Results and Conclusions. Patients self-reported abnormally lowered well-being, activity, and mood only in winter before the treatment. Physiological sleep propensity was neither abnormal nor linked to significant changes in well-being, activity, and mood following the treatment and change in season. It seems unlikely that the mechanisms regulating the sleep-wake cycle contributed to the development of the physical depressive symptoms. 
26294202	This study's objective was to examine association between sleep duration and sleep quality, and metabolic syndrome (MetS) and its components in Taiwanese male police officers.Male police officers who underwent annual health examinations were invited to join the study and eventually a total of 796 subjects was included in it. The study subjects were divided into 5 groups according to the length (duration) of sleep: < 5, 5-5.9, 6-6.9, 7-7.9 and ≥ 8 h per day, and the global Pittsburgh Sleep Quality Index was used to categorize their sleep quality as good or poor. To analyze the association between sleep problems and MetS, adjusted odds ratio and respective 95% confidence intervals (CI) were computed.	The prevalence of MetS in Taiwanese male police officers was 24.5%. Abdominal obesity had the highest proportion (36.2%) among 5 components of MetS. More than 1/2 of the police officers (52.3%) had poor sleep quality. Police officers with higher scores of sleep disturbances had a higher prevalence of MetS (p = 0.029) and abdominal obesity (p = 0.009). After adjusting for age, low-density lipoprotein cholesterol, smoking status, alcohol drinking habit, physical habitual exercise, snoring and type of shift work, the police officers who slept less than 5 h were 88% more likely to suffer from abdominal obesity than those who slept 7-7.9 h (95% CI: 1.01-3.5). Sleep quality was not associated with MetS and its components.	The police officers who slept less than 5 h were more likely to experience abdominal obesity in Taiwan, and those with higher scores of sleep disturbances had a higher prevalence of MetS and abdominal obesity. It is recommended that police officers with short sleep duration or sleep disturbances be screened for MetS and waist circumference in order to prevent cardiovascular diseases.	
26293583	The anxiolytic effect of Silexan, a patented active substance with an essential oil produced from Lavandula angustifolia flowers, was investigated in patients with anxiety-related restlessness and disturbed sleep. 170 out-patients with a diagnosis of restlessness (ICD-10 R45.1), a Hamilton Anxiety Scale (HAMA) total score ≥18 points and ≥2 points for HAMA items 'Tension' and 'Insomnia' participated in this randomized, double-blind trial and received 80mg Silexan or placebo once daily for 10 weeks. Patients with clinically important other psychiatric or neurological disorders potentially interfering with the assessment of treatment efficacy were excluded. Outcome variables were the HAMA as well as the Pittsburgh Sleep Quality Index (PSQI), the Zung Self-rating Anxiety Scale, a State Check inventory and the Clinical Global Impressions questionnaire. In the Silexan group the HAMA total score decreased from an average of 25.5±6.0 points at baseline to 13.7±7.0 points at treatment end, compared to a decrease from 26.5±6.1 to 16.9±9.8 for placebo, corresponding to decreases of 12.0 and 9.3 points (marginal means), respectively (group difference: p=0.03, ANCOVA with factor treatment and baseline value as covariate). In all outcome measures the treatment effect of Silexan was more pronounced than with placebo. According to the HAMA, 48.8% and 33.3% of the patients were responders (Silexan, placebo; reduction ≥50%; p=0.04) and 31.4% and 22.6% achieved remission (HAMA<10; p=0.20). 33.7% (Silexan) and 35.7% (placebo) of the participants reported adverse events. The study confirms the calming and anxiolytic efficacy of Silexan. 
26291524	Poor sleep quality is a common health problem for coronary artery bypass graft patients, however few studies have evaluated sleep quality during the period immediately following hospital discharge.The aim of this study was to investigate changes in sleep quality and emotional correlates in coronary artery bypass graft patients in Taiwan at 1 week and 1 month after hospital discharge.	We used a descriptive correlational design for this study. One week after discharge, 87 patients who had undergone coronary artery bypass surgery completed two structured questionnaires: the Pittsburgh Sleep Quality Index and the Hospital Anxiety and Depression Scale. Three weeks later (1 month after discharge) the patients completed the surveys again. Pearson correlations, t-tests, ANOVA and linear multiple regression analysis were used to analyze the data.	A majority of the participants had poor sleep quality at 1 week (82.8%) and 1 month (66.7%) post-hospitalization, based on the global score of the Pittsburgh Sleep Quality Index. Despite poor sleep quality at both time-points the sleep quality at 1 month was significantly better than at 1-week post hospitalization. Poorer sleep quality correlated with older age, poorer heart function, anxiety and depression. The majority of participants had normal levels of anxiety at 1 week (69.0%) and 1 month (88.5%) as measured by the Hospital Anxiety and Depression Scale. However, some level of depression was seen at 1 week (78.1%) and 1 month (59.7%). Depression was a significant predictor of sleep quality at 1 week; at 1 month after hospital discharge both anxiety and depression were significant predictors of sleep quality.	Sleep quality, anxiety and depression all significantly improved 1 month after hospital discharge. However, more than half of the participants continued to have poor sleep quality and some level of depression. Health care personnel should be encouraged to assess sleep and emotional status in patients after coronary artery bypass surgery and offer them appropriate management strategies to improve sleep and reduce anxiety and depression.	
26289935	Nonmotor symptoms in dystonia are increasingly recognized to impair the quality of life. The primary objective of this study was to determine the prevalence of fatigue and sleep disturbances in dystonia and to ascertain their impact on quality of life using standardized questionnaires.Dystonia patients presenting to a Botulinum toxin clinic were prospectively administered Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory (MFI), Epworth Sleepiness Scale (ESS) and Parkinson's Disease Sleep Scale (PDSS) for assessment of fatigue and sleep disturbances. Health-related Quality of life (HRQOL) was determined using MOS SF-36 scale and depressive symptoms were assessed using the Beck Depression Inventory II.	Ninety-one patients with dystonia participated (66 women, 25 men, mean age 60 ± 17 years). Nine subjects had generalized dystonia, 18 segmental dystonia and 64 had focal dystonia. Moderate to severe fatigue was present in 43% of the cohort (FSS), excessive daytime somnolence in 27% (ESS) and other sleep disturbances in 26% (PDSS). FSS and MFI scores correlated significantly with HRQOL even when controlled for depression and sleep disturbances. Excessive daytime somnolence and nocturnal sleep disturbances correlated significantly with the HRQOL; however, these effects were not seen for daytime somnolence when controlled for depression. Psychometric testing found adequate reliabilities and convergent validities for both fatigue and sleep scales.	Fatigue and sleep disturbances revealed high prevalence rates in this large, first of its dystonia study. They negatively impacted the quality of life even when controlled for comorbid depression.	

26289259	Sleep disturbances are common in cancer patients, but little is known about the complex interplay between the background psychological profile, coping with health stressors capacities and psychological distress in the formation of sleep difficulties in colorectal cancer.To study the course and to identify psychological predictors of sleep difficulties in early non-metastatic colorectal cancer patients over a one-year period.	In this 1-year prospective study, we assessed in 84 early non-metastatic colorectal cancer patients the association of psychological distress (SCL-90-R), sense of coherence (SOC-29), and defense styles (Defense Style Questionnaire) with sleep difficulties (SCL-90-R) in multiple regression models. Eighty-two patients with breast cancer and 50 patients with cancer of unknown primary site served as disease controls, and 84 matched for age and sex alleged healthy individuals served as healthy controls.	Colorectal cancer patients presented more sleep difficulties compared to healthy participants but fewer than patients with breast cancer and cancer of unknown primary site. Colorectal cancer patients' trouble falling asleep (p = 0.033) and wakening up early in the morning (p < 0.001) deteriorated over time. Sleep that was restless or disturbed was independently associated with low SOC (p = 0.046) and maladaptive defenses (p = 0.008). Anxiety symptoms (p < 0.001) predicted deterioration in trouble falling asleep, while depressive symptoms (p = 0.022) and self-sacrificing defense style (p = 0.049) predicted deterioration in wakening up early in the morning.	Psychological parameters and coping with health stressors capacities are independently associated with sleep difficulties in colorectal cancer patients, indicating the need for psychological interventions aiming at improving adjustment to the disease.	
26289164	Cluster headache is characterized by unilateral attacks of severe pain accompanied by cranial autonomic features. Apart from these there are also sleep-related complaints and strong chronobiological features. The interaction between sleep and headache is complex at any level and evidence suggests that it may be of critical importance in our understanding of primary headache disorders. In cluster headache several interactions between sleep and the severe pain attacks have already been proposed. Supported by endocrinological and radiological findings as well as the chronobiological features, predominant theories revolve around central pathology of the hypothalamus. We aimed to investigate the clinical presentation of chronobiological features, the presence of concurrent sleep disorders and the relationship with particular sleep phases or phenomena, the possible role of hypocretin as well as the possible involvement of cardiac autonomic control. We conducted a questionnaire survey on 275 cluster headache patients and 145 controls as well an in-patient sleep study including 40 CH-patients and 25 healthy controls. The findings include: A distinct circannual connection between cluster occurrence and the amount of daylight, substantially poorer sleep quality in patients compared to controls which was present not only inside the clusters but also outside, affected REM-sleep in patients without a particular temporal connection to nocturnal attacks, equal prevalence of sleep apnea in both patient and control groups, reduced levels of hypocretin-1 in the cerebrospinal fluid of patients and finally a blunted response to the change from supine to tilted position in the head-up tilt table test indicating a weakened sympathoexcitatory or stronger parasympathetic drive. Overall, these findings support a theory of involvement of dysregulation in hypothalamic and brainstem nuclei in cluster headache pathology. Further, it is made plausible that the headache attacks are but one aspect of a more complex syndrome of central dysregulation manifesting as sleep-related complaints, sub-clinical autonomic dysregulation and of course the severe attacks of unilateral headache. Future endeavors should focus on pathological changes which persist in the attack-free periods but also heed the possibility of long-lived, cluster-induced pathology.
26287582	Orexin, which is also called as hypocretin (Hcrt), a product of the prepro-orexin (pp-orexin//Hcrt) gene, affects various physiological and behavioral functions, such as the sleep-wake cycle and appetite. The developmental changes in the hypothalamic mRNA levels of pp-prexin and the orexin receptors OX1R and OX2R and their sensitivity to fasting were evaluated in both male and female rats. During development, hypothalamic pp-orexin/Hcrt mRNA expression increased in both male and female rats, whereas hypothalamic OX1R mRNA expression decreased in both sexes. In addition, hypothalamic OX2R mRNA expression increased in male rats, but did not change in female rats. Fasting did not affect hypothalamic pp-orexin/Hcrt mRNA expression in either sex. Hypothalamic OX1R mRNA expression was increased by fasting in the prepubertal period (postnatal days 20 and 30) in female rats, but was not affected by fasting in males. In male rats, hypothalamic OX2R mRNA expression was decreased by fasting during the neonatal period (postnatal day 10), but not the prepubertal period (postnatal days 20 and 30). In females, hypothalamic OX2R mRNA expression was also decreased by fasting; however, the fasting-induced downregulation of hypothalamic OX2R expression persisted until postnatal day 20. These results indicate that the developmental patterns of components of the orexin system and their sensitivity to fasting during the neonatal and prepubertal periods only differ slightly between the sexes. These differences might be involved in the development of some physiological and behavioral functions. 
26285591	The present study determined whether EEG and/or EMG recordings could be used to reliably define activity states in the Brazilian black and white tegu lizard (Tupinambis merianae) and then examined the interactive effects of temperature and activity states on strategies for matching O2 supply and demand. In a first series of experiments, the rate of oxygen consumption (VO2), breathing frequency (fR), heart rate (fH), and EEG and EMG (neck muscle) activity were measured in different sleep/wake states (sleeping, awake but quiet, alert, or moving). In general, metabolic and cardio-respiratory changes were better indictors of the transition from sleep to wake than were changes in the EEG and EMG. In a second series of experiments, the interactive effects of temperature (17, 27 and 37 °C) and activity states on fR, tidal volume (VT), the fraction of oxygen extracted from the lung per breath (FIO2-FEO2), fH, and the cardiac O2 pulse were quantified to determine the relative roles of each of these variables in accommodating changes in VO2. The increases in oxygen supply to meet temperature- and activity-induced increases in oxygen demand were produced almost exclusively by increases in fH and fR. Regression analysis showed that the effects of temperature and activity state on the relationships between fH, fR and VO2 was to extend a common relationship along a single curve, rather than separate relationships for each metabolic state. For these lizards, the predictive powers of fR and fH were maximized when the effects of changes in temperature, digestive state and activity were pooled. However, the best r(2) values obtained were 0.63 and 0.74 using fR and fH as predictors of metabolic rate, respectively.
26285462	Depression is a major public health problem. According to the World Health Organization (OMS), depression is currently the second cause of disability in developing countries. Depression is also one of the most frequent mental illnesses. When treating depression, the main objective is to achieve complete remission and to prevent recurrence. Unfor-tunately, in clinical practice, this aim is particularly difficult to reach. Indeed, in clinical trials and in naturalistic studies, remission levels are rather low. The challenge is to individualize the treatment of depression taking account clinical specificities, but also advances in the field of biological and genetic research. Today, intense psychiatric research tries to discover biomarkers to predict treatment response. Because individuals are highly different from a biological, psychological and sociological point of view, more personalized therapeutic approaches are recommended.
26285110	Portable and automated sleep monitoring technology is becoming widely available to consumers, and one wireless system (WS) has recently surfaced as a research tool for sleep and sleep staging assessment outside the hospital/laboratory; however, previous research findings indicate low sensitivity for wakefulness detection. Because difficulty discriminating between wake and sleep is likely to affect staging performance, we sought to further evaluate the WS by comparing it to the gold-standard polysomnography (PSG) and actigraphy (ACT) for overall sleep/wakefulness detection and sleep staging, within high and low sleep efficiency sleepers.Twenty-nine healthy adults (eight females) underwent concurrent WS, PSG, and ACT assessment in an overnight laboratory study. Epoch-by-epoch agreement was determined by comparing sleep/wakefulness decisions between the WS to both PSG and ACT, and for detection of light, deep, and rapid eye movement (REM) sleep stages between the WS and PSG.	Sensitivity for wakefulness was low (40%), and an overestimation of total sleep time and underestimation of wake after sleep onset was observed. Prevalence and bias adjusted kappa statistic indicated moderate-to-high agreement between the WS and PSG for sleep staging. However, upon further inspection, WS performance varied by sleep efficiency, with the best performance during high sleep efficiency.	The benefit of the WS as a sleep monitoring device over ACT is the ability to assess sleep stages, and our findings suggest this benefit is only realized within high sleep efficiency. Care should be taken to collect data under conditions where this is expected.	
26285003	To test a collaborative care model for interfacing sleep specialists with primary care providers to enhance patients' sleep disorders management.This study used a randomized, parallel group, clinical intervention trial design. A total of 137 adult (29 women) VA outpatients with sleep complaints were enrolled and randomly assigned to (1) an intervention (INT) consisting of a one-time consultation with a sleep specialist who provided diagnostic feedback and treatment recommendations to the patient and the patient's primary care provider; or (2) a control condition consisting of their usual primary care (UPC). Provider-focused outcomes included rates of adherence to recommended diagnostic procedures and sleep-focused interventions. Patient-focused outcomes included measures taken from sleep diaries and actigraphy; Pittsburgh Sleep Quality Index (PSQI) scores; and self-report measures of sleepiness, fatigue, mood, quality of life, and satisfaction with health care.	The proportions of provider-initiated sleep-focused interventions were significantly higher in the INT group than in the UPC group for polysomnography referrals (49% versus 6%; P < 0.001) and mental health clinic referrals (19% versus 6%; P = 0.02). At the 10-mo follow up, INT recipients showed greater estimated mean reductions in diary total wake time (-17.0 min; 95% confidence interval [CI]: -30.9, -3.1; P = 0.02) and greater increases in sleep efficiency (+3.7%; 95% CI: 0.8, 6.5; P = 0.01) than did UPC participants. A greater proportion of the INT group showed ≥ 1 standard deviation decline on the PSQI from baseline to the 10-mo follow-up (41% versus 21%; P = 0.02). Moreover, 69% of the INT group had normal (≤ 10) Epworth Sleepiness Scale scores at the 10-mo follow-up, whereas only 50% of the UPC group fell below this clinical cutoff (P = 0.03).	A one-time sleep consultation significantly increased healthcare providers' attention to sleep problems and resulted in benefits to patients' sleep/wake symptoms.	
26283658	The periaqueductal gray region (PAG) is one of several brain areas identified to be vulnerable to structural and functional change following peripheral nerve injury. Sciatic nerve constriction injury (CCI) triggers neuropathic pain and three distinct profiles of changes in complex behaviours, which include altered social and sleep-wake behaviours as well as changes in endocrine function. The PAG encompasses subgroups of the A10 dopaminergic and A6 noradrenergic cell groups; the origins of significant ascending projections to hypothalamic and forebrain regions, which regulate sleep, complex behaviours and endocrine function. We used RT-PCR, western blots and immunohistochemistry for tyrosine hydroxylase to determine whether (1) tyrosine hydroxylase increased in the A10/A6 cells and/or; (2) de novo synthesis of tyrosine hydroxylase, in a 'TH-naïve' population of ventral PAG neurons characterized rats with distinct patterns of behavioural and endocrine change co-morbid with CCI evoked-pain.Evidence for increased tyrosine hydroxylase transcription and translation in the constitutive A10/A6 cells was found in the midbrain of rats that showed an initial 2-3 day post-CCI, behavioural and endocrine change, which recovered by days 5-6 post-CCI. Furthermore these rats showed significant increases in the density of TH-IR fibres in the vPAG.	Our data provide evidence for: (1) potential increases in dopamine and noradrenaline synthesis in vPAG cells; and (2) increased catecholaminergic drive on vPAG neurons in rats in which transient changes in social behavior are seen following CCI. The data suggests a role for dopaminergic and noradrenergic outputs, and catecholaminergic inputs of the vPAG in the expression of one of the profiles of behavioural and endocrine change triggered by nerve injury.	
26282891	Orexins (A and B) are hypothalamic peptides that interact with OX1 and OX2 receptors and are involved in the sleep/wake cycle. We previously demonstrated that OX1 receptors are highly expressed in colon cancer tumours and colonic cancer cell lines where orexins induce apoptosis and inhibit tumour growth in preclinical animal models. The present study explored the structure-function relationships of orexin-B and OX1 receptors.The contribution of all orexin-B residues in orexin-B-induced apoptosis was investigated by alanine scanning. To determine which OX1 receptor domains are involved in orexin-B binding and apoptosis, a 3D model of OX1 receptor docked to the orexin-B C-terminus (AA-20-28) was developed. Substitution of residues present in OX1 receptor transmembrane (TM) domains by site-directed mutagenesis was performed.	Alanine substitution of orexin-B residues, L(11) , L(15) , A(22) , G(24) , I(25) , L(26) and M(28) , altered orexin-B's binding affinity. Substitution of these residues and of the Q(16) , A(17) , S(18) , N(20) and T(27) residues inhibited apoptosis in CHO-S-OX1 receptor cells. The K(120) , P(123) , Y(124) , N(318) , K(321) , F(340) , T(341) , H(344) and W(345) residues localized in TM2, TM3, TM6 and TM7 of OX1 receptors were shown to play a role in orexin-B recognition and orexin-B/OX1 receptor-induced apoptosis.	The C-terminus of orexin-B (i) plays an important role in its pro-apoptotic effect; and (ii) interacts with some residues localized in the OX1 receptor TM. This study defines the structure-function relationship for orexin-B recognition by human OX1 receptors and orexin-B/OX1 receptor-induced apoptosis, an important step for the future development of new agonist molecules.	
26281947	Cognitive-behavioral therapy (CBT) is effective in reducing the frequency and intensity of chronic pain in adolescents. However, CBT seems not to be considered acceptable by all adolescents. The main aim of our study was therefore to evaluate the effects of guided Internet-delivered self-help for adolescents with chronic pain. Adolescents (N = 69) were assessed on the outcome measures of pain, coping, disability, catastrophizing, rewarding of pain behavior by parents, and quality of life. Measures were taken 7 weeks before treatment and at pretreatment, posttreatment, and 3-month follow-up. Multilevel modeling was used for longitudinal analysis of the data. Pain intensity, interference caused by pain, rewarding of pain behavior by parents, and sleep problems significantly decreased during the intervention. The quality-of-life scores for pain, general behavior, mental health, family activities, and health changes also significantly improved during the intervention. With regard to coping, only problem-focused avoidance behavior significantly increased. No significant differences were found for pain-related disability and pain catastrophizing. Contrary to expectations, guided Internet-delivered self-help for chronic pain is difficult to use in adolescents, resulting in treatment attrition and loss to follow-up.Dutch Trial Register NTR1926.	The results of this trial suggest that Internet-based self-management is effective in decreasing pain intensity in adolescents with chronic pain. Because the intervention is grounded in CBT, we expect the underlying mechanism to be a change in self-management skills and in the ability of challenging dysfunctional thoughts.	

26279176	Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers. 
26279058	Up to 80 % of individuals with schizophrenia spectrum disorders experience sleep disturbances, which impact physical and mental health, as well as quality of life. In this paper, we review and integrate emerging literature, published between 2012 and 2014, regarding approaches to diagnosis and treatment of major sleep disorders for people with schizophrenia spectrum disorders, including insomnia, obstructive sleep apnea (OSA), circadian rhythm dysfunction, and restless legs syndrome (RLS). We advocate for (1) the need to evaluate the utility of nonpharmacological approaches in people with schizophrenia spectrum disorders; (2) documentation of guidelines to assist providers in clinically tailoring such interventions when their clients experience positive, negative, and/or cognitive symptoms; (3) research on the best ways providers can capitalize on clients' self-identified needs and motivation to engage in sleep treatments through shared decision making; and (4) the importance of investigating whether and how mental health and sleep treatment services should be better connected to facilitate access for people with schizophrenia spectrum disorders. Assessment and tailored treatment of sleep disorders within mental health treatment settings has the potential to reduce sleep problems and improve functioning, quality of life, and recovery of this population. 

26278274	Various causes have been suggested for multiple sclerosis (MS) related fatigue. Hypothalamus-brainstem fibres play a role in sleep-wake regulation and in hypothalamic deactivation during inflammatory states. Hence, they may play a role for experiencing fatigue by changing bottom-up hypothalamic activation.Multiple sclerosis patients with and without self-reported cognitive fatigue and healthy controls were analysed with respect to the integrity of hypothalamus-brainstem fibres using diffusion-tensor imaging based tractography, focusing on the anterior, medial and posterior hypothalamic areas, controlling for clinical impairment and excluding participants with depressive mood.	Multiple sclerosis patients without self-reported cognitive fatigue showed increased axial and radial diffusivity levels specifically for fibres connecting the right posterior hypothalamus with the right locus coeruleus, but not for the medial hypothalamus and the corpus callosum. Moreover, there were no differences between MS patients with and without fatigue in brain atrophy and lesion load, which could explain our results.	Multiple sclerosis patients not experiencing fatigue show increased axial and radial diffusivity for fibres connecting the posterior hypothalamus and the brainstem, which might prevent bottom-up activation of the posterior hypothalamus and therefore downregulation of structures responsible for wakefulness and exploratory states of mind.	
26277741	The brain is a target of environmental toxic pollutants that impair cerebral functions. Uranium is present in the environment as a result of natural deposits and release by human applications. The first part of this review describes the passage of uranium into the brain, and its effects on neurological functions and cognitive abilities. Very few human studies have looked at its cognitive effects. Experimental studies show that after exposure, uranium can reach the brain and lead to neurobehavioral impairments, including increased locomotor activity, perturbation of the sleep-wake cycle, decreased memory, and increased anxiety. The mechanisms underlying these neurobehavioral disturbances are not clearly understood. It is evident that there must be more than one toxic mechanism and that it might include different targets in the brain. In the second part, we therefore review the principal mechanisms that have been investigated in experimental models: imbalance of the anti/pro-oxidant system and neurochemical and neurophysiological pathways. Uranium effects are clearly specific according to brain area, dose, and time. Nonetheless, this review demonstrates the paucity of data about its effects on developmental processes and the need for more attention to the consequences of exposure during development. 
26276926	The objective of the study was to evaluate the prevalence of sleep continuity disorders in women during menopausal transition, to evaluate the relationship between disturbances of sleep continuity and the severity of menopausal syndrome and the occurrence of various symptoms of this syndrome, as well as to evaluate the association between the presence of sleep disturbances and serum concentrations of gonadotropins, prolactin and sex hormones.Consecutive 140 women (mean age 54.4 ± 4.7 years) searching for the treatment in the Clinic for Gynaecological Endocrinology who reported symptoms of menopausal syndrome were investigated. The type and severity of disturbances of sleep continuity were evaluated using a survey based on the sleep related questions from Hamilton Depression Rating Scale. The severity of symptoms of menopausal syndrome was assessed using the Kupperman Index. The concentration of the following hormones in blood serum was tested: FSH, LH, 17β-estradiol, PRL, total testosterone, DHEAS and SHBG.	Disturbances of sleep continuity were a prevalent complaint in the studied group of women. Difficulties in falling asleep were found in 57.8% of women, difficulties in maintaining sleep in 70%, waking up too early in 60.7%. The severity of all three types of sleep continuity disturbances was related to the severity of menopausal syndrome as measured with Kupperman Index (Spearman correlation coefficient r = 0.63, r = 0.61, r = 0.52, respectively; p < 0.001). Difficulties in maintaining sleep were negatively correlated with the concentration of FSH (r = - 0.19; p < 0.05), 17β-estradiol (r = - 0.19; p < 0.05) and SHBG (r = - 0.18; p < 0.05), difficulties in falling asleep negatively correlated with the concentration of 17β-estradiol in the blood serum (r = - 0.19; p < 0.05).	Sleep continuity disturbances are frequently reported by women during the menopausal transition. Interventions aimed at reducing the symptoms of menopausal syndrome should be considered as important action to improve sleep quality in this population of patients.	
26276922	The aim of the study was to determine the level of life satisfaction and the various dimensions of self-esteem of pierced or tattooed people, and evaluate their mental health, compared to those without similar body modifications.The study was conducted on a sample of 449 people aged 16-58 years (mean age 26.7 ± 6.35), of whom 308 had body modifications: tattoo (n = 90), body piercings in places other than the ear lobe (n = 53), or both tattoos and piercings (n = 165). The control group consisted of 141 people without such modifications. The participants completed a questionnaire concerning their socio-demographic status, as well as the following psychological tests: The Satisfaction with Life Scale (SWLS), Multidimensional Self-Esteem Inventory (MSEI) and General Health Questionnaire (GHQ-28).	Our findings show no significant differences in terms of life satisfaction between the group with tattoos or piercings and the control group. People with body modifications were characterized by higher self-esteem, with regard to their competence and leadership abilities. They also display fewer symptoms of social impairment and sleep disorders than the control group.	Tattoos and piercings should not be considered as indicators of psychopathology.	
26276917	Analysis of changes in prevalence and intensity of suicidal ideation (SI) in patients who underwent an intensive psychotherapy conducted in integrative approach with predominance of psychodynamic approach in the Day Hospital for Neurotic and Behavioral Disorders.Symptom checklist KO"O" and Life Inventory completed by 461 women and 219 men who were treated in the day hospital due to neurotic, behavioral and personality disorders in 2005-2013.	Patients initially reporting SI showed greater than others global intensity of the neurotic symptoms (p < 0.001 for both sexes) and greater intensity in almost all the neurotic symptoms scales. Improvement (elimination or reduction of intensity) in terms of SI was observed in 84.3% of women and 77.5% of men. The prevalence of SI-reporting patients decreased substantially from 29.1% to 10.2% in women and from 36.5% to 13.7% in men.	The patients reporting SI before the commencement of psychotherapy constituted a large part of the studied population - approximately 1/3. They showed greater intensity of neurotic symptoms than those who were not reporting SI. Intensive psychotherapy in the day hospital was characterized by high effectiveness in terms of reduction and elimination of SI. Prevalence of SI in both women and men until the end of therapy decreased almost three times. Cases of improvement in terms of SI were several times more frequent than cases of deterioration in terms of SI (increase in its intensity or its occurrence at the end of therapy). Etiopathogenesis of SI and its methods of treatment require further research.	
26273194	Anxiety disorders are among the most common psychiatric illnesses, with generalized anxiety disorder (GAD) being one of the most common. Sleep disturbances are highly prevalent in GAD patients. While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials, mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin. Thus, the objective of this study was to model the longitudinal latent effect of pregabalin or usual care (UC) therapies on changes in sleep in outpatients with GAD under routine clinical practice.Male and female GAD outpatients, aged 18 years or above, from a 6-month prospective noninterventional trial were analyzed. Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms (assessed with Hamilton Anxiety Scale) and sleep disturbances (assessed with Medical Outcomes Study-Sleep Scale [MOS-S]) were estimated by a conditional latent curve model applying structural equation modeling.	A total of 1,546 pregabalin-naïve patients were analyzed, 984 receiving pregabalin and 562 UC. Both symptoms of anxiety and sleep disturbances were significantly improved in both groups, with higher mean (95% confidence interval) score reductions in subjects receiving pregabalin: -15.9 (-15.2; -16.6) vs -14.5 (-13.5; -15.5), P=0.027, in Hamilton Anxiety Scale; and -29.7 (-28.1; -31.3) vs -24.0 (-21.6; -26.4), P<0.001, in MOS-S. The conditional latent curve model showed that the pregabalin effect on sleep disturbances was significant (γ =-3.99, P<0.001), after discounting the effect on reduction in anxiety symptoms. A mediation model showed that 70% of the direct effect of pregabalin on sleep remained after discounting the mediated effect of anxiety improvement.	A substantial proportion of the incremental improvements in anxiety-related sleep disturbances with pregabalin vs UC were explained by its direct effect, not mediated by improvements in anxiety symptoms.	
26271951	Inflammation and oxidative stress are involved in the process of chronic renal failure (CRF). CRF patients show indication of sleep disturbances, and the melatonin rhythm, which modulates sleep, is abnormal in these patients; however, it is still unclear whether inflammation could be related to the blockage of melatonin production and sleep disturbances in this population. The aim of this study was to characterize and correlate sleep, the melatonin rhythm, and the levels of the inflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-6 in patients with CRF and controls.Sleep was evaluated by the "Sleep Quality Index Pittsburgh" (PSQI) questionnaire, and melatonin and cytokine contents in saliva and blood samples, respectively, were analyzed by ELISA.	The CRF group scored higher on the global PSQI, which indicates a lower sleep quality and a higher prevalence of sleep disorders, than the control group. The CRF individuals also showed lower melatonin content than the control groups, both during the day and at night, and lacked rhythmicity in melatonin production. The CRF group also showed higher contents of TNF and IL-6 than the control group and a negative correlation between TNF and melatonin content.	These results suggest that the sleep disorders observed in the CRF group were probably related to the low production of melatonin observed in this population. The high level of TNF, as previously demonstrated in other pathologies, is probably involved in this blockage of melatonin production in CRF.	
26271816	This cross-sectional study evaluates the prevalence and factors associated with sleep disturbances in French adult HIV-infected outpatients. Patients fullfilled a self-administered questionnaire on their health behavior, sleep attitudes (Pittsburgh sleep quality index, PSQI), quality of life and depression; 1354 patients were enrolled. Median sleeping time was 7 h. Poor sleep quality was observed in 47 % of the patients, and moderate to serious depressive symptoms in 19.7 %. Factors significantly associated with sleep disturbances were depression, male gender, active employment, living single, tobacco-smoking, duration of HIV infection, nevirapine or efavirenz-including regimen. Prevalence of poor sleepers is high in this HIV adult outpatient population. Associated factors seem poorly specific to HIV infection and more related to social and psychological status. Taking care of these disturbances may prove to be an effective health management strategy.
26271474	The relationship between sleep quality and pain has been studied in populations with chronic pain and in nonclinical populations using experimental paradigms. Little is known about the familial contributions to this relationship. This study examines self-reported sleep quality and pain in a nonclinical sample and to explore familial (i.e., shared genetic and common family environment) confounding in those relationships.Cross-sectional.	Ninety nine community-based female twin pairs (N = 198) with a mean age of 29 years; 72% monozygotic.	The short form McGill Pain Questionnaire (McGill), a visual analog scale (VAS), a body map, and the Pittsburgh Sleep Quality Index (PSQI) measured self-reported pain and sleep quality. Mixed model regression adjusted for age was used to examine relationships between the pain indices and PSQI in overall and within-pair models.	Higher PSQI total scores were significantly associated with higher scores across the McGill sensory (B = 0.37, p < 0.001), affective (B = 0.16, p < 0.001), total scores (B = 0.54, p < 0.001), the VAS (B = 2.41, p < 0.001), and number of sites with any pain on the body map (B = 0.42, p = 0.001). All of these associations were diminished and rendered nonsignificant in within-pair analyses that accounted for genetic and familial factors (all p's ≥ 0.01; Bonferroni α = 0.01).	These findings support an association between poor sleep quality and pain and suggest that this relationship may be confounded by shared genetic and environmental factors, which could elucidate biological mechanisms that underlie the development and maintenance of pain and sleep problems.	
26270951	Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children.We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two reviewers will independently screen titles and abstracts for inclusion, followed by full-text screening of potentially relevant articles to determine final inclusion. Data synthesis will be performed at three levels: (1) an analysis of the number, publication type, publication year, and country of publication of the studies; (2) a summary of the study designs, outcomes measures used; (3) a thematic analysis of included studies by subgroups.	This study will provide a wide and rigorous overview of the evidence on the use of long-term NIV in children and provide critical information for healthcare professionals and policymakers to better care for this group of children. We will disseminate our findings through conference proceedings and publications, and evaluate the results for further systematic reviews and meta-analyses.	
26270646	An increasing number of grandparents in rural USA are serving as primary caregivers for their grandchildren because of parental incarceration, addiction, joblessness, or illness. Low-income, African American women from the South are overrepresented in this growing population. There is a paucity of research exploring the challenges faced by rural grandparent caregivers, and past studies have not explicitly addressed the potential consequences of rural grandparent caregiving for health. The purpose of this qualitative study was to explore grandparent caregiving among rural, low-income, African American grandmothers in a community in the American South, and to identify challenges to health that arose in that context. McLeroy's social ecological model (SEM) was used to examine these challenges at multiple levels of influence.This qualitative interview-based study was conducted in a high-poverty community in rural Georgia. In-depth interviews were conducted with African American grandparent caregivers and key informants from local community-based organizations. A key informant assisted in identifying initial interview participants, and then snowball sampling was used to recruit additional participants. Interview questions were grouped under five domains (intrapersonal, interpersonal, community, organizational, and policy), according to the levels of the SEM. Iterative content analysis of interview transcripts was utilized. Transcripts were coded to identify text segments related to each domain of the SEM, which were grouped together for analysis by domain. Reflexive memo-writing aided in development of themes, and data quality was assessed using Lincoln and Guba's trustworthiness criteria.	Rural African American grandparent caregivers faced a range of challenges to health. Direct physical challenges included chronic pain that interfered with sleep and daily functioning, mobility issues exacerbated by child care, and the pressure of managing their own medical conditions as well as their grandchildren's. Financial scarcity added to their vulnerability to poor health outcomes, especially when caregivers would forego purchase of medications or visits to the doctor because of expenses related to their grandchildren. In addition, lack of child care made health appointments and hospitalizations logistically difficult. Emotional strain was common as grandparent caregivers struggled to protect their grandchildren in communities where rates of drug use, HIV, and incarceration were high. Caregivers worried about their mortality and the related consequences for their grandchildren. Chronic stress, which is linked to a number of poor health outcomes, was self-reported by most rural grandparent caregivers.	In this study, the challenges of rural grandparent caregiving among African American women posed multiple threats to health and wellbeing. Further research is needed, in different rural contexts and with different caregiver populations, to more thoroughly examine the health risks of grandparent caregiving. In addition, the development of multi-faceted interventions and programs will be critical to meeting the needs of rural grandparent caregivers. A few models for such programs exist, although resource shortfalls have often limited their impact.	
26269217	Various intestinal functions exhibit circadian rhythmicity. Disruptions in these rhythms as in shift workers and transcontinental travelers are associated with intestinal discomfort. Circadian rhythms are controlled at the molecular level by core clock and clock-controlled genes. These clock genes are expressed in intestinal cells, suggesting that they might participate in the circadian regulation of intestinal functions. A major function of the intestine is nutrient absorption. Here, we will review absorption of proteins, carbohydrates, and lipids and circadian regulation of various transporters involved in their absorption. A better understanding of circadian regulation of intestinal absorption might help control several metabolic disorders and attenuate intestinal discomfort associated with disruptions in sleep-wake cycles.
26266918	Complex interrelations exist between the master central clock, located in the suprachiasmatic nuclei of the hypothalamus, and several peripheral clocks, such as those found in different immune cells of the body. Moreover, external factors that are called 'timekeepers', such as light/dark and sleep/wake cycles, interact with internal clocks by synchronizing their different oscillation phases. Chronobiology is the science that studies biologic rhythms exhibiting recurrent cyclic behavior. Circadian rhythms have a duration of approximately 24 h and can be assessed through chronobiologic analysis of time series of melatonin, cortisol, and temperature. Critically ill patients experience severe circadian deregulation due to not only the lack of effective timekeepers in the intensive care unit (ICU) environment but also systemic inflammation. The latter has been found in both animal and human studies to disrupt circadian rhythmicity of all measured biomarkers. The aims of this article are to describe circadian physiology during acute stress and to discuss the effects of ICU milieu upon circadian rhythms, in order to emphasize the value of considering circadian-immune disturbance as a potential tool for personalized treatment. Thus, besides neoplastic processes, critical illness could be linked to what has been referred as 'chronomics': timing and rhythm. In addition, different therapeutic perspectives will be presented in association with environmental approaches that could restore circadian connection and hasten physical recovery. 
26265731	Sleep and melatonin have been associated with healthy aging. In this study, we examine the association between melatonin levels and sleep among older men.Cross-sectional study of a community-dwelling cohort of 2,821 men aged 65 years or older recruited from six U.S. centers. First morning void urine samples were collected to measure melatonin's major urinary metabolite, 6-sulfatoxymelatonin (aMT6s). We also assessed objective and subjective sleep parameters. We used logistic regression models to calculate multivariate (MV) odds ratios (ORs), and 95% confidence intervals (CIs) adjusted for important demographic variables and comorbidities.	In the overall sample, the only significant finding in fully adjusted models was that aMT6s levels were inversely associated with subjectively measured daytime sleepiness (sleepiness mean score of 5.79 in the top aMT6s quartile, and 6.26 in the bottom aMT6s quartile, MV OR, 1.32; 95% CI, 0.95-1.84; p trend ≤ .02). When restricting to men without β-blocker use (a known melatonin suppressant), aMT6s levels were significantly associated with shorter sleep time, that is, less than 5 hours (MV OR, = 1.90; 95% CI, 1.21-2.99; p trend = .01), and worse sleep efficiency, that is, less than 70% (MV OR, 1.58; 95% CI, 1.28-2.65; p trend < .001). aMT6s were not associated with subjective sleep quality or respiratory disturbance in any of our analyses.	Lower nocturnal melatonin levels were associated with worsened daytime sleepiness, sleep efficiency, and shorter sleep time in older men. The role of circadian interventions, and whether melatonin levels are a modifiable risk factor for poor sleep in older men, warrants further study.	
26264411	Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of poor subjective sleep quality with glycaemic control, self-care and daytime functioning; (3) possible risk markers for poor sleep quality.In a cross-sectional study, Dutch adults with type 1 (n=267) or type 2 diabetes (n=361) completed an online survey, including the Pittsburgh Sleep Quality Index (PSQI), socio-demographic, clinical, self-care and psychological measures.	Poor sleep quality (PSQI-score >5) was reported by 31% of adults with type 1 and 42% of adults with type 2 diabetes. Participants with good and poor sleep quality did not differ in self-reported HbA1c or the frequency of meeting lifestyle recommendations. Poor sleep quality was related to a higher self-care burden and higher levels of daytime sleepiness, fatigue, depressive and anxiety symptoms, and diabetes-specific distress. In multivariable logistic regression analyses examining risk markers, poor sleep quality was associated with depressive symptoms in adults with type 1 (OR=1.39, 95% CI 1.25-1.54) and type 2 diabetes (OR=1.31, 1.16-1.47), and with being female in those with type 2 diabetes (OR=2.72, 1.42-5.20).	Poor subjective sleep quality is prevalent both in adults with type 1 and type 2 diabetes, and is related to poor daytime functioning and higher self-care burden. The temporal relation with depression and merits of therapy should be explored.	
26261097	This study proposes a method of automatically classifying sleep apnea/hypopnea events based on sleep states and the severity of sleep-disordered breathing (SDB) using photoplethysmogram (PPG) and oxygen saturation (SpO2) signals acquired from a pulse oximeter. The PPG was used to classify sleep state, while the severity of SDB was estimated by detecting events of SpO2 oxygen desaturation. Furthermore, we classified sleep apnea/hypopnea events by applying different categorisations according to the severity of SDB based on a support vector machine. The classification results showed sensitivity performances and positivity predictive values of 74.2% and 87.5% for apnea, 87.5% and 63.4% for hypopnea, and 92.4% and 92.8% for apnea + hypopnea, respectively. These results represent better or comparable outcomes compared to those of previous studies. In addition, our classification method reliably detected sleep apnea/hypopnea events in all patient groups without bias in particular patient groups when our algorithm was applied to a variety of patient groups. Therefore, this method has the potential to diagnose SDB more reliably and conveniently using a pulse oximeter. 
26259903	Two neuropeptides, orexin-A and orexin-B (also called hypocretin-1 and -2), have been implicated in sleep/wake regulation, feeding behaviors via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). While the expression of orexins and orexin receptors is immunohistochemically revealed in retinal neurons, the function of these peptides in the retina is largely unknown. Using whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that orexin-A increased L-type-like barium currents (IBa,L) in ganglion cells (GCs), and the effect was blocked by the selective OX1R antagonist SB334867, but not by the OX2R antagonist TCS OX2 29. The orexin-A effect was abolished by intracellular dialysis of GDP-β-S/GPAnt-2A, a Gq protein inhibitor, suggesting the mediation of Gq. Additionally, during internal dialysis of the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor U73122, orexin-A did not change the IBa,L of GCs, whereas the orexin-A effect persisted in the presence of the phosphatidylcholine (PC)-PLC inhibitor D609. The orexin-A-induced potentiation was not seen with internal infusion of Ca(2+)-free solution or when inositol 1,4,5-trisphosphate (IP3)-sensitive Ca(2+) release from intracellular stores was blocked by heparin/xestospongins-C. Moreover, the orexin-A effect was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, but was eliminated when PKC was inhibited by bisindolylmaleimide IV (Bis-IV)/Gö6976. Neither adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) nor guanosine 3',5'-cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway was likely involved, as orexin-A persisted to potentiate the IBa,L of GCs no matter these two pathways were activated or inhibited. These results suggest that, by activating OX1R, orexin-A potentiates the IBa,L of rat GCs through a distinct Gq/PI-PLC/IP3/Ca(2+)/PKC signaling pathway. 
26256520	Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. In fact, hydrocortisone replacement in AD patients likely induces disrupted sleep. Given that healthy sleep plays an important role in improving quality of life, optimizing cognition, and ensuring affect regulation, the aim of this study was to investigate whether poor quality of life, mood alterations, and memory complaints reported by AD patients are associated with their disrupted sleep patterns. Sixty patients with AD and 60 matched healthy controls completed a battery of self-report questionnaires assessing perceived physical and mental health (Short-Form 36), mood (Beck Depression Inventory-II), sleep quality (Pittsburgh Sleep Quality Index), and cognition (Cognitive Failures Questionnaire). A latent variable model revealed that although AD had a significant direct effect on quality of life, the indirect effect of sleep was significantly greater. Furthermore, although AD had no direct effect on cognitive functioning, the indirect effect of sleep was significant. The overall model showed a good fit (comparative fit index = 0.91, root mean square of approximation = 0.09, and standardized root mean square residual = 0.05). Our findings suggest that disrupted sleep, and not the disease per se, may induce poor quality of life, memory impairment, and affect dysregulation in patients with AD. We think that improving sleep architecture may improve cognitive, affective, and physical functioning.
26255640	In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases. 
26255301	The purpose of this work is to investigate the efficacy of exogenous melatonin in the treatment of sleep disorders in patients with neurodegenerative disease. We searched Pubmed, the Cochrane Library, and ClinicalTrials.gov, from inception to July 2015. We included randomized clinical trials (RCTs) that compared melatonin with placebo and that had the primary aim of improving sleep in people with neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). We pooled data with the weighted mean difference in sleep outcomes. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I (2) statistic. 9 RCTs were included in this research. We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in PD patients (MD: 4.20, 95 % CI: 0.92-7.48; P = 0.01), and by changes in PSQI component 4 in AD patients (MD: 0.67, 95 % CI: 0.04-1.30; P = 0.04), but not on objective sleep outcomes in both AD and PD patients. Treatment with melatonin effectively improved the clinical and neurophysiological aspects of rapid eye movement (REM) sleep behavior disorder (RBD), especially elderly individuals with underlying neurodegenerative disorders. This meta-analysis provided some evidence that melatonin improves sleep quality in patients with AD and PD, and melatonin can be considered as a possible sole or add-on therapy in neurodegenerative disorders patients with RBD.
26250860	This cross-sectional study examined the association between objectively measured sleep patterns and body composition in very elderly community-dwelling women. Participants included 191 community-dwelling adults aged ≥ 80 years (mean age: 83.4 ± 2.6 years; age range: 80-92 years). Sleep and physical activity were monitored via accelerometer (ActiGraph GT3X+) during at least five consecutive 24-h periods. Night-to-night sleep pattern variability across all nights of recording was assessed using standard deviations (SDs). Body composition was assessed using dual-energy X-ray absorptiometry. Simple and multivariable linear regression analyses were performed. The mean number of nights with usable actigraphy data was 7.3 ± 1.3. On average, participants went to bed at 22:57 hours (SD: 1.11 h) and rose from bed at 6:27 hours (SD: 1.01 h). Night-to-night bedtime, sleep duration and sleep timing mid-point variations correlated slightly with the percentage body fat and percentage lean mass (P < 0.05). Multiple linear regression analysis revealed significant associations of night-to-night bedtime variations and inconsistent sleep-wake patterns with all body composition indices after adjusting for potential confounding factors, including mean nightly sleep duration, self-reported nap duration and daily physical activity. After further adjusting for night-to-night wake time, sleep timing mid-point and sleep duration variations, greater bedtime variability remained associated significantly with all body composition indices except lean/fat mass ratio. Inconsistent sleep-wake patterns were associated independently with an increased fat mass and decreased lean mass among very elderly women. These findings suggest that in most elderly individuals, sleep patterns might be an important modifiable factor associated with obesity and sarcopenia development.
26250541	The aims of this paper are to study the associations between objective and subjective sleep in pregnant women, to examine which specific aspects of women's sleep are associated with depressive and anxiety symptoms and to test the moderating role of depressive and anxiety symptoms in the relations between objective and subjective sleep. The sample included 148 pregnant women. Objective sleep was measured by actigraphy for five nights at the participants' home, and subjective sleep was measured with the Pittsburgh sleep quality index. Depressive symptoms were assessed with the Edinburgh postnatal depression scale and anxiety symptoms with the Beck anxiety inventory. Significant associations were found between the subjective sleep measures and the depressive and anxiety scores, but there were no significant associations between actigraphic sleep measures and the depressive and anxiety scores. Depressive and anxiety scores emerged as significant moderators of the links between objective and subjective sleep. The findings suggest that emotional distress (i.e., depressive and anxiety symptoms severity) during pregnancy is associated with subjective sleep disturbances but not with objective sleep disturbances. Importantly, only among women with higher levels of emotional distress was subjective sleep quality associated with objective sleep quality. These findings may suggest that women with higher levels of emotional distress are not necessarily biased in their perception of sleep quality. However, they may perceive fragmented sleep as more detrimental to their wellbeing.
26250061	Use of common data elements (CDEs), conceptually defined as variables that are operationalized and measured in identical ways across studies, enables comparison of data across studies in ways that would otherwise be impossible. Although healthcare researchers are increasingly using CDEs, there has been little systematic use of CDEs for symptom science. CDEs are especially important in symptom science because people experience common symptoms across a broad range of health and developmental states, and symptom management interventions may have common outcomes across populations.The purposes of this article are to (a) recommend best practices for the use of CDEs for symptom science within and across centers; (b) evaluate the benefits and challenges associated with the use of CDEs for symptom science; (c) propose CDEs to be used in symptom science to serve as the basis for this emerging science; and (d) suggest implications and recommendations for future research and dissemination of CDEs for symptom science.	The National Institute of Nursing Research (NINR)-supported P20 and P30 Center directors applied published best practices, expert advice, and the literature to identify CDEs to be used across the centers to measure pain, sleep, fatigue, and affective and cognitive symptoms.	We generated a minimum set of CDEs to measure symptoms.	The CDEs identified through this process will be used across the NINR Centers and will facilitate comparison of symptoms across studies. We expect that additional symptom CDEs will be added and the list will be refined in future work.	Symptoms are an important focus of nursing care. Use of CDEs will facilitate research that will lead to better ways to assist people to manage their symptoms.	
26248036	It is not well known whether high altitude acclimatization could help lowlanders improve their sleep architecture as well as Native Tibetans. In order to address this, we investigated the structural differences in sleep between Native Tibetans and partially acclimatized lowlanders and examined the association between sleep architecture and subjective sleep quality. Partially acclimatized soldiers from lowlands and Native Tibetan soldiers stationed at Shangri-La (3800 m) were surveyed using the Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Rating Scale (HAMD). The sleep architecture of those without anxiety (as determined by HAMA>14) and/or depression (HAMD>20) was analyzed using polysomnography and the results were compared between the two groups. One hundred sixty-five male soldiers, including 55 Native Tibetans, were included in the study. After partial acclimatization, lowlanders still exhibited differences in sleep architecture as compared to Native Tibetans, as indicated by a higher PSQI score (8.14±2.37 vs. 3.90±2.85, p<0.001), shorter non-rapid eye movement (non-REM) sleep (458.68±112.63 vs. 501±37.82 min, P=0.03), lower nocturnal arterial oxygen saturation (Spo2; mean 91.39±1.24 vs. 92.71±2.12%, p=0.03), and increased times of Spo2 reduction from 89% to 85% (median 48 vs.17, p=0.04) than Native Tibetans. Sleep onset latency (β=0.08, 95%CI: 0.01 to 0.15), non-REM latency (β=0.011, 95%CI 0.001 to 0.02), mean Spo2 (β=-0.79, 95%CI: -1.35 to -0.23) and time in stage 3+4 sleep (β=-0.014, 95%CI: -0.001 to -0.028) were slightly associated with the PSQI score. Partially acclimatized lowlanders experienced less time in non-REM sleep and had lower arterial oxygen saturation than Native Tibetans at an altitude of 3800 m. The main independent contributors to poor sleep quality are hypoxemia, difficulty in sleep induction, and time in deep sleep.
26246488	In this paper, we propose a novel method to determine the circadian variation of scalp electroencephalogram (EEG) in both individual and group levels using a correlation sum measure, quantifying self-similarity of the EEG relative energy across waking epochs.We analysed EEG recordings from central-parietal and occipito-parietal montages in nine healthy subjects undergoing a 72 h ultradian sleep-wake cycle protocol. Each waking epoch (∼ 1 s) of every nap opportunity was decomposed using the wavelet packet transform, and the relative energy for that epoch was calculated in the desired frequency band using the corresponding wavelet coefficients. Then, the resulting set of energy values was resampled randomly to generate different subsets with equal number of elements. The correlation sum of each subset was then calculated over a range of distance thresholds, and the average over all subsets was computed. This average value was finally scaled for each nap opportunity and considered as a new circadian measure.	According to the evaluation results, a clear circadian rhythm was identified in some EEG frequency ranges, particularly in 4-8 Hz and 10-12 Hz. The correlation sum measure not only was able to disclose the circadian rhythm on the group data but also revealed significant circadian variations in most individual cases, as opposed to previous studies only reporting the circadian rhythms on a population of subjects. Compared to a naive measure based on the EEG absolute energy in the frequency band of interest, the proposed measure showed a clear superiority using both individual and group data. Results also suggested that the acrophase (i.e., the peak) of the circadian rhythm in 10-12 Hz occurs close to the core body temperature minimum.	These results confirm the potential usefulness of the proposed EEG-based measure as a non-invasive circadian marker.	
26246454	To examine factors predicting the onset of perioperative delirium and acute exacerbation of behavioral and psychological symptoms of dementia (BPSD), based on patient background, operative background and laboratory data obtained on admission, in elderly patients with proximal femoral fracture.The participants were 152 patients (aged >70 years) who underwent surgery between 1 November 2012 and 31 March 2014. The participants were classified into group B (with onset of perioperative delirium or acute exacerbation of BPSD, n = 52), or group N, (without onset, n = 100), and risk factors were retrospectively examined. Onset was judged based on the presence or absence of common items; that is, "hallucination and delusion," "disturbing speech," "excitatory behavior" and "altered sleep-wake cycle." The participants were observed for 1 week after admission.	The incidence of perioperative delirium or acute exacerbation of BPSD was 34.2% in total. In univariate analysis, the incidence was significantly higher (P < 0.005) in group B for the age, history of dementia and serum albumin level items. In multivariate analysis, history of dementia, serum albumin level and peripheral lymphocyte count (odds ratio 3.55, 0.17, 1.00, respectively) were identified as independent predictive factors. In the subanalysis, the incidence was 91.3% in the group with a history of dementia, serum albumin level <3.7 g/dL and peripheral lymphocyte count < 1200/μL.	History of dementia, a low serum albumin level and low peripheral lymphocyte count were found to be useful factors for predicting the onset of perioperative delirium and acute exacerbation of BPSD. Geriatr Gerontol Int 2016; 16: 821-828.	
26244952	To study the association of nocturnal enuresis with sleep, behavior and school performance.Hospital-based, cross-sectional descriptive study of 216 children (?6-year-old) using structured questionnaire and behavioral tools.	Two hospitals at Lucknow in Northern India.	Prevalence of enuresis was 37.0%. Nocturnal enuresis was significantly associated with abnormal behaviour (P=0.049) and poor sleep hygiene (P%0.05). School performance was not associated with enuresis.	Children with nocturnal enuresis were at an increased risk of behavioral problems and poor sleep hygiene.	
26244417	Delayed sleep phase disorder (DSPD) is common among young people, but there is still no evidence-based treatment available. In the present study, the feasibility of cognitive behavioral therapy (CBT) was evaluated as an additive treatment to light therapy (LT) in DSPD. A randomized controlled trial with participants aged 16 to 26 years received LT for two weeks followed by either four weeks of CBT or no treatment (NT). LT advanced sleep-wake rhythm in both groups. Comparing LT+CBT with LT+NT, no significant group differences were observed in the primary endpoints. Although anxiety and depression scores were low at pretreatment, they decreased significantly more in LT+CBT compared to LT+NT. The results are discussed and some suggestions are given for further studies. 
26244223	Adolescents and young adults recovering from a concussion may experience subjective changes in their normal sleeping patterns. These subjective sleep complaints may influence a patient's perceived concussion symptoms and negatively impact cognition and school function. Clinicians should be cognizant of these changes in normal sleeping patterns for adolescent and young adult concussion patient and familiarize themselves with available treatment options.
26241867	Bipolar Disorder is characterized by episodes running the full mood spectrum, from mania to depression. Between mood episodes, residual symptoms remain, as sleep alterations, circadian cycle disturbances, emotional deregulation, cognitive impairment and increased risk for comorbidities. The present review intends to reflect about the most recent and relevant information concerning the biunivocal relation between bipolar disorder and circadian cycles.It was conducted a literature search on PubMed database using the search terms "bipolar", "circadian", "melatonin", "cortisol", "body temperature", "Clock gene", "Bmal1 gene", "Per gene", "Cry gene", "GSK3β", "chronotype", "light therapy", "dark therapy", "sleep deprivation", "lithum" and "agomelatine". Search results were manually reviewed, and pertinent studies were selected for inclusion as appropriate.	Several studies support the relationship between bipolar disorder and circadian cycles, discussing alterations in melatonin, body temperature and cortisol rhythms; disruption of sleep/wake cycle; variations of clock genes; and chronotype. Some therapeutics for bipolar disorder directed to the circadian cycles disturbances are also discussed, including lithium carbonate, agomelatine, light therapy, dark therapy, sleep deprivation and interpersonal and social rhythm therapy.	This review provides a summary of an extensive research for the relevant literature on this theme, not a patient-wise meta-analysis.	In the future, it is essential to achieve a better understanding of the relation between bipolar disorder and the circadian system. It is required to establish new treatment protocols, combining psychotherapy, therapies targeting the circadian rhythms and the latest drugs, in order to reduce the risk of relapse and improve affective behaviour.	
26239768	The effect of bright light therapy (BLT) on the symptoms of night eating syndrome was evaluated. Fifteen adults completed two weeks of daily 10,000 lux BLT administered in the morning. Significant reductions were found pre-to-post treatment in night eating symptomatology, mood disturbance, and sleep disturbance. This pilot trial provides preliminary support for the efficacy of BLT for the treatment of night eating syndrome. 
26239295	Canine cognitive impairment syndrome (CDS) represents a group of symptoms related to the aging of the canine brain. These changes ultimately lead to a decline of memory function and learning abilities, alteration of social interaction, impairment of normal housetraining, and changes in sleep-wake cycle and general activity. We have clinically examined 215 dogs, 28 of which underwent autopsy. With canine brains, we performed extensive analysis of pathological abnormalities characteristic of human Alzheimer's disease and frontotemporal lobar degeneration, including β-amyloid senile plaques, tau neurofibrillary tangles, and fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP43) inclusions. Most demented dogs displayed senile plaques, mainly in the frontal and temporal cortex. Tau neurofibrillary inclusions were found in only one dog. They were identified with antibodies used to detect tau neurofibrillary lesions in the human brain. The inclusions were also positive for Gallyas silver staining. As in humans, they were distributed mainly in the entorhinal cortex, hippocampus, and temporal cortex. On the other hand, FUS and TDP43 aggregates were not present in any of the examined brain samples. We also found that CDS was characterized by the presence of reactive and senescent microglial cells in the frontal cortex. Our transcriptomic study revealed a significant dysregulation of genes involved in neuroinflammation. Finally, we analyzed tau phosphoproteome in the synaptosomes. Proteomic studies revealed a significant increase of hyperphosphorylated tau in synaptosomes of demented dogs compared with nondemented dogs. This study suggests that cognitive decline in dogs is related to the tau synaptic impairment and neuroinflammation. J. Comp. Neurol. 524:874-895, 2016. © 2015 Wiley Periodicals, Inc. 
26239174	Sleep disturbances are common in Alzheimer's disease (AD) and now assumed to contribute to disease onset and progression. Here, we investigated whether activity, sleep/wake pattern, and electroencephalogram (EEG) profiles are altered in the knock-in PLB1Triple mouse model from 5 to 21 months of age. PLB1Triple mice displayed a progressive increase in wakefulness and non-rapid eye movement sleep fragmentation from 9 months onward, whereas PLB1WT wild type controls showed such deterioration only at 21 months. Impaired habituation to spatial novelty was also detected in PLB1Triple mice. Hippocampal power spectra of transgenic mice revealed progressive, vigilance stage-, brain region-, and age-specific changes. Age had an impact on EEG spectra in both cohorts but led to accelerated genotype-dependent differences, ultimately affecting all bands at 21 months. Overall, although PLB1Triple animals display only subtle amyloid and tau pathologies, robust sleep-wake and EEG abnormalities emerged. We hypothesize that such endophenotypes are sensitive, noninvasive, and reliable biomarker to identify onset and progression of AD.
26238451	This paper analyzes data from a nationally representative survey of adults in the United Kingdom (Understanding Society, N = 37,253) to explore the marital status/health nexus (using categories that include a measure of relationship distress) and to assess the role that sleep problems play as a potential mediator. Findings indicate how it is not just the "form" marital status takes but also the absence or presence of relationship distress that is essential to self-rated health. We demonstrate two further findings that: (1) sleep problems act as a mediator of the link between marital status/relationship distress and self-rated health, most notably for those in cohabiting relationships with medium/high distress or who have a history of relationship loss, and (2) the mediating role of sleep problems differs for divorced men and women. 
26238150	Parents of children with special healthcare needs (CSHCNs) report poorer sleep than parents of typically developing (TD) children, which has been associated with poorer mental health. The relations between sleep disturbances and general health and memory among this population are unknown. The current study aimed to replicate the findings that parents of CSHCNs report poorer sleep quality than parents of TD children, and further examine how sleep is related to general health and memory. Participants (75 parents of TD children; 97 parents of CSHCNs) completed an online questionnaire consisting of: demographics, the Pittsburgh Sleep Quality Index (PSQI), the Prospective Retrospective Memory Questionnaire (PRMQ) and the Healthy Days Measure. Parents of CSHCNs reported worse global sleep than parents of TD children. Parents of CSHCNs took longer to fall asleep at night, had shorter sleep duration and worse subjective sleep quality than parents of TD children. Parents of CSHCNs also had worse prospective memory and were more likely to report poor general health than parents of TD children. Poorer sleep quality was associated with worse memory and health among both parents of TD children and parents of CSHCNs. Results from this study highlight the importance of addressing the sleep of parents of CSHCNs and support the need for more research in this area. By recognizing factors associated with parent's health and functioning, service providers may be better able to implement support programs for parents of CSHCNs.
26237776	The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more, but direct evidence is lacking.We performed in vivo microdialysis experiments in adult (9-10 weeks old) C57BL/6 mice implanted for chronic electroencephalographic recordings. Cortical NA levels were measured during spontaneous sleep and wake (n = 8 mice), and in the course of sleep deprivation (n = 6).	We found that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC.	Locus coeruleus (LC) neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation.	A commentary on this article appears in this issue on page 11.	
26237770	To examine sleep patterns and sleep problems and their relationship with daytime functioning in adults with a diagnosis of an autism spectrum disorder and no comorbid intellectual disability (high-functioning autism spectrum disorder [HFASD]) compared to neurotypical (NT) adults.Cross-sectional.	Home-based study.	36 adults with HFASD and 36 age-, intelligence quotient- and sex-matched NT adults.	Participants completed an online questionnaire battery including the Pittsburgh Sleep Quality Index (PSQI), a 14-d sleep wake diary and 14-d actigraphy data collection.	Adults with HFASD had significantly more general sleep disturbances and higher scores on the PSQI, longer sleep onset latencies (actigraphy), and poorer sleep efficiency (diary) and these results remained significant after accounting for the False Discovery Rate. Those adults with HFASD who did not have a comorbid diagnosis of anxiety/depression had significantly shorter total sleep time (diary and actigraphy) compared to NT adults. Compared to NT adults, the HFASD group self-reported significantly poorer refreshment scores upon waking in the morning and higher scores on the daytime dysfunction due to sleepiness subscale of the PSQI.	These findings support the notion that problems related to sleep, in particular insomnia, continue into adulthood in individuals with high-functioning autism spectrum disorder.	
26235161	The purpose of this study was to analyze differences between preadolescents and adolescents on the use of technology and to test the contribution of using Internet and mobile phone, and circadian preference on sleep quality.We recruited a sample of 850 (364 males) preadolescents and adolescents. Self-report questionnaires about sleep schedule, sleep wake behavior problems, circadian preferences, and the use of technology (e.g., Internet and mobile phone) were administered. Students were asked to fill out the School Sleep Habits Survey, a self-report questionnaire on the use of technology, the Mobile Phone Involvement Questionnaire (MPIQ), and the Shorter Promis Questionnaire (SPQ).	Adolescents reported more sleep problems, a tendency toward eveningness, and an increase of Internet and phone activities, as well as social network activities, while preadolescents were more involved in gaming console and television viewing. The regression analysis performed separately in the two age groups showed that sleep quality was affected by the circadian preference (eveningness) in both groups. Adolescents' bad sleep quality was consistently associated with the mobile phone use and number of devices in the bedroom, while in preadolescents, with Internet use and turning-off time.	The evening circadian preference, mobile phone and Internet use, numbers of other activities after 21:00, late turning off time, and number of devices in the bedroom have different negative influence on sleep quality in preadolescents and adolescents.	
26235156	For the first time ever, as emphasized by inclusion in the Healthy People 2020 goals, sleep health is an emphasis of national health aims. The National Healthy Sleep Awareness Project (NHSAP) was tasked to propose questions for inclusion in the next Behavioral Risk Factor Surveillance System (BRFSS), a survey that includes a number of questions that target behaviors thought to impact health, as a means to measure community sleep health. The total number of questions could not exceed five, and had to include an assessment of the risk for obstructive sleep apnea (OSA).An appointed workgroup met via teleconference and face-to-face venues to develop an inventory of published survey questions being used to identify sleep health, to develop a framework on which to analyze the strengths and weaknesses of current survey questions concerning sleep, and to develop recommendations for sleep health and disease surveillance questions going forward.	The recommendation was to focus on certain existing BRFSS questions pertaining to sleep duration, quality, satisfaction, daytime alertness, and to add to these other BRFSS existing questions to make a modified STOP-BANG questionnaire (minus the N for neck circumference) to assess for risk of OSA.	Sleep health is an important dimension of health that has previously received less attention in national health surveys. We believe that 5 questions recommended for the upcoming BRFSS question banks will assist as important measures of sleep health, and may help to evaluate the effectiveness of interventions to improve sleep health in our nation.	
26233628	Cataract decreases blue light transmission. Because of the selective blue light sensitivity of the retinal ganglion cells governing circadian photoentrainment, cataract may interfere with normal sleep-wake regulation and cause sleep disturbances. The purpose was to investigate the effect of cataract surgery on circadian photoentrainment and to determine any difference between blue-blocking and neutral intraocular lenses (IOLs).The study was a single-center, investigator-driven, double-masked, block-randomized clinical trial.	One eye in 76 patients with bilateral age-related cataract eligible for cataract surgery was included.	Intervention was cataract surgery by phacoemulsification. Patients were randomized to receive a blue-blocking or neutral IOL.	Primary outcome was activation of intrinsic photosensitive ganglion cells using post-illumination pupil response (PIPR) to blue light from 10 to 30 seconds after light exposure as a surrogate measure. Secondary outcomes were circadian rhythm analysis using actigraphy and 24-hour salivary melatonin measurements. Finally, objective and subjective sleep quality were determined by actigraphy and the Pittsburgh Sleep Quality Index.	The blue light PIPR increased 2 days (17%) and 3 weeks (24%) after surgery (P < 0.001). The majority of circadian and sleep-specific actigraphy parameters did not change after surgery. A forward shift of the circadian rhythm by 22 minutes (P = 0.004) for actigraphy and a tendency toward an earlier melatonin onset (P = 0.095) were found. Peak salivary melatonin concentration increased after surgery (P = 0.037). No difference was detected between blue-blocking and neutral IOLs, whereas low preoperative blue light transmission was inversely associated with an increase in PIPR (P = 0.021) and sleep efficiency (P = 0.048).	Cataract surgery increases photoreception by the photosensitive retinal ganglion cells. Because of inconsistency between the significant findings and the many parameters that were unchanged, we can conclude that cataract surgery does not adversely affect the circadian rhythm or sleep. Longer follow-up time and fellow eye surgery may reveal the significance of the subtle changes observed. We found no difference between blue-blocking and neutral IOLs, and, because of the minor effect of surgery in itself, an effect of IOL type seems highly unlikely.	
26233596	To explore the associations of severe musculoskeletal injuries (joint and muscles) and surgeries with symptoms of common mental disorders (distress, anxiety/depression, sleeping disturbance, adverse alcohol behaviour , smoking, adverse nutrition behaviour) among male European professional footballers.Cross-sectional analyses were conducted on electronic questionnaires completed by professional footballers recruited from the national players' unions of Finland, France, Norway, Spain or Sweden. The number of severe (time loss of more than 28 days) musculoskeletal injuries (total, joint, muscle) and surgeries during a professional football career was examined through four questions, while symptoms of common mental disorders were evaluated through validated scales.	A total of 540 professional footballers (mean age of 27 years; 54 % playing in the highest leagues) participated in the study. Sixty-eight per cent of the participants had already incurred one or more severe joint injuries and 60 % one or more severe muscle injuries. Prevalence of symptoms of common mental disorders ranged from 3 % for smoking to 37 % for anxiety/depression and 58 % for adverse nutrition behaviour. The number of severe musculoskeletal injuries during a football career was positively correlated with distress, anxiety and sleeping disturbance, while the number of surgeries was correlated with adverse alcohol behaviour and smoking. Professional footballers who had sustained one or more severe musculoskeletal injuries during their career were two to nearly four times more likely to report symptoms of common mental disorders than professional footballers who had not suffered from severe musculoskeletal injuries.	It can be concluded that the number of severe musculoskeletal injuries and surgeries during a career is positively correlated and associated with symptoms of common mental disorders among male European professional footballers. This study emphasises the importance of applying a multidisciplinary approach to the clinical care and support of professional footballers, especially when a player faces lengthy periods without training and competition as a consequence of recurrent severe joint or muscle injuries.	III.	
26228520	Long working hours may impact human health. In Japan, teachers tend to work long hours. From 2002 to 2012, the number of leaves of absence due to diseases other than mental disorders, or mental disorders among public school teachers increased by 1.3 times (from 2,616 to 3,381), or 1.8 times (from 2,687 to 4,960), respectively. The present study aimed to investigate the association between long working hours and sleep problems among public school teachers.This cross-sectional study was conducted from mid-July to September 2013 in Hokkaido Prefecture, Japan. Questionnaires were distributed to 1,245 teachers in public junior high schools. Information about basic characteristics including working hours, and responses to the Pittsburgh Sleep Quality Index were collected anonymously. Multiple logistic regression analysis was used to calculate odds ratios (ORs) for the association between long working hours and sleep problems separately by sex.	The response rate was 44.8% (n=558). After excluding ineligible responses, the final sample comprised 515 teachers (335 males and 180 females). Sleep problems was identified in 41.5% of males and 44.4% of females. Our results showed a significantly increased risk of sleep problems in males working >60 hours per week (OR 2.05 [95% CI 1.01-4.30]) compared with those working ≤40 hours per week. No significant association was found in females.	There is a significant association between long working hours and sleep problems in male teachers. Reducing working hours may contribute to a reduction in sleep problems.	
26228404	There is ample data suggesting that individuals with bipolar disorder more frequently suffer from disturbed sleep even when euthymic. Since sleep is a process that is crucial for affective homeostasis, disturbed sleep in healthy individuals may be a risk factor for the subsequent onset of bipolar disorder. Utilizing data from a large cohort of adolescents and young adults, this study tests the hypothesis that disturbed sleep constitutes a risk factor for the later onset of bipolar disorder. A representative community sample of N = 3021 adolescents and young adults (baseline age 14-24) was assessed using the standardized Composite International Diagnostic Interview and followed-up prospectively up to 3 times over up to 10 years. Disturbed sleep at baseline was quantified utilizing the corresponding items from the self-report inventory SCL-90-R. The compound value (insomnia-score) as an ordinal parameter for the severity of sleep disturbances was used to assess associations with the incidence of bipolar disorder among participants free of major mental disorder at baseline (N = 1943) using odds ratios (OR) from logistic regressions. Analyses were adjusted for age, gender, parental mood disorder and lifetime alcohol or cannabis dependence. Poor sleep quality significantly increased the risk for the subsequent development of bipolar disorder (OR = 1.75; p = 0.001). Regarding individual sleep items, trouble falling asleep and early morning awakening were predictive for the subsequent onset of bipolar disorder. Disturbed sleep in persons otherwise free of major mental disorders appears to confer an increased risk for the subsequent onset of bipolar disorder.
26224419	Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage.We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x-ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain.	Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations.	The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology.	
26224197	Postnatal depression affects the well-being of women and families. While several studies have shown an association between mode of birth and symptoms of postnatal depression, others have found no relationship.To determine whether women who have instrumental or caesarean births report higher levels of poor coping, sleep or appetite disturbance, or relationship difficulties, than women who have vaginal births, at the time of Universal Postnatal Contact (7-10 days post-discharge).	Retrospective cohort study of term, singleton births from 1st January 2013 to 31st December 2013 at a tertiary obstetric facility. Outcomes were compared for 1816 women having vaginal births versus 1205 women having instrumental or caesarean births.	When adjusted for confounders, no association could be demonstrated between mode of birth and reporting of any postnatal symptom of psychological morbidity. However, the model did demonstrate an association between reporting of symptoms and nulliparity (aOR 1.69 (1.08-2.63); P = 0.02), as well as having an unplanned pregnancy with a supportive partner (aOR 0.54 (0.29-0.97); P = 0.04).	Mode of birth does not appear to be associated with the reporting of symptoms of psychological morbidity in the early postnatal period. However, these symptoms may be associated with nulliparity and in the context of an unplanned pregnancy, a lack of partner support. These findings highlight the ongoing need for antenatal screening with respect to pregnancy intention and the presence of a social support system, to facilitate the implementation of interventions for women at risk of postnatal depression.	
26223804	The hypothalamus is composed of many heterogeneous nuclei that control distinct physiological functions. Investigating molecular mechanisms that regulate the specification of these nuclei and specific neuronal subtypes, and their contribution to diverse hypothalamic functions, is an exciting research focus. Here, we begin by summarizing the hypothalamic functions of feeding regulation, sleep-wake cycles, stress responses, and circadian rhythm, and describing their anatomical bases. Next, we review the molecular regulation of formation of hypothalamic territories, specification of nuclei and subnuclei, and generation of specific neurons. Finally, we highlight physiological and behavioral consequences of altered hypothalamic development. Identifying molecules that regulate hypothalamic development and function will increase our understanding of hypothalamus-related disorders, such as obesity and diabetes, and aid in the development of therapies aimed specifically at their etiologies. 

26223541	Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimer's disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways. 

26222511	Irritable bowel syndrome (IBS) is the most common functional gastrointestinal (GI) disorder observed in patients who visit general practitioners for GI-related complaints. A high prevalence of psychiatric comorbidities, particularly anxiety and depressive disorders, has been reported in patients with IBS. However, a clear temporal relationship between IBS and psychiatric disorders has not been well established.We explored the relationship between IBS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.	We selected patients who were diagnosed with IBS caused by gastroenteritis, according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort was formed of patients without IBS who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on psychiatrist diagnoses.	The IBS cohort consisted of 4689 patients, and the comparison cohort comprised 18756 matched control patients without IBS. The risks of depressive disorder (HR = 2.71, 95% confidence interval [CI] = 2.30-3.19), anxiety disorder (HR = 2.89, 95% CI = 2.42-3.46), sleep disorder (HR = 2.47, 95% CI = 2.02-3.02), and bipolar disorder (HR = 2.44, 95% CI = 1.34-4.46) were higher in the IBS cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0-1, 1-5, ≥5 y).	IBS may increase the risk of subsequent depressive disorder, anxiety disorder, sleep disorder, and bipolar disorder. The risk ratios are highest for these disorders within 1 year of IBS diagnosis, but the risk remains statistically significant for more than 5 years. Clinicians should pay particular attention to psychiatric comorbidities in IBS patients.	
26220853	At-risk mental states (ARMS) are clinical syndromes that are associated with higher risk, compared with the general population, for developing psychosis and bipolar disorder. Circadian rhythm misalignments have been proposed to be part of this early phase of the clinical course.To compare circadian rhythm of activity and rest changes between ARMS individuals and a healthy control group.	Forty volunteers of both genders, aged between 13 and 27years old, participated in this study (n=20 ARMS group, and n=20 healthy controls). The ARMS individuals were classified as ultra-high risk for psychosis according to the CAARMS (Comprehensive Assessment of At-risk Mental State) or at high risk for bipolar disorder according to criteria proposed by Bechdolf and colleagues. Participants used an actigraph for fifteen days, kept a sleep diary, and completed the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, and a Morningness-Eveningness Questionnaire.	Compared with healthy volunteers, the ARMS group presented worse sleep quality (P=0.010); longer nap durations (P=0.038), shorter wake times (P=0.001), higher total sleep times (P=0.011), and shorter activity duration (P=0.021), sleep rhythms were more fragmented, the circadian rest-activity rhythms were less synchronized with the dark-light cycle and had lower amplitudes of motor activity.	The results suggest alterations in the circadian rest-activity rhythms (and likely in sleep-wake cycle patterns) in ARMS individuals compared with healthy controls. It is possible that circadian rhythms of activity and rest changes are one of the prodromal clinical and behavioral expressions of the brain changes that underlie ARMS individuals.	
26220388	The clinically important interaction between epilepsy and sleep is complex. The aim of this paper is to review the frequency of sleep complaints and the comorbidity of sleep disorders in people with epilepsy attending an outpatient clinic.Sleep complaints and presence of sleep disorders were assessed by means of a standard questionnaire form composed of 132 questions in 208 patients and 212 controls. The questionnaire includes Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Beck Depression Scale, and the Berlin Questionnaire for sleep apnea.	We showed poorer sleep quality, a higher frequency of subjective sleep disturbances in epilepsy patients. The major complaints of patients related to poor sleep quality included the symptoms of insomnia, sleep apnea, and parasomnias. They have higher frequency of sleep onset and maintenance insomnia, REM behavioral disorders, and sleep apnea. Nocturnal seizures (47%) and epileptiform activities on EEG (47%) were more frequent in patients with insomnia (p=0.02, p=0.06). Furthermore, the patients with a high risk of sleep apnea frequently used more than one antiepileptic drugs (AED) (41%, p<0.01) and the duration of epilepsy was longer in these patients (p=0.02). Moreover insomnia (p=0.01) was significantly lower in patients having no seizures in the last 2 years and the risk of apnea (p=0.04) and bad quality of sleep (p=0.01) was higher in patients with seizures.	The results emphasize the extent of the comorbidity of sleep disorders and epilepsy in an outpatient clinic. They have higher frequency of sleep onset, maintenance insomnia, probable RBD, and sleep apnea than healthy controls do. The severity of epilepsy can increase the risk of some sleep disorders like insomnia and sleep apnea. Aggressive treatment of nocturnal seizures and EEG can be considered to prevent insomnia. On the other hand, chronicity can lead to sleep apnea and so PSG investigations can be routinely done in patients having video-EEG monitoring due to refractory epilepsy.	
26218004	To examine sleep disturbances in the POINT cohort study consisting of participants prescribed long-term opioids for chronic noncancer pain (CNCP), and to examine the relationship between sleep and measures of pain, physical and mental health, substance use, and medication use at the baseline interview.A convenience sample of 1243 participants with current CNCP and prescription opioid use were recruited from community settings and underwent a structured interview examining subjective sleep symptoms (Medical Outcomes Study [MOS] Sleep Scale and the Sleep Problems Index [SLP-9]), the pain severity and interference using the Brief Pain Inventory (BPI), mental and physical health symptoms, and recent substance and medication use. Linear regression models assessed independent predictors of SLP-9 scores.	The median hours of sleep per night was 6 (IQR, 5 to 7.5), with 26% reporting optimal sleep (7 to 8 hours), and a mean SLP-9 score of 47.3 (SD=20.9). In multivariate analysis, age, frequent/severe headaches, BPI pain severity and pain interference scores, moderate to severe anxiety or depression, daily tobacco use, and benzodiazepine use in the past week were significant predictors of SLP-9 scores and sleep quality. Higher MOS respiratory impairment was observed in men, in those with a high body mass index, frequent/severe headaches, and high pain interference scores, and in patients taking anticonvulsants and antipsychotic medications. Opioid use was not associated with SLP-9 or respiratory sleep impairment.	High levels of sleep problems were reported in this community sample of CNCP patients prescribed long-term opioids, and were associated with mental health problems and increased medication use. Nonmedication approaches to addressing sleep problems should be prioritized in this population.	
26216310	Sleep disorders can affect health and occupational performance of physicians as well as outcomes in patients. The purpose of this study was to assess the prevalence of excessive daytime sleepiness (EDS) measured by the Epworth Sleepiness Scale (ESS) among academic physicians at a tertiary academic medical center in an urban area in the northwest region of Turkey, and to establish a relationship between the self-perceived sleepiness and the quality of life using the EuroQol-5 dimensions (EQ-5D).A questionnaire prepared by the researchers after scanning the literature on the subject was e-mailed to the academic physicians of a tertiary academic medical center in Istanbul. The ESS and the EQ-5D were also included in the survey. The e-mail database of the institution directory was used to compile a list of active academic physicians who practiced clinical medicine. Paired and independent t tests were used for the data analysis at a significance level of p < 0.05.	Three hundred and ninety six academic physicians were e-mailed and a total of 252 subjects replied resulting in a 63.6% response rate. There were 84 (33.3%) female and 168 (66.7%) male academic physicians participating in the study. One hundred and eight out of 252 (42.8%) academic physicians were taking night calls (p < 0.001). Ninety study subjects (35.7%) felt they had enough sleep and 84 (33.3%) reported napping daily (p < 0.001). In our sample, 28.6% (N = 72) of the physicians felt sleepy during the day (ESS score > 10) (p < 0.001). In the case of the EQ-5D index and visual analogue scale of the EQ-5D questionnaire (EQ-5D VAS), the status of sleepiness of academic physicians was associated with a poorer quality of life (p < 0.001).	More than a 1/4 of the academic physicians suffered from sleepiness. There was an association between the poor quality of life and daytime sleepiness. There was also a positive relationship between habitual napping and being sleepy during the day.	
26216211	Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may represent a novel strategy to preserve or recover muscle health in older adults. Promising research results regarding the associations between sleep variables and sarcopenia biomarkers and clinical parameters are required to confirm this hypothesis.

26215674	The aim of this study is to examine the relationship between dialysis adequacy and sleep quality in haemodialysis patients.Sleep problems are common in haemodialysis patients. Dialysis adequacy is one of the factors associated with sleep quality. Studies evaluating the association between dialysis adequacy and sleep quality in haemodialysis patients present different results.	Descriptive and cross-sectional study.	This study was performed with a total of 119 patients who had applied to dialysis centres for haemodialysis treatment between January and March 2014. The data collection form consists of socio-demographic and medical characteristics as well as laboratory parameters. A modified Post-Sleep Inventory was used to examine sleep quality in the research.	There were no statistically significant relationship between sleep quality and dialysis adequacy (p > 0·05). When the Post-Sleep Inventory scores were evaluated according to sleep quality, 63·0% of patients had poor sleep quality, and 37·0% had good sleep quality. Sleep quality was worse in unemployed patients (X(2) = 4·852; p = 0·025) and patients who smoked heavily (Z = 2·289; p = 0·022).	In this study, there is no statistically significant relationship between dialysis adequacy and sleep quality. However, it was found that the majority of haemodialysis patients had poor sleep quality.	Even if the dialysis adequacy of patients is at the recommended level, their sleep qualities may be poor. Therefore, evaluations of the sleep quality of haemodialysis patients during the clinical practice must be taken into consideration.	
26215351	To evaluate disturbances in primary tooth eruption and their management with nonpharmacological remedies.In this nonrandomized clinical trial, 270 children aged between 8 and 36 months were selected and divided into 5 groups with 54 children initially enrolled in each group. The children were seen during an 8-day period during tooth eruption. At each appointment data were recorded from oral examination, tympanic temperature measurement and a questionnaire. The five methods used as remedies to reduce teething symptoms were: 1) cuddle therapy, 2) ice, 3) rubbing the gums, 4) teething rings and 5) food for chewing. Teething symptoms, the type of erupted tooth, symptoms of recovery and the mother's satisfaction with treatment were evaluated.	Two hundred and fifty four children (mean age 16 ± 7.2 months) completed the study. The most frequent teething symptoms were drooling (92%), sleep disturbances (82.3%) and irritability (75.6%). These symptoms were more pronounced in low birth weight children (p > 0.05). Canine eruption led to more loss of appetite than incisor (p = 0.033) or molars eruption (p = 0.014). Low grade increases in body temperature were observed only on the day of eruption (36.70 ± 0.39 °C), when body temperature was significantly different compared to the day before and the day after eruption (both p < 0.001). There was no significant correlation between fever as reported by mothers and temperature readings obtained by the investigators. The most favorable results for time to recovery and the mother's satisfaction were seen when teething rings were used, followed by cuddle therapy and rubbing the gums.	There was no association between teething and symptoms such as fever or diarrhea. Low birth weight children may have more teething symptoms. Teething rings, cuddle therapy and rubbing the gums were the most effective methods to reduce symptoms.	Iranian Registry of Clinical Trials: code IRCT201211127402N3.	
26212726	Systemic sclerosis (SSc) is a chronic multi-system autoimmune disease associated with disability and reduced quality of life. There is no effective treatment or cure to SSc, so it is important improve global health of these patients and reduce morbidity and mortality associated with SSc. It was made a literature review about quality of life in patients with SSc, regarding the several factors that should be considered and evaluated when attending to SSc patients. It was also considered the validated scales and questionnaires used to measure outcomes in patients with SSc. We concluded that it is important to have an interdisciplinary approach to SSc patients considering the patient's cognitive representations of the disease and what they value most like mobility and hand function, pain, fatigue, sleep, depression and body image. 

26208951	Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems. 
26206862	Although self-harm and sleep problems are major public health problems in adolescence, detailed epidemiological assessment is essential to understand the nature of this relationship.To conduct a detailed assessment of the relationship between sleep and self-harm in adolescence.	A large population-based study in Norway surveyed 10 220 adolescents aged 16-19 years on mental health, including a comprehensive assessment of sleep and self-harm.	Adolescents with sleep problems were significantly more likely to report self-harm than those without sleep problems. Insomnia, short sleep duration, long sleep onset latency, wake after sleep on set as well as large differences between weekdays versus weekends, yielded higher odds of self-harm consistent with a dose-response relationship. Depressive symptoms accounted for some, but not all, of this association.	The findings highlight a strong relationship between sleep problems and self-harm. Interventions to reduce adolescent self-harm ought to incorporate sleep problems as a treatment target.	
26206724	In elite soccer, players are frequently exposed to various situations and conditions that can interfere with sleep, potentially leading to sleep deprivation. This article provides a comprehensive and critical review of the current available literature regarding the potential acute and chronic stressors (i.e., psychological, sociological and physiological stressors) placed on elite soccer players that may result in compromised sleep quantity and/or quality. Sleep is an essential part of the recovery process as it provides a number of important psychological and physiological functions. The effects of sleep disturbance on post-soccer match fatigue mechanisms and recovery time course are also described. Physiological and cognitive changes that occur when competing at night are often not conducive to sleep induction. Although the influence of high-intensity exercise performed during the night on subsequent sleep is still debated, environmental conditions (e.g., bright light in the stadium, light emanated from the screens) and behaviours related to evening soccer matches (e.g., napping, caffeine consumption, alcohol consumption) as well as engagement and arousal induced by the match may all potentially affect subsequent sleep. Apart from night soccer matches, soccer players are subjected to inconsistency in match schedules, unique team schedules and travel fatigue that may also contribute to the sleep debt. Sleep deprivation may be detrimental to the outcome of the recovery process after a match, resulting in impaired muscle glycogen repletion, impaired muscle damage repair, alterations in cognitive function and an increase in mental fatigue. The role of sleep in recovery is a complex issue, reinforcing the need for future research to estimate the quantitative and qualitative importance of sleep and to identify influencing factors. Efficient and individualised solutions are likely needed.
26206535	Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms.This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses.	Higher white matter lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality.	White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.	
26205911	Older adults experience parallel changes in sleep, circadian rhythms, and episodic memory. These processes appear to be linked such that disruptions in sleep contribute to deficits in memory. Although more variability in circadian patterns is a common feature of aging and predicts pathology, little is known about how alterations in circadian activity rhythms within older adults influence new episodic learning. Following 10 days of recording sleep-wake patterns using actigraphy, healthy older adults underwent fMRI while performing an associative memory task. The results revealed better associative memory was related to more consistent circadian activity rhythms, independent of total sleep time, sleep efficiency, and level of physical activity. Moreover, hippocampal activity during successful memory retrieval events was positively correlated with associative memory accuracy and circadian activity rhythm (CAR) consistency. We demonstrated that the link between consistent rhythms and associative memory performance was mediated by hippocampal activity. These findings provide novel insight into how the circadian rhythm of sleep-wake cycles are associated with memory in older adults and encourage further examination of circadian activity rhythms as a biomarker of cognitive functioning. 
26205768	To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients.HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment ("watch and wait"), chlorambucil treatment only, and patients with other treatment(s).	HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy.	CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment.	
26204994	Major depression and type 2 diabetes often co-occur. Novel treatment strategies for depression in type 2 diabetes patients are warranted, as depression in type 2 diabetes patients is associated with poor prognosis and treatment results. Major depression and concurrent sleep disorders have been related to disturbances of the biological clock. The biological clock is also involved in regulation of glucose metabolism by modulating peripheral insulin sensitivity. Light therapy has been shown to be an effective antidepressant that 'resets' the biological clock. We here describe the protocol of a study that evaluates the hypothesis that light therapy improves mood as well as insulin sensitivity in patients with a major depressive episode and type 2 diabetes.This study is a randomised, double-blind, parallel-arm trial in 98 participants with type 2 diabetes and a major depressive episode, according to DSM-IV criteria. We will assess whether light therapy improves depressive symptoms and insulin sensitivity, our primary outcome measures, and additionally investigate whether these effects are mediated by restoration of the circadian rhythmicity, as measured by sleep and hypothalamic-pituitary-adrenal axis activity. Participants will be randomly allocated to a bright white-yellowish light condition or dim green light condition. Participants will undergo light therapy for half an hour every morning for 4 weeks at home. At several time points, namely before the start of light therapy, during light therapy, after completion of 4 weeks of light therapy and after 4 weeks follow-up, several psychometrical, psychophysiological and glucometabolic measures will be performed.	If light therapy effectively improves mood and insulin sensitivity in type 2 diabetes patients with a major depressive episode, light therapy may be a valuable patient friendly addition to the currently available treatment strategies. Additionally, if our data support the role of restoration of circadian rhythmicity, such an observation may guide further development of chronobiological treatment strategies in this patient population.	The Netherlands Trial Register (NTR) NTR4942 . Registered 13 January 2015.	
26204460	Patients with mood disorders show a high dependence of behavior on the molecular characteristics of the biological clock. CLOCK rs1801260 gene polymorphism influences circadian behavior in bipolar disorder (BD), with *C carriers showing a delayed sleep onset and worse insomnia. Sleep phase delay and insomnia associate with suicide in the general population.We investigated the effects of rs1801260, and of exposure to stressful life events, on current suicidal ideation and history of suicide attempts in 87 depressed patients with BD.	rs1801260*C carriers currently showed worse Hamilton Depression Rating Scale scores for suicide and worse ratings for depressive cognitive distortions. Previous history of attempted suicide associated with exposure to higher stressful events in the early life, with rs1801260*C carriers showing a higher dependency of the modeled probability of attempting suicide on the severity of exposure to early stress.	CLOCK rs1801260 modulated the relationship between early stress, adult history of attempted suicide and current suicide ideation. Factors affecting the biological clock can influence "non-clock" core psychopathological features of mood disorders.	
26203935	Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light. 
26202848	Medical residency can be a time of increased psychological stress and sleep disturbance. We examine the prospective associations between self-reported sleep quality and resident wellness across a single training year.Sixty-nine (N=69) resident physicians completed the Brief Resident Wellness Profile (M=17.66, standard deviation [SD]=3.45, range: 0-17) and the Pittsburgh Sleep Quality Index (M=6.22, SD=2.86, range: 12-25) at multiple occasions in a single training year. We examined the 1-month lagged effect of sleep disturbances on residents' self-reported wellness.	Accounting for residents' overall level of sleep disturbance across the entire study period, both the concurrent (within-person) within-occasion effect of sleep disturbance (B=-0.20, standard error [SE]=0.06, p=0.003, 95% confidence interval [CI]: -0.33, -0.07) and the lagged within-person effect of resident sleep disturbance (B=-0.15, SE=0.07, p=0.037, 95% CI: -0.29, -0.009) were significant predictors of decreased resident wellness. Increases in sleep disturbances are a leading indicator of resident wellness, predicting decreased well-being 1 month later.	Sleep quality exerts a significant effect on self-reported resident wellness. Periodic evaluation of sleep quality may alert program leadership and the residents themselves to impending decreases in psychological well-being.	
26201171	Existing research shows that hospitalized patients, especially pediatric burn patients, are often sleep deprived. A pre-existing diagnosis of attention deficit/hyperactivity disorder (ADHD) further compounds a burn patient's inability to sleep. This retrospective study compared the effectiveness of zolpidem on patients with acute burns with ADHD (n = 23) and patients with acute burns without ADHD (n = 23). Effectiveness was defined based on the need for a change in the sleep medication or an increase in the zolpidem dose during the first 12 days of treatment. This study found that sleep dysfunction was similar in pediatric burn patients with and without a concurrent diagnosis of ADHD. Sixteen (69.6%) patients with and 13 (56.5%) patients without ADHD required a sleep medication change (p = 0.541). Further, while patients with ADHD required a sleep medication change (median = 5 days) sooner than those without ADHD (median = 9 days), it appears that zolpidem is not an effective drug for managing sleep in pediatric burn patients with or without ADHD.
26200520	To examine whether sleep disturbance is associated with poor physical function in older veterans in an adult day healthcare (ADHC) program.Cross-sectional.	One ADHC program in a Veterans Affairs Ambulatory Care Center.	Older veterans (N = 50) enrolled in a randomized controlled trial of a sleep intervention program who had complete baseline data.	Information on participant characteristics (e.g., age, depression, relationship to caregiver, pain, comorbidity) was collected using appropriate questionnaires. Physical function was measured using activity of daily living (ADL) and instrumental ADL (IADL) total scores from the Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire. Sleep was assessed subjectively (Pittsburgh Sleep Quality Index, Insomnia Severity Index) and objectively (wrist actigraphy).	Participants required substantial assistance with ADLs and IADLs. A regression model showed that participant characteristics (marital status, use of sleep medication, comorbidity, posttraumatic stress disorder) and living arrangement (living with a spouse or others) were significantly associated with poor physical function. Poorer objective sleep (total sleep time, total numbers of awakenings, total wake time) was significantly associated with poor physical function, accounting for a significant proportion of the variance other than participant characteristics.	Objective measures of nighttime sleep disturbance were associated with poor physical function in older veterans in an ADHC program. Further research is needed to determine whether interventions to improve sleep will delay functional decline in this vulnerable population.	
26198818	Childhood maltreatment can disturb brain development and subsequently lead to adverse socioemotional and mental health problems across the life span. The long-term association between childhood maltreatment and resting-wake brain activity during adulthood is unknown and was examined in the current study. Forty-one medically stable and medication-free military veterans (M = 29.31 ± 6.01 years, 78% male) completed a battery of clinical assessments and had [18F]-fluorodeoxyglucose positron emission tomography neuroimaging scans during quiet wakefulness. After statistically adjusting for later-life trauma and mental health problems, childhood maltreatment was negatively associated with brain activity within a priori defined regions that included the left orbital frontal cortex and left hippocampus. Childhood maltreatment was significantly associated with increased and decreased brain activity within six additional whole-brain clusters that included the frontal, parietal-temporal, cerebellar, limbic, and midbrain regions. Childhood maltreatment is associated with altered neural activity in adulthood within regions that are involved in executive functioning and cognitive control, socioemotional processes, autonomic functions, and sleep/wake regulation. This study provides support for taking a life span developmental approach to understanding the effects of early-life maltreatment on later-life neurobiology, socioemotional functioning, and mental health. 
26198763	Nonmotor symptoms (NMS) of idiopathic Parkinson's disease (IPD), specifically fatigue, depression and sleep disturbances, are important contributors for worse quality of life and poor patient outcomes. The aim of this research is to determine the relationship between fatigue and other NMS and the independent effect of fatigue on health-related quality of life (HRQoL) in patients with IPD. 86 IPD patients and 85 healthy individuals were included in our study. Participants were evaluated by their answers to the Beck Depression Inventory, Fatigue Severity Scale, Epworth Sleepiness Scale and Parkinson's Disease Questionnaire-39. Hoehn-Yahr stage, disease duration, medications and demographical characteristics were also noted. ROC analysis was used to determine the cutoff point for HRQoL. Nonparametric Spearman correlation analysis was used for determining the relationship between variables. Independent factors which affect HRQoL were detected by multiple forward stepwise logistic regression analysis. NMS were associated with each other and with HRQoL when they act concomitantly (p < 0.001). Of these three frequent NMS, depression (p < 0.05) and fatigue (p < 0.001) had independent worsening effect on HRQoL, whereas sleep disturbances did not (p > 0.05). The stage of IPD and levodopa-entacapone treatment had independent effects on HRQoL too (p < 0.05). Fatigue was found as the most important factor which affects HRQoL among all investigated NMS. So, it is important to ask about fatigue in routine controls of IPD patients and try to treat it for improving life quality.

26194730	Although empirical evidence is limited, critical illness in children is associated with disruption of the normal sleep-wake rhythm. The objective of the current study was to examine the temporal characteristics of the sleep electroencephalogram (EEG) in a sample of children with critical illness.Limited montage EEG recordings were collected for at least 24 hours from 8 critically ill children on mechanical ventilation for respiratory failure in a pediatric intensive care unit (PICU) of a tertiary-care hospital. Each PICU patient was age- and gender-matched to a healthy subject from the community. Power spectral analysis with the fast Fourier transform (FFT) was used to characterize EEG spectral power and categorized into 4 frequency bands: δ (0.8 to 4.0 Hz), θ (4.1 to 8.0 Hz), α (8.1 to 13.0 Hz), and β1/β2 (13.1 to 20.0 Hz).	PICU patients did not manifest the ultradian variability in EEG power spectra including the typical increase in δ-power during the first third of the night that was observed in healthy children. Differences noted included significantly lower mean nighttime δ and θ power in the PICU patients compared to healthy children (p < 0.001). Moreover, in the PICU patients, mean δ and θ power were higher during daytime hours than nighttime hours (p < 0.001).	The results presented herein challenge the assumption that children experience restorative sleep during critical illness, highlighting the need for interventional studies to determine whether sleep promotion improves outcomes in critically ill children undergoing active neurocognitive development.	
26194570	Little is known about the effect of lead exposure on children's sleep. This study examined the association between blood lead levels (BLL) and sleep problems in a longitudinal study of children.Four community-based elementary schools in Jintan City, China.	1,419 Chinese children.	BLL were measured when children were aged 3-5 y, and sleep was assessed at ages 9-13 y. Sleep was assessed by both parents' report, using the Children's Sleep Habits Questionnaire (CSHQ), and children's report, using an adolescent sleep questionnaire. A total of 665 children with complete data on BLL and sleep at both ages were included in the current study. Mean age of the sample at BLL assessment was 4.74 y (standard deviation [SD] = 0.89) and at sleep assessment was 11.05 y (SD = 0.88). Mean BLL was 6.26 μg/dL (SD = 2.54). There were significant positive correlations between BLL and 3 CSHQ subscales: Sleep onset delay (r = 0.113, P < 0.01), sleep duration (r = 0.139, P < 0.001), and night waking (r = 0.089, P < 0.05). Excessive daytime sleepiness (EDS) (26.1% versus 9.0%, P < 0.001) and use of sleeping pills (6.5% versus 1.8%, P = 0.03) were more prevalent in children BLL ≥ 10.0 μg/dL than in those children BLL < 10.0 μg/dL. After adjusting for demographics, BLL ≥ 10.0 μg/dL was significantly associated with increased risk for insomnia symptoms (odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.03-3.95) and EDS (OR = 2.90, 95% CI = 1.27-6.61).	The findings indicate that elevated blood lead levels in early childhood are associated with increased risk for sleep problems and excessive daytime sleepiness in later childhood.	
26194566	Examine the role of sleep in the consolidation of declarative memory in children with autism spectrum disorder (ASD).Case-control study.	Home-based study with sleep and wake conditions.	Twenty-two participants with ASD and 20 control participants between 9 and 16 y of age.	Participants were trained to criterion on a spatial declarative memory task and then given a cued recall test. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with home-based polysomnography; Wake and Sleep conditions were counterbalanced. Children with ASD had poorer sleep efficiency than controls, but other sleep macroarchitectural and microarchitectural measures were comparable after controlling for age and medication use. Both groups demonstrated better memory consolidation across Sleep than Wake, although participants with ASD had poorer overall memory consolidation than controls. There was no interaction between group and condition. The change in performance across sleep, independent of medication and age, showed no significant relationships with any specific sleep parameters other than total sleep time and showed a trend toward less forgetting in the control group.	This study shows that despite their more disturbed sleep quality, children with autism spectrum disorder (ASD) still demonstrate more stable memory consolidation across sleep than in wake conditions. The findings support the importance of sleep for stabilizing memory in children with and without neurodevelopmental disabilities. Our results suggest that improving sleep quality in children with ASD could have direct benefits to improving their overall cognitive functioning.	
26194564	Quantify the homeostatic and circadian effects on sleepiness and performance of adolescents. Examine age-related changes in homeostatic and circadian regulation of sleepiness and performance by comparing younger and older adolescent groups.Three-week laboratory study including 12 cycles of a 28-h forced desynchrony protocol.	Controlled laboratory environment with individual sleep and performance testing rooms and shared common areas.	Twenty-seven healthy adolescents including 16 females. Ages ranged from 9.6-15.2 years and participants were split into younger (n = 14 ages 9-12) and older (n = 13 ages 13-15) groups based on median age split of 13.0 years.	N/A.	Testing occurred every 2 h during scheduled wake periods. Measures included sleep latency during repeated nap opportunities and scores from a computerized neurobehavioral assessment battery including a 10-min psychomotor vigilance task, a digit symbol substitution task, and the Karolinska Sleepiness Scale. Significant main effects of circadian and homeostatic factors were observed, as well as several circadian and homeostatic interaction effects. Age group did not have a significant main effect on sleep and performance data. A significant interaction of circadian phase and age group was found for sleep latency, with younger adolescents showing greater circadian modulation than older teens during the circadian night.	Adolescents demonstrated a similar pattern of response to forced desynchrony as reported for adults. Sleepiness and performance were affected by homeostatic and circadian factors, and age group did not interact with homoeostatic and circadian factors for subjective sleepiness and most performance metrics. Younger adolescents had a shorter latency to sleep onset than older during the circadian bin spanning 4 to 8 h after the onset of melatonin secretion.	

26190532	To analyze relevance of sleep quality with CVD in T2D patients and determine whether inflammation prompted by poor sleep has impact on the CVD.332 T2D patients were recruited and their sleep qualities were evaluated by PSQI. The patients with PSQI score >7 were in the poor sleep group, and the others were in the good sleep group. Plasma samples of the patients were obtained to measure inflammatory markers. Correlation analyses and regression analyses were performed to examine the cross-sectional relationships among the poor sleep, inflammatory markers and CVD.	The morbidity of CVD was significantly higher in the poor sleep patients compared to the good sleep patients (P=0.000). PSQI score ORs were both >1 for CVD in model 1 and model 2 (P<0.05). PSQI score were positively related to IL-6 and ICAM-1(P<0.05), negatively to FBI (P<0.05), but not related to CRP in linear regression models. Multiple logistic regression analysis showed IL-6 and ICAM-1, but not FBI and CRP, were related to CVD (P<0.05).	Poor sleep is regarded as a plausible risk factor for CVD in T2D patients, and may be mediated by certain inflammatory markers.	
26189834	Recently, two high-quality clinical randomized controlled trials (RCTs) regarding the preventive effect of exogenous melatonin on delirium drew inconsistent conclusions. We therefore performed a systemic review to explore whether melatonin had a benefit on delirium prevention. MEDLINE, EMBASE, and Cochrane Library were searched from January 1980 to April 2015 for English language studies. After strict selection and evaluation, the data were extracted from the included four RCTs. The primary outcome of this meta-analysis was the incidence of delirium. The secondary outcome was the improvement of sleep-wake rhythm. A total of four RCTs with 669 elderly patients were included in the present study. Melatonin group showed a tendency to decrease the incidence of delirium (relative risk [RR] 0.41, 95 % confidence interval [CI] 0.15 to 1.13; P = 0.08) compared with control group. In subgroup analysis of the elderly patients in medical wards, melatonin supplementation decreased the incidence of delirium by 75 % (RR 0.25, 95 % CI 0.07 to 0.88; P = 0.03), but not in sleep-wake disturbance (RR 1.24, 95 % CI 0.51 to 3.00; P = 0.64). No differences were found in the incidence of delirium between the two groups in the elderly patients that were presented to surgical wards. In conclusion, melatonin supplementation had a significant preventive effect in decreasing the incidence of delirium in elderly patients that were presented to medical wards. Further studies should provide sufficient evidence about the effect of melatonin on delirium in a large sample size. 
26189583	A small number of recent papers have described individuals with intellectual disabilities and microdeletions in chromosome band 19p13.2. However, little is known about the behavioral characteristics of individuals with microdeletions in this area. The current study examines behavioral characteristics of a series of 10 participants ranging in age from 2 to 20 years with 19p13.2 microdeletions. Parents/caregivers completed a series of established behavioral measures which have aided the elucidation of the behavioral phenotypes of a number of genetic neurodevelopmental syndromes. All but the youngest two participants (aged 2 and 3 years) were verbal, ambulant, and classified as "partly able" or "able" with regard to self-help skills. Six of eight participants for whom a screening measure for autism spectrum disorders (ASD) could be deployed met criteria for an ASD. Six of the 10 participants had displayed self-injurious behavior in the month prior to assessment, eight had displayed destruction/disruption of property, and eight had shown physically aggressive behaviors. Repetitive behaviors were prevalent in the sample (with all participants displaying at least one repetitive behavior to a clinically relevant level), as were problems with sleep. Low mood was not prevalent in this group, and nor were overactivity or impulsivity. Full determination of a behavioral phenotype for this group would require a larger sample size, distinguishing between genetic subtypes. However, the current data suggest that ASD characteristics, repetitive, and challenging behaviors (such as aggression and self-injury) might be associated with 19p13.2 microdeletions, providing a basis for future investigation.
26188954	Our goal was to estimate the pooled prevalence of self-reported sleep disturbances in HIV-infected people through meta-analysis, taking into account variations in geographic region, gender, age group, CD4 counts, and instrument used to measure sleep disturbances.The authors conducted systematic searches of PubMed and PsycINFO to include studies that met our criteria. A random effect meta-analysis model was used to estimate the pooled prevalence of self-reported sleep disturbances in HIV-infected people. The potential moderators of self-reported sleep disturbances were explored with meta-regression analysis.	Twenty-seven articles comprising a total of 9246 HIV-positive participants were finally included in our analysis. The overall prevalence of self-reported sleep disturbances in HIV-infected people was 58.0% (95% CI = 49.6-66.1). Meta-regression analysis indicates that geographic region, gender, and instrument significantly explain part of the heterogeneity of the prevalence estimates between the included studies.	The findings suggest that HIV-infected people suffer from a heavy burden of sleep disturbances. It is therefore recommended that sleep quality should be routinely assessed in HIV-infected people in order to identify the medical treatment needs and the potential impact of sleep problems on antiretroviral therapy outcomes in this population.	
26188599	In an increasingly aged population, sleep disturbances and neurodegenerative disorders have become a major public health concern. Poor sleep quality and cognitive changes are complex health problems in aging populations that are likely to be associated with increased frailty, morbidity, and mortality, and to be potential risk factors for further cognitive impairment. We aimed to evaluate whether sleep quality and excessive daytime sleepiness may be considered as early predictors of cognitive impairment.The objective of this study was to examine whether subjective sleep quality and daytime sleepiness are associated with cognition in middle-aged males.	A total of 189 healthy males born in 1953 were considered as participants for the study. Based on previous cognitive assessments, the participants were selected for the study as cognitively improved (N = 97) or cognitively impaired (N = 92).	The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale measured subjective sleep quality and daytime sleepiness, respectively. Depressive symptoms were determined using Beck's Depression Inventory (BDI-II). A neuropsychological battery was administered to confirm group differences in cognitive functioning at the time when sleep data were collected.	Compared with cognitively improved males, the cognitively impaired group reported significantly lower subjective sleep quality (5.40 ± 3.81 vs. 4.39 ± 2.40, p = 0.03). Forty-one percent of the sample exhibited poor sleep quality and 15% experienced excessive daytime sleepiness. There were few correlations between sleep parameters and cognitive test performance in the combined sample.	Self-reported poor sleep quality was related to cognitive changes, whereas daytime sleepiness was not related. Our results suggest that sleep quality may be an early marker of cognitive decline in midlife.	
26188127	Bruxism is associated with an increase in the activity of the jaw-closing muscles during sleep and wakefulness. However, the changes in jaw-closing muscle activity across states of vigilance over a 24-h period are unclear. In this study, we investigated the effects of dark/light transition and sleep/wake state on EMG activity of the masseter (jaw-closing) muscle in comparison with the activity of the upper trapezius muscle (a neck muscle) over a 24-h period in mice. The activities of the masseter and neck muscles during wakefulness were much greater than during non-REM and REM sleep. In contrast, the activities of both muscles slightly, but significantly, decreased during the transition period from dark to light. Histograms of masseter activity during wakefulness and non-REM sleep showed bimodal distributions, whereas the neck muscle showed unimodal activation in all states. These results suggest that the activities of jaw-closing and neck muscles are modulated by both sleep/wake state and dark/light transition, with the latter being to a lesser degree. Furthermore, even during non-REM sleep, jaw-closing muscles display bimodal activation, which may contribute to the occurrence of exaggerated aberrant muscle activity, such as sleep bruxism. 
26187185	Recent research has suggested that the prevalence of problematic substance use within the Asperger syndrome population has previously been underestimated. Furthermore, there is some indication that problematic substance use might take place to manage the traits of Asperger syndrome; however this possibility has yet to be examined in detail. This study aimed to address this omission by exploring individuals' perceptions of their substance use in relation to their diagnosis of Asperger syndrome.Eight participants were recruited from either a specialist Asperger syndrome service or a drug and alcohol service. Participants were interviewed regarding their views of which factors led to their development and maintenance of problematic substance use, specifically in relation to their experience of having been diagnosed with Asperger syndrome. Thematic analysis was conducted on the interview transcripts.	Six main themes were identified: self-medication; social facilitation; discrepancy between need and support; defining problematic substance use; substance use of peers, and recreational use of substances. The two themes of social facilitation and self-medication are focused on within this paper as they most closely reflect the more prominent bodies of literature in relation to the research aim.	Participants reported that substances were used to act as a social facilitator to compensate for social deficits by increasing confidence in social settings and increasing participants' ease with which they communicate. The self-medication of psychological distress was reported and was associated with depression, anxiety and sleep difficulties. The study ends with a reflection on the method of data collection, the implications for clinical practice and suggestions for future research.	
26184700	The aim of this study is to identify patterns of sleep difficulty in older women, to investigate whether sleep difficulty is an indicator for poorer survival, and to determine whether sleep difficulty modifies the association between disease and death. Data were from the Australian Longitudinal Study on Women's Health, a 15-year longitudinal cohort study, with 10 721 women aged 70-75 years at baseline. Repeated-measures latent class analysis identified four classes of persistent sleep difficulty: troubled sleepers (N = 2429, 22.7%); early wakers (N = 3083, 28.8%); trouble falling asleep (N = 1767, 16.5%); and untroubled sleepers (N = 3442, 32.1%). Sleep difficulty was an indicator for mortality. Compared with untroubled sleepers, hazard ratios and 95% confidence intervals for troubled sleepers, early wakers, and troubled falling asleep were 1.12 (1.03, 1.23), 0.81 (0.75, 0.91) and 0.89 (0.79, 1.00), respectively. Sleep difficulty may modify the prognosis of women with chronic diseases. Hazard ratios (and 95% confidence intervals) for having three or more diseases (compared with 0 diseases) were enhanced for untroubled sleepers, early wakers and trouble falling asleep [hazard ratio = 1.86 (1.55, 2.22), 1.91 (1.56, 2.35) and 1.98 (1.47, 2.66), respectively], and reduced for troubled sleepers [hazard ratio = 1.57 (1.24, 1.98)]. Sleep difficulty in older women is more complex than the presence or absence of sleep difficulty, and should be considered when assessing the risk of death associated with disease.
26181470	Sleep-related problems, such as symptoms of insomnia, daytime sleepiness, shorter sleep duration, or a delayed sleep-wake schedule, are known to be risk factors for depression. In general, depression is more prevalent in women than in men, but sleep-related problems do not necessarily show similar gender predominance. Hence, it can be speculated that the impact of sleep-related problems on the development process of depression differs between genders; however, so far, few studies have focused on this issue. The aim of this study was to clarify gender differences in the rates of depression of people with the above sleep-related problems, and to examine gender differences in factors associated with depression in Japanese young adults. A web-based questionnaire survey comprising assessments of demographic variables, sleep-related variables (bed time, wake time, sleep onset latency, frequency of difficulty in initiating sleep and that in maintaining sleep, i.e. symptom components of insomnia, and daytime sleepiness), and the 12-item version of the Center for Epidemiologic Studies Depression Scale was administered to 2502 participants (males:females = 1144:1358, age range = 19-25 years). Female predominance in the rate of depression was observed only in subjects with a delayed sleep-wake schedule (χ(2)(1) = 15.44, p < 0.001). In men, daytime sleepiness and difficulty in initiating sleep were significantly associated with depression (odds ratio [OR] = 2.39, 95% confidence interval [CI] = [1.69, 3.39], p < 0.001; OR = 3.50, 95% CI = [2.29, 5.35], p < 0.001, respectively), whereas in women, significant associations were found between depression and a delayed sleep-wake schedule (OR = 1.75, 95% CI = [1.28, 2.39], p < 0.001), daytime sleepiness (OR = 2.13, 95% CI = [1.60, 2.85], p < 0.001), and difficulty in initiating sleep (OR = 4.37, 95% CI = [3.17, 6.03], p < 0.001). These results indicate that in younger generations, the impact of a delayed sleep-wake schedule on the development of depression is greater in women; specifically, women are vulnerable to depression when they have an eveningness-type lifestyle, which is possibly attributable to the female-specific intrinsic earlier and shorter circadian rhythm. These results suggest the necessity of gender-based approaches to treating sleep-related problems for alleviating or preventing depressive symptoms in young adults.
26179453	The burden and psychological impact of providing care to a loved one with cancer is significant and associated with a number of problems including sleep disturbance and fatigue. While engaging in healthy behaviors such as proper nutrition, exercise, and stress reduction may improve sleep and fatigue, few studies have focused on this relationship. The objective of this study is to examine the relationship of health behaviors with sleep quality and fatigue in transplant caregivers.Data were analyzed from a cross-sectional survey of 78 caregivers of patients undergoing allogeneic hematopoietic stem cell transplantation. Measures included: Health-Promoting Lifestyle Profile II (HPLP-II), Brief Symptom Inventory (Distress), Caregiver Reaction Assessment (Caregiver Burden), Pittsburgh Sleep Quality Index, and the Multidimensional Fatigue Symptom Inventory Short-Form.	Controlling for age, gender, BMI, burden and distress, health behaviors predicted sleep quality (B = -0.408, p = 0.021) and fatigue (B = -0.966, p < 0.001). Stress management (B = -0.450, p = 0.001), nutrition (B = -0.249, p = 0.048), and interpersonal relationships (B = -0.319, p = 0.049) were the HPLP-II subscales that significantly predicted sleep quality; nearly every HPLP-II subscale predicted fatigue.	Despite the burden and distress associated with caregiving, engaging in healthy behaviors may help to improve sleep and fatigue in transplant caregivers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.	
26179331	Nonmotor symptoms (NMS) are an important prodromal feature of Parkinson's disease (PD). However, their frequency, treatment rates, and impact on health-related quality of life (HRQoL) in the early motor phase is unclear. Rates of NMS in enriched at-risk populations, such as first-degree PD relatives, have not been delineated. We assessed NMS in an early cohort of PD, first-degree PD relatives and control subjects to address these questions. In total, 769 population-ascertained PD subjects within 3.5 years of diagnosis, 98 first-degree PD relatives, and 287 control subjects were assessed at baseline across the following NMS domains: (1) neuropsychiatric; (2) gastrointestinal; (3) sleep; (4) sensory; (5) autonomic; and (6) sexual. NMS were much more common in PD, compared to control subjects. More than half of the PD cases had hyposmia, pain, fatigue, sleep disturbance, or urinary dysfunction. NMS were more frequent in those with the postural instability gait difficulty phenotype, compared to the tremor dominant (mean total number of NMS 7.8 vs. 6.2; P < 0.001). PD cases had worse HRQoL scores than controls (odds ratio: 4.1; P < 0.001), with depression, anxiety, and pain being stronger drivers than motor scores. NMS were rarely treated in routine clinical practice. First-degree PD relatives did not significantly differ in NMS, compared to controls, in this baseline study. NMS are common in early PD and more common in those with postural instability gait difficulty phenotype or on treatment. Despite their major impact on quality of life, NMS are usually under-recognized and untreated.
26179204	Research looking at the association between sleep and psychiatric symptoms in elderly Asian populations is lacking. The present study examines the sleep correlates of depression and anxiety in a sample of cognitively healthy older adults.The Geriatric Depression Scale, Geriatric Anxiety Inventory, and the Pittsburgh Sleep Quality Index were administered to a community sample of elderly participants (n = 107; 81 women; Mage = 71.3 years, SD = 5.7) RESULTS: Geriatric Depression Scale and Geriatric Anxiety Inventory scores are both significantly correlated with sleep disturbance. Geriatric Depression Scale scores are uniquely associated with daytime dysfunction, and Geriatric Anxiety Inventory scores are uniquely associated with perceived sleep quality, sleep latency, and global Pittsburgh Sleep Quality Index scores.	Depression and anxiety in a cohort of elderly Asian subjects are associated with a number of sleep-related issues; both are related to a somewhat different profile of sleep problems.	
26177462	In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC).A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD.	Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC.	Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.	
26176212	Patients with cirrhosis are known to experience sleep disturbance, which negatively impacts health-related quality of life.To assess the prevalence and predictors of sleep disturbance before and after liver transplantation (LT).	Both pre- and post-LT patients were administered the Basic Nordic Sleep Questionnaire. The primary outcome was overall sleep satisfaction; the secondary outcomes were sleep latency and sleep duration.	Eighty-three patients participated pre-LT and 273 post-LT. Overall, participants having completed both pre- and post-LT questionnaires reported satisfactory sleep 61% of the time before LT and 65% of the time after LT. However, on review of all questionnaires, patients with alcoholic liver disease (ETOH) experienced dramatically less sleep disturbance (OR 0.13 [95% CI 0.03 to 0.60]) post-LT, whereas those with hepatitis C remained without improvement (OR 0.90 [95% CI [0.38 to 2.15]). On logistic regression, patients with ETOH had statistically less sleep satisfaction pre-LT (OR 5.8 [95% CI 1.0 to 40.5]) and significantly better sleep satisfaction post-LT (OR 0.50 [95% CI 0.20 to 1.00]) compared with those with hepatitis C. In addition, both ETOH and other conditions had significantly better sleep latency than hepatitis C patients.	Sleep parameters for patients who undergo LT for hepatitis C do not improve following LT as much as they do in patients transplanted for ETOH. Following LT, patients transplanted for ETOH are significantly more satisfied with their sleep than those transplanted for hepatitis C. Physicians should address and manage sleep quality after LT, so as to ultimately improve quality of life.	
26175547	System epilepsy is an emerging concept interpreting major nonlesional epilepsies as epileptic dysfunctions of physiological systems. I extend here the concept of reflex epilepsy to epilepsies linked to input dependent physiological systems. Experimental and clinical reseach data were collected to create a coherent explanation of underlying pathomechanism in AE and NFLE. We propose that AE should be interpreted as epilepsy linked to the corticothalamic burst-firing mode of NREM sleep, released by evoked vigilance level oscillations characterized by reactive slow wave response. In the genetic variation of NFLE the ascending cholinergic arousal system plays an essential role being in strong relationship with a gain mutation of the nicotinic acethylcholin receptors, rendering the arousal system hyperexcitable. I try to provide a more unitary interpretation for the variable seizure manifestation integrating them as different degree of pathological arosuals and alarm reactions. As a supporting hypothesis the similarity between arousal parasomnias and FNLE is shown, underpinned by overlaping pathomechanism and shared familiarity, but without epileptic features. Lastly we propose that both AE and NFLE are system epilepsies of the sleep-wake system representing epileptic disorders of the antagonistic sleep/arousal network. This interpretation may throw new light on the pathomechanism of AE and NFLE. 
26174508	TN is one of the most common causes of facial pain. A higher prevalence of psychiatric co-morbidities, especially depressive disorder, has been proven in patients with TN; however, a clear temporal-causal relationship between TN and specific psychiatric disorders has not been well established. We performed a nationwide population-based retrospective cohort study to explore the relationship between TN and the subsequent development of psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.We identified subjects who were newly diagnosed with TN between January 1, 2000 and December 31, 2010 in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed for patients without TN who were matched according to age and sex. All TN and control patients were observed until diagnosed with psychiatric disorders, death, withdrawal from the National Health Institute system, or until December 31, 2010.	The TN cohort consisted of 3273 patients, and the comparison cohort consisted of 13,092 matched control patients without TN. The adjusted hazard ratio (aHR) of depressive disorder, anxiety disorder and sleep disorder in subjects with TN was higher than that of the controls during the follow-up [aHR: 2.85 (95% confidence interval: 2.11-3.85), aHR: 2.98 (95% confidence interval: 2.12-4.18) and aHR: 2.17 (95% confidence interval: 1.48-3.19), respectively].	TN might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder, but not schizophrenia or bipolar disorder. Additional prospective studies are required to confirm these findings.	
26174134	Antidepressants often disrupt sleep. Vortioxetine, a multimodal antidepressant acting through serotonin (5-HT) transporter (SERT) inhibition, 5-HT3, 5-HT7 and 5-HT1D receptor antagonism, 5-HT1B receptor partial agonism, and 5-HT1A receptor agonism, had fewer incidences of sleep-related adverse events reported in depressed patients. In the accompanying paper a polysomnographic electroencephalography (sleep-EEG) study of vortioxetine and paroxetine in healthy subjects indicated that at low/intermediate levels of SERT occupancy, vortioxetine affected rapid eye movement (REM) sleep differently than paroxetine. Here we investigated clinically meaningful doses (80-90% SERT occupancy) of vortioxetine and paroxetine on sleep-EEG in rats to further elucidate the serotoninergic receptor mechanisms mediating this difference. Cortical EEG, electromyography (EMG), and locomotion were recorded telemetrically for 10 days, following an acute dose, from rats receiving vortioxetine-infused chow or paroxetine-infused water and respective controls. Sleep stages were manually scored into active wake, quiet wake, and non-REM or REM sleep. Acute paroxetine or vortioxetine delayed REM onset latency (ROL) and decreased REM episodes. After repeated administration, vortioxetine yielded normal sleep-wake rhythms while paroxetine continued to suppress REM. Paroxetine, unlike vortioxetine, increased transitions from non-REM to wake, suggesting fragmented sleep. Next, we investigated the role of 5-HT3 receptors in eliciting these differences. The 5-HT3 receptor antagonist ondansetron significantly reduced paroxetine's acute effects on ROL, while the 5-HT3 receptor agonist SR57227A significantly increased vortioxetine's acute effect on ROL. Overall, our data are consistent with the clinical findings that vortioxetine impacts REM sleep differently than paroxetine, and suggests a role for 5-HT3 receptor antagonism in mitigating these differences. 

26173613	This pilot study explores sleep disruption after total knee arthroplasty and the impact of melatonin on sleep and postoperative pain. Sleep time was decreased on the last preoperative night and first two postoperative nights. Sleep efficiency was decreased on all three postoperative nights. Compared to placebo, melatonin increased sleep efficiency by 4.4% (mean; 95% CI -1.6, 10.4; P=0.150) and sleep time by 29 min (mean; 95% CI -2.0, 60.4; P=0.067). Melatonin appeared to have no effect on subjective sleep quality or daytime sleepiness, pain at rest or pain with standardized activity. In conclusion, sleep quality is impaired after total knee arthroplasty and exogenous melatonin does not appear to improve postoperative sleep or pain to a significant degree.
26172955	A population-level relative risk assessment for comorbidities associated with myotonic dystrophy has not been performed.In this study we utilized the Utah Population Database to identify patients with myotonic dystrophy in Utah according to ICD-9 coding. Comorbidity cases listed in the medical record were compared with those of the Utah population.	Individuals with myotonic dystrophy were found to possess an increased risk of central and obstructive sleep apnea, hypothyroidism, and intellectual disability. The risk of cardiac conduction disorder is 60 times the population risk.	This study provides a population-level relative risk assessment of comorbidities in myotonic dystrophy. This allows for improved counseling of patients regarding these increased risks.	


26169747	Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and additional associated symptoms, such as fatigue, sleep disturbances and depressive moods. The pathophysiology of pain in FMS is unclear. In recent years, an involvement of the thinly myelinated A-delta and the unmyelinated C-nerve fibers has been reported in FMS patients. Independent research groups published consistent objective and multidimensional findings of damage to these small nerve fibers, such as disturbances of fiber function, electrical properties and morphological changes. All these alterations are not specific for FMS; however, they were described for the first time in subgroups of FMS patients. While the reasons for this small fiber pathology and its contribution to FMS pain are still unclear, a new research field has now been opened that will focus on uncovering the underlying pathophysiology. This review article summarizes these new findings and discusses the significance for the understanding of FMS. 
26168016	Several studies have reported that both short and long sleep durations are associated with the metabolic syndrome, but whether a dose-response relationship exists is unclear.We performed a metaanalysis to study the magnitude of the association between the different durations of sleep and metabolic syndrome.	We searched in the databases of PubMed, Web of Science, and Ovid (all Journals@Ovid) from inception to October 4, 2014 for cross-sectional studies where an association between metabolic syndrome and sleep duration was analyzed.	Eighteen studies with 75,657 participants were included. Daily sleep duration of 7 to 8 hours was used as the reference group. The odds ratio (OR) of having metabolic syndrome for short (<7 h) sleep was 1.23 (95% CI, 1.11-1.37; P < 0.001; I(2), 71%). The ORs for less than 5 hours, 5 to 6 hours, and 6 to 7 hours of sleep were 1.51 (95% CI, 1.10-2.08; P = 0.01), 1.28 (95% CI, 1.11-1.48; P < 0.001), and 1.16 (95% CI, 1.02-1.31; P = 0.02), respectively. The coefficient of sleep duration on log of ORs was -0.06 ± 0.02 (P = 0.02). The OR for long sleep duration was 1.13 (95% CI, 0.97-1.32; P = 0.10; I(2), 89%).	A dose-response relationship exists between short sleep duration and metabolic syndrome. Those who report a sleep duration of less than 5 hours have a 1.5 higher odds of having metabolic syndrome. Our study does not support the notion that long sleep is associated with metabolic syndrome.	
26167964	Diagnosis of sleep apnea syndrome (SAS) depends on nocturnal polysomnography (nPSG), but waiting time for the test is long. Although, performing PSG in patients with excessive daytime sleepiness (EDS) at daytime (dPSG) was questioned, role and methods are not clear. The aim of the study was to assess the role of dPSG in the diagnosis of SAS, and the correlation between nPSG and dPSG.Forty eight subjects, who were referred to our sleep laboratory with EDS were included to a cross-over study. Half of the patients underwent nPSG after dPSG, vice versa. Seven subjects excluded due to lack of participation. The rest (n= 41) had nPSG and dPSG. PSG recordings and analysis were performed according to AASM 2007 guideline. Results were analyzed for sleep efficiency, respiratory disturbance index (RDI), oxygen desaturation index (ODI), SAS severity and correlation between dPSG and nPSG.	Total 41 subjects were analyzed. All patients had diagnosis of SAS. Sleep efficiency was higher at nPSG (86%), however also enough at dPSG (80%). Sleep stages of dPSG and nPSG were similar except stage 3 sleep, which was longer at nPSG. Undergoing dPSG or nPSG first did not correlate with sleep efficiency, respiratory disturbance (RDI) index, oxygen desaturation index (ODI) or severity of SAS. Despite BMI, neck circumference was closely related with RDI, ODI and severity.	Daytime PSG, when performed appropriately, is an effective tool for diagnosing sleep disorders in patients with EDS. dPSG may decrease the amount of times that patients must wait to undergo PSG.	
26167837	An important developmental task for adolescents is to become increasingly responsible for their own health behaviors. Establishing healthy sleep routines and controlling media use before bedtime are important for adequate, quality sleep so adolescents are alert during the day and perform well at school. Despite the prevalence of adolescent social media use and the large percentage of computers and cell phones in adolescents' bedrooms, no studies to date have investigated the link between problematic adolescent investment in social networking, their sleep practices, and associated experiences at school. A sample of 1,886 students in Australia aged between 12 and 18 years of age completed self-report data on problematic social networking use, sleep disturbances, sleep quality, and school satisfaction. Structural equation modeling (SEM) substantiated the serial mediation hypothesis: for adolescents, problematic social networking use significantly increased sleep disturbances, which adversely affected perceptions of sleep quality that, in turn, lowered adolescents' appraisals of their school satisfaction. This significant pattern was largely driven by the indirect effect of sleep disturbances. These findings suggest that adolescents are vulnerable to negative consequences from social networking use. Specifically, problematic social networking is associated with poor school experiences, which result from poor sleep habits. Promoting better sleep routines by minimizing sleep disturbances from social media use could improve school experiences for adolescents with enhanced emotional engagement and improved subjective well-being. 
26166952	Fatigue is a major debilitating symptom after stroke. The biological mechanisms underlying poststroke fatigue (PFS) are unknown. We hypothesized that PSF is associated with an alteration in the balance between Th17 and Treg cells. To test this hypothesis we assessed fatigue in 30 stroke survivors using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Peripheral blood was collected for assessment of Th17 and Treg cell populations and measurement of interleukin-10 (IL-10). Participants were dichotomized into severe fatigue (n = 14) and low-moderate fatigue (n = 16) groups by K-mean cluster analysis of FSMC scores. There were no group differences in age, gender, stroke type, stroke severity, or time since stroke. Stroke survivors in the severe fatigue group reported greater anxiety (p = 0.004) and depression (p = 0.001) than in the low-moderate fatigue group. The ratio of Th17 to Treg cells was significantly increased in the severe fatigue group relative to the mild-moderate fatigue group (p = 0.035). Serum levels of IL-10 negatively correlated withTh17/Treg ratio (r = -0.408,  p = 0.025). Our preliminary findings suggest that an imbalance in the Th17/Treg ratio is associated with the severity of PSF. 
26166591	To identify the level of depression, the level of life quality, and the relationship between these, in patients applying to sleep centers for various sleep problems.This cross-sectional study included 229 patients who applied for polysomnography at sleeping centers under supervision of the Neurology and Chest Diseases Clinics of Kayseri Education and Research Hospital, Kayseri, Turkey between June and August 2013. The data collection tools were a socio-demographical data form, Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), and the World Health Organization Quality of Life Scale (WHOQOL-BREF). For statistical analyses, the Student t-test, Kruskal-Wallis-variant analysis, and chi-square tests were used. Significance level was considered as p<0.05.	In our study, patients who were older aged, married, not working, and who had a chronic disease, and a severe depressive symptom were observed to have significantly poorer sleep quality. While patients with any chronic disease had significantly higher scores for total PSQI and depression, their physical, mental, and social WHOQOL-BREF scores were significantly lower. The PSQI total scores, and depression scores of the smoking patients were significantly higher for physical, mental, and social WHOQOL-BREF fields. There was a positive correlation between PSQI scores and BDI scores while there was a negative correlation among BDI, PSQI, and WHOQOL-BREF life quality sub-scale scores.	Sleep quality was significantly poorer in patients who were older aged, married, not working, and who had a chronic disease, and a severe depressive symptom. There was a significantly negative correlation among depression, sleep quality, and life quality, while there was a significantly positive correlation between life quality and depression.	
26166297	Sleep disorders in amyotrophic lateral sclerosis (ALS) present a significant challenge to the management of patients. Issues include the maintenance of adequate ventilatory status through techniques such as non-invasive ventilation, which has the ability to modulate survival and improve patient quality of life. Here, a multidisciplinary approach to the management of these disorders is reviewed, from concepts about the underlying neurobiological basis, through to current management approaches and future directions for research. 
26166233	Tardive dystonia is a serious extrapyramidal side effect emerging after long-term treatment with antipsychotics, frequently with a deteriorating course, and unsatisfactory treatment. Presently, clozapine is used for the cotreatment of tardive dystonia and psychosis, at the cost of serious side effects. Apart from clozapine, there have been case reports describing positive effects of quetiapine on dystonic symptoms. Aim of the present study was to demonstrate the ameliorating effects of quetiapine on dystonic symptoms, in a sample of patients suffering from antipsychotic-induced tardive dystonia.Quetiapine was administered to 16 consecutively enrolled stabilized patients with psychotic or mood disorders and tardive dystonia, replacing the "offending drugs," over a 3-month cross-tapering period. Target dose of quetiapine was set according to the defined daily dose of the received antipsychotic(s) at baseline, as reviewed by the World Health Organization Center of Drug Statistics Methodology, aiming at both maintenance of psychosis control and reduction of dystonic symptoms.	Patients were found to have significant positive results in amelioration of dystonia (P < 0.001) over a 1-year period, without loss of antipsychotic efficacy. Reduction of dystonic symptoms with the use of quetiapine could be considered comparable with the positive effects of clozapine, with the additional advantage of relatively lacking serious side effects.	Quetiapine may represent a valuable therapeutic choice for the treatment of tardive dystonia.	
26166105	Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD).We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD.The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database. Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group. Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex. Patients who had used hypnotics within 1 month meant active users. The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models.Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively. After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11-17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68-14.2) compared with the adjusted ORs of those who never used hypnotics.The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD.
26165012	To evaluate effectiveness therapeutic regimens for obstructive sleep apnea hypopnea syndrome (OSAHS) children at an acceptable cost.This study was performed at Yuying Children's Hospital of Wenzhou Medical University from Mar. 2008 to Dec. 2010. Prospective random number table method was used for the analysis; 60 children with mild OSAHS were divided into Mild OSAHS Montelukast Treatment (MM) group and Mild OSAHS Adenotonsillectomy Treatment (MAT) group. 32 children in MM group were treated with leukotriene receptor antagonists (LTRAs), while 28 children in MAT group were treated with adenotonsillectomy. Also, 58 children with moderate and severe OSAHS were divided into severe OSAHS Montelukast Treatment (SM) group and severe OSAHS Adenotonsillectomy Treatmen (SAT) group. Twenty-two children in SM group were treated with LTRAs, while 36 children in SAT group were treated with adenotonsillectomy. All selected children were evaluated by polysomnography (PSG) and Obstructive Sleep Apnea-18 (OSA-18) items before and after a six-month treatment. Both records were taken and analyzed, surgical complications and the reason for non-remission after operation were also analyzed. Two therapies were compared based on economic consideration and therapeutic effect. Result (1) PSG: A significant change of a significant change of Apnea Hypopnea Index (AHI) was observed in MM group after the treatment (before receiving the treatment 4.56 ± 1. 26, and after receiving the treatment 3. 48 ± 1. 52, t =3. 50, P <0. 05). But for oxygen desaturation Index (ODI) (MM group 2. 18 ± 2. 19, and MAT group 1. 80 ± 2. 34) and Lowest Oxygen satuation (LSaO2) (MM group 91. 66 ± 2. 34, and MAT group 92. 79 ± 2. 18), there was no significant difference in MM group and MAT group after the treatment (ODI, t =0. 65, and LSaO2 t = - 1. 93, P >0. 05). (2) OSA-18 scores: Significant differences were found in sleeping disorder (before 14. 81 ± 6. 28, and after 10. 56 ± 3. 57), the degree of familial stress (before 13. 56 ± 3. 54, and after 8. 97 ± 2. 96), and OSA-18 total scores (before 52. 66 ± 1. 11, and after 42. 56 6. 48) in MM group after the treatment (sleeping disorder Z - 3. 14, the degree of familial stress Z = -4. 50, and OSA-18 total scores Z= -4. 01, P <0. 05). (3) In addition to the cost of drugs, groups with surgical treatment had a larger economic burden than those with LTRAs treatment. (4) Treatment was totally effective for 28 children (88%) in MM group, and 28 children (100%) in MAT group. Meanwhile, treatment also achieved an obvious effect on 2 children (9%) in SM group, and in 35 children (97%) in SAT group. In MAT group, 3 children improved (11%). And in SAT group, 7 children improved (19%), but treatment was found to be ineffective in 1 case (3%). Among those effective and ineffective cases in groups with surgical treatment, there were 9 children with nasal diseases.	(1) Surgical treatment is recommended as the first choice for children with moderate and severe OSAHS. And for those who also suffer from nasal diseases, treatment combining drugs with surgery is necessary. (2) LTRAs therapy has a good effect for mild OSAHS. Surgery is also recommended when drugs could not achieve any obvious improvement in clinical symptoms of children with mild OSAHS.	
26164549	Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties. 
26164370	During the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique "in vivo" neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed.
26164369	Patients with primary dystonia, the third most prevalent movement disorder, suffer from a markedly reduced quality of life. This might, at least in part, be mediated by non-motor symptoms, including sleep disturbances. Characterising and treating sleep disturbances might provide new inroads to improve relevant patient-centred outcomes. This review evaluates the state of research on sleep in patients with dystonia and outlines an agenda for future research. A literature search was performed in July 2014 using PubMed, Medline via Ovid, PsycInfo, PsycArticles via Proquest and Embase via Ovid. Search results were screened for eligibility by two independent raters. Peer-reviewed publications reporting on sleep in patients with primary dystonia were included. Of 1445 studies identified through the search strategy, 18 met the inclusion criteria. In total, the included studies reported on 708 patients diagnosed with focal dystonia (cervical dystonia or blepharospasm), torsion dystonia, and dopa-responsive dystonia. The results indicate that at least half of the patients with focal cranial dystonia suffer from sleep disturbances, but excessive daytime sleepiness is uncommon. Sleep disturbance is associated with depressive symptoms. The frequency and duration of dystonic movements is markedly reduced during sleep. Reduced sleep quality appears to persist after treatment with botulinum toxin that successfully reduces motor symptoms. The findings are limited by a high clinical and methodological heterogeneity. Future research is needed to i) further characterize subjective and PSG sleep in patients with different types of dystonia, ii) determine the aetiology of sleep disturbances (e.g., abnormal brain function associated with dystonia, side effects of medication, psychological reasons), and iii) test whether targeted sleep interventions improve sleep and quality of life in patients with primary dystonia. 
26163057	This review appraises the process of development and the measurement properties of the Pittsburgh sleep quality index (PSQI), gauging its potential as a screening tool for sleep dysfunction in non-clinical and clinical samples; it also compares non-clinical and clinical populations in terms of PSQI scores. MEDLINE, Embase, PsycINFO, and HAPI databases were searched. Critical appraisal of studies of measurement properties was performed using COSMIN. Of 37 reviewed studies, 22 examined construct validity, 19 - known-group validity, 15 - internal consistency, and three - test-retest reliability. Study quality ranged from poor to excellent, with the majority designated fair. Internal consistency, based on Cronbach's alpha, was good. Discrepancies were observed in factor analytic studies. In non-clinical and clinical samples with known differences in sleep quality, the PSQI global scores and all subscale scores, with the exception of sleep disturbance, differed significantly. The best evidence synthesis for the PSQI showed strong reliability and validity, and moderate structural validity in a variety of samples, suggesting the tool fulfills its intended utility. A taxonometric analysis can contribute to better understanding of sleep dysfunction as either a dichotomous or continuous construct. 
26163055	Parkinson disease is one of the neurodegenerative diseases that benefited the most from the use of non-human models. Consequently, significant advances have been made in the symptomatic treatments of the motor aspects of the disease. Unfortunately, this translational success has been tempered by the recognition of the debilitating aspect of multiple non-motor symptoms of the illness. Alterations of the sleep/wakefulness behavior experienced as insomnia, excessive daytime sleepiness, sleep/wake cycle fragmentation and REM sleep behavior disorder are among the non-motor symptoms that predate motor alterations and inevitably worsen over disease progression. The absence of adequate humanized animal models with the perfect phenocopy of these sleep alterations contribute undoubtedly to the lack of efficient therapies for these non-motor complications. In the context of developing efficient translational therapies, we provide an overview of the strengths and limitations of the various currently available models to replicate sleep alterations of Parkinson's disease. Our investigation reveals that although these models replicate dopaminergic deficiency and related parkinsonism, they rarely display a combination of sleep fragmentation and excessive daytime sleepiness and never REM sleep behavior disorder. In this light, we critically discuss the construct, face and predictive validities of both rodent and non-human primate animals to model the main sleep abnormalities experienced by patients with PD. We conclude by highlighting the need of integrating a network-based perspective in our modeling approach of such complex syndrome in order to celebrate valid translational models. 
26163054	Primary care is a critical setting for screening and management of pediatric sleep difficulties. This review summarizes studies examining the prevalence of sleep problems in primary care settings as well as current practices in screening, diagnosis, and management, including behavioral recommendations and medications. Potential barriers to effectively addressing sleep are also reviewed. Despite the high prevalence of pediatric sleep problems in primary care, rates of screening and management are low. Primary care providers receive minimal sleep training and have resulting gaps in knowledge and confidence. Parents similarly have gaps in knowledge and many factors contribute to their identification of sleep as problematic. Recommendations to improve the provision of sleep services in pediatric primary care are made in the areas of research, practice, and education. 
26163053	Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. There is an increasing need to find objective measures and markers of the disorder in order to assess the efficacy of the therapies and to improve follow-up strategies. Actigraphy is an objective method for recording motor activity and sleep parameters that has been used in many studies in ADHD. Our meta-analysis aimed to assess the current evidence on the role of actigraphy in both the detection of changes in motor activity and in sleep patterns in ADHD. A systematic review was carried out to find studies comparing children with unmedicated ADHD versus controls, using actigraphic measures as an outcome. The primary outcome measures were "sleep duration" and daytime "activity mean". As secondary outcome measures we analyzed "sleep onset latency", "sleep efficiency" and "wake after sleep onset". Twenty-four studies comprising 2179 children were included in this review. We show evidence that ADHD compared to typically developing children present a higher mean activity during structured sessions, a similar sleep duration, and a moderately altered sleep pattern. This study highlights the role of actigraphy as an objective tool for the ambulatory monitoring of sleep and activity in ADHD. 
26161567	Sleep disturbances are frequently reported by patients with chronic hepatitis C virus (HCV) during treatment with interferon (IFN) α plus ribavirin. Poor sleep quality is related to the onset of depression and impaired quality of life in patients receiving treatment. The aims of this study were to apply the Mini Sleep Questionnaire (MSQ) as a screening tool to assess the self-reported sleep quality and the prevalence of sleep disorders.We conducted a transversal, observational, descriptive study comprising 41 subjects with HCV, divided into two groups, treatment (N.=16) and control (N.=25). A structured questionnaire was used to collect sociodemographic and clinical data and the MSQ was applied to assess the sleep quality. A Chi-square test was applied to compare sleep quality between groups.	Significant differences between groups in the classification of sleep quality were observed (P<0.05). The group of patients under treatment presented higher frequency of sleep disorders (63%) when compared to the control group (12%). Additionally, the apnea domain was the most impacted.	This study identified a higher prevalence of sleep disorders and self-reported poor sleep quality in HCV patients under treatment. The MSQ may be useful as a screening tool for sleep disorders in HCV patients during the treatment with IFN-α plus ribavirin.	
26160555	Genetic underpinnings for sleep disorders in humans remain poorly identified, investigated and understood. This is due to the inherent complexity of sleep and a disruption of normal sleep parameters in a number of neurological disorders. On the other hand, there have been steady and remarkable developments in the investigation of sleep using model organisms such as Drosophila. These studies have illuminated conserved genetic pathways, neural circuits and intra-cellular signaling modules in the regulation of sleep. Additionally, work in model systems is beginning to clarify the role of the circadian clock and basal sleep need in this process. There have also been initial efforts to directly model sleep disorders in flies in a few instances where a genetic basis has been suspected. Here, we discuss the opportunities and limitations of studying sleep disorders in Drosophila and propose that a greater convergence of basic sleep research in model organisms and human genetics should catalyze better understanding of sleep disorders and generate viable therapeutic options. 
26159605	Sleep disturbances and disruption of the neural regulation of the sleep-wake rhythm appear to be involved in the cellular and molecular mechanisms of cognitive decline. Although sleep problems are highly prevalent in mild cognitive impairment (MCI) and many types of dementia, they have not been systematically investigated in the clinical setting and are often only investigated by sleep specialists upon individual request.This review discusses sleep disorders in the context of cognitive decline and provides an overview of the clinical diagnosis and management of these disorders in patients with dementia and MCI. Key Messages: Sleep disorders are largely underestimated and do not receive sufficient attention in the global management of dementia patients. Sleep disturbances have a significant impact on cognitive and physical functions in individuals with cognitive decline and may be associated with important psychological distress and depression. They are positively associated with the severity of behavioral problems and cognitive impairment.	The recent recommendations by the Sleep Study Group of the Italian Dementia Research Association can be used as a guideline for the clinical assessment and management of sleep disorders in MCI and dementia patients. Sleep disorders should be carefully investigated using an in-depth sleep history, physical examination, questionnaires and clinical scales and should be validated with the support of a direct caregiver. The recommendations for older adults can be used as a framework to guide the diagnosis and treatment of sleep disorders in individuals with dementia and MCI. The management strategy should be based on the choice of different treatments for each sleep problem present in the same patient, while avoiding adverse interactions between treatments.	
26158893	Excessive daytime sleepiness commonly affects obese people, even in those without sleep apnea, yet its causes remain uncertain. We sought to determine whether acute dietary changes could induce or rescue wake impairments independent of body weight.We implemented a novel feeding paradigm that generates two groups of mice with equal body weight but opposing energetic balance. Two subsets of mice consuming either regular chow (RC) or high-fat diet (HFD) for 8 w were switched to the opposite diet for 1 w. Sleep recordings were conducted at Week 0 (baseline), Week 8 (pre-diet switch), and Week 9 (post-diet switch) for all groups. Sleep homeostasis was measured at Week 8 and Week 9.	Young adult, male C57BL/6J mice.	Differences in total wake, nonrapid eye movement (NREM), and rapid eye movement (REM) time were quantified, in addition to changes in bout fragmentation/consolidation. At Week 9, the two diet switch groups had similar body weight. However, animals switched to HFD (and thus gaining weight) had decreased wake time, increased NREM sleep time, and worsened sleep/wake fragmentation compared to mice switched to RC (which were in weight loss). These effects were driven by significant sleep/wake changes induced by acute dietary manipulations (Week 8 → Week 9). Sleep homeostasis, as measured by delta power increase following sleep deprivation, was unaffected by our feeding paradigm.	Acute dietary manipulations are sufficient to alter sleep and wakefulness independent of body weight and without effects on sleep homeostasis.	
26158542	Wearable fitness-tracker devices are becoming increasingly available. We evaluated the agreement between Jawbone UP and polysomnography (PSG) in assessing sleep in a sample of 28 midlife women. As shown previously, for standard actigraphy, Jawbone UP had high sensitivity in detecting sleep (0.97) and low specificity in detecting wake (0.37). However, it showed good overall agreement with PSG with a maximum of two women falling outside Bland-Altman plot agreement limits. Jawbone UP overestimated PSG total sleep time (26.6 ± 35.3 min) and sleep onset latency (5.2 ± 9.6 min), and underestimated wake after sleep onset (31.2 ± 32.3 min) (p's < 0.05), with greater discrepancies in nights with more disrupted sleep. The low-cost and wide-availability of these fitness-tracker devices may make them an attractive alternative to standard actigraphy in monitoring daily sleep-wake rhythms over several days.
26156958	To review sleep related consumer technologies, including mobile electronic device "apps," wearable devices, and other technologies. Validation and methodological transparency, the effect on clinical sleep medicine, and various social, legal, and ethical issues are discussed.We reviewed publications from the digital libraries of the Association for Computing Machinery, Institute of Electrical and Electronics Engineers, and PubMed; publications from consumer technology websites; and mobile device app marketplaces. Search terms included "sleep technology," "sleep app," and "sleep monitoring."	Consumer sleep technologies are categorized by delivery platform including mobile device apps (integrated with a mobile operating system and utilizing mobile device functions such as the camera or microphone), wearable devices (on the body or attached to clothing), embedded devices (integrated into furniture or other fixtures in the native sleep environment), accessory appliances, and conventional desktop/website resources. Their primary goals include facilitation of sleep induction or wakening, self-guided sleep assessment, entertainment, social connection, information sharing, and sleep education.	Consumer sleep technologies are changing the landscape of sleep health and clinical sleep medicine. These technologies have the potential to both improve and impair collective and individual sleep health depending on method of implementation.	

26156003	Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS-diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025-.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea. 
26154455	To assess short-term tomographic changes in the upper airway dimensions and quality of life of mouth breathers after rapid maxillary expansion (RME).A total of 25 mouth breathers with maxillary atresia and a mean age of 10.5 years old were assessed by means of cone-beam computed tomography (CBCT) and a standardized quality of life questionnaire answered by patients' parents/legal guardians before and immediately after rapid maxillary expansion.	Rapid maxillary expansion resulted in similar and significant expansion in the width of anterior (2.8 mm, p < 0.001) and posterior nasal floor (2.8 mm, p < 0.001). Although nasopharynx and nasal cavities airway volumes significantly increased (+1646.1 mm3, p < 0.001), oropharynx volume increase was not statistically significant (+1450.6 mm3, p = 0.066). The results of the quality of life questionnaire indicated that soon after rapid maxillary expansion, patients' respiratory symptoms significantly decreased in relation to their initial respiratory conditions.	It is suggested that RME produces significant dimensional increase in the nasal cavity and nasopharynx. Additionally, it also positively impacts the quality of life of mouth-breathing patients with maxillary atresia.	
26153282	Two patients each developed a single, fixed somatic delusion complicating their existing bipolar disorder. Both failed to respond to a range of antidepressant and antipsychotic medications. They each showed a partial response to clozapine and to electroconvulsive therapy, with resolution of mood symptoms and diminution of their ongoing somatic preoccupation. A review of case reports suggests a possible relationship between somatic delusions and affective disorders. 
26151994	The aims of the study were: evaluation of depressive symptoms in climacteric women, comparison of depressive symptoms between peri- and post-menopausal women, and assessment of a possible relationship between the presence of depressive symptoms and the hormonal profile of the studied women.The study included 45 peri-menopausal and 95 post-menopausal women admitted to the Department of Gynecological Endocrinology, Poznafi University of Medical Sciences, because of climacteric symptoms. The following parameters were evaluated in all studied women: intensity of climacteric symptoms (Kupperman Index), intensity of depressive symptoms (Hamilton depression scale), serum concentrations of hypothalamic-pituitary-gonadal axis hormones (FSH, LH, 17β-estradiol), prolactin (PRL) and androgens [total testosterone, dehydroepiandrosterone sulfate (DHEAS)]. FSH, LH, 17β-estradiol, PRL, and total testosterone were evaluated by the immunoenzymatic methods and DHEAS was measured by the radioimmunological method.	Psychic and somatic manifestations of anxiety and fear, shallow sleep, and general somatic symptoms were the most frequent depressive symptoms in both studied groups. Both investigated groups differed in relation to the incidence and intensity of symptoms from the genital system (observed more often in post-menopausal women) and hypochondria (noted more frequently in peri-menopausal women). Numerous relationships between the incidence and intensity of certain symptoms and serum concentrations of the investigated hormones were found in both groups. The correlations were different in peri- and post-menopausal subjects.	
26151909	The basal forebrain (BF) plays a crucial role in cortical activation. Our previous study showed that activation of cholinergic BF neurons alone is sufficient to suppress slow-wave sleep (SWS) and promote wakefulness and rapid-eye-movement (REM) sleep. However, the exact role of silencing cholinergic BF neurons in the sleep-wake cycle remains unclear. We inhibitied the cholinergic BF neurons genetically targeted with archaerhodopsin (Arch) with yellow light to clarify the role of cholinergic BF neurons in the sleep-wake cycle. Bilateral inactivation of cholinergic BF neurons genetically targeted with archaerhodopsin prolonged SWS and decreased the probability of awakening from SWS in mice. However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep. Furthermore, silencing these neurons for 6 h within the inactive or active period increased the duration of SWS at the expense of the duration of wakefulness, as well as increasing the number of prolonged SWS episodes (120-240 s). The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable. Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems. 
26151614	This study examined the differential associations between parent-reported child sleep problems in preschool and specific aspects of executive control in early elementary school in a large sample of typically developing children (N = 215). Consistent with expectations, sleep problems were negatively associated with performance on tasks assessing working memory and interference suppression inhibition, even after controlling for general cognitive abilities, but not with flexible shifting or response inhibition. The findings add to the literature on cognitive impairments associated with pediatric sleep loss and highlight the need for early intervention for children with sleep problems to promote healthy cognitive development. 
26151612	Two sources of information (parent-reported sleep diaries and actigraph records) were used to investigate how toddler sleep characteristics (bed time/sleep onset, wake time/sleep offset, total nighttime sleep, and total sleep time) are related to sleep problems and temperament. There were 64 toddler participants in the study. Consistent with studies of older children, parent reports differed from actigraph-based records. The findings that parent-reported and actigraph-recorded sleep characteristics varied as a function of parent report of toddler sleep problems and temperament add needed information on toddler sleep. Such information may contribute to improving parents' awareness of their child's sleep characteristics and correlates of problem sleep. 
26151611	This longitudinal study assessed the role of early sleep patterns in predicting attention regulation and behavior problems. Sleep of 43 infants was assessed using actigraphy at 12 months of age and then reassessed when the children were 3-4 years old. During this follow-up, their attention regulation and behavior problems were also assessed using a computerized test and parental reports. Lower quality of sleep in infancy significantly predicted compromised attention regulation and behavior problems. These findings underscore the need to identify and treat early sleep problems. 
26151610	This meta-analysis examined the effect experimental sleep restriction has on youth's attention and hyperactivity outcomes. Thirteen published studies containing 17 independent samples were included (N = 496). Random- and fixed-effects models were used to estimate pooled effect sizes and moderator effects, respectively. Results indicate that sleep-restricted youth had significantly worse attention outcomes than youth with extended sleep, but no differences were evident regarding hyperactivity. Significant moderators of this effect included age and sex. These results have important implications for both the prevention and treatment of attention problems, highlighting the need for health professionals to screen for and treat underlying sleep issues. 
26150021	The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high-frequency (100 Hz) electroacupuncture (EA) at Feng-Chi acupoints deteriorates both pilocarpine-induced focal epilepsy and sleep disruptions. This study investigated the effects of low-frequency (10 Hz) EA on epileptic activities and epilepsy-induced sleep disruptions.In rats, the Feng-Chi acupoint is located 3 mm away from the center of a line between the two ears. Rats received 30 min of 10 Hz EA stimuli per day before each day's dark period for three consecutive days. Our results indicated that administration of pilocarpine into the left CeA at the beginning of the dark period induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep during the consequent light period. Low-frequency (10 Hz) EA at Feng-Chi acupoints suppressed pilocarpine-induced epileptiform EEGs, and this effect was in turn blocked by naloxone (a broad-spectrum opioid receptor antagonist), but not by naloxonazine (a μ-receptor antagonist), naltrindole (a δ-receptor antagonist) and nor-binaltorphimine (a κ-receptor antagonist). Ten Hz EA enhanced NREM sleep during the dark period, and this enhancement was blocked by all of the opioid receptor antagonists. On the other hand, 10 Hz EA reversed pilocarpine-induced NREM suppression during the light period, and the EA's effect on the sleep disruption was only blocked by naloxonazine.	These results indicate that low-frequency EA stimulation of Feng-Chi acupoints is beneficial in improving epilepsy and epilepsy-induced sleep disruptions, and that opioid receptors in the CeA mediate EA's therapeutic effects.	
26149307	We examined associations between asthma and sleep in a sample of inner-city adolescents with asthma-like symptoms who are undiagnosed, and to assess the extent to which youth's report of perceived stress moderates this association.A total of 349 adolescents (83% girls), with a mean age of 15.8 years, and their primary caregivers participated. Large segments of the sample were Latinos (46%) or African Americans (37%). Adolescents reported on asthma-namely, rate of waking up at night due to asthma-like symptoms and perceived severity of breathing problems-and sleep, specifically sleep-wake behavior problems and daytime sleepiness during activities. Caregivers provided demographic information by telephone.	Night awakenings and perceived severity of breathing problems were each independently associated with sleep-wake behavior problems and daytime sleepiness during activities. Youth report of perceived stress moderated the association between perceived severity of breathing problems and sleep-wake behavior problems, and perceived severity of breathing problems and daytime sleepiness during activities.	Results suggest the importance of interventions that consider undiagnosed asthma and its effects on sleep indicators related to daytime functioning in this high risk group of youth. This study highlights the need for interventions that consider asthma severity, nocturnal asthma, and sleep problems among urban adolescents with no asthma diagnosis.	
26149168	A significant delay in the timing of endogenous circadian rhythms has been associated with delayed sleep phase disorder (DSPD). More recently, other mechanisms have also been proposed to account for this disorder. To further explore the etiology of DSPD, the present study compared nocturnal melatonin profiles of 26 DSPD patients (18 males, 8 females; age, 21.73 ± 4.98 years) and 17 normally timed good sleepers (10 males, 7 females; age, 23.82 ± 5.23 years) in a time-free, dim-light (<10 lux) laboratory environment. A 30-h modified constant routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the endogenous melatonin circadian rhythm. Salivary melatonin was sampled half-hourly from 1820 h to 0020 h and then hourly from 0120 h to 1620 h. DSPD patients had significantly later timed melatonin profiles that were delayed by approximately 3 h compared to normal sleepers, and there were no notable differences in the relative duration of secretion between groups. However, melatonin secretion between dim-light melatonin onset (DLMO) and acrophase was less prominent in DSPD patients compared to good sleepers, who showed a more acute initial surge of melatonin following the DLMO. Although the regulatory role of melatonin is unknown, abnormal melatonin profiles have been linked to psychiatric and neurological disorders (e.g., major depression, obsessive compulsive disorder, Parkinson disease). These results therefore suggest that in addition to a delayed endogenous circadian rhythm, a diminished initial surge of melatonin secretion following DLMO may contribute to the etiology of DSPD. 
26148316	To characterize patient-reported and objective sleep assessments and provide a preliminary examination of the relationships among sleep, quality of life, and demographic or treatment factors.A secondary data analysis using a descriptive-correlational design.	University of Illinois Hospital and Health Sciences System.	40 patients undergoing a hematopoietic stem cell transplantation (HCT) hospitalized for the conditioning regimen, stem cell infusion, and immediate recovery period.	Each patient wore a wrist actigraph continuously from the fourth day following HCT to the eighth day to objectively assess sleep patterns (total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, and number of awakenings). At the end of the five-day period, patients completed measures of sleep disturbance and quality of life.	Objective sleep (total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, and number of awakenings), subjective sleep (sleep disturbance), and quality of life.	The mean total nighttime sleep (objectively obtained) was 232 minutes (SD = 71 minutes), with 14 patients (35%) sleeping less than three consecutive hours during one or more study days. Age was negatively correlated with patient-reported sleep disturbance. Patient-reported sleep disturbance was significantly associated with length of hospital stay. No correlations were found between patient-reported and objective sleep assessments.	This study objectively documents inadequate and irregular sleep in hospitalized patients undergoing HCT. Sole reliance on patient-reported sleep assessments may not represent the full extent of the problem.	Attempts to streamline care during the night by not waking patients for routine care unless indicated by the patient's condition (as advocated by the American Academy of Nursing) and providing supportive care for symptoms (such as diarrhea) during the night may reduce the number of awakenings and possibly improve overall sleep quality.	
26147097	This study compared the sociodemographic characteristics, comorbidities, healthcare resource utilization, and work productivity among Japanese adults who reported being diagnosed with attention-deficit/hyperactivity disorder (ADHD) to those of a non-ADHD control population.Data for this study were captured from an online survey of adults in Japan conducted by Kantar Health using consumer panels. A total of 84 survey participants reported they had received a diagnosis of ADHD from a physician. Survey responses pertaining to functional status and resource utilization from this ADHD group were compared to those from a non-ADHD control group of 100 participants. Comparisons between the ADHD and non-ADHD groups were made using chi-square tests for categorical variables and t-tests for continuous variables.	Participants in the ADHD group were on average slightly younger with a higher proportion of males. ADHD respondents reported significantly more comorbid depression, sleep difficulties, headaches, and anxiety than non-ADHD controls. Over the previous 6 months, the ADHD group made more visits to healthcare providers and the emergency room, and had more hospitalizations than non-ADHD controls. The ADHD group also rated their overall health status lower than the non-ADHD control group. Respondents with ADHD reported a significantly higher degree of health-related work impairment compared to non-ADHD, with greater absenteeism and decreased work productivity. The ADHD group indicated their symptoms negatively impacted relationships, self-esteem, and regular daily activities.	Japanese adults with ADHD face a substantial burden of illness, including lower overall health status, increased number of comorbidities, greater healthcare utilization, and significant health-related occupational impairment compared to those without ADHD. Additional research is needed to develop a better understanding of both the consequences and treatment approaches for Japanese adults with ADHD.	
26146026	Animal and human studies have shown that disorders of the autonomic nervous system may influence sleep physiology. Conversely, sleep disorders may be associated with autonomic dysfunctions. The current review describes the clinical presentation, supposed pathogenetic mechanisms and the diagnostic and prognostic implications of impaired cardiovascular autonomic control in sleep disorders. This dysfunction may result from a common pathogenetic mechanism affecting both autonomic cardiovascular control and sleep, as in fatal familial insomnia, or it may be mainly caused by the sleep disorder, as observed in obstructive sleep apnoea. For other sleep disorders, like primary insomnia, restless legs syndrome, narcolepsy type 1 and rapid eye movement sleep behaviour disorder, the causal link with the autonomic dysfunction and its possible impact on health remains unsettled. Given its clinical implications, most of the data available suggest that a systematic assessment of the association between sleep disorders and impaired autonomic control of the cardiovascular system is warranted. Understanding the mechanism of this association may also yield insights into the interaction between the autonomic nervous system and sleep. 
26144943	The earth rotates on its axis around the sun, creating a day and night cycle, that caused the development of circadian rhythms. The circadian rhythm is primarily entrained by light, which is detected by the retina. Retinal ganglion cells project to a part of the hypothalamus termed suprachiasmatic nucleus. Here, we find the master molecular clock, composed of a transcription-translation-loop at its core. The master clock indirectly influences the innate immune system via different biological systems. Also, the master clock controls the peripheral clocks, which are present in innate immune cells. Here, circadian rhythm proteins influence the response of immune cells to pathogens. Furthermore, the master clock influences our sleep-pattern, the most important restorative physiological function. In critically ill patients the circadian rhythm is substantially altered, supporting a dysfunctional innate immune response. This review discusses recent basic science findings on the interaction of the circadian rhythm and the innate immune system. Furthermore we give an outlook on potential future therapeutic strategies. 
26144941	The confinement of critically ill patients in intensive care units (ICU) imposes environmental constancy throughout both day and night (continuous light, noise, caring activities medications, etc.), which has a negative impact on human health by inducing a new syndrome known as circadian misalignment, circadian disruption or chronodisruption (CD). This syndrome contributes to poor sleep quality and delirium, and may impair septic states frequently observed in critically ill patients. However, and although the bidirectional crosstalk between CD with sleep impairment, delirium and inflammation in animal models has been known for years and has been suspected in ICU patients, few changes have been introduced in the environment and management of ICU patients to improve their circadian rhythmicity. Delirium, the most serious condition because it has a severe effect on prognosis and increases mortality, as well as sleep impairment and sepsis, all three of them linked to disorganization of the circadian system in critically ill patients, will be revised considering the functional organization of the circadian system, the main input and output signals that synchronize the clock, including a brief description of the molecular circadian clock machinery, the non-visual effects of light, and the ICU light environment. Finally, the potential usefulness of increased light/dark contrast and melatonin treatment in this context will be analyzed, including some practical countermeasures to minimize circadian disruption and improve circadian system chronoenhancement, helping to make these units optimal healing environments for patients. 
26144940	The cardiovascular system exhibits significant daily rhythms in physiologic processes (heart rate, blood pressure, cardiac contractility and function), and molecular gene and protein expression. An increasing number of clinical and experimental studies demonstrate the circadian system is an important underlying mechanism that coordinates these rhythmic processes for the health of the cardiovascular system. However, what happens when rhythms are disturbed has been generally clinically unappreciated. Here we describe the profound adverse impact of disturbed circadian rhythms and sleep on the cardiovascular system, including recovery from myocardial infarction in acute care settings, shift work and heart disease, sleep disorders including obstructive sleep apnea, and cardiovascular pathophysiology associated with disturbed nocturnal blood pressure profiles. We also discuss therapeutic applications of circadian rhythms for the cardiovascular system. Cardiovascular disease is a leading cause of death worldwide, and applying circadian biology to cardiology (and indeed medicine in general) provides a new translational approach to benefit patients clinically. 
26144937	This article reviews our current understanding of the relationships between critical illness, circadian disruption, and delirium.Delirium is a common and morbid complication of hospitalization, particularly in the setting of critical illness and intensive care unit (ICU) admission. Critical illness involves a host of acute metabolic, hormonal and inflammatory responses that appear to disrupt normal sleep architecture and precipitate cerebral dysfunction. The intervention-heavy environment of the ICU further disrupts normal circadian rhythms and increases delirium risk. Despite strong evidence for correlation of sleep disruption, critical illness and delirium, causal relationships remain difficult to prove. Delirium is almost certainly a multifactorial condition. This article reviews proposed pathophysiologic mechanisms and potential therapeutic targets. In the absence of definitive pharmacologic therapy, interventions prioritizing maintenance of normal circadian, sleep, and behavioral patterns have shown promise in delirium risk reduction.	
26144935	A robust circadian timekeeping system is important for human health and well-being. Inappropriately timed light exposure can cause circadian and sleep disruption, which has been shown to have negative health consequences. Lighting in medical care facilities, such as the NICU, ICU, and nursing homes, is not typically controlled and may be associated with circadian disruption observed in such settings. Cycled lighting and increased exposure to sunlight in medical care facilities have been shown to have positive effects on patient recovery and well-being, and expedite hospital discharge. Additional clinical research is needed to determine the optimal light exposure timing, duration, intensity, and spectrum to best promote recovery, health and well-being in the context of medical care. 
26144934	Angiogenesis plays an important role in the treatment of acute myocardial infarction (MI). Formation of micro-vessels has the potential to prevent apoptosis of the ischemic myocardium and to improve cardiac function after MI. Delivery of growth factors or administration of stem/progenitor cells (mainly from bone marrow) are the dominant therapies to induce angiogenesis after MI. Nevertheless, clinical trials have shown that delivery of a single growth factor or single type of cell does not provide sufficient angiogenesis to promote cardiac repair. Circadian rhythms control many physiological and pathological processes in mammals. Many studies show a close relationship between circadian rhythms and MI. Disruption of the circadian rhythms in humans leads to increased incidence of MI. The onset and infarct area of MI are markedly elevated at certain time points. Determining the mechanisms of angiogenesis and vessel maturation in the ischemic heart under the control of circadian rhythms could help in the development of novel and angiogenesis- targeted therapeutics for the treatment of MI. 

26143449	Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months.	346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39-1.16). Rates of clinical improvement of the SD did not differ between groups.	Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs.	
26143166	Previous literature lacks the analysis of non-apnea sleep disorder (NASD) and peripheral arterial disease (PAD). The aim of this study was to evaluate the association between NASD and risk of developing PAD using retrospective data from a national database in Taiwan.We identified 46,064 patients with NASD using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD) from 1996 to 2010. We also selected a comparison cohort of 92,128 subjects who were randomly frequency-matched by age, sex, and entry year of the NASD cohort from the same database.	non-apnea sleep disorders.	The study followed up all subjects from their entry date to the occurrence of PAD. We evaluated the risks of PAD using Cox proportional hazards regression models. The survival function for PAD was assessed using the Kaplan-Meier method.	The risk of PAD was 1.49-fold in patients with NASD compared with patients without NASD after adjusting for age, sex, and comorbidities. Patients with NASD and diabetes or with NASD and hyperlipidemia had an increased risk of PAD compared to those without NASD and diabetes or hyperlipidemia.	We demonstrated the significantly increased risk of PAD in NASD patients through a nationwide population-based retrospective cohort study.	
26143147	We examined the effect of daily negative and positive mood on the sleep quality of knee osteoarthritis (OA) patients (N = 152) and whether a partner's daily responses to a patient's pain behaviors moderated these associations. Patients and their partners completed a baseline interview and 22 daily diary assessments. After controlling for demographic characteristics, OA severity, comorbidities, medication use, relationship satisfaction, and depressed mood, multilevel modeling analyses demonstrated main effects of negative and positive mood on sleep quality indicators. Mood and partner responses interacted such that high solicitous and punishing responses strengthened the association between negative mood and worse sleep. Further, high solicitous responses increased the degree of association between low positive mood and poor sleep, and empathic responses combined with positive mood were associated with better sleep. Results demonstrate that daily negative and positive mood fluctuations can interact with partner responses to affect sleep quality among older adults with chronic pain.
26143012	The type 1 equilibrative nucleoside transporter (ENT1) is implicated in regulating levels of extracellular adenosine ([AD]ex). In the basal forebrain (BF) levels of [AD]ex increase during wakefulness and closely correspond to the increases in the electroencephalogram (EEG) delta (0.75-4.5Hz) activity (NRδ) during subsequent non-rapid eye movement sleep (NREMS). Thus in the BF, [AD]ex serves as a biochemical marker of sleep homeostasis. Waking EEG activity in theta range (5-9Hz, Wθ) is also described as a marker of sleep homeostasis. An hour-by-hour temporal relationship between the Wθ and NRδ is unclear. In this study we examined the relationship between these EEG markers of sleep homeostasis during spontaneous sleep-wakefulness and during sleep deprivation (SD) and recovery sleep in the ENT1 gene knockout (ENT1KO) mouse. We observed that baseline NREMS amount was decreased during the light period in ENT1KO mice, accompanied by a weak correlation between Wθ of each hour and NRδ of its subsequent hour when compared to their wild-type (WT) littermates. Perfusion of low dose of adenosine into BF not only strengthened the Wθ-NRδ relationship, but also increased NREMS to match with the WT littermates suggesting decreased [AD]ex in ENT1KO mice. However, the SD-induced [AD]ex increase in the BF and the linear correlation between the EEG markers of sleep homeostasis were unaffected in ENT1KO mice suggesting that during SD, sources other than ENT1 contribute to increase in [AD]ex. Our data provide evidence for a differential regulation of wakefulness-associated [AD]ex during spontaneous vs prolonged waking. 
26142812	A significantly increased rate of positive preinterventional psychiatric histories in the unruptured aneurysm collective was demonstrated previously. The current study was designed to analyze the influence of the preinterventional psychiatric status on the outcome after treatment of unruptured intracranial aneurysms.Patients treated due to meningioma World Health Organization °I and unruptured intracranial aneurysms in 2 German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm, and neurologic deficits among others. The preinterventional psychiatric histories and the rates of postinterventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome, and quality of life (QOL) were determined by questionnaires that were mailed to the patients in a printed version.	A total of 58 M patients and 45 iA patients who met the inclusion criteria returned the questionnaires; 10 M (17.2%) and 17 iA patients (37.8%) had a positive psychiatric history. The overall Incidental aneurysm collective demonstrated significantly lower overall QOL scores (P = 0.003) and significant greater rates of chronic fatigue syndrome (P = 0.009) compared with the M collective. After we excluded all patients with positive pre-interventional psychiatric histories, those differences were no longer reproducible. Subjectively, the patients did not realize any significant changes in their QOL after successful aneurysm treatment.	The results of the current study demonstrate the importance of taking the preinterventional psychiatric history into considerations when evaluating the outcome after unruptured aneurysm treatment. The unfavorable outcome of the aneurysm group seems to be caused by factors that are not related the aneurysm diagnosis or treatment itself.	
26142303	The purposes of this study, in a sample of women with breast cancer receiving chemotherapy (CTX), were to identify subgroups of women with distinct experiences with the symptom cluster of pain, fatigue, sleep disturbance, and depressive symptoms and evaluate differences in demographic and clinical characteristics, differences in psychological symptoms, and differences in pain characteristics among these subgroups.Patients completed symptom questionnaires in the week following CTX administration. Latent class profile analysis (LCPA) was used to determine the patient subgroups.	Three subgroups were identified: 140 patients (35.8 %) in the "low," 189 patients (48.3 %) in the "moderate," and 62 patients (15.9 %) in the "all high" latent class. Patients in the all high class had a lower functional status, a higher comorbidity profile, a higher symptom burden, and a poorer quality of life.	Study findings provide evidence of the utility of LCPA to explain inter-individual variability in the symptom experience of patients undergoing CTX. The ability to characterize subgroups of patients with distinct symptom experiences allows for the identification of high-risk patients and may guide the design of targeted interventions that are tailored to an individual's symptom profile.	
26141542	Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light-induced melatonin suppression (LIMS) at night. The effective proportion of day-time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS.Twelve male subjects between the ages of 19 and 23 years (mean ± S.D., 20.8 ± 1.1) gave informed consent to participate in this study. They were exposed to various light conditions (<10, 100, 300, 900 and 2700 lx) between the hours of 09:00 and 12:00 (day-time light conditions). They were then exposed to bright light (300 lx) again between 01:00 and 02:30 (night-time light exposure). They provided saliva samples before (00:55) and after night-time light exposure (02:30).	A one-tailed paired t test yielded significant decrements of melatonin concentration after night-time light exposure under day-time dim, 100- and 300-lx light conditions. No significant differences exist in melatonin concentration between pre- and post-night-time light exposure under day-time 900- and 2700-lx light conditions.	Present findings suggest the amount of light exposure needed to prevent LIMS caused by ordinary nocturnal light in individuals who have a general life rhythm (sleep/wake schedule). These findings may be useful in implementing artificial light environments for humans in, for example, hospitals and underground shopping malls.	
26141442	Many chronic diseases are associated with both fatigue and disrupted or nonrestorative sleep. In addition, so-called 'sickness behaviors' (for example, anorexia, anhedonia, reduced social interaction, fatigue) are common during infectious and inflammatory disease and have been linked to facets of the immune response. To study these relationships, we used murine gammaherpesvirus (MuGHV), a natural pathogen of wild rodents that provides an experimental model for studying the pathophysiology of an Epstein-Barr (EBV)-like γ-herpesvirus infection in mice. We exposed male and female C57BL/6J mice that were either uninfected or latently infected with MuGHV to either sleep fragmentation (SF) or control conditions and measured the effects on behavior and markers of inflammation. Exposure of infected male mice to SF during the normal somnolent (light) phase significantly reduced locomotor activity during the subsequent active phase, despite an intervening 6-h rest period. Infection was associated with significant increases in lung IFNγ and CXC motif ligand (CXCL) 10 in both male and female mice. In both infected and uninfected male mice, exposure to SF was associated with lower levels of IL1β and C-C motif ligand (CCL) 3 in lung. Exposure of infected female mice to SF led to reductions in lung IL2, CXCL1, and CCL 3. Thus, compared with control conditions, SF was generally associated with lower concentrations of various cytokines in lung. These findings, together with our previous work, indicate that complex interactions among several host factors likely contribute to the behavioral and inflammatory changes associated with viral infection and sleep disruption even in a well-controlled mouse model. 


26140870	Traumatic events have been increasingly recognized as important precipitants of clinically significant insomnia. Trauma is an extreme form of stressful life event that generates a sustained neurobiological response triggering the onset and maintenance of insomnia. Trauma may disrupt the normal sleep-wake regulatory mechanism by sensitizing the central nervous system's arousal centers, leading to pronounced central and physiological hyperarousal. The central concept of hyperarousal has been linked to both the pathogenesis of insomnia and to the neurobiological changes in the aftermath of traumatic events, and may be a neurobiological commonality underlying trauma and insomnia. This paper presents evidence for trauma-induced insomnia and advances a model of it as an important nosological and neurobiological entity. Trauma-induced insomnia may occur in the absence of full-blown posttraumatic stress disorder (PTSD), and may also be a precursor of subsequent PTSD development. Converging lines of evidence from the neuroscience of insomnia with the neurobiology and psychophysiology of stress, fear, trauma and PTSD will be integrated to advance understanding of the condition. Preclinical and clinical stress and fear paradigms have informed the neurobiological pathways mediating the production of insomnia by trauma. Elucidating the underlying neurobiological substrates can establish novel biological markers to identify persons at risk for the condition, and help optimize treatment of the trauma-insomnia interface. Early identification and treatment of trauma-induced insomnia may prevent the development of PTSD, as well as other important sequelae such as depression, substance dependence, and other medical conditions. 
26140867	No systematic review of epidemiological evidence has examined risk factors for sleep disturbances among older adults. We searched the PubMed database combining search terms targeting the following domains 1) prospective, 2) sleep, and 3) aging, and identified 21 relevant population-based studies with prospective sleep outcome data. Only two studies utilized objective measures of sleep disturbance, while six used the Pittsburgh sleep quality index (PSQI) and thirteen used insomnia symptoms or other sleep complaints as the outcome measure. Female gender, depressed mood, and physical illness were most consistently identified as risks for future sleep disturbances. Less robust evidence implicated the following as potentially relevant predictors: lower physical activity levels, African-American race, lower economic status, previous manual occupation, widowhood, marital quality, loneliness and perceived stress, preclinical dementia, long-term benzodiazepine and sedative use, low testosterone levels, and inflammatory markers. Chronological age was not identified as a consistent, independent predictor of future sleep disturbances. In conclusion, prospective studies have identified female gender, depressed mood, and physical illness as general risk factors for future sleep disturbances in later life, although specific physiological pathways have not yet been established. Research is needed to determine the precise mechanisms through which these factors influence sleep over time. 
26140865	Intrauterine growth restriction (IUGR) complicates 5-10% of pregnancies and is associated with increased risk of preterm birth, mortality and neurodevelopmental delay. The development of sleep and cardiovascular control are closely coupled and IUGR is known to alter this development. In the long-term, IUGR is associated with altered sleep and an increased risk of hypertension in adulthood. Melatonin plays an important role in the sleep-wake cycle. Experimental animal studies have shown that melatonin therapy has neuroprotective and cardioprotective effects in the IUGR fetus. Consequently, clinical trials are currently underway to assess the short and long term effects of antenatal melatonin therapy in IUGR pregnancies. Given melatonin's role in sleep regulation, this hormone could affect the developing infants' sleep-wake cycle and cardiovascular function after birth. In this review, we will 1) examine the role of melatonin as a therapy for IUGR pregnancies and the potential implications on sleep and the cardiovascular system; 2) examine the development of sleep-wake cycle in fetal and neonatal life; 3) discuss the development of cardiovascular control during sleep; 4) discuss the effect of IUGR on sleep and the cardiovascular system and 5) discuss the future implications of melatonin therapy in IUGR pregnancies. 
26140864	Although individuals with delayed sleep wake phase disorder (DSWPD) and chronic insomnia disorder (CID) share many of the same phenomenological experiences, theories relating to the development and maintenance of these disorders are distinct in focus. Unlike CID, theory relating to DSWPD is primarily physiologically based and assumes almost no cognitive pathway. However, recent research findings suggest that individuals with DSWPD also display many of the sleep-disordered cognitive processes that were previously assumed to be unique to the insomnia experience. As such, this review aims to summarise current research findings to address the question "Could cognitive processes be involved in the development and maintenance of DSWPD?" In particular, the presence of cognitive and physiological pre-sleep arousal, sleep-related attentional bias, distorted perception of sleep and daytime functioning, dysfunctional beliefs and safety behaviours will be investigated. As this emerging area of research requires a stronger evidence base, we highlight suggestions for future investigation and provide preliminary practice points for clinicians assessing and treating "insomnia" in patients with DSWPD. 

26138280	Sleep quality affects all aspects of daily functioning, and it is vital for facilitating recovery from illness and injury. Sleep commonly becomes disrupted following moderate to severe brain injury, yet little is known about the prevalence of sleep disruption over time and how it impacts on recovery following mild injury.This was a longitudinal study of 346 adults who experienced a mild brain injury (aged ≥16 years) identified within a population-based incidence sample in New Zealand. The prevalence of sleep difficulties was assessed at baseline (within two weeks), one, six and 12 months, alongside other key outcomes.	One year post injury, 41.4% of people were identified as having clinically significant sleep difficulties, with 21.0% at a level indicative of insomnia. Poor sleep quality at baseline was significantly predictive of poorer post-concussion symptoms, mood, community integration, and cognitive ability one year post injury. The prevalence of insomnia following mild traumatic brain injury (TBI) was more than three times the rate found in the general population. Of those completing a sleep assessment at six and 12 months, 44.9% of the sample showed improvements in sleep quality, 16.2% remained stable, and 38.9% worsened.	Screening for sleep difficulties should occur routinely following a mild brain injury to identify adults potentially at risk of poor recovery. Interventions to improve sleep are needed to facilitate recovery from injury, and to prevent persistent sleep difficulties emerging.	
26132393	Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized.1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified-Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age.	The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age<40-and-low-baseline-aggression (N=40) statin-difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: β=0.64(SE=0.30)P=0.034, particularly on simvastatin: β=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: β=2.2(SE=0.55)P<0.001, particularly on simvastatin (potentially explaining two of the outliers): β=3.3(SE=0.83)P<0.001. Among (postmenopausal) women, a borderline aggression-increase on statins became significant with exclusion of one younger, surgically-menopausal woman (N=310) β=0.70(SE=0.34)P=0.039. The increase was significant, without exclusions, for women of more typical postmenopausal age (≥45): (N=304) β=0.68(SE=0.34)P=0.048 - retaining significance with modified age-cutoffs (≥50 or ≥55). Significance was observed separately for simvastatin. The aggression-increase in women on statins was stronger in those with low baseline aggression (N=175) β=0.84(SE=0.30)P=0.006. No statin effect on whole blood serotonin was observed; and serotonin-change did not predict aggression-change.	Statin effects on aggression differed by sex and age: Statins generally decreased aggression in men; and generally increased aggression in women. Both findings were selectively prominent in participants with low baseline aggression - bearing lower change-variance, rendering an effect more readily evident.	
26131982	To assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity.Prospective cohort study.	University of Chicago Medical Center general medicine wards.	Community-dwelling inpatients aged 50 and older (N = 120) MEASUREMENTS: Physical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random-effects linear regression analysis was used to examine the association between in-hospital sleep and physical activity.	From March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51-121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 ± 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 ± 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50-75; youngest quartile 121, 95% CI = 98-145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60-83; lowest tertile 125, 95% CI = 104-147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = -5.65 to -0.43, P = .02) for each additional hour of inpatient sleep.	Older, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community.	
26131842	The cause of sudden sensorineural hearing loss (SSNHL) remains unclear and therefore it is often considered as idiopathic. Sleep disturbance has been linked to SSNHL and circadian rhythm disruption, but the link between circadian rhythm disruption and SSNHL has never been investigated.In this study, we surveyed the sleep quality of 38 patients with SSNHL using a simple insomnia sleep questionnaire. The expression of circadian clock genes in peripheral blood (PB) leukocytes from 38 patients with SSNHL and 71 healthy subjects was accessed using real-time quantitative reverse transcriptase-polymerase chain reaction and validated using immunocytochemical staining.We found that 61.8% of patients with SSNHL suffered from insomnia before the insult of hearing loss. Besides, significantly decreased expression of PER1, CRY1, CRY2, CLOCK, BMAL1, and CKlε was found in PB leukocytes of patients with SSNHL when compared with healthy subjects. SSNHL patients with vertigo had significantly lower expression of CRY1 and CKlε than patients without vertigo symptoms. Our results imply the association of sleep disturbance and disrupted circadian rhythm in SSNHL. 
26130364	How cancer history and distress relate to sleep outcomes of adolescents and young adults (AYAs) is unclear. The current study compares AYA cancer survivors to controls on indicators of sleep and fatigue; examines the concurrent association between psychological status, sleep, and fatigue; and investigates the lagged relationship between sleep and fatigue problems with psychological functioning.AYA cancer survivors (n = 167) and controls (n = 170), ages 16 to 30, completed measures at a survivorship clinic/primary care visit (time 1) and 2 months later (time 2). Participants completed questions about sleep quality, quantity, sleep medication use, self-reports of sleep problems, and fatigue in addition to measures of depression, anxiety, and posttraumatic stress symptoms (PTSS).	There were no differences in sleep quantity or quality between survivors and controls, but survivors reported significantly more fatigue. Within groups, AYAs with self-reported sleep and fatigue problems reported significantly higher depression, anxiety, and PTS symptoms. Controlling for baseline depression, sleep, and fatigue problems at time 1 significantly predicted depression at time 2 in survivors but not in controls.	This study offers important insight into the psychological functioning of childhood cancer survivors and prospectively describes sleep and fatigue as risk factors for poor psychological functioning in survivors. These findings support screening for sleep problems in AYA survivors as these difficulties are closely related to mental health functioning.	
26126749	Sleep problems in children with autism spectrum disorders (ASD) are under-recognized and under-treated. Identifying treatment value accounting for health effects on family members (spillovers) could improve the perceived cost-effectiveness of interventions to improve child sleep habits. A prospective cohort study (N = 224) was conducted with registry and postal survey data completed by the primary caregiver. We calculated quality of life outcomes for the child and the primary caregiver associated with treatments to improve sleep in the child based on prior clinical trials. Predicted treatment effects for melatonin and behavioral interventions were similar in magnitude for the child and for the caregiver. Accounting for caregiver spillover effects associated with treatments for the child with ASD increases treatment benefits and improves cost-effectiveness profiles.
26126746	Given the recognition that sleep may influence obesity risk, there is increasing interest in measuring sleep parameters within obesity studies. The goal of the current analyses was to determine whether the SenseWear(®) Pro3 Armband (armband), typically used to assess physical activity, is reliable at assessing sleep parameters. The armband was compared with the AMI Motionlogger(®) (actigraph), a validated activity monitor for sleep assessment, and with polysomnography, the gold standard for assessing sleep. Participants were 20 adolescents (mean age = 15.5 years) with a mean body mass index percentile of 63.7. All participants wore the armband and actigraph on their non-dominant arm while in-lab during a nocturnal polysomnographic recording (600 min). Epoch-by-epoch sleep/wake data and concordance of sleep parameters were examined. No significant sleep parameter differences were found between the armband and polysomnography; the actigraph tended to overestimate sleep and underestimate wake compared with polysomnography. Both devices showed high sleep sensitivity, but lower wake detection rates. Bland-Altman plots showed large individual differences in armband sleep parameter concordance rates. The armband did well estimating sleep overall, with group results more similar to polysomnography than the actigraph; however, the armband was less accurate at an individual level than the actigraph.
26124812	We aimed to assess the effect of anemia on subjective sleep quality in patients with iron deficiency anemia (IDA).One hundred and four patients diagnosed with IDA and 80 healthy individuals, who are gender and age matched, were included in the study. All participants were requested to fill 3 forms: a socio-demographic form (age, gender, marital status, income level and educational status), hospital anxiety and depression (HAD) scale and pittsburgh sleep quality index (PSQI).	According to the HAD scale, the average anxiety score was found 9.24±4.37 in patients and 7.58± 4.07 in controls. And, the average depression score was 7.53±4.10 in patients and 6.41±2.74 in controls. The total sleep quality score was 6.71±3.02 in patients and 4.11±1.64 in controls. There was a statistically significant difference in terms of anxiety, depression and sleep quality scores. Linear regression analysis showed no association between anxiety and depression with poor sleeping.	IDA affects sleep quality irrespective of psychological symptoms such as depression and anxiety.	
26123629	Residual sleeping disturbances after improvement of depression in major depressed patients are associated with more functional problems, increased relapses and more risk of becoming resistant to treatment. The aim of this study was to compare the efficacy of gabapentin with clonazepam for treating residual sleeping disturbances.This comparative trial was designed as a randomized, controlled, double-blind study. Sixty-three patients with a DSM-IV diagnosis of major depressive disorder (MDD) who had been treated with one of the selective serotonin reuptake inhibitors (SSRIs; fluoxetine, citalopram or sertraline) were included in the study. The patients' depression had improved [Hamilton Depression Rating Scale (HDRS) <10] but they were complaining of sleeping problems [Pittsburgh Sleep Quality Index (PSQI) >5; Insomnia Severity Index (ISI) >8]. Patients were randomized to receive a flexible dose of gabapentin (100-600 mg/day) or clonazepam (0.5-2 mg/day) beside their current antidepressant medication for a period of 4 weeks. Outcome measures were PSQI, ISI and Clinical Global Impression (CGI).	Our results demonstrated that similar to the clonazepam group, sleeping problems improved significantly in the gabapentin group at the end of the trial (PSQI: P = 0.001, Z = 3.549; ISI: P = 0.001, Z = 3.347). The two groups did not show a significant difference in treating residual sleep disturbances (PSQI: P = 0.234, Z = 1.432; ISI: P = 0.456, Z = 1.347).	This study revealed that gabapentin is comparable to clonazepam for treating sleeping problems associated with major depression.	
26123586	Sleep participates in the regulation of body weight. The amount of sleep and synchronization of the biological clock are both necessary to achieve the energy balance and the secretion of hormones that contribute to weight regulation. In this review, we first reconsider what normal physiological sleep is and what the normative values of sleep are in the general population. Second, we explain how the biological clock regulates the hormones that may be involved in weight control. Third, we provide some recent data on how sleep may be disturbed by sleep disorders or reduced by sleep debt with consequences on weight. Finally, we explore the relationships between sleep debt and obesity. 
26122904	Parkinson's disease is a well known representent of the movement disorder group of neurological disorders. The diagnosis of Parkinson's disease is based on specific symptoms and signs of movement abnormalities. In addition to classic motor symptoms, Parkinson's disease has characteristic non-motor features, and some of these emerges the classic signs.The authors discuss characteristics and therapeutic interventions in Parkinson's disease related sleep disturbances.	The authors reviewed and summarised literature data on sleep disorders in Parkinson's disease published in the PubMed database up to January 2015.	Sleep problems are important non-motor complains (insomnia, hypersomnia, REM behaviour disorder, sleep apnea and restless legs syndrome). The neurodegenerative process of the brain-stem, the effect of symptoms of Parkinson's disease on sleep and concomitant sleep disorders constitute the background of the patient's complains.	Appropriate diagnosis and therapy of the consequential or concomitant sleep disorders in Parkinson's disease will help to improve the patient's quality of life.	
26122671	The links between attention-deficit hyperactivity disorder (ADHD) and sleep disorders remain unclear. Specific sleep disorders are a frequent comorbid condition associated with ADHD according to a categorical approach. However, sleep disorders can also induce ADHD-like symptoms according to a dimensional approach and are thought to be the consequence of excessive daytime sleepiness. It may thus be difficult for clinicians to differentiate the diagnosis of ADHD comorbid with a sleep disorder from sleep disorders with ADHD-like symptoms. This distinction could be important for the appropriate management of patients with dual complaints of trouble maintaining attention and daytime sleepiness. This paper summarizes the main sleep disorders associated with ADHD: sleep-related breathing disorders, sleep-related movement disorders, circadian rhythm sleep-wake disorders, and central disorders of hypersomnolence (aka hypersomnias). The history of presenting symptoms should be taken into account since ADHD is a neurodevelopmental disorder whereas ADHD symptoms comorbid with sleep disorder are not. Finally, we propose a model to clarify the links between ADHD, ADHD symptoms, and excessive daytime sleepiness induced by sleep disorders. Clinicians should therefore routinely assess, monitor, and manage the sleep problems of patients with ADHD who have both comorbidities and should search for the presence of ADHD symptoms in subjects with sleep disorders. 
26121385	Sleep effort is generally defined as the attempt to force and induce sleep in a voluntary manner. This study aimed to document the psychometric properties of a brief measure of sleep effort--the Glasgow Sleep Effort Scale--in its European (Portuguese) version using a large sample (N = 2,995). The results supported the good internal consistency of the overall scale scores (α = .79). Potential construct validity was evaluated with various methods, including criterion validity. There was also a convergent validity indicator. Principal components analysis revealed a 1-dimensional structure that accounted for 45% of the total variance. This preliminary study suggests that this Portuguese version of the Glasgow Sleep Effort Scale is a measure of sleep behavior suitable for research and clinical purposes. However, more studies are needed, particularly with clinical groups.
26120865	Sleep disorders are one of the most common difficulties facing older people. Meditative movement interventions (MMIs), a new category of exercise integrating physical activity and meditation (e.g., t'ai chi, yoga, and qigong), may benefit older people with sleep problems. This systematic review synthesized the evidence on the effect of MMIs on older people's quality of sleep.PubMed, EMBASE, CINAHL, PsycINFO, Scopus, the Cochrane Library, the China Science and Technology Journal Database (CSTJ) and the China National Knowledge Infrastructure (CNKI) were searched-from 1950 to March 2014-for randomized controlled trials. Articles were screened and selected by two researchers. Data were extracted from the included studies using specified forms. The same researchers independently evaluated the quality of each article. A meta-analysis was conducted to examine the pooled effect of MMI on sleep quality compared with the control groups.	Fourteen of 1049 studies were included, involving 1225 participants. Interventions included t'ai chi, yoga, qigong, and multicomponent MMI and lasted 12-24 weeks. Ten studies had a low risk of bias. The interventions resulted in significantly better sleep quality scores than either active therapy or usual care/wait-list controls (standardized mean difference, -0.70;95% confidence interval, -0.96 to -0.43). Subgroup analyses revealed that the effect of MMI on sleep quality was not influenced by the type or duration of the intervention. However, pooled results of studies with intervention frequency of fewer than 3 times per week did not show a positive effect on sleep quality. Lower-quality studies had larger effect sizes than high-quality studies. No adverse events were reported.	The current review demonstrated that MMI had a moderate effect on improving the quality of sleep for older people with sleep complaints. However, the evidence is inconclusive because of the varying study quality and MMI modalities. This study highlights the need for higher-quality randomized, controlled trials and more sufficient fidelity of intervention implementation to confirm the results. It also highlights the need for comparing the effectiveness of MMI on different subgroups of the elderly population.	
26120745	Chronic pain has a significant negative impact on the quality of life, including sleep disruption. There is compelling evidence that cognitive-behavioral therapy can be effective in treating sleep disorders. To our knowledge, no research has been carried out on brief cognitive-behavioral educational interventions in individuals with chronic pain. This study was conducted to determine whether a brief education session that incorporates sleep hygiene and cognitive-behavioral strategies would help improve the sleep of individuals with chronic pain.Eighty-five patients from a tertiary care Multidisciplinary Pain Centre completed all aspects of the study. This sample was randomized into 2 groups: a treatment group who received a brief cognitive-behavioral educational session, and a control group who did not. All participants completed a daily sleep diary for 28 days. Measures on sleep quality, beliefs and attitudes about sleep, pain, disability, and mood were recorded at baseline.	No significant differences were found between groups on demographic, pain, disability, mood measures, or sleep quality at baseline. Overall, 42% of the individuals who completed this study had depression scores above the clinical cutoff. This sample reported a high level of pain-related disability. Individuals in the treatment group had significantly reduced sleep onset latency compared to controls. No significant differences between groups on the number of times waking or hours slept.	Our findings suggest that there is potential for a brief educational intervention to have a positive impact on some aspects of sleep in the chronic pain population.	
26119209	Irregular sleep patterns can adversely affect physiological functions and have been associated with increased physiological and psychological stress. Nocturnal work of physicians during 24-hour on-call shifts (OCS) disrupts the sleep/wake cycle. Chronic exposure to distress has been shown to affect cardiovascular homeostasis and to impair performance in neurocognitive and simulated clinical tasks.In a prospective cohort study, biochemical and physiological stress parameters were assessed in 11 female and 9 male physicians (median age: 32 years, range 26-42 years) before a normal working day and after a 24-hour OCS in internal medicine. In addition, various tests of attentional performance (TAP) were conducted.	The levels of thyroid stimulating hormone (TSH) were significantly higher after a 24- hour OCS, while there were no significant changes in cortisol, epinephrine, and norepinephrine levels. Heart rate variability and skin resistance increased following an OCS, although the differences were not statistically significant. Intrinsic alertness was comparable, while phasic alertness was significantly improved following a 24-hour OCS. Focused attention tended to be better following a night shift. There was no correlation with age or medical working experience; however, men experienced more stress than women.	Following a 24-hour OCS, (i) TSH may be an early and sensitive biochemical predictor of stress; (ii) other classical biochemical stress parameters do not depict the psychological stress perceived by physicians; (iii) there may be a mismatch between experienced and objective stress levels; (iv) neurocognitive functions are not impaired, while performance may even be improved; and (v) men might be more sensitive to distress.	
26118920	More than one-half million patients are hospitalized annually for traumatic brain injury (TBI). One-quarter demonstrate sleep-disordered breathing, up to 50% experience insomnia, and half have hypersomnia. Sleep disturbances after TBI may result from injury to sleep-regulating brain tissue, nonspecific neurohormonal responses to systemic injury, ICU environmental interference, and medication side effects. A diagnosis of sleep disturbances requires a high index of suspicion and appropriate testing. Treatment starts with a focus on making the ICU environment conducive to normal sleep. Treating sleep-disordered breathing likely has outcome benefits in TBI. The use of sleep promoting sedative-hypnotics and anxiolytics should be judicious. 
26118919	Sleep-disordered breathing (SDB) is a frequent presenting manifestation of neuromuscular disorders and can lead to significant morbidity and mortality. If not recognized and addressed early in the clinical course, SDB can lead to clinical deterioration with respiratory failure. The pathophysiologic basis of SDB in neuromuscular disorders, clinical features encountered in specific neuromuscular diseases, and diagnostic and management strategies for SDB in neuromuscular patients in the critical care setting are reviewed. Noninvasive positive pressure ventilation has been a crucial advance in critical care management, improving sleep quality and often preventing or delaying mechanical ventilation and improving survival in neuromuscular patients. 
26118918	Sleep is disrupted in most patients hospitalized in the intensive care unit and the disturbances are even more profound in patients impacted by epilepsy. Nocturnal seizures must be differentiated from other common nocturnal events, such as delirium, parasomnias, and sedation. Many antiepileptic drugs produce undesirable side effects on sleep architecture that may further predispose patients to insomnia during the night and excessive sedation and hypersomnolence during the day. Failure to recognize, correctly diagnose, and adequately manage these disturbances may lead to more prolonged hospitalization, increased risk for nosocomial infections, poorer health-related qualify of life, and greater health care financial burden. 
26118911	Circadian rhythms underlie nearly all physiologic functions and organ systems. Circadian abnormalities have attendant implications for critical illness survival. The intensive care unit (ICU) environment, with its lack of diurnal variation in sound, light, and social cues, may precipitate circadian dysrhythmias. Additional features of critical care, including mechanical ventilation and sedation, likely perpetuate circadian misalignment. Critical illness itself, from sepsis to severe brain injury, can compromise circadian health. Use of daylight, time-restricted feedings, and administration of melatonin can possibly restore circadian rhythm. However, further study is necessary to assess the effectiveness of these interventions and their impact on ICU outcomes. 
26118910	The intensive care unit (ICU) environment is not propitious for restoring sleep and many studies have reported that critically ill patients have severe sleep disruptions. However, sleep alterations in critically ill patients are specific and differ significantly from those in ambulatory patients. Polysomnographic patterns of normal sleep are frequently lacking in critically ill patients and the neurobiology of sleep is important to consider regarding alternative methods to quantify sleep in the ICU. This article discusses elements of sleep neurobiology affecting the specificity of sleep patterns and sleep alterations in patients admitted to the ICU. 
26118877	If several studies analyse the working abilities of cancer survivors two years after the diagnosis, few of them analyse the long term becoming at work of these patients. Here we study a cohort of 153 workers, 6 years after they returned to work after experiencing a cancer in 2005 or 2006. All these workers participated in a previous study realised in 2008, two years after the diagnosis.Fourty occupational physicians included 153 workers out of the 319 particpating in a first study conducted in 2008. Two questionnaires were completed by both the worker and the occupationnal physician. Twenty four patients' interviews and nine physician's interviews were also realized for qualitative analysis.	Six years after they returned to work, 46% were still working in the same company. Among patients aged less than 55 years (113 out of 153), they were 20% to leave the company (a 4% annual rate). Concerning the 83 salaries still at work, sequelaes of the disease are often still present: fatigue (57%), sleep disorders (56% vs 34% at 2 years), memory and concentration disorders (34%) and chronic pain (16%). Thirty one percent reported serious anxious disorders vs 29% in 2008. Difficulties are still present in 71% of the responders. Fourty percent of the nonexecutive workers feeled penalized. Qualitative study shows that a successfull return to work is associated with a friendly environement, the support of the company, and a long term accompagnying policy.	Six years after returning to work, one employee out of two is still working in the same company. Far to disappear, the identified difficulties two years after the diagnosis are still present, long time after stopping the treatments. A successfull return to work needs an important support from both the company and the co-workers.	
26118822	Diurnal preference towards eveningness among adults has been associated with unhealthy habits and a range of health hazards, such as sleeping problems and higher odds for depression. We wanted to analyse whether diurnal preference towards eveningness is associated with more severe symptoms regarding sleep problems and mental disorders among young adults.Our sample consists of 469 young adults, aged 18-29 years, from the Mental Health in Early Adulthood Study in Finland (MEAF) conducted in 2003-2005. Chronotype was based on the assessment of one question that was asked first in 2000-2001 and the second time in 2003-2005. Those 73 participants who changed their chronotype were excluded from the main analysis, but separate analyses were performed with this group.	Concerning sleep, E-types reported higher dependency on alarm clocks (p < 0.001), and E-types and I-types had more problems in feeling refreshed after waking up (p < 0.0001 and p < 0.05 respectively) than M-types. Regarding mental health, E-types and I-types had lower odds for any lifetime DSM-IV Axis I disorder (p < 0.05 and p < 0.01 respectively) than M-types.	Our results are in line with previous findings that those with the diurnal preference towards eveningness have more frequently three or more lifetime mental disorders, more sleeping problems, more seasonal variation in mood and behaviour, and more burnout compared with those with the diurnal preference towards morningness.	
26118559	There is limited knowledge about the prospective relationship between major work characteristics (psychosocial, physical, scheduling) and disturbed sleep. The current study sought to provide such knowledge.Prospective cohort, with measurements on two occasions (T1 and T2) separated by two years.	Naturalistic study, Sweden.	There were 4,827 participants forming a representative sample of the working population.	Questionnaire data on work factors obtained on two occasions were analyzed with structural equation modeling. Competing models were compared in order to investigate temporal relationships. A reciprocal model was found to fit the data best. Sleep disturbances at T2 were predicted by higher work demands at T1 and by lower perceived stress at T1. In addition, sleep disturbances at T1 predicted subsequent higher perception of stress, higher work demands, lower degree of control, and less social support at work at T2. A cross-sectional mediation analysis showed that (higher) perceived stress mediated the relationship between (higher) work demands and sleep disturbances; however, no such association was found longitudinally.	Higher work demands predicted disturbed sleep, whereas physical work characteristics, shift work, and overtime did not. In addition, disturbed sleep predicted subsequent higher work demands, perceived stress, less social support, and lower degree of control. The results suggest that remedial interventions against sleep disturbances should focus on psychosocial factors, and that such remedial interventions may improve the psychosocial work situation in the long run.	


26116435	The choroid plexus (CP) comprises an epithelial monolayer that forms an important physical, enzymatic and immunologic barrier, called the blood-cerebrospinal fluid barrier (BCSFB). It is a highly vascularized organ located in the brain ventricles that is key in maintaining brain homeostasis as it produces cerebrospinal fluid (CSF) and has other important secretory functions. Furthermore, the CP-CSF interface plays a putative role in neurogenesis and has been implicated in neuropsychiatric diseases such as the neurodevelopmental disorders schizophrenia and autism. A role for this CNS border was also implicated in sleep disturbances and chronic and/or severe stress, which are risk factors for the development of neuropsychiatric conditions. Understanding the mechanisms by which disturbance of the homeostasis at the CP-CSF interface is involved in these different chronic low-grade inflammatory diseases can give new insights into therapeutic strategies. Hence, this review discusses the different roles that have been suggested so far for the CP in these neuropsychiatric disorders, with special attention to potential therapeutic applications. 
26115386	To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elderly adults with mobility limitations.Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors prespecified as a tertiary outcome over a planned intervention period ranging from 24 to 30 months.	Lifestyle Interventions and Independence for Elders Study.	Community-dwelling persons aged 70 to 89 who were initially sedentary and had a Short Physical Performance Battery score less than 10 (N = 1,635).	Sleep-wake behaviors were evaluated using the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (>5 defined poor sleep quality) administered at baseline and 6, 18, and 30 months.	The randomized groups were similar in terms of baseline demographic variables, including mean age (79) and sex (67% female). Structured physical activity resulted in a significantly lower likelihood of having poor sleep quality (adjusted odds ratios (aOR) for PSQI >5 = 0.80, 95% confidence interval (CI) = 0.68-0.94), including fewer new cases (aOR for PSQI >5 = 0.70, 95% CI = 0.54-0.89), than health education but not in resolution of prevalent cases (aOR for PSQI ≤5 = 1.13, 95% CI = 0.90-1.43). No significant intervention effects were observed for the ISI or ESS.	Structured physical activity resulted in a lower likelihood of developing poor sleep quality (PSQI >5) over the intervention period than health education but had no effect on prevalent cases of poor sleep quality or on sleep-wake behaviors evaluated using the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated using the PSQI.	
26112305	Obstructive sleep apnea (OSA), which is characterized by recurrent upper airway obstruction during sleep with resultant hypoxia-reoxygenation and sleep fragmentation, is prevalent among patients with cardiovascular disease. Refractory hypertension, nocturnal angina or arrhythmias, and stroke in particular should prompt consideration of OSA. The symptoms of OSA include snoring and excessive daytime sleepiness; risk factors include obesity and reduced upper airway dimensions. Up to 50% of patients with congestive heart failure (CHF) may manifest OSA, central sleep apnea-Cheyne-Stokes respiration (CSA-CSR), or both. Patients with CSA-CSR may present with fatigue, disrupted sleep, and paroxysmal nocturnal dyspnea. Objective sleep recording is required to document the nature and severity of sleep apnea. The gold standard is in-laboratory overnight polysomnography (PSG), including monitoring of electroencephalography and other signals to determine sleep-wake state, and recording of body position, airflow, respiratory effort, and pulse oximetry. Portable cardiorespiratory recorders are now approved for diagnosis in patients without comorbidities. Full PSG is recommended for diagnosis in all other cases, although OSA and CSA-CSR can be identified from portable recorders in some patients with CHF and other conditions. The objectives of treatment are to improve symptoms, quality of life, and cardiovascular outcomes. The mainstay of treatment for moderate-to-severe OSA is positive airway pressure (PAP). Automated PAP devices may be used in uncomplicated OSA, whereas continuous fixed PAP is the treatment of choice for other patients with OSA, and may also treat a proportion of patients with CSA-CSR. A form of bi-level PAP known as adaptive servoventilation is effective in treating a majority of patients with CSA-CSR. 
26110875	After a patient encounter, the physician uses two coding systems to bill for the service rendered to the patient. The Current Procedural Terminology (CPT) code is used to describe the encounter or procedure. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code is used to describe the diagnosis(es) of the patient. On October 1, 2015, ICD-9-CM coding will end, and all physicians will be required to use a new diagnostic coding system, the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). This article describes the new diagnostic coding system and how it differs from the old system. There are resources and costs involved for physicians and physician practices to prepare properly for ICD-10-CM. Similar to other important events, the more thorough the preparation, the more likely a positive outcome will occur. Resource use is very important in preparation for the transition from ICD-9-CM to ICD-10-CM. Greater familiarity with ICD-10-CM plus a thorough, effective preparation will lead to reduced costs and a smooth transition. Coding descriptor changes and additional codes occur in ICD-10-CM for chronic bronchitis and emphysema, asthma, and respiratory failure. These changes will affect the coding of these diseases and disorders by physicians. Because the number of codes will increase more than fivefold, the complexity of documentation to support ICD-10-CM will increase substantially. The documentation in the patient's chart to support the ICD-10-CM codes used will need to be enhanced. The requirement for accurate and comprehensive documentation cannot be emphasized enough. All of the coding and documentation changes will be a challenge to pulmonary, critical care, and sleep physicians. They must be prepared fully when ICD-10-CM coding begins and ICD-9-CM coding stops abruptly on October 1, 2015. 
26109502	To examine whether a mismatch between chronotype (i.e., preferred sleep timing) and work schedule is associated with type 2 diabetes risk.In the Nurses' Health Study 2, we followed 64,615 women from 2005 to 2011. Newly developed type 2 diabetes was the outcome measure (n = 1,452). A question on diurnal preference ascertained chronotype in 2009; rotating night shift work exposure was assessed regularly since 1989.	Compared with intermediate chronotypes, early chronotypes had a slightly decreased diabetes risk after multivariable adjustment (odds ratio 0.87 [95% CI 0.77-0.98]), whereas no significant association was observed for late chronotypes (1.04 [0.89-1.21]). Among early chronotypes, risk of type 2 diabetes was modestly reduced when working daytime schedules (0.81 [0.63-1.04]) and remained similarly reduced in women working <10 years of rotating night shifts (0.84 [0.72-0.98]). After ≥10 years of shift work exposure, early chronotypes had a nonsignificant elevated diabetes risk (1.15 [0.81-1.63], Ptrend = 0.014). By contrast, among late chronotypes, the significantly increased diabetes risk observed among day workers (1.51 [1.13-2.02]) appeared largely attenuated if their work schedules included night shifts (<10 years: 0.93 [0.76-1.13]; ≥10 years: 0.87 [0.56-1.34]; Ptrend = 0.14). The interaction between chronotype and shift work exposure was significant (Pinteraction = 0.0004). Analyses restricting to incident cases revealed similar patterns.	In early chronotypes, type 2 diabetes risk increased with increasing duration of shift work exposure, whereas late types had the highest diabetes risk working daytime schedules. These data add to the growing body of evidence that workers could benefit from shift schedules minimizing interference with chronotype-dependent sleep timing.	



26107227	Though a large proportion of cancer survivors are assumed to be commonly affected by sleep disturbance, few studies have focused on short sleep problems and its correlates among Korean cancer survivors. The purpose of this study was to evaluate the prevalence of short sleep in adult cancer survivors from a nationwide population-based sample and to identify risk factors for short sleep duration.Based on the fourth and fifth Korea National Health and Nutrition Examination Surveys (2007-2012), 1,045 cancer survivors and 33,929 non-cancer controls were analyzed. The prevalence of short sleep was compared between these two groups. Associations between short sleep and its correlates were evaluated using multiple logistic regression among cancer survivors: odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated after adjusting for sociodemographic factors, lifestyle factors, psychological conditions, and cancer-related factors.	About 8.1% of cancer survivors slept for less than 5 hours per day (6.2% men and 9.3% women), whereas this was the case for only 3.7% of non-cancer controls. Cancer survivors who had the lowest household income level showed a significantly higher likelihood for short sleep (adjusted OR 2.82, 95%CI 1.06-7.54). Self-reported poor health and depressive symptoms were found to be associated with significantly increased likelihood for short sleep in cancer survivors (adjusted OR 3.60, 95%CI 1.40-9.26 and adjusted OR 2.00, 95%CI 1.17-3.42). Gastric cancer survivors had a 3.97-fold increased risk for short sleep (95%CI 1.60-9.90).	The prevalence of short sleep occurs at a high rate among the Korean cancer survivors, which may indicate a poorer quality of life and a higher risk of future complications in survivorship. Targeted interventions that can assist cancer survivors to cope with sleep disturbances as well as ensuring psychological stability are warranted to reduce the latent disease burden.	
26106238	Chronic insomnia is associated with many physical and psychiatric illnesses, and its underlying aetiology needs to be identified in order to achieve safe and effective treatment. Obstructive sleep apnoea (OSA) and periodic limb movement disorder (PLMD) are common primary sleep disorders that can lead to chronic insomnia. Patients with these conditions are evaluated using polysomnography (PSG).The PSG records of 106 patients with chronic insomnia who presented to a multidisciplinary sleep clinic in Singapore over a five-year period were reviewed. To examine the utility of PSG in the evaluation of chronic insomnia, the clinical diagnoses of the patients before and after the sleep studies were compared.	Among the 106 patients, 69 (65.4%) were suspected to have primary sleep disorders based on clinical history and examination alone. Following PSG evaluation, 42.5% and 4.7% of the study population were diagnosed with OSA and PLMD, respectively. OSA was found in 35.9% of the 39 patients who had underlying psychiatric conditions.	This study illustrates that many patients with chronic insomnia have underlying primary sleep disorders. It also highlights the danger of attributing chronic insomnia in psychiatric patients to their illness, without giving due consideration to other possible aetiologies. Clinicians should maintain a high index of suspicion for the presence of other aetiologies, and make timely and targeted referrals for sleep studies where appropriate.	
26106127	Previous research has examined how age and health can shape workability (WA). This study seeks to explore how a lack of WA (inability) may affect the health of the employee.To explore the effects of work inability on mental wellbeing among therapeutic prison officers.	An anonymous cross-sectional study of prison officers conducted in a category B English prison using the Work Ability Index (WAI) and General Health Questionnaire-28 (GHQ).	Fifty-seven officers (59%) participated and of those 95% achieved GHQ caseness. Officers with poorer WA reported significantly higher GHQ scores. Work inability for mental demands had significant associations with anxiety (β = -0.58, 95% CI -4.21 to -1.88, particularly sleep loss; Pearson's r = -0.66).	Our findings present clear associations between poor WA and its impact upon mental wellbeing. The results of this study may help to focus on areas for intervention such as improving WA and promoting mental wellbeing.	
26105183	The circadian cycle is a genetically encoded clock that drives cellular rhythms of transcription, translation and metabolism. The circadian clock interacts with the diurnal environment that also drives transcription and metabolism during light/dark, sleep/wake, hot/cold and feast/fast daily and seasonal cycles. Epigenetic regulation provides a mechanism for cells to integrate genetic programs with environmental signals in order produce an adaptive and consistent output. Recent studies have revealed that DNA methylation is one epigenetic mechanism that entrains the circadian clock to a diurnal environment. We also review recent circadian findings in the epigenetic neurodevelopmental disorders Prader-Willi, Angelman and Rett syndromes and hypothesize a link between optimal brain development and intact synchrony between circadian and diurnal rhythms.
26105013	Down syndrome (DS) is the most common genetic cause of intellectual disability and results from an extra chromosome 21 (Trisomy 21). Sleep issues and/or obstructive sleep apnea (OSA) are assumed to be part of the DS phenotype with a high prevalence but are often under recognized. This cross-sectional study of children with DS examines the caregiver-reported sleep behaviors of 108 children with DS, ranging in age from 1.50 to 13.40 years (mean = 5.18 years) utilizing a standardized assessment tool, the Children's Sleep Habit Questionnaire (CSHQ). The CSHQ revealed 76% of children with DS had sleep problems, which began at a young age, and continue to persist and may recur with increasing age. Furthermore, children with DS who undergone adenoidectomy and tonsillectomy for OSA continued to have sleep problems suggesting that ongoing monitoring of sleep issues is needed in this population. Implications of sleep problems and recommended anticipatory guidance and intervention are discussed.
26103109	Care for Alzheimers' patients is quite a burden on the caregivers. Guides have been devoted to improve their knowledge about the disease and to help to provide the best care for the patient. A recent study on the reluctance of caregivers'spouses to seek external help, shows that none of 31 spouses had read a caregiver's guide. The aim of this study was to assess if caregiver's guides would help caregivers to deal with sleep/wake disorders. Amongst the 46 French guides, published between 1988 and 2013, thirty three raised the subject of the night sleep with more or less details. In these guides sleep disturbances are considered either as a symptom to be monitored or a natural aging process to be supported. We made a survey of the content of the caregiver's guides, of their goals and why they have been designed to. Then we analyze how the night sleep issue is dealt with in the guides, and eventually we consider the place to be granted to the patient in the management of his/her sleep disturbances. 
26102995	We examined sleep-related problems in adolescents and young adults after a mild traumatic brain injury (MTBI) or orthopedic injury. We extended the analysis of data from a study of early emotional and neuropsychological sequelae in these populations (McCauley et al. 2014. J Neurotrauma. 31:914).We gave the Pittsburgh Sleep Quality Index to 77 participants with MTBI, 71 with orthopedic injury, and 43 non-injured controls. The age range was 12 to 30 years. We tested sleep quality within 96 hours of injury and at 1- and 3-month follow-up. Participants also completed measures of pain and fatigue, drug and alcohol use, and post-traumatic stress symptoms.	Older participants (mean age=25 years) in the MTBI group exhibited a sharp increase in sleep-related symptoms between the baseline assessment and 1 month, and still had difficulties at 3 months. Younger participants with MTBI (mean age=15 years) and older participants with an orthopedic injury had modest increases in sleep difficulties between baseline and 1 month. The participants with MTBI also had more clinically significant sleep difficulties at all 3 assessments. At 3 months, Pittsburgh Sleep Quality Index scores in younger participants with MTBI and all participants with orthopedic injury did not differ significantly from the non-injured controls'. The controls had no significant change in their sleep symptoms during the 3 months.	Sleep difficulties in young adults may persist for ≤3 months after MTBI and exceed those after orthopedic injury. Clinicians should seek and treat sleep-related problems after MTBI.	
26102093	To clarify the significance of melatonin secretion under intensive care conditions, we investigated melatonin secretion profiles and sleep parameters of 23 patients just after admission to the coronary care unit (CCU) and 19 age-matched controls. Sleep parameters were evaluated by actigraphy, and melatonin secretion was assessed by measuring the urinary 6-sulphatoxy melatonin (6-SMT). 6-SMT secretion was lower and nocturnal sleep parameters were less satisfactory in the subjects than those in the controls, and there were positive correlations between these variables, particularly in the subject patients. The lowered melatonin secretion might be involved in the mechanism of insomnia in CCU patients. 
26101944	The quality of life of hemodialysis (HD) patients is hampered by reduced nocturnal sleep quality and excessive daytime sleepiness. In addition to the sleep/wake cycle, levels of circadian biomarkers (e.g. melatonin) are disturbed in end-stage renal disease (ESRD). This suggests impaired circadian clock performance in HD patients, but the underlying mechanism is unknown. In this observational study, diurnal rhythms of sleep, serum melatonin and cortisol concentrations and clock gene mRNA expression are compared between HD patients (n = 9) and healthy control subjects (n = 9). In addition, the presence of circulating factors that might affect circadian rhythmicity is tested in vitro with cell culture experiments. Reduced sleep quality (median sleep onset latency [interquartile range] of 23.9 [17.3] min for patients versus 5.0 [10] minutes for controls, p < 0.01; mean (± SD) sleep efficiency 70.2 ± 8.1% versus 82.9 ± 10.9%, p = 0.02 and mean awake minutes after sleep onset 104.8 ± 27.9 versus 54.6 ± 41.6 minutes, p =  0.01) and increased daytime sleepiness (mean Epworth Sleepiness Score of 10.0 ± 4.8 versus 3.9 ± 2.0, p < 0.01) were confirmed in HD patients. Reduced nocturnal melatonin concentrations (1 AM: 98.1 [122.9] pmol/L versus 12.5 [44.2] pmol/L, p =  0.019; 5 AM: 114.0 [131.6] pmol/L versus 11.8 [86.8] pmol/L, p =  0.031) and affected circadian control of cortisol rhythm and circadian expression of the clock gene REV-ERBα were found. HD patient serum had a higher capacity to synchronize cells in vitro, suggesting an accumulated level of clock resetting compounds in HD patients. These compounds were not cleared by hemodialysis treatment or related to frequently used medications. In conclusion, the abovementioned results strongly suggest a disturbance in circadian timekeeping in peripheral tissues of HD patients. Accumulation of clock resetting compounds possibly contributes to this. Future studies are needed for a better mechanistic understanding of the interaction between renal failure and perturbation of the circadian clock.
26100997	To evaluate the association between irregular sleep/wake cycle in shift workers and autonomic regulation.Cross-sectional, analytical study.	Dow University Hospital, Karachi, from August to November 2013.	All healthcare providers working in rotating shifts making a total (n=104) were included. Instrument was an integrated questionnaire applied to assess autonomic regulation, taken from Kröz et al. on scoring criteria, ranging from 18 - 54, where higher rating signifies strong autonomic regulation, indicating a stable Autonomic Nervous System (ANS) and vice versa. Participants were interviewed and their response was recorded by the investigator. Influence of sleep misalignment was measured quantitatively to extract index of autonomic activity.	There was a reduced trend in autonomic strength amongst shift workers. The mean score obtained on the Autonomic Scale was 37.8 ± 5.9.	Circadian misalignment has an injurious influence on ANS which might be valuable in controlling autonomic dysfunction that leads to fatal triggers in rotating shift workers.	
26100750	Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system. 
26100444	To test whether sleep-deprived, healthy subjects who do not always signal spontaneously perceived sleepiness (SPS) before falling asleep during the Maintenance of Wakefulness Test (MWT) would do so in a driving simulator.Twenty-four healthy subjects (20-26 years old) underwent a MWT for 40 min and a driving simulator test for 1 h, before and after one night of sleep deprivation. Standard electroencephalography, electrooculography, submental electromyography, and face videography were recorded simultaneously to score wakefulness and sleep. Subjects were instructed to signal SPS as soon as they subjectively felt sleepy and to try to stay awake for as long as possible in every test. They were rewarded for both "appropriate" perception of SPS and staying awake for as long as possible.	After sleep deprivation, seven subjects (29%) did not signal SPS before falling asleep in the MWT, but all subjects signalled SPS before falling asleep in the driving simulator (p <0.004).	The previous results of an "inaccurate" SPS in the MWT were confirmed, and a perfect SPS was shown in the driving simulator. It was hypothesised that SPS is more accurate for tasks involving continuous feedback of performance, such as driving, compared to the less active situation of the MWT. Spontaneously perceived sleepiness in the MWT cannot be used to judge sleepiness perception while driving. Further studies are needed to define the accuracy of SPS in working tasks or occupations with minimal or no performance feedback.	
26099949	Dementia is a debilitating degenerative disorder where the sufferer's cognitive abilities decline over time, depending on the type of dementia. The more common types of dementia include Alzheimer's disease and vascular or multi-infarct dementia. In this study, 20 subjects with dementia (9 of Alzheimer's type, and 11 with vascular dementia) were treated using qEEG-guided neurofeedback training. The Mini Mental Status Examination (MMSE) was used as the primary outcome measure. The results showed an increase of the MMSE scores for all subjects regardless of dementia type with an average MMSE score increase of 6 points, which was found to be significant. To our knowledge this is the first time the same modality was shown to be beneficial in both dementia groups. 
26099901	Patient Generated Index (PGI) is designed to both ask and document quality of life (QOL) concerns. Its validity with respect to standard QOL measures has not been fully established for advanced cancer when QOL concerns predominate. The specific objective of this study is to identify, for people with advanced cancer, similarities and differences in ratings of global QOL between personalized and standard measures.A total of 192 patients completed five QOL measures at study entry: PGI, generic measures (SF-6D, EQ-5D), and cancer-specific measures of QOL (McGill Quality of Life Questionnaire and Edmonton Symptoms Assessment Scale). Comparisons among total scores were compared using Generalized Estimating Equations (GEE).	Patients voiced 114 areas of QOL concerns by the PGI with the top three being fatigue, sleep, and pain (39.2, 22.6, and 21.6%, respectively). PGI total QOL score was 25 to 30 percentage points lower than those documented by the other measures, particularly when QOL was poor. Correlations between PGI and other measures were low.	PGI allowed patients to express a wide range of QOL concerns, many that were not assessed by other QOL measures. If only one QOL measure is to be included, either in a clinical setting or for research, the PGI would satisfy many of the criteria for "best choice." PGI could be considered a cancer-specific QOL measure.	This study provides evidence that the PGI would be a good measure for patients and clinicians to use together to identify areas of concern that require attention and monitor changing needs.	

26096790	LDLT is a well-established treatment for most terminal liver diseases in children. Survival rates have improved, yet few studies have considered HRQoL or sleep problems in LDLT recipients. In this cross-sectional study, we enrolled 51 children who had undergone LDLT in Renji Hospital. PedsQL(™) 4.0 Generic Core Scales, PedsQL(™) 3.0 Transplant Module, and Pediatric Sleep Questionnaire were used to assess outcomes. Of all participants, 11.8% (6/51) reported low total HRQoL scores. Participants' scores on most HRQoL subscales were comparable to the scores of healthy children. However, compared with solid organ transplant recipients, LDLT recipients scored significantly lower in About My Medicines II (t = 3.092, p = 0.002) and Worry (t = 2.760, p = 0.006). Sleep problems (41.2%) were common among participants. Hierarchical regression analyses showed that SRBD accounted for significant variance in HRQoL on total generic HRQoL (R(2) = 0.446, p < 0.001), psychosocial health (R(2) = 0.372, p = 0.001), physical health (R(2) = 0.345, p = 0.003), total transplant-specific HRQoL (R(2) = 0.514, p < 0.001), About My Medicines I (R(2) = 0.365, p = 0.013), My Transplant and Others (R(2) = 0.334, p = 0.005), Pain and Hurt (R(2) = 0.544, p < 0.001), Worry (R(2) = 0.401, p = 0.001), Treatment Anxiety (R(2) = 0.526, p < 0.001), How I Look (R(2) = 0.221, p = 0.040), and Communication (R(2) = 0.343, p = 0.012). In conclusion, sleep problems are non-negligible in children after LDLT and predicted significant variance on HRQoL.

26094934	To compare the use of sleep diagnostic tests, the risks, and cofactors, and outcomes of the care of Indigenous and non-indigenous Australian adults in regional and remote Australia in whom sleep related breathing disorders have been diagnosed.A retrospective cohort study of 200 adults; 100 Aboriginal and Torres Strait Islander and 100 non-indigenous adults with a confirmed sleep related breathing disorder diagnosed prior to September 2011 at Alice Springs Hospital and Cairns Hospital, Australia.	Results showed overall Indigenous Australians were 1.8 times more likely to have a positive diagnostic sleep study performed compared with non-indigenous patients, 1.6 times less likely in central Australia and 3.4 times more likely in far north Queensland. All regional and remote residents accessed diagnostic sleep studies at a rate less than Australia overall (31/100,000/y (95% confidence interval, 21-44) compared with 575/100,000/y).	The barriers to diagnosis and ongoing care are likely to relate to remote residence, lower health self-efficacy, the complex nature of the treatment tool, and environmental factors such as electricity and sleeping area. Indigeneity, remote residence, environmental factors, and low awareness of sleep health are likely to affect service accessibility and rate of use and capacity to enhance patient and family education and support following a diagnosis. A greater understanding of enablers and barriers to care and evaluation of interventions to address these are required.	A commentary on this article appears in this issue on page 1255.	
26094928	Sleep disturbance is among the most common complaints of veterans and military personnel who deployed to the conflicts in Iraq and Afghanistan. A growing body of research has examined cross-sectional and longitudinal relationships between sleep disturbance and mental health symptoms and specific diagnoses in this population. However, prior research has not examined these relationships in terms of the presence or absence of any mental health diagnosis. The objective of the current study is to characterize the sleep complaints (sleep characteristics, sleep quality, insomnia symptoms, and distressing dreams and nightmares) of previously deployed military personnel in terms of the presence or absence of a mental health disorder, diagnosed using structured clinical diagnostic interviews.Participants (n = 1,238) were veterans and active duty military personnel serving in the military since September 11, 2001, and deployed at least once. Scale scores and item-level data from the Pittsburgh Sleep Quality Index (PSQI), the PSQI-Addendum, the Davidson Trauma Scale, and the Symptom Checklist-90 were used to compare sleep across mental health status (with/without mental health disorder).	As expected, self-reported sleep impairments were worse among those meeting criteria for a mental health disorder. However, findings also revealed very poor sleep among those without a mental health diagnosis as well. Mean values for both groups were suggestive of short sleep duration, low sleep efficiency, long sleep onset latencies, poor sleep quality, frequent insomnia symptoms, and nightmare frequencies that are well above norms for the general population.	Given the evidence for adverse mental and physical health sequelae of untreated sleep disturbance, increased attention to sleep in this population may serve as a primary prevention strategy.	
26094926	This study investigated the prevalence and risk factors of insufficient sleep syndrome (ISS), and factors associated with daytime dysfunction in the disorder in Japanese young adults.In this cross-sectional study, a web-based questionnaire survey was used to assess demographic variables, sleep habits and quality, depressive symptoms, and health-related quality of life (HRQOL) in 2,276 participants aged 20-25.	Eleven percent of participants were classified as having ISS. Multiple logistic regression analysis revealed that the presence of ISS was significantly associated with social status (student or full-time employee). The participants with ISS had significantly higher depression scores and lower mental component summary scores than healthy sleepers. In the participants with ISS, a delayed sleep-wake schedule was extracted as a factor associated with worse mental component summary.	Results indicate a relatively high proportion of Japanese young adults suffer from ISS, and that the condition is associated with a social status of student or full-time employee. Moreover, a delayed sleep-wake schedule may lead to further deterioration of mental HRQOL in ISS-affected persons.	
26094915	A case report highlighting a rare and striking, but perhaps under-recognized, cause of reported sleep-talking to a specialist sleep clinic, involving "gas-lighting" by the bed partner.

26093368	Despite the known importance of sleep for brain development, and the sharp increase in poor sleep during adolescence, we know relatively little about how sleep impacts the developing brain. We present the first longitudinal study to examine how sleep during adolescence is associated with white matter integrity. We find that greater variability in sleep duration one year prior to a DTI scan is associated with lower white matter integrity above and beyond the effects of sleep duration, and variability in bedtime, whereas sleep variability a few months prior to the scan is not associated with white matter integrity. Thus, variability in sleep duration during adolescence may have long-term impairments on the developing brain. White matter integrity should be increasing during adolescence, and so sleep variability is directly at odds with normative developmental trends. 
26092820	Access to electric light might have shifted the ancestral timing and duration of human sleep. To test this hypothesis, we studied two communities of the historically hunter-gatherer indigenous Toba/Qom in the Argentinean Chaco. These communities share the same ethnic and sociocultural background, but one has free access to electricity while the other relies exclusively on natural light. We fitted participants in each community with wrist activity data loggers to assess their sleep-wake cycles during one week in the summer and one week in the winter. During the summer, participants with access to electricity had a tendency to a shorter daily sleep bout (43 ± 21 min) than those living under natural light conditions. This difference was due to a later daily bedtime and sleep onset in the community with electricity, but a similar sleep offset and rise time in both communities. In the winter, participants without access to electricity slept longer (56 ± 17 min) than those with access to electricity, and this was also related to earlier bedtimes and sleep onsets than participants in the community with electricity. In both communities, daily sleep duration was longer during the winter than during the summer. Our field study supports the notion that access to inexpensive sources of artificial light and the ability to create artificially lit environments must have been key factors in reducing sleep in industrialized human societies. 
26092394	The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK). To test the validity of the model, we studied the effect of standard antimanic medications lithium (47.5 mg/kg) or valproic acid (200 mg/kg) twice/day for 15 days in attenuating manic-like behaviors in the LHK rat. Compared with pre-kindling behaviors, LHK rats displayed significantly increased sexual self-stimulation (P = 0.034), excessive rearing (P = 0.0005), feeding (P = 0.013), and grooming (P = 0.007) during the kindling interval. LHK rats also drank more alcohol during the mania-induction days compared with baseline ethanol consumption levels (P = 0.01). Moreover, LHK rat exhibited increased total locomotor activity (P = 0.02) with reduced rest interval (P < 0.001) during the mania induction and post-mania days compared with baseline activity levels and rest intervals. Chronic administration of lithium or valproic acid significantly attenuated manic-like behaviors in the LHK rat model. Given the behavioral phenotype and the response to standard antimanic medications, the LHK rats may provide a model for studying manic psychopathology in humans. 
26092248	Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization. 
26090878	Sleep-disordered breathing is an important comorbidity for several diseases, including stroke. Initial screening tools comprise simple yes/no questions about known risk factors for sleep-disordered breathing, e.g., obesity, sex. But walking speed has not been investigated in this context. We examined the cross-sectional association between walking pace and sleep-disordered breathing in the population-level Multi-Ethnic Study of Atherosclerosis. A sample of 2912 men and 3213 women (46-87 years) reported perceived walking pace outside their homes. A walking pace<0.89 m/s was deemed "slow", with ≥ 0.89 m/s considered "average/brisk" according to validated thresholds. Sample prevalences were: sleep apnoea (3.5%), self-reported apnoeas (8.4%), loud snoring (20.5%), daytime tiredness (22.2%) and slow-walking pace (26.9%). The 95% CI risk differences (multivariable-adjusted) for slow vs. faster walking pace were; sleep apnoea (0.4-2.5%), self-reported apnoeas (0.1-3.8%), loud snoring (1.2-8.3%), and daytime tiredness (3.0-7.8%). Risk differences were similar between sexes. The multivariable-adjusted risk ratio indicated that slower walkers had 1.5 (95% CI: 1.0 to 2.1) times the risk of sleep apnoea vs. faster walkers. In conclusion, a slower walking speed was associated with a greater prevalence of sleep-disordered breathing, independently from other common screening factors. Therefore, a simple walking speed question may help consolidate screening for this disorder.
26085303	To evaluate the effect of sleep deprivation on time-based prospective memory performance, that is, realizing delayed intentions at an appropriate time in the future (e.g., to take a medicine in 30 minutes).Between-subjects experimental design. The experimental group underwent 24 h of total sleep deprivation, and the control group had a regular sleep-wake cycle. Participants were tested at 08:00.	Laboratory.	Fifty healthy young adults (mean age 22 ± 2.1, 31 female).	24 h of total sleep deprivation.	Participants were monitored by wrist actigraphy for 3 days before the experimental session. The following cognitive tasks were administered: one time-based prospective memory task and 3 reasoning tasks as ongoing activity. Objective and subjective vigilance was assessed by the psychomotor vigilance task and a visual analog scale, respectively. To measure the time-based prospective memory task we assessed compliance and clock checking behavior (time monitoring). Sleep deprivation negatively affected time-based prospective memory compliance (P < 0.001), objective vigilance (mean RT: P < 0.001; slowest 10% RT: P < 0.001; lapses: P < 0.005), and subjective vigilance (P < 0.0001). Performance on reasoning tasks and time monitoring behavior did not differ between groups.	The results highlight the potential dangerous effects of total sleep deprivation on human behavior, particularly the ability to perform an intended action after a few minutes. Sleep deprivation strongly compromises time-based prospective memory compliance but does not affect time check frequency. Sleep deprivation may impair the mechanism that allows the integration of information related to time monitoring with the prospective intention.	


26085291	To assess the prevalence of sleep problems and their association with psychotic symptoms using a global database.Community-based cross-sectional study.	Data were analyzed from the World Health Organization's World Health Survey (WHS), a population-based survey conducted in 70 countries between 2002 and 2004.	261,547 individuals aged ≥ 18 years from 56 countries.	N/A.	The presence of psychotic symptoms in the past 12 months was established using 4 questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Sleep problems referred to severe or extreme sleep problems in the past 30 days. Multivariable logistic regression was used to estimate the associations. The overall prevalence of sleep problems was 7.6% and ranged from 1.6% (China) to 18.6% (Morocco). Sleep problems were associated with significantly higher odds for at least one psychotic symptom in the vast majority of countries. In the pooled sample, after adjusting for demographic factors, alcohol consumption, smoking, and chronic medical conditions, having sleep problems resulted in an odds ratio (OR) for at least one psychotic symptom of 2.41 (95% confidence interval [CI] 2.18-2.65). This OR was 1.59 (1.40-1.81) when further adjusted for anxiety and depression.	A strong association between sleep problems and psychotic symptoms was observed globally. These results have clinical implications and serve as a basis for future studies to elucidate the causal association between psychotic symptoms and sleep problems.	
26084960	While poor sleep quality can worsen cardiovascular risk factors such as glucose and lipid profiles in patients with type 2 diabetes mellitus (T2DM), the relationship between sleep quality and atherosclerosis remains largely unknown. The aim of this study was to examine this relationship.The study participants comprised 724 Japanese T2DM outpatients free of history of cardiovascular diseases. The relationships between sleep quality (assessed by the Pittsburgh Sleep Quality Index (PSQI)) and various clinical and laboratory parameters were investigated.	The mean PSQI was 5.1 ± 3.0 (±SD). Patients were divided into three groups based on the total PSQI score; subjects with good sleep quality (n = 462), average sleep quality (n = 185), and poor sleep quality (n = 77). In the age/gender-adjusted model, patients with poor sleep quality tended to be obese, evening type and depressed. However, other lifestyles showed no significant trends. Alanine aminotransferase, fasting blood glucose, HbA1c, systolic blood pressure, urinary albumin excretion, and brachial-ankle pulse wave velocity (baPWV) tended to be higher in patients with poor sleep quality. High baPWV was the only parameter that correlated with poor sleep in a model adjusted for several other lifestyle factors.	Our study indicates that poor sleep quality in T2DM patients correlates with increased arterial wall stiffness, a marker of atherosclerosis and a risk factor for cardiovascular diseases.	

26083787	We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants.Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then 131I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ2 test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after 131I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar's test.	Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After 131I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%).	DTC patients suffer from sleep disturbance, 131I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.	
26083174	This cross-sectional study analyzed the association between poor quality of sleep and adherence to highly active antiretroviral therapy (HAART) in 389 Peruvian patients with HIV/AIDS. Poor quality of sleep was measured with the Pittsburgh Sleep Quality Index (PSQI) and adherence with the CEAT-VIH (Peruvian adaptation). A Poisson generalized linear model with robust standard errors was used to estimate prevalence ratios and 95%CI. A crude model showed that mild, moderate, and severe poor quality of sleep were associated with inadequate treatment adherence. In the adjusted model for variables associated in the bivariate analysis or variables theoretically associated with adherence, only moderate/severe poor quality of sleep remained associated (PR = 1.34, 95%CI: 1.17-1.54; and PR = 1.34, 95%CI: 1.16-1.57, respectively). The study concluded that moderate/severe poor quality of sleep was independently associated with adherence to HAART. Assessing quality of sleep may be helpful in the comprehensive evaluation of HIV patients. 
26081795	This study aimed to examine the association between self-reported sleep problems and cognitive decline in community-dwelling older people. We hypothesized that daytime somnolence predicts subsequent cognitive decline.This is a longitudinal study in a 3.2-year follow-up, with 18-month intervals. The setting is the Washington Heights-Inwood Community Aging Project. There were 1098 participants, who were over 65 years old and recruited from the community. Sleep problems were estimated using five sleep categories derived from the RAND Medical Outcome Study Sleep Scale: sleep disturbance, snoring, awaken short of breath/with a headache, sleep adequacy, and daytime somnolence. Four distinct cognitive composite scores were calculated: memory, language, speed of processing, and executive functioning. We used generalized estimating equations analyses with cognitive scores as the outcome, and time, sleep categories and their interactions as the main predictors. Models were initially unadjusted and then adjusted for age, gender, education, ethnicity, depression, and apolipoprotein E-ε4 genotype.	Increased daytime somnolence (including feeling drowsy/sleepy, having trouble staying awake, and taking naps during the day) was linked to slower speed of processing both cross-sectionally (B = -0.143, p = 0.047) and longitudinally (B = -0.003, p = 0.027). After excluding the demented participants at baseline, the results remained significant (B = -0.003, p = 0.021).	Our findings suggest that daytime somnolence may be an early sign of cognitive decline in the older population.	
26081502	To explore the association between sleep disorders and dawn phenomenon in patients with type 2 diabetes mellitus (T2DM).From July 2011 to July 2014 at Metabolic Disease Hospital, Tianjin Medical University, 316 T2DM patients on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index, i.e. those without sleep disorders (n = 186) and those with sleep disorders (n = 130). Biochemical parameters including hepatorenal functions, blood lipids, glycosylated hemoglobin (HbA1c) and fructosamine were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inter-group differences of glucose concentration and α-cell and β-cell functions after fasting and glucose loading. And the correlation and regression analyses were performed between sleep disorders and other parameters.	The level of HbA1c, fructosamine, increment of fasting glucose and nocturnal nadir glucose, glucose increment before and after breakfast, 24 h mean glucose, fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorders than those without sleep disorders (8.2% ± 2.0% vs 7.4% ± 1.7%, (0.33 ± 0.10) vs (0.29 ± 0.07) mmol/L, (1.511 ± 0.294) vs (0.889 ± 0.233) mmol/L, (2.144 ± 0.400) vs (1.522 ± 0.378) mmol/L, (9.917 ± 1.800) vs (8.694 ± 1.622) mmol/L, (13.49 ± 4.68) vs (12.16 ± 4.56) mU/L, 4.98 ± 0.90 vs 3.82 ± 0.82, (8.47 ± 0.59) vs (8.25 ± 0.54), all P < 0.05). Insulin sensitivity index was lower in patients with sleep disorders than that in those without sleep disorders (-4.28 ± 0.62 vs -4.03 ± 0.52, P < 0.05). The level of glucagon at each timepoint and area-under-curve of glucagon were significantly higher in patients with sleep disorders than those without sleep disorders. The levels of 0, 30, 180 min glucagon/insulin ratio and glucagon/glucose ratio were significantly higher in patients with sleep disorders (all P < 0.05). Sleep disorder was positively correlated with HOMA-IR, glucagon/insulin ratio, increment of fasting glucose and nocturnal nadir glucose and dawn phenomenon (all P < 0.05). Yet there was a negative correlation with insulin sensitivity index (P < 0.05).	Sleep disorders are associated with dawn phenomenon. And improving sleep disorder helps to improve the dawn phenomenon and optimize overall glycemic control.	
26081297	Polysomnography is the gold standard for studying sleep, but it is complex to use, and this can be problematic in clinically unstable preterm infants. We evaluated the reliability of actigraphy and polysomnography in detecting sleep-wake patterns in newborn infants.A prospective, monocentric study was conducted that measured the sleep patterns of 48 infants: 24 late preterm neonates born at 34-36 weeks of gestational age and 24 term neonates. We used both polysomnography and the Actiwatch Mini during a three-hour period and then compared the results from the two methods.	The baseline measurements for the preterm and terms groups were as follows: gestational age (34.5 weeks and 39.2 weeks), birthweight (2368 g and 3393 g) and age (6.4 days and 0.72 days). With the Actiwatch Mini, sensitivity for the late preterm and full-term infants was 78% and 87% for the leg actigraph and 78% and 93% for the arm actigraph. For specificity, the respective figures were 42% and 31% for the leg and 34% and 20% for the arm.	Actigraphy using the Actiwatch Mini was not a reliable method for measuring sleep patterns in healthy late preterm and term neonates a few days after birth.	
26080620	To explore somatic conditions in a sample of 2299 child and adolescent survivors of an earthquake and their relationship to posttraumatic stress disorder (PTSD) symptoms.The Children's Revised Impact of Event Scale, the Patient Health Questionnaire (PHQ)-13 scale, a short version of PHQ-15 scale that omits two items involving sexual pain/problems and menstrual problems, and a project-developed questionnaire were administered to participants three and six months after the earthquake.	Among child and adolescent survivors, the prevalence rates of probable PTSD were 37.4 and 24.2% three and six months, respectively, after the earthquake. The most common somatic symptoms were trouble sleeping (58.4 and 48.4%), feeling tired or having low energy (52.0 and 46.1%), and stomach pain (45.8 and 45.4%) after three and six months, respectively. Several specific somatic symptoms evaluated three months after the earthquake including trouble sleeping, headache, and shortness of breath were predictors of the overall PTSD symptoms evaluated six months after the earthquake. Additionally, the symptom of hyperarousal evaluated after three months could predict the overall somatic symptoms evaluated after six months.	PTSD and somatic symptoms were common after the earthquake, and a longitudinal association between PTSD and somatic symptoms was detected among child and adolescent survivors. These findings have implications in China and possibly elsewhere.	
26080022	Long working hours are a worldwide problem and may increase the risk of various health issues. However, the health effects of long working hours on suicidal thoughts have not been frequently studied. Our goal was to investigate the relationship between long working hours and suicidal thoughts in the rapidly developing country of Korea.Data from 12,076 participants (7,164 men, 4,912 women) from the 4th and 5th Korean National Health and Nutrition Examination Surveys were used for the current analysis. Multivariate logistic regression models were used to estimate odds ratios and 95% confidence intervals for suicidal thoughts. Combined effects of long working hours and lower socioeconomic status or sleep disturbance were also estimated.	Compared to groups who worked less than 52 hours per week, odds ratios (95% confidence intervals) for suicidal thoughts in groups who worked 60 hours or more per week were 1.36 (1.09-1.70) for males and 1.38 (1.11-1.72) for females, even after controlling for household income, marital status, history of hypertension or diabetes mellitus, health-related behaviors, and past two weeks' experience of injury, intoxication, or acute or chronic diseases, as well as type of work. The combined effects of long working hours with lower socioeconomic status, or with sleep disturbance, were also significantly higher compared to participants who worked less than 52 hours per week with higher socioeconomic status, or with 6-8 hours of nighttime sleep.	In this study, long working hours were linked to suicidal thoughts for both genders. Additionally, the odds of those suicidal thoughts were higher for lower socioeconomic groups. To prevent adverse psychological health problems such as suicidal thoughts, a strategy regarding long working hours should be investigated.	
26079973	Advancements in sleep medicine have been escalating ever since research began appearing in the 1950s. As with most early clinical trials, women were excluded from participation. Even if researchers included women or addressed sex differences by age, reproductive stage was seldom considered. Recently, there has been an exponential increase in research on sleep in midlife and older women. This Practice Pearl briefly reviews the importance of adequate sleep, clinical assessment for sleep disorders, and guidelines for practice. 
26077958	Chronic liver disease affects over 30 million people worldwide, and despite advances in medical management that have increased survival, a majority of these individuals report multiple symptoms that severely impair function and quality of life. The purpose of this integrative review was to examine and summarize the current literature focused on self-reported symptoms in individuals with chronic liver disease in order to inform the development and delivery of symptom management strategies in clinical practice.Combinations of search terms related to the symptom experience were used to search three electronic databases. Inclusion criteria were empirical studies that measured self-reported symptoms in populations with chronic liver disease published in English between 2003 and 2014. The literature search initially yielded 112 results; 26 quantitative studies met the inclusion criteria.	The symptom of fatigue was commonly reported across chronic liver disease populations and was often found to co-occur with other distressing symptoms, including depression, sleep disturbance, pain, cognitive impairment, and dizziness associated with autonomic dysfunction. Due to the high prevalence and persistence of these "core" symptoms, the use of core symptom measures integrated longitudinally across populations would inform the development and delivery of symptom management interventions as well as enhance the ability of nurses to incorporate population-level symptom management programs.	Nurses play an important role in symptom assessment and may use the findings from the integrative review to incorporate core symptom measures across chronic liver disease populations and advance the development and delivery of symptom management interventions.	
26076412	The discovery of benzodiazepines has represented a milestone in the history of pharmacological treatments and in relation to the management of anxiety, sleep and other psychiatric disorders. After several decades, these agents still represent one of the largest and most widely prescribed groups of medications, not only in the psychiatric clinical practice, but also in the whole medical field. Over the last decade, however, multiple concerns have been raised on the risks related to the prescription of benzodiazepines, for their addictive potential and for cognitive side-effects. Therefore, benzodiazepines are today considered as a double-edge sword, which should be carefully handled and preferentially prescribed by specialists (or at least under their supervision), after an adequate training. Unfortunately, this is not the case in many situations, and the need to improve training on benzodiazepines management has been recently emphasized. 
26076358	In addition to cognitive decline, individuals affected by Alzheimer's disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD. 
26076002	The goal of this study was to examine the bidirectional relationship of sleep and pain to determine whether changes in sleep complaints over the course of a chronic pain treatment trial predict pain outcomes and vice versa, controlling for changes in depression and anxiety.Data were analyzed from a 12-month randomized, controlled trial that tested the effectiveness of a collaborative care intervention for veterans with chronic musculoskeletal pain. Participants were 250 veterans from 5 primary care clinics in a Veteran Affairs (VA) medical center. Measures of pain, sleep, and depression/anxiety symptoms were collected at baseline, 3 months, and 12 months. Factor analysis was used to clarify the boundaries of these domains, and structural equation modeling was used to examine whether changes in sleep complaints and depression/anxiety during the trial predicted pain at the end of the trial, controlling for covariates. An alternative model was also tested in which changes in pain predicted sleep complaints.	Changes in sleep complaints at 3 months significantly predicted changes in pain at 12 months (standardized path coefficient = .29, p < .001). To a lesser extent, changes in pain predicted changes in sleep (standardized path coefficient = .15, p < .05). Changes in depression/anxiety did not significantly predict changes in pain or sleep. There was also evidence of differential relations of specific sleep complaints with pain.	This work helps to further disentangle the complex relationship between pain and sleep. This bidirectional relationship may need to be considered to improve pain outcomes.	
26075423	Despite substantial public interest, few recommendations on the promotion of good sleep health exist to educate health care providers and the general public on the importance of sleep for overall health.The aim of this American Thoracic Society (ATS) statement is to provide a review of the current scientific literature to assist health care providers, especially pulmonologists and sleep physicians, in making recommendations to patients and the general public about the importance of achieving good quality and adequate quantity of sleep.	ATS members were invited, based on their expertise in sleep medicine, and their conclusions were based on both empirical evidence identified after comprehensive literature review and clinical experience.	We focus on sleep health in both children and adults, including the impact of occupation on sleep, the public health implications of drowsy driving, and the common sleep disorders of obstructive sleep apnea and insomnia. This ATS statement also delineates gaps in research and knowledge that should be addressed and lead to new focused research priorities to advance knowledge in sleep and sleep health.	Good quality and quantity of sleep are essential for good health and overall quality of life; therefore a strong recommendation was made for the implementation of public education programs on the importance of sleep health.	
26074034	To explain the controversy about whether midlife women who self-report hot flashes have relatively increased affective symptoms, poor cognitive performance or worse sleep.Retrospective data from 88 women seeking relief from bothersome day and night hot flashes were submitted to mixed linear regression modeling to find if estimated hot flashes, as measured by Women's Health Questionnaire (WHQ) items, or diary-documented hot flashes recorded daily, were associated with each other, or with affective, cognitive or sleep measures.	Subjects averaged 6.3 daytime diary-documented hot flashes and 2.4 nighttime diary-documented hot flashes per 24h. Confounder-controlled diary-documented hot flashes but not estimated hot flashes were associated with increased Leeds anxiety scores (F=4.9; t=2.8; p=0.01) and Leeds depression scores (3.4; 2.5; 0.02), decreased Stroop Color-Word test performance (9.4; 3.5; 0.001), increased subjective sleep disturbance (effect size=0.83) and increased objective sleep disturbance (effect size=0.35). Hot flash effects were small to moderate in size. Univariate but not multivariate analyses revealed that all hot flash measures were associated with all affect measures. Different measures of hot flashes associated differently with affect, cognition and sleep. Only nighttime diary-document hot flash consistently correlated with any affect measures in multivariate analyses.	The use of differing measures for hot flashes, affect, cognition and sleep may account for the continually reported inconsistencies in menopause study outcomes. This problem impedes forging a consensus on whether hot flashes correlate with neuropsychological symptoms.	
26073849	Sleep problems and substance use are strongly linked. Sleep problems play a role in the etiology of substance use, but also may be a result of it. After detoxification, sleep problems may worsen leading to relapse. Nowadays, most substance dependence treatment programs aim at recovery rather than total abstinence, and in that view health-related quality of life (HRQL) is a relevant construct. This article describes the association between self-perceived sleep problems and HRQL in a naturalistic population of polydrug-using inpatients.At the start of treatment, 388 polydrug-using inpatients completed questionnaires concerning their sleep quality and HRQL. Three categories were established based on reported sleep problems: patients without sleep problems (21.6%), those with clinically relevant sleep problems (34.5%), and patients with sleep disorders (43.8%).	Mean grades for quality of sleep were M = 7.3 (sd 1.7), M = 6.6 (sd 1.7) and M = 5.3 (sd 1.9) for the three categories, respectively. In addition, patients in the disorder category perceived a lower HRQL than those in the other categories. In the explanation of HRQL, both sleep problems and sleep disorders added significantly to the model when controlling for baseline characteristics.	Our findings stress the need for clinicians to pay attention to the quality of sleep of recovering polydrug users, since this may play an important role in the recovery process. Monitoring sleep during treatment is advocated. This study adds to the knowledge about the way HRQL and sleep are related in a naturalistic sample of substance-dependent patients.	
26073574	The present study aims to determine the prevalence of self-reported sleep duration and sleep habits and their associated factors in patients with type 2 diabetes in Trinidad. This was a cross-sectional multicenter study. There were 291 patients with type 2 diabetes studied. Sleep habits were assessed using the Epworth Sleepiness Scale (ESS) and the National Health and Nutrition Examination Survey sleep disorder questionnaire. Demographic, anthropometric and biochemical data were also collected. The sample had a mean age of 58.8 years; 66.7% were female. The mean BMI was 28.9 kg/m(2). The prevalence of Excessive Daytime Sleepiness (EDS) was 11.3%. The prevalence of patients with short sleep (⩽6h) was 28.5%. The prevalence of patients with poor sleep was 63.9%. Poor sleep was associated with age, intensive anti-diabetic treatment and longer duration of diabetes. Short sleep was associated with intensive anti-diabetic treatment and BMI, while EDS was associated with increased BMI. In a sample of patients with type 2 diabetes, a high prevalence of self-reported sleep duration and unhealthy sleep habits was found. There needs to be an increased awareness of sleep conditions in adults with type 2 diabetes by doctors caring for these patients.
26072344	"What will you give my child to help him sleep?" is a common question parents ask and some health care providers abhor hearing. Entire families may suffer when one member does not sleep well. Poor sleep may complicate the management of other comorbid conditions. Health care providers may have received only limited education on sleep disorders and are frequently forced to choose between treatment options that are poorly studied in children. Fortunately, when addressed correctly, many children with chronic sleep disorders may improve their sleep and daytime behavior in a relatively short time. This review provides a framework to help understand the causes of poor sleep in children and the potential pharmacologic options. 
26072342	There is a close relationship between sleep and childhood neurodevelopmental/neurodegenerative disorders. Understanding the sleep issues may provide greater insight into pathophysiology and treatment of these disorders. 
26072341	Sleep problems are common in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Sleep problems in these disorders may not only worsen daytime behaviors and core symptoms of ASD and ADHD but also contribute to parental stress levels. Therefore, the presence of sleep problems in ASD and ADHD requires prompt attention and management. This article is presented in 2 sections, one each for ASD and ADHD. First, a detailed literature review about the burden and prevalence of different types of sleep disorders is presented, followed by the pathophysiology and etiology of the sleep problems and evaluation and management of sleep disorders in ASD and ADHD. 
26072340	The interaction between sleep and headache or migraine is powerful and an elevated comorbidity between these 2 disorders has been reported in either adults or children. This comobidity is linked to common neurophysiological and neuroanatomical substrates that are genetically based strongly. The first reports on this relationship were related to the prevalence of parasomnias and sleep-disordered breathing in headache but recent research has expanded the comorbidity to several other sleep disorders, such as restless legs syndrome, periodic limb movements during sleep, and narcolepsy. The assessment of children with headache should always include an accurate anamnesis for the presence of sleep problems either in the child or in the relatives; no correct approach for treating children and adolescents is possible without an integrated method of evaluation and management. 
26072338	Sleep and epilepsy are common bedfellows. Sleep can affect frequency and occurrence of interictal spikes and occurrence, timing, and threshold of seizure. Epilepsy can worsen sleep architecture and severity of sleep disorders. Thus, a vicious cycle is set. Certain epilepsy syndromes are so intertwined with sleep that they are considered sleep-related epilepsies. Poor sleep in epilepsy is multifactorial and is worsened by poorly controlled seizures. On the contrary, poor sleep is associated with worsened quality of life, psychological function, and memory. Improving sleep has been noted to improve seizure frequency and an overall well-being in patients with epilepsy. Hence, an emphasis should be given to address sleep in patients with epilepsy. These interactions are discussed in detail in this review. 
26072337	Obstructive sleep apnea (OSA) is a frequent disorder in children and is primarily associated with adenotonsillar hypertrophy. The prominent increases in childhood overweight and obesity rates in the world even among youngest of children have translated into parallel increases in the prevalence of OSA, and such trends are undoubtedly associated with deleterious global health outcomes and life expectancy. Even an obesity phenotype in childhood OSA, more close to the adult type, has been recently proposed. Reciprocal interactions between sleep in general, OSA, obesity, and disruptions of metabolic homeostasis have emerged in recent years. These associations have suggested the a priori involvement of complex sets of metabolic and inflammatory pathways, all of which may underlie an increased risk for increased orexigenic behaviors and dysfunctional satiety, hyperlipidemia, and insulin resistance that ultimately favor the emergence of metabolic syndrome. Here, we review some of the critical evidence supporting the proposed associations between sleep disruption and the metabolism-obesity complex. In addition, we describe the more recent evidence linking the potential interactive roles of OSA and obesity on metabolic phenotype. 

26072264	Sleep disturbances in children with autism spectrum disorder (ASD) exist worldwide, but little is known about this issue in non-Western cultures. This study aimed to characterize sleep disturbances in Chinese children with ASD and to examine associated sociodemographic factors and emotional/behavioral problems. Parents of 60 Chinese children with ASD (aged 6-17 years) from Shenzhen, China completed the Children's Sleep Habits Questionnaire (CSHQ), and the Strengths and Difficulties Questionnaire (SDQ). Sleep disturbances were severe and common, with rates of 70.0% for overall disturbances and 15.0% (daytime sleepiness) to 40.0% (sleep duration) for specific domains. The severity and rate of sleep disturbances were higher compared to previous studies in typically developing children from the same region of China and American children with ASD, respectively. Further, there were significant correlations between most CSHQ and SDQ domains. Female gender, older parental age, higher hyperactivity, and poorer prosocial behavior were associated with increased overall sleep disturbances.
26071851	The sleep of patients admitted to coronary care unit (CCU) may be compromised. A feasible and cost-effective tool to evaluate sleep in this scenario could provide important data. The aim of this study was to evaluate sleep with a questionnaire developed specifically for the CCU and to validate it with polysomnography (PSG).Ninety-nine patients (68% male; 56 ± 10 years old) with acute coronary syndrome were included. PSG was performed within 36 h of admission. A specific 18-question questionnaire (CCU questionnaire) was developed and applied after the PSG. Cronbach's alpha test was used to validate the questionnaire. The Spearman test was used to analyze the correlation between the PSG variables and the questionnaire, and the Kruskal-Wallis test was used to compare the PSG variables among patients with good, regular, or poor sleep.	The total sleep time was 265 ± 81 min, sleep efficiency 62 ± 18%, REM sleep 10 ± 7%, apnea/hypopnea index 15 ± 23, and the arousal index 24 ± 15. Cronbach's alpha test was 0.69. The CCU questionnaire showed correlation with the sleep efficiency evaluated by PSG (r: 0.52; p < 0.001). Sleep quality was divided into three categories according to the CCU questionnaire: patients with good sleep had a sleep efficiency of 72 ± 9%, better than those with a regular or poor sleep (60 ± 16% and 53 ± 20%, respectively; p < 0.01).	The CCU questionnaire is a feasible and reliable tool to evaluate sleep in the CCU, showing correlation with the PSG sleep efficiency.	
26071309	Determine if individuals with poor sleep characteristics (i.e., late sleep onset or wake times, short sleep duration, long sleep latency, low sleep efficiency, high wake after sleep onset) have greater body mass index (BMI = kg/m(2)) or body fat.Data for these cross-sectional analyses were from the Energy Balance Study (University of South Carolina). Participants were between 21 and 35 years of age and had a BMI of 20 to 35 kg/m(2). Body fat percent was measured by dual X-ray absorptiometry. Sleep and physical activity were measured by actigraphy (BodyMedia's SenseWear physical activity armband). General linear models were used to estimate mean BMI and body fat percent by sleep metric categories.	Greater BMI and body fat percent were associated with low sleep efficiency (BMI = 25.5 vs. 24.8 kg/m(2), P < .01; body fat = 27.7% vs. 26.5%, P = .04) and high wake after sleep onset (BMI = 25.6 vs. 25.0 kg/m(2), P = .02; body fat = 28.0% vs. 26.7%, P = .03). Elevated BMI or body fat percent also were observed for later wake times, shorter sleep duration, and longer sleep latency. Sex modified the association between wake times and body composition.	Understanding the complex relationships between sleep and health outcomes could help reduce chronic disease burden by incorporating sleep components, measured through novel noninvasive techniques (SenseWear armband), into weight loss interventions.	

26070854	Sleep complaints are one of the most frequent and relevant symptoms that characterize fibromyalgia syndrome (FMS). However, objective sleep disturbances have not been consistently described across FMS studies. It is therefore commonly accepted that FMS patients experience sleep misperception, even though no studies have investigated the contribution of polysomnographic parameters to determine subjective sleep quality in FMS. We aimed to compare sleep variables (polysomnographic parameters and subjective sleep quality) between FMS patients and healthy controls. Furthermore, we also aimed to define the predictors of subjective sleep quality in FMS.We performed in-home polysomnography to 99 women (53 FMS patients and 36 healthy controls). We also collected subjective ratings of sleep quality, daytime sleepiness, pain, depression, and anxiety.	Multivariate analysis showed that groups differed in polysomnographic parameters (p = 0.015)--after accounting for age, body mass index, and antidepressant consumption. Specifically, FMS patients exhibited lower sleep efficiency, greater percentage of stage N1 and wakefulness, and more frequent awakenings than controls (p-values < 0.05). Patients also complained about poorer subjective sleep quality (p <0.001). Percentage of time awake (as obtained by polysomnography), depression levels, and antidepressant consumption predicted self-reported sleep quality in FMS patients (adjusted R2 = 0.33, p <0.001).	One night of in-home polysomnography supports the hypothesis that women with FMS show polysomnographic alterations compared to age-matched controls. In addition, the time spent awake is the best predictor of subjective sleep quality, although greater levels of depression and antidepressant consumption might result in exaggerated complaints. These findings contribute to our understanding of FMS symptoms and its management.	
26068863	Evidence suggests that short and long sleep durations are associated with a higher risk of type 2 diabetes. Using successive data waves spanning >20 years, we examined whether a change in sleep duration is associated with incident diabetes.Sleep duration was reported at the beginning and end of four 5-year cycles: 1985-1988 to 1991-1994 (n = 5,613), 1991-1994 to 1997-1999 (n = 4,193), 1997-1999 to 2002-2004 (n = 3,840), and 2002-2004 to 2007-2009 (n = 4,195). At each cycle, change in sleep duration was calculated for participants without diabetes. Incident diabetes at the end of the subsequent 5-year period was defined using 1) fasting glucose, 2) 75-g oral glucose tolerance test, and 3) glycated hemoglobin, in conjunction with diabetes medication and self-reported doctor diagnosis.	Compared with the reference group of persistent 7-h sleepers, an increase of ≥2 h sleep per night was associated with a higher risk of incident diabetes (odds ratio 1.65 [95% CI 1.15, 2.37]) in analyses adjusted for age, sex, employment grade, and ethnic group. This association was partially attenuated by adjustment for BMI and change in weight (1.50 [1.04, 2.16]). An increased risk of incident diabetes was also seen in persistent short sleepers (average ≤5.5 h/night; 1.35 [1.04, 1.76]), but this evidence weakened on adjustment for BMI and change in weight (1.25 [0.96, 1.63]).	This study suggests that individuals whose sleep duration increases are at an increased risk of type 2 diabetes. Greater weight and weight gain in this group partly explain the association.	
26068429	Chinese herbal products (CHPs) are commonly prescribed for sleep disorder and major depressive disorder (MDD). The aim of this study was to investigate the prescription patterns of CHPs and Western medicine for patients with these disorders in Taiwan, and analyze the frequency of using single herbs (SHs) and herbal formulas (HFs).In this retrospective population-based study secondary data analysis was performed using data from Taiwan's Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011. In total, 1000,000 beneficiaries from the LHID were randomly selected from the 2010 registry for beneficiaries of the National Health Insurance Research Database. Patients with sleep disorder and MDD according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 307.40 and 311, respectively.	Among a total of 11,030 patients with sleep disorder, 9619 used Western medicine, 1334 used CHPs, and 77 used both, Among a total of 11,571 patients with MDD, 11,389 used Western medicine, 131 used CHPs, and 51 used both. Regardless of disorder type, women were predominant The majority of the patients were aged 22-44 years, had a monthly income of NT$17,281-NT$22,800, and lived in an area with Level 1 and Level 2 urbanization. Of the patients with sleep disorder, 1411 had used CHPs and visited a clinic 5298 times on average. Of the patients with MDD, 182 had used CHPs and visited a clinic 755 times on average. The three most commonly used SHs and HFs were Ziziphi Spinosae Semen, Polygoni Multiflori Caulis, and Polygalae Radix, and Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang, respectively.	Chinese herbal products including SHs and HFs are prescribed for patients with sleep disorder and MDD. However, the efficacy and safety of CHPs for sleep disorder and MDD need to be further evaluated.	
26067449	Dialysis patients frequently have anxiety and sleeping disorders and that explains a benzodiazepine treatment. A significant proportion of dialysis patients are long-term users even though it is not recommended to take benzodiazepine for more than 3 months. Risks of such a use are well identified. Nephrologists frequently have to prescribe benzodiazepines. This prescription is complex and there are few studies regarding the factors of benzodiazepine use among this population.To determine the prevalence and the factors related to a long-term benzodiazepine use by dialysis patients. To determine the prevalence and the motivation of patients to stop taking medication among the long-term users who got information about the risk of such a use.	The study includes 91 dialysis chronic patients. Their characteristics were collected from medical records and interviews with the patients.	The average age of patients is 65,8 years. In all, 50.5% take benzodiazepines. Among benzodiazepine users, the prevalence of long-term use is 78.3%. Long-term benzodiazepine users (a) are older, (b) less active, (c) frequently diabetic, (d) depressive, (e) unable to walk, (f) less often registered on the kidney transplant waiting list, and (g) had less kidney transplant previously. Benzodiazepine doses of long-term users were higher than the doses of short-term users. Moreover, 60% of patients who are chronic users want to take action and stop the treatment. Observation of side effects, impression of ineffectiveness and fear of addiction are the most identified motivation to stop treatment.	The prevalence of benzodiazepine chronic use by dialysis patients is high. Giving information to the patient about the use of these molecules seems to have a positive impact on the decision to stop.	
26067127	Sleep-wake disturbances are extremely common after a traumatic brain injury (TBI). The most common disturbances are insomnia (difficulties falling or staying asleep), increased sleep need, and excessive daytime sleepiness that can be due to the TBI or other sleep disorders associated with TBI, such as sleep-related breathing disorder or post-traumatic hypersomnia. Sleep-wake disturbances can have a major effect on functional outcomes and on the recovery process after TBI. These negative effects can exacerbate other common sequelae of TBI-such as fatigue, pain, cognitive impairments, and psychological disorders (eg, depression and anxiety). Sleep-wake disturbances associated with TBI warrant treatment. Although evidence specific to patients with TBI is still scarce, cognitive-behavioural therapy and medication could prove helpful to alleviate sleep-wake disturbances in patients with a TBI. 
26065140	Sleep disorder is associated with the lifestyle-related diseases including obesity, insulin resistance and atherosclerosis. Adipose tissue functions as an endocrine organ by producing bioactive secretory proteins, also known as adipokines, that can directly act on nearby or remote organs. Recently, the associations between these adipokines and sleep disorders such as obstructive sleep apnea have been reported. In this review, we focus on the relationship between sleep disorder and lifestyle-related diseases.
26065139	The current understanding is that sleep associates profoundly with mental and physical health and life style-related diseases. Under the Ministry of Health, Labour and Welfare "The Sleep Guidelines for health promotion" was devised in 2003 and revised it in 2014. It is to promote that a citizen carries out a better sleep behavior in every life stage from infancy to old age. We comment on the 12 clauses of "The Sleep Guidelines" in this report. It shows the concrete methods for sleep well and the sleep disorder-related disease. We hope the 12 clauses will contribute to reducing a citizen troubled with daytime sleepiness. The night pleasant sleep is important in keeping mental and physical health.
26065136	Orexin A and orexin B are hypothalamic neuropeptides that were discovered in 1998. Several studies suggested that orexin deficiency causes narcolepsy in humans and other mammalian species, highlighting roles of this hypothalamic neuropeptide in the regulation of sleep and wakefulness. The orexin system regulates sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis. This system regulates sleep and wakefulness to occur at appropriate times that are in accordance with our internal and external environments. Recent findings have brought about the possibility of novel therapies targeting orexin system for sleep disorder including insomnia and narcolepsy-cataplexy. In this review, I will discuss the current understanding of the integrative physiology and clinical perspectives of the orexin system.
26065135	Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.
26065130	Successful aging is characterized by minimal age-associated loss of the physiological functions of sleep and circadian clock. Sleep health education is necessary to have normal, quality nighttime sleep and full daytime alertness. Elderly people show changes of sleep parameters, accompanied by increased napping. Many studies have reported that daytime sleepiness or napping in elderly people could have potentially serious effects such as dementia and life-style related diseases. The main topics of sleep health education for elderly people are as follows: Right knowledge of sleep mechanism, understanding the bad influence of excessive napping, the effects of light on the circadian rhythm and negative effects of caffeine, alcohol and television.
26065128	In clinical practice, assessment usually involves self-report; however, objective measures are available. The multiple sleep latency test(MSLT) is performed during the main period of wakefulness and is designed to determine a patient's propensity to fall asleep. To be valid, the MSLT should be performed the day after nocturnal polysomnography (PSG). It is the standard test for the assessment of objective sleepiness and diagnosis of narcolepsy, that is a mean sleep latency equal to or under 8 minutes and equal to or greater than two sleep onset REM periods (SOREMPs). As opposed to the MSLT, the maintenance of wakefulness test (MWT) is designed to test the patient's ability to stay awake. The MWT is a 40-minutes protocol consisting of four trials separated by 2-hour intervals and is performed in much the same way as the MSLT. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on the MWT with risk of accidents in real world circumstances. The suggestive immobilization test(SIT) was designed during which sensor and motor symptoms of restless legs syndrome are quantified during a period of immobility taking place in the evening before PSG. The patient is instructed to avoid moving voluntary for the entire duration of the test, which is designed to last 1 hour. The subjective leg discomfort evaluation and periodic leg movement by surface electromyograms from right and left anterior tibialis support diagnosis for restless legs syndrome. Many factors, such as clinical setting, pretest condition or aging effects etc. can alter the findings of the test and considerable clinical judgment is needed to avoid an error in interpretation. Above those three sleep-wake related tests provide us useful information.
26065126	Sleep related movement disorders (SRMD) are characterized by simple, stereotyped movements occur during sleep, with the exception of restless legs syndrome (RLS). RLS has the following essential features; an urge to move the legs usually accompanied by uncomfortable sensation in the legs, improvement of symptoms after movement (non-stereotypical movements, such as walking and stretching, to reduce symptoms), and symptoms occur or worsen during periods of rest and in the evening and night. However, RLS is closely associated with periodic limb movement, which shows typical stererotyped limb movements. In the International Classification of Sleep Disorders, 3rd edition, sleep disturbances or daytime symptoms are prerequiste for a diagnosis of SRMD. We here review diagnosis and treatment of SRMD.
26065124	The role of the circadian system is forecasting the daily and yearly change of environment. Circadian rhythm sleep-wake disorder (CRSWD) is defined as physical and social impairment caused by misalignment between circadian rhythm and desirable social schedule. CRSWDs are induced by medical or environmental factors as well as dysfunctions of circadian system. Clinicians should be aware that sleep-inducing medications, restless legs syndrome, delirium and less obedience to social schedule are frequent cause of CRSWD among elderly. Bright light therapy and orally administered small dose of melatonin or melatonin agonist at proper circadian phase are recommended treatments. Sleep-inducing medications should not be considered as CRSWD treatments, especially to elderly.
26065120	The American Academy of Sleep Medicine Board of Directors published the International Classification of Sleep Disorders, 3rd edition (ICSD -3) in 2014. In the 3rd edition, the most drastic change in the content was the unity of secondary insomnia categories into single "chronic insomnia" category. In the central disorders of hypersomnolence section, the nomenclature for narcolepsy was changed to narcolepsy type 1 and type 2. In the sleep related breathing disorder section, several new diagnostic categories were added, and diagnosis of a sleep related hypoventilation disorder was set to require the confirmation of elevated PaCO2. This manuscript overviews the differences and the similarities in the content between the ICSD-3 and the former edition.
26065119	The purpose of this paper is to provide an overview of the effects of the sleep health promotion. Sleep health promotion that included short naps and exercise in the evening was effective in promoting sleep with elderly people. The interventions demonstrated that the proper awakening maintenance and keeping proper arousal level during the evening were effective in improving sleep quality. Sleep health promotion that included sleep education and cognitive-behavioral interventions improved sleep-related habits and the quality of sleep. Sleep health promotion were developed. Mental and physical health were also improved along with improving sleep with the elderly. These results suggest that cognitive-behavioral interventions to improve the sleep are effective for the activity of daily living, and the quality of life.
26065118	There are three major neurophysiological mechanisms underlying the sleep-waking cycle: the sleep system, the waking system, and the system that determines sleep-waking timing. Sleep dlisorders of older adults seem to be caused by functional or organic changes in one or more of the three systems, and are roughly classified into two categories: (i) normal age-related, and (ii) pathological. The former includes decreased amplitude and advanced phase of circadian rhythms (body temperature, melatonin secretion, and sleep-waking), as well as reduced sleep duration, sleep fragmentation, and a decrease of slow-wave sleep in sleep architecture. Pathological sleep disorders include medical and psychiatric diseases (e.g., lifestyle-related diseases, dementia, delirium, and depression) and primary age-related sleep disorders (e.g., REM sleep behavior disorder and periodic limb move- ment disorders). This mini-review delineates the clinical features of sleep disorders in older adults.
26065117	One of the issues facing our super-aging society of Japan is to secure the elderly's safety and health. According to the latest 10-year statistics of the National Police Agency, the number of elderly driving deaths 75 years of age and over has risen 1.3 times from 2003 to 2013, whereas driving deaths decreased by less than half among the people under age 75 during the same period of time. This paper reviews the current literature on epidemiologic studies investigating the associations of sleep disturbances with adverse driving events and driving practice among elderly drivers. The results suggest a cognitive behavioral therapy for insomnia as a promising method for improving their driving capacity. Key words: elderly driving, epidemiology, sleep disturbances

26063636	Previous studies investigating the relationship between sleep duration and cognitive function in older adults have suggested that longer sleep durations are associated with decreased cognitive performance.The intent of this study is to determine if performance on the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Exam (MMSE) is associated with self-reported sleep duration in older adults.	Data from 189 cognitively normal older adults aged 75 and older (mean age 89.29 ± 7.62) and free of severe depression were used for this analysis. Individuals were grouped based on their self-reported hours of sleep (short duration = <7, normal duration = 7, >9, and long duration = ≥9). The Kruskal-Wallis test was used to discern group differences on the MoCA scores, while multinomial logistic regression was used to assess the association between MoCA and MMSE scores and sleep group.	The long duration group had significantly lower MoCA scores than the normal duration group (p = 0.02). The short duration group was not significantly different from the normal duration group (p = 0.33). Individuals in the short duration group were more likely to have higher MoCA scores than those in long duration group after adjusting for age, gender, and presence of depressive symptoms [OR 0.86, 95 % CI (0.76, 0.98), p = 0.02].	The results of this study suggest that in a group of non-demented, very old subjects, self-reported sleep duration of nine or more hours is associated with decreased cognitive performance on the MoCA in older adults, even after accounting for age, gender, and presence of depressive symptoms.	
26063054	The estimated prevalence of poor sleep in patients with non-specific chronic low back pain is estimated to 64% in the adult population. The annual cost for musculoskeletal pain and reported poor sleep is estimated to be billions of dollars annually in the US. The aim of this cohort study with one-year follow-up was to explore the role of impaired sleep with daytime consequence on the prognosis of non-specific neck and/or back pain.Secondary analysis of a randomized controlled trial, including 409 patients.	Patients with good sleep at baseline were more likely to experience a minimal clinically important difference in pain [OR 2.03 (95% CI 1.22-3.38)] and disability [OR 1.85 (95% CI 1.04-3.30)] compared to patients with impaired sleep at one-year follow-up.	Patients with non-specific neck and/or back pain and self-reported good sleep are more likely to experience a minimal clinically important difference in pain and disability compared to patients with impaired sleep with daytime consequence.	
26062945	Sleep disorders can be diagnosed in approximately 15 % of the population and have been shown to increase with age. The relationship between sleep disorders and neurological disorders, however, is still insufficiently considered in the clinical practice. Sleep disorders can be an early symptom of the disease, such as the presence of rapid eye movement (REM) sleep behavior disorder (RBD) as an early indicator of neurodegeneration. Sleep disorders have also been shown to be a main symptom of various neurological syndromes, such as in restless legs syndrome (RLS), periodic limb movement disorder (PLMD) and narcolepsy. The international classification of sleep disorders 2nd edition (ICSD 2) describes the main diagnoses, insomnia, circadian rhythm sleep disorders, sleep-related breathing disorders and hypersomnia but all of these can also appear as symptoms in various neurological diseases. Parasomnias are largely considered a differential diagnosis to nocturnal epilepsy. In this review, the main sleep disorders are described with a particular focus on how they relate to neurological diseases; in particular, how they influence disease-related symptoms and how they affect the course of the disease. 
26062619	Acute stress in patients experiencing cancer diagnosis and the post-traumatic stress disorder in cancer survivors results in impaired overall quality of life mainly due to associated psychological and physical alterations, including anxiety, depression, sleep disturbances, cognitive dysfunctions, fatigue, pain, cachexia and others. Recent studies revealed a new insight into molecular mechanisms contributing to the development of cancer-related co morbidities. It has been shown that adverse psychosomatic reactions including cancer depression to emotional cancer distress result from neuroendocrinne dysfunctions, disruption of the hypothalamus- pituitary-adrenal axis and sympathetic nervous system, serotonin-dopamine interactions and circadian sleep- wake rhythm disruption.The aim of the present study was to evaluate clinical studies oriented toward elucidation of the hypothesis that cancer-related anxio- depressive syndrome is the major disorder leading to the development of accompanying psychosomatic disruptions.	The data of the biopsychosocial approach in the treatment of cancer presented in the current literature were collecting using appropriate electronic databases and were elaborated in the form of meta-analysis of 24 selected publications.	According to relevant clinical studies, psychosocial interventions and psychopharmacological treatment has been shown to reduce cancer symptomatology and to improve the ability of patients to cope with the disease. Thus, one of the key pillars of supportive care in oncology is stress reduction. Cognitive- behavioral interventions and group psychosocial therapies have shown to reduce stress from the diagnosis and treatment, to palliate depression and to help in restoring the circadian rhythm. Psychopharamacological interventions are the most useful approaches in the reduction of stress-induced cancer comorbidities. In the presented study, a plausible role of stress reduction in the protection of cancer patients from posttraumatic and anxio- depressive syndrome, physical and psychical suffering, from decrease of patients quality of life, ability to cope with the disease and cooperate in cancer treatment has been analyzed.	Implementation of the biopsychosocial model of cancer care needs further cooperation between behavioral scientists and clinical oncologists attempted to elucidate further possibilities of psychosocial and pharmacological interventions leading to the regulation of stress-induced alterations of the neurotransmitter system and neuroendocrinne dysfunctions reduction of cancer-related co morbidities and improvement of patients survival time.	
26059712	Midlife may be an ideal window for intervention in Alzheimer's disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late midlife, we imaged brain amyloid deposits using positron emission tomography with [C-11]Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale and the Medical Outcomes Study Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimer's Prevention. We used multiple regressions to test the extent to which sleep scores predicted regional amyloid burden. Participants reporting less adequate sleep, more sleep problems, and greater somnolence on the Medical Outcomes Study had greater amyloid burden in AD-sensitive brain regions (angular gyrus, frontal medial orbital cortex, cingulate gyrus, and precuneus). Amyloid was not associated with reported sleep amount, symptoms of sleep-disordered breathing, trouble falling asleep, or Epworth Sleepiness Scale. Poor sleep may be a risk factor for AD and a potential early marker of AD or target for preventative interventions in midlife.
26059658	Socio-demographic indicators closely relate to sleep in industrialized populations. However we know very little about how such factors impact sleep in populations undergoing industrialization. Within populations transitioning to the global economy, the preliminary evidence has found an inconsistent relationship between socio-demographics and sleep complaints across countries and social strata.Surveys were conducted on a sample of rural Sakha (Yakut) adults (n = 168) during the autumn of 2103 to assess variation in socio-demographics and sleep complaints, including trouble sleeping and daytime sleepiness. Socio-demographic variables included age, gender, socioeconomic measures, and markers of traditional/market-based lifestyle. We tested whether the socio-demographic variables predicted sleep complaints using bivariate analyses and multiple logistic regressions.	Trouble sleeping was reported by 18.5% of the participants and excessive daytime sleepiness (EDS) by 17.3%. Trouble sleeping was significantly predicted by older age, female gender, and mixing traditional and market-based lifestyles. EDS was not significantly predicted by any socio-demographic variable.	These findings support the few large-scale studies that found inconsistent relationships between measures of socioeconomic status and sleep complaints in transitioning populations. Employing a mix of traditional and market-based lifestyles may leave Sakha in a space of vulnerability, leading to trouble sleeping.	
26059271	We assessed the efficacy and safety of extended-release gabapentin in a 15-week, open-label, single-arm, single-center study in patients with fibromyalgia (FM).Subjects with documented diagnosis of FM were allowed to participate in the study. We opened enrollment to those who have tried and failed gabapentinoids such as gabapentin or pregabalin due to side effects. Subjects with autoimmune conditions, and or taking opioids for management of their FM pain, were excluded from the study. Subjects were given an extended-release gabapentin starter pack and treated for total of 12 weeks. The primary study endpoint of pain relief was measured using Numeric Pain Rating System (NPRS) scores, and secondary study endpoints were measured with Fibromyalgia Impact Questionnaire (FIQ), Patient's Global Impression of Change (PGIC), and Medical Outcome Sleep questionnaires (MOS).	A total of 34 subjects were enrolled and 29 subjects completed the starter pack (85%). Patients reported significant pain relief on NPRS by end of 4 weeks (P < 0.0001) on NPRS. Subjects also reported similar magnitude of improvements in FM and its impact on daily life by end of 4 weeks on FIQ (P < 0.0001). Survey of MOS showed our subjects reporting improved sleep quantity (on average, 1.2 hours over baseline) with gradual and statistically significant improvement in quality. Improvements in primary and secondary measurements were reflected in PGIC, with significant improvement in patient's impression of FM by week 8.	Small sample size, geographical bias, relatively short duration of treatment, and single-arm study without control group.	Extended-release gabapentin relieved FM pain symptoms and improved quality-of-life for the FM subjects studied. Subjects reported improvements in both quantity and quality of sleep.	
26058323	Continence care commonly disrupts sleep in residential aged care facilities, however, little is known about what staff do when providing continence care, and the factors that inform their practice.To describe nurses' and personal careworkers' beliefs and experiences of providing continence care at night in residential aged care facilities.	Eighteen nurses and personal careworkers were interviewed about continence care, and 24 hours of observations were conducted at night in two facilities.	Most residents were checked overnight. This practice was underpinned by staffs' concern that residents were intractably incontinent and at risk of pressure injuries. Staff believed pads protected and dignified residents. Decisions were also influenced by beliefs about limited staff-to-resident ratios.	Night-time continence care should be audited to ensure decisions are based on residents' preferences, skin health, sleep/wake status, ability to move in bed, and the frequency, severity and type of residents' actual incontinence.	
26057316	The relationship between circadian disruptions and depressive disorders is a topic of great interest in contemporary psychiatry. Circadian rhythms include all physiological processes displaying a period around 24 hours. Sleep/wake cycles, body temperature, hormone secretion and other functions are subjected to person's individual circadian rhythm. Circadian typology includes three chronotypes: morning, neither and evening. The aim of this study was to examine the chronobiological aspects of depression.This cross-sectional study aimed to determine circadian rhythmic expression in 60 patients suffering from depression. The patients were in remission and were treated as outpatients at the Department of Psychiatry of the University Hospital Center Zagreb. The data were compared to a control group consisting of 40 medical workers employed at the University Hospital Centre Zagreb. A self-report measure of circadian typology was utilized - the Morningness-Eveningness Questionnaire.	According to our findings, among depressed patients 35% were morning, 58.3% neither and 6.7% evening types. In the control group 46% were morning, 48% neither and 6.0% evening types. Depressed patients reported stronger morning fatigue. Further, they tended to go to sleep earlier and felt more tired earlier in the evening, and they were less prone to choosing morning periods for completing complex cognitive tasks.	This study supports the association between depression and some alterations in circadian rhythms of behavior and sleep. Depression may be considered as the consequence or trigger of circadian disturbances. However, both depression and circadian rhythm disturbances may have a common aetiology: a decreased cellular resilience associated with lower resistance to stressful events.	
26056516	Sleep deficiency, which can be caused by acute sleep deprivation, chronic insufficient sleep, untreated sleep disorders, disruption of circadian timing, and other factors, is endemic in the U.S., including among professional and non-professional drivers and operators. Vigilance and attention are critical for safe transportation operations, but fatigue and sleepiness compromise vigilance and attention by slowing reaction times and impairing judgment and decision-making abilities. Research studies, polls, and accident investigations indicate that many Americans drive a motor vehicle or operate an aircraft, train or marine vessel while drowsy, putting themselves and others at risk for error and accident. In this chapter, we will outline some of the factors that contribute to sleepiness, present evidence from laboratory and field studies demonstrating how sleepiness impacts transportation safety, review how sleepiness is measured in laboratory and field settings, describe what is known about interventions for sleepiness in transportation settings, and summarize what we believe are important gaps in our knowledge of sleepiness and transportation safety.
26055866	Melatonin is commonly recommended to treat sleep problems in children with developmental disabilities. However, few studies document the efficacy and safety of melatonin in these populations. This article reviews recent studies of melatonin efficacy in developmental disabilities. Overall, short treatment trials were associated with a significant decrease in sleep onset latency time for each of the disorders reviewed, with 1 notable exception-tuberous sclerosis. Reported side effects were uncommon and mild. Across disorders, additional research is needed to draw disability-specific conclusions. However, studies to date provide positive support for future trials that include larger groups of children with specific disabilities/syndromes. 
26055862	Basic assumptions about ADHD in children and sleep are not supported by research. It is unclear that children with hyperactivity or inattention have disrupted sleep. Parents of children with ADHD consistently report more bedtime resistance, but there is no objective evidence that sleep is subsequently disrupted. Treatment of ADHD with stimulants may disrupt sleep. Studies of comorbid sleep or psychiatric disorders consistently show that they disrupt sleep. Melatonin is an effective treatment of sleep problems in children with ADHD. Before any child is placed on stimulants, the pediatrician or other health care professional should insure that the child is obtaining adequate sleep. 
26055861	Sleep problems are not a core feature of obsessive-compulsive disorder (OCD), but emerging empirical data indicate some form of sleep disruption to be highly common. Available research in both adult and child patients is limited in several important ways, including the use of subjective reports (particularly in children), high rates of comorbid depression, and concurrent use of psychotropic medication. The presence of sleep disruption in OCD patients may compound severity and impairment of the disorder. More research is needed to fully understand the nature and consequences of sleep-wake disruption in children with OCD. 
26055860	Sleep problems are common in children and adolescents. A growing body of research has explored the relationship between sleep problems and anxiety in youth. When reviewing the literature, methodologic inconsistencies need to be considered, such as variation in conceptualization of sleep problems, measurement of sleep, and the classification of anxiety. Despite this, there seems to be good evidence of concurrent and longitudinal associations between sleep difficulties and anxiety in community and clinical samples of young people. Potential mechanisms are proposed. There is a need for further exploration of these relationships, with the hope of aiding preventive capability and developing useful treatments. 
26055859	According to recent meta-analyses, adolescents across different countries and cultures do not get the recommended amount of sleep. Extracurricular activities, part-time jobs, and use of electronic devices in the evening delay bedtime in adolescents. Early school start times also shorten the time for sleep. Insufficient sleep in adolescents has been associated with weakened emotional-behavioral regulation and poor academic achievement. Multicomponent intervention programs have been developed on the basis of cognitive-behavioral therapy for insomnia to improve sleep in youth. 
26055858	Several observational, cross-sectional, and longitudinal studies as well as a few well-controlled experimental studies have examined the impact of sleep loss on children's daytime functioning. The emerging results indicate that sleep plays a critical role in various aspects of daytime functioning in children, including cognitive and emotional functioning. Furthermore, studies indicate that daytime functioning may be impaired by even small amounts of sleep restriction in children. 

26055676	Hypnosis has been used to manage insomnia and disorders of arousal. The alteration in the state of consciousness produced during hypnotic trance is more similar to relaxed reverie than sleep. Hypnosis typically occurs in a state of repose and the accomplished subject may have no recollection of the experience during a trance, 2 commonalities with sleep. Because hypnosis allows for relaxation, increased suggestibility, posthypnotic suggestion, imagery rehearsal, access to preconscious cognitions and emotions, and cognitive restructuring, disorders of sleep such as the insomnias, parasomnias, and related mood or anxiety disorders can be amenable to this therapeutic intervention. 
26055673	Both subjective and objective assessments of sleep patterns in schizophrenia include a wide range of dyssomnias, with insomnia being the most frequently cited. Early and middle insomnia can range from mild disruption to total sleeplessness. Severe insomnia is a prodromal sign of clinical exacerbation or relapse. In general, most antipsychotic agents (APs) ameliorate this insomnia. However, in some schizophrenics APs can be associated with residual insomnia or with significant daytime somnolence. Furthermore, in some schizophrenics APs can induce or exacerbate comorbid sleep disorders such as restless legs syndrome, sleep-disordered breathing, and parasomnias such as sleepwalking. 
26055672	The purpose of this article is to provide a brief overview of sleep in the context of posttraumatic stress disorder (PTSD) and focus on the treatment of the most common sleep disorders encountered by patients with PTSD: insomnia and nightmares. The effects of the standard treatments for PTSD are discussed along with a review of available treatments for insomnia and nightmares. Particular emphasis is placed on nonpharmacologic treatments for these sleep disorders and how they may be adapted for delivery to patients with PTSD. 
26055671	Suicide occurs in the presence of psychiatric illness, and is associated with biological, psychological, and social risk factors. Insomnia symptoms and nightmares appear to present elevated risk for suicidal ideation, attempts, and death by suicide. Failure to account for the presence of psychopathology and frequent use of single item assessments of sleep and suicidal ideation are common methodological problems in this literature. Preliminary research, addressing these issues, suggests that subjective sleep complaints may confer independent risk for suicidal behaviors. 
26055670	During the perinatal period, compromises in sleep duration and quality are commonly reported by women and confirmed by objective measurements of sleep. Self-reported poor sleep has been associated with concurrent mood disturbance and with increased risk for future mood problems during pregnancy and the postpartum period. Findings on the relationship between objectively measured sleep and mood in perinatal women have been mixed. This article reviews the literature on the nature of and contributing factors to perinatal sleep disturbance, the relationship between sleep and mood, and intervention studies that aim to improve maternal sleep. 
26055669	Major depressive disorder is frequently accompanied by sleep disturbances such as insomnia or hypersomnia and polysomnographic sleep findings of increased rapid-eye-movement sleep and decreased slow wave sleep. For many patients, insomnia persists even after mood symptoms have been adequately treated. These patients have poorer outcomes than patients without sleep problems. These outcomes suggest that overlapping neural mechanisms regulate sleep and mood. Treatment of these patients can incorporate sedating antidepressants, nonbenzodiazepine γ-aminobutyric acid agonists, and cognitive behavioral therapy. Sleep restriction has been found to improve mood in depressed patients; however, the benefits typically disappear after recovery sleep. 

26055094	This is the first prospective study of the reciprocal association between sleep restriction and weight among adolescents. Evidence on sleep duration and obesity in youth is sparse and the results have been equivocal.Data are from a community-based, two-wave cohort study. The setting was a metropolitan area with a population of over 4 million. The cohort consisted of 4175 youths 11-17 at baseline and 3134 of these followed up a year later. Obesity was defined as body mass index >95th percentile for children of the same age and sex. Sleep restriction was defined as 6 or fewer hours of sleep per night on weeknights or on both weekends and weeknights. Covariates examined were age, gender, family income and depression.	Results clearly demonstrated that there was no association between sleep restriction and obesity at baseline. In prospective analyses, sleep restriction did not increase future risk of obesity, nor did obesity increase risk of future sleep restriction.	These findings call into question previous research based primarily on cross-sectional data suggesting a positive correlation between sleep restriction and obesity. However, the results for adolescents in this study are supported by one study of adolescents and by studies of adults using prospective designs. At this point, there appears to be little evidence for a temporal relation between sleep duration and obesity among adults or adolescents.	
26055056	Serotonin receptors (5-HTRs) mediate both central and peripheral control on numerous physiological functions such as sleep/wake cycle, thermoregulation, food intake, nociception, locomotion, sexual behavior, gastrointestinal motility, blood coagulation, and cardiovascular homeostasis. Six families of the G-protein-coupled receptors comprise most of serotonin receptors besides the conserved 5-HT3R Cys-loop type which belongs to the family of Cys-loop ligand-gated cation channel receptors. Many of these receptors are targets of pharmaceutical drugs, justifying the importance for elucidating their coupling, signaling and functioning. Recently, special interest has been focused on their trafficking inside cell lines or neurons in conjunction with their interaction with partner proteins. In this review, we describe the trafficking of 5-HTRs including their internalization, desensitization, or addressing to the plasma membrane depending on specific mechanisms which are peculiar for each class of serotonin receptor. 
26053990	We investigated the sleep problems and sleep habits of adolescents at three public primary schools and two high schools. Our study included 428 Turkish school children (244 girls and 184 boys). We used a questionnaire to determine the time they went to sleep at night; waking time in the morning; incidence of nightmares, snoring, daytime sleepiness, and intrafamilial physical trauma; concentration difficulty in class; and school success. The students were divided into age-related groups (group 1 = 11 to 13 years of age; group 2 = 14 to 15 years; group 3 = 16 to 18 years). The time they went to sleep was mostly between 10 and 11 p.m. in groups 1 and 2, and 11 to 12 p.m. in group 3. Difficulty in falling asleep was reported by 16.8 to 19.6% of the students in the three groups. Difficulty in waking up in the morning was reported by 12.7% of group 1, 16.0% of group 2, and 16.8% of group 3. Snoring was present in 12.1% of females and 22.0% of males. The occurrence of one nightmare in the preceding 3 months was reported by 11.3% of the students; 17.9% of the students reported having nightmares several times. Daytime sleepiness was present in 65.1%, and concentration difficulty was present in 56.8% of the students. We conclude that difficulty in falling asleep, snoring, and daytime sleepiness may be seen in adolescents who are in both primary and high schools. Watching inappropriate programs and movies on television and intrafamilial physical trauma may cause nightmares and sleeping problems in these adolescents. Students and families should be educated about the importance of sleep in academic performance. Countries' public health policies should address sleep problems and related educational activities. 
26053839	Sleep disturbance and poor sleep quality has been associated with trauma exposure and posttraumatic stress disorder (PTSD) symptoms; however, the associated emotional consequences of sleep disturbance have not been examined within this context (i.e., emotional reactivity, emotion modulation). The current study examined the relationship between sleep disturbance, poor sleep quality, and emotion regulation difficulties. In a sample of college students reporting exposure to at least 1 traumatic event, online survey methodology was used to assess PTSD symptom severity (PTSS), sleep disturbances, including PTSD-specific sleep disturbances, and emotion regulation difficulties. After controlling for PTSS, sleep disturbance and poor sleep quality domains were related to both global and specific difficulties in emotion regulation domains. The findings suggest that sleep disturbance and emotion regulation difficulties associated with PTSD may not be a mere extension of the clinical picture of PTSD. Sleep disturbances following trauma exposure may contribute to emotion regulation difficulties and exacerbate negative consequences. Future research should examine the effects of treatments that simultaneously address sleep disturbances and PTSD symptoms on emotion regulation processes.
26052727	In contrast with randomized controlled trials, observational studies have suggested that physiological levels of melatonin are reduced in patients with dementia or depression, but the relationship has not been evaluated in large populations.The objective was to determine the relationships between physiological levels of melatonin and cognitive function and depressive symptoms.	A cohort of 1105 community-dwelling elderly individuals was enrolled in this cross-sectional study (mean age, 71.8 ± 7.1 y).	Urinary 6-sulfatoxymelatonin excretion (UME) and Mini-Mental State Examination (MMSE; n = 935) and Geriatric Depression Scale (GDS; n = 1097) scores were measured as indices of physiological melatonin levels, cognitive function, and depressive symptoms, respectively.	With increases in UME quartiles, the prevalence of cognitive impairment (MMSE score ≤ 26) and depressed mood (GDS score ≥ 6) significantly decreased (P for trend = .003 and .012, respectively). In multivariate logistic regression models, after adjusting for confounders such as age, gender, socioeconomic status, physical activity, and sleep/wake cycles, higher UME levels were significantly associated with lower odds ratios (ORs) for cognitive impairment and depressed mood (ORs: Q1 = 1.00; Q2 = 0.88 and 0.76; Q3 = 0.66 and 0.85; Q4 = 0.67 and 0.53; P for trend = .023 and .033, respectively). In addition, the highest UME group showed a significantly lower OR for depressed mood than the lowest UME group (Q4 vs Q1: OR, 0.53; 95% confidence interval, 0.32-0.89; P = .033). UME levels above the median value were significantly associated with a lower OR for cognitive impairment, even after further adjustment for depressive symptoms (OR = 0.74; 95% confidence interval, 0.55-0.99; P = .043).	Significant associations of higher physiological melatonin levels with lower prevalence of cognitive impairment and depressed mood were revealed in a large general elderly population. The association between physiological melatonin levels and cognitive function was independent of depressive symptoms.	
26052150	The effects of two food materials, γ-aminobutyric acid (GABA) produced by natural fermentation and Apocynum venetum leaf extract (AVLE), on the improvement of sleep were investigated in humans. The electroencephalogram (EEG) test revealed that oral administration of GABA (100 mg) and AVLE (50 mg) had beneficial effects on sleep. GABA shortened sleep latency by 5.3 min and AVLE increased non-rapid eye movement (REM) sleep time by 7.6%. Simultaneous intake of GABA and AVLE shortened sleep latency by 4.3 min and increased non-REM sleep time by 5.1%. The result of questionnaires showed that GABA and AVLE enabled subjects to realize the effects on sleep. These results mean that GABA can help people to fall asleep quickly, AVLE induces deep sleep, and they function complementarily with simultaneous intake. Since both GABA and AVLE are materials of foods and have been ingested for a long time, they can be regarded as safe and appropriate for daily intake in order to improve the quality of sleep. 
26051427	The mammalian locus coeruleus (LC) is a brainstem structure that displays extensive interconnections with numerous brain regions, and in particular plays a prominent role in the regulation of sleep and arousal. Postnatal LC development is known to drastically alter sleep-wake switching behavior through early infancy, and, in rats, exerts its most significant influence from about postnatal day 8 to postnatal day 21 (P8-P21). Physiologically, several dramatic changes are seen in LC functionality through this time period. Prior to P8, LC neurons are extensively coupled via electrical gap junctions and chemical synapses, and the entire LC network exhibits synchronized ~0.3 Hz subthreshold oscillations and spiking. From P8 to P21, the network oscillation frequency rises up to ~3 Hz (at P21) while the amplitude of the network oscillation decreases. Beyond P21, synchronized network oscillations vanish and gap junction coupling is sparse or nonexistent. In this work, we develop a large-scale, biophysically realistic model of the rat LC and we use this model to examine the changing physiology of the LC through the pivotal P8-P21 developmental period. We find that progressive gap junction pruning is sufficient to account for all of the physiological changes observed from P8 to P21.
26050245	Peer victimization (PV) is a key interpersonal stressor that can be traumatizing for youth. This study evaluated the relationships between overt, relational, reputational, and cyber PV and adolescents' somatic complaints and sleep problems. Symptoms of depression and social anxiety were examined as potential mediators.Adolescents (N = 1,162; M age = 15.80 years; 57% female; 80% Hispanic) were assessed at three time points, 6 weeks apart, using standardized measures of PV, depression, social anxiety, sleep problems, and somatic complaints. Structural equation modeling evaluated key study aims.	Relational, reputational, and cyber PV, but not overt PV, were directly or indirectly associated with subsequent somatic complaints and/or sleep problems. Depression and social anxiety mediated relationships between relational PV and health outcomes, whereas reputational PV was indirectly associated with somatic complaints via depression only.	The stress of PV may contribute to adolescents' sleep problems and somatic complaints and has implications for pediatric psychologists.	
26049768	Primary headache and attention-deficit/hyperactivity disorder (ADHD) are common disorders in children and adolescences, frequently associated to severe cognitive, emotional, and behavioral impairments. They both are a disabling condition with consequences on family and child's quality of life. Literature data on their association are contrasting. Dopaminergic system dysfunction, brain iron deficiency, and sleep disturbance should be considered to better understand headache and ADHD overlap. In this review, we analyze the complex association between these two diseases and the potential impact on child neurodevelopment. 
26049205	Caffeine and nicotine are commonly used stimulants that enhance alertness and mood. Discontinuation of both stimulants is associated with withdrawal symptoms including sleep and mood disturbances, which may differ in males and females. The present study examines changes in sleep quality, daytime sleepiness and psychological distress associated with use and dependence on caffeine and nicotine.An online survey comprising validated tools to assess sleep quality, excessive daytime sleepiness and psychological distress was completed by 166 participants (74 males, 96 females) with a mean age of 28 years. Participants completed the study in their own time, and were not offered any inducements to participate.	Sleep quality was poorer in those dependent upon caffeine or nicotine, and there were also significant interaction effects with gender whereby females reported poorer sleep despite males reporting higher use of both stimulants. Caffeine dependence was associated with poorer sleep quality, increased daytime dysfunction, and increased levels of night time disturbance, while nicotine dependence was associated with poorer sleep quality and increased use of sleep medication and sleep disturbances. There were strong links between poor sleep and diminished affect, with psychological distress found to co-occur in the context of disturbed sleep.	Stimulants are widely used to promote vigilance and mood; however, dependence on commonly used drugs including caffeine and nicotine is associated with decrements in sleep quality and increased psychological distress, which may be compounded in female dependent users.	
26046965	Short sleep duration and poor sleep quality are associated with cardiovascular outcomes. One mechanism proposed to explain this association is altered diurnal cortisol secretion.The objective of the study was to examine the associations of sleep duration and sleep quality with diurnal salivary cortisol levels.	This was a cross-sectional analysis using data from examination 5 (2010-2012) of the Multi-Ethnic Study of Atherosclerosis. Actigraphy-based measures of sleep duration and efficiency were collected over 7 days, and salivary cortisol samples were collected over 2 days from participants aged 54-93 years (n = 600 with analyzable data).	Shorter average sleep duration (<6 h/night) was associated with less pronounced late decline in cortisol [2.2% difference in slope; 95% confidence interval (CI) 0.8-3.7; P ≤ .01] and less pronounced wake-to-bed slope (2.2% difference; 95% CI 1.0-3.4; P ≤ .001) compared with longer sleep duration (≥6 h/night). Lower sleep efficiency (<85%) was associated with less pronounced early decline in cortisol (29.0% difference in slope; 95% CI 4.1-59.7; P < .05) compared with higher sleep efficiency (≥85%). Subjects reporting insomnia had a flatter cortisol awakening response (-16.1% difference in slope; 95% CI -34.6 to -0.1; P < .05) compared with those not reporting insomnia.	Shorter sleep duration, lower sleep efficiency, and insomnia are associated with alterations in diurnal cortisol levels consistent with changes in hypothalamic-pituitary-adrenal regulation.	
26046367	Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain.
26045032	Specific neurons in the lateral hypothalamus produce the orexin neuropeptides (orexin-A and orexin-B). The orexin-peptides are transported to areas of the brain regulating sleep-wake cycles, controlling food intake or modulating emotional states such as panic or anxiety. The orexin system, consisting of the two orexin-neuropeptides and two G-protein-coupled receptors (the orexin-1 and the orexin-2 receptor) is as well involved in reward and addictive behaviors. The review reflects on the most recent activities in the field of orexin research. 
26045018	The aims were to identify in-home concerns about sleep in children and young people with cerebral palsy (CP) across age and Gross Motor Function Classification Scale (GMFCS) levels.This was a retrospective review of clinical notes of 154 children and young people with CP, aged 1-18 years (M = 7.8; standard deviation = 5.4) who received a home-based sleep service. Reported concerns were synthesised, for analysis according to age groups (1-5, 6-13, 14-18) and GMFCS levels.	Sixteen factors of concern were derived from the home-based assessment reports. Most children and young people had multiple factors of concern. These varied across age groups and GMFCS levels. Body position was of concern across all age groups, for over 90% at GMFCS levels IV and V, and for 10% at GMFCS level I. Settling routines were of concern for more than 90% at GMFCS levels I and II, but for less than 50% at GMFCS levels IV and V. Settling routines were of concern to over 65% of those under 6 years but less than 25% of those over 14 years. Conversely, pain and pressure care concerned less than 10% of children under 6, and more than 35% of those over 14 years.	Concerns about sleep vary across ages and GMFCS levels of children and young people with CP. Concerns relate to impairment of body structure and function, activity, environment, and personal supports. Multi-disciplinary, home-based assessment and interventions are recommended to address these concerns.	
26044918	Integrative medicine (IM) is a rapidly growing field whose providers report clinical success in treating significant stress, chronic pain, and depressive and anxiety symptoms. While IM therapies have demonstrated efficacy for numerous medical conditions, IM for psychological symptoms has been slower to gain recognition in the medical community.This large, cross-sectional study is the first of its kind to document the psychosocial profiles of 4182 patients at 9 IM clinics that form the BraveNet Practice-Based Research Network (PBRN).	IM patients reported higher levels of perceived stress, pain, and depressive symptoms, and lower levels of quality of life compared with national norms. Per provider reports, 60% of patients had at least one of the following: stress (9.3%), fatigue (10.2%), anxiety (7.7%), depression (7.2%), and/or sleep disorders (4.8%). Pain, having both physiological and psychological components, was also included and is the most common condition treated at IM clinics. Those with high stress, psychological conditions, and pain were most frequently treated with acupuncture, IM physician consultation, exercise, chiropractic services, diet/nutrition counseling, and massage.	With baseline information on clinical presentation and service utilization, future PBRN studies can examine promising interventions delivered at the clinic to treat stress and psychological conditions.	
26044362	The impact of growth restriction on perinatal morbidity is well known, but electroencephalographic (EEG) data on its influence are still scarce.We aimed to analyze the influence of being born small for gestational age (SGA; defined as a birth weight <10th percentile) on the amplitude-integrated EEG (aEEG) score in the first 2 weeks of life in preterm infants born before 30 weeks of gestation, and its impact on later outcome.	aEEG data obtained within the first 2 weeks of life on preterm infants born SGA and before 30 weeks of gestational age (GA) were analyzed retrospectively using a combined score [including background activity, occurrence of sleep-wake cycles (SWC) and suspected seizure activity]. Neurodevelopmental outcome was evaluated at 24 months by means of the Bayley Scales of Infant Development II and a standardized neurological examination.	One hundred and thirty-six patients were included (47 SGA and 89 controls). Infants with SGA had abnormal aEEG scores significantly more often (57 vs. 24%, p = 0.002) than infants born appropriate for gestational age (AGA). They also displayed SWC less frequently (65 vs. 96%, p = 0.001), were more likely to develop seizure activity (15 vs. 4%, p = 0.013) and had a normal neurodevelopmental outcome at the age of 2 years less frequently (36.2 vs. 59.6%, p = 0.02).	Preterm infants born SGA and before 30 weeks of GA had less optimal scores on early aEEG and a poorer neurodevelopmental outcome at 24 months than the AGA controls.	
26044075	It is unknown whether supplementation with calcium and vitamin D has an impact on menopause-related symptoms.As part of the Women's Health Initiative Calcium/Vitamin D Supplementation Trial (CaD), women were randomized at 40 clinical sites to elemental calcium carbonate 1000 mg with vitamin D 400 IU daily or placebo. At the CaD baseline visit (year 1 or year 2) and during a mean follow-up of 5.7 years, participants provided data on menopause-related symptoms via questionnaires. Generalized linear mixed effects techniques were used to address research questions.	After excluding participants with missing data (N=2125), we compared menopause-related symptoms at follow-up visits of 17,101 women randomized to CaD with those of 17,056 women given the placebo. Women in the CaD arm did not have a different number of symptoms at follow-up compared to women taking the placebo (p=0.702). Similarly, there was no difference between sleep disturbance, emotional well-being, or energy/fatigue at follow-up in those who were randomized to CaD supplementation compared to those taking the placebo.	Our data suggest that supplementation with 1000 mg of calcium plus 400 IU of vitamin D does not influence menopause-related symptoms over an average of 5.7 years of follow-up among postmenopausal women with an average age of 64 at the WHI baseline visit.	

26043207	Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual's circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. 
26042199	The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery.	In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.	
26041958	Sleep-wake abnormalities in patients with cirrhosis have been traditionally associated with hepatic encephalopathy (HE). In recent years, a certain amount of work has been devoted to the study of this relationship. This has lead to a modified picture, with weakening of the association between HE and poor night sleep, and the emergence of stronger links between HE and excessive daytime sleepiness. This brief review focuses on the evidence in favor of the interpretation of HE as a sleepiness syndrome, and on the diagnostic, therapeutic and social implications of such an interpretation. 
26041007	In view of the regulatory function of the thalamus in the sleep-wake cycle, the impact of deep brain stimulation (DBS) of the anterior nucleus thalami (ANT) on sleep was assessed in a small consecutive cohort of epilepsy patients with standardized polysomnography (PSG). In nine patients treated with ANT-DBS (voltage 5 V, frequency 145 Hz, cyclic mode), the number of arousals during stimulation and nonstimulation periods, neuropsychiatric symptoms (npS), and seizure frequency were determined. Electroclinical arousals were triggered in 14.0 to 67.0% (mean 42.4 ± SD 16.8%) of all deep brain stimuli. Six patients reported npS. Nocturnal DBS voltages were reduced in eight patients (one patient without npS refused) and PSGs were repeated. Electroclinical arousals occurred between 1.4 and 6.7 (mean 3.3 ± 1.7) times more frequently during stimulation periods compared to nonstimulation periods; the number of arousals positively correlated with the level of DBS voltage (range 1 V to 5 V) (Spearman's rank coefficient 0.53121; p < 0.05). No patient experienced seizure deterioration and four patients reported remission of npS. This case-cohort study provides evidence that ANT-DBS interrupts sleep in a voltage-dependent manner, thus putatively resulting in an increase of npS. Reduction of nocturnal DBS voltage seems to lead to improvement of npS without hampering efficacy of ANT-DBS. 
26039965	Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women.Prospective cohort study.	Four sites across the United States.	330 women (46-57 y of age) enrolled in the Study of Women's Health Across the Nation (SWAN) Sleep Study.	N/A.	Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints.	Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time.	
26039910	To evaluate the association between temporomandibular disorder (TMD) and anxiety, quality of sleep, and quality of life in nursing professionals at the Hospital de Clínicas de Uberlândia of the Universidade Federal de Uberlandia--HCU-UFU (Medical University Hospital of the Federal University of Uberlândia), four questionnaires were given to nursing professionals. The questionnaires were completed by 160 of these professionals. The Fonseca's questionnaire was used to evaluate the presence and severity of TMD, the IDATE was used to evaluate anxiety, the SAQ was used to evaluate quality of sleep, and the SF-36 was used to evaluate quality of life. Forty-one nurses (25.6%) reported having no TMD (Fonseca's questionnaire score ≤ 15), 66 (41.3%) had mild TMD (Fonseca's questionnaire score 20-40), 39 (24.4%) had moderate TMD (Fonseca's questionnaire score 45-65), and 14 (8.8%) had severe TMD (Fonseca's questionnaire score ≥ 70). According to Fonseca's questionnaire, the presence of TMD was associated with trait anxiety, but the TMD severity was associated with state anxiety classification (mild, moderate, severe). The SAQ score differed significantly from Fonseca classification. The Fonseca's questionnaire score correlated negatively with the score of each dimension of the SF-36 (r = -0.419 to -0.183). We conclude that TMD is common among nursing professionals; its presence was associated with trait anxiety, and its severity was associated with state anxiety. Hence, the presence of TMD may reduce quality of sleep and quality of life.
26039388	OBJECTIVE To analyze the perception of and motivation for the chronic use of benzodiazepine among older adults. METHODS A qualitative study was conducted on 22 older adults living in Bambuí, MG, Southeastern Brazil, who were taking benzodiazepines and had the clinical and cognitive ability to respond to interview questions. The collected data were analyzed on the basis of the "signs, meanings, and actions" model. RESULTS The main reasons pointed out for the use of benzodiazepines were "nervousness", "sleep problems", and "worry" due to family and financial problems, everyday problems, and existential difficulties. None of the interviewees said that they used benzodiazepines in a dose higher than that recommended or had been warned by health professionals about any risks of their continuous use. Different strategies were used to obtain the prescription for the medication, and any physician would prescribe it, indicating that a bond was established with the drug and not with the health professional or healthcare service. Obtaining and consuming the medication turned into a crucial issue because benzodiazepine assumes the status of an essential food, which leads users to not think but sleep. It causes a feeling of relief from their problems such as awareness of human finitude and fragility, existential difficulties, and family problems. CONCLUSIONS Benzodiazepine assumes the characteristics of polyvalence among older adults, which extrapolate specific clinical indications, and of essentiality to deal with life's problems in old age. Although it relieves the "nerves", the chronic use of benzodiazepines buffers suffering and prevents older adults from going through the suffering. This shows important difficulties in the organization and planning of strategies that are necessary for minimizing the chronic use in this population. 
26037823	It is increasingly recognized that disruption of sleep and reduced amounts of sleep can have significant adverse cardiovascular consequences. For example, obstructive sleep apnea (OSA) is a common underdiagnosed disorder characterized by recurrent nocturnal asphyxia resulting from repetitive collapse of the upper airway; this leads to repetitive episodes of nocturnal hypoxemia and arousal from sleep. Risk factors for disease include obesity, increased age, male sex, and family history. In epidemiologic studies, OSA appears to be an independent risk factor for cardiovascular disease (CVD), and treatment is associated with better outcomes. Habitual short sleep duration is common in today's society. In epidemiologic studies, short sleep duration is associated with a number of adverse health effects, including all-cause mortality, weight gain, and incident CVD. Given the links between sleep disorders and adverse health outcomes, obtaining adequate quality and amounts of sleep should be considered a component of a healthy lifestyle, similar to good diet and exercise. 
26037372	The aim of this study was to describe the tolerability of high-dose baclofen taken by patients with alcohol disorders during their first year of treatment.The medical records of all patients prescribed baclofen by one general practitioner were examined and all patients who could be contacted were retrospectively interviewed about adverse effects.	Of the 146 eligible patients, 116 (79%) could be interviewed. Ninety (78%) reported at least one adverse effect (mean number per patient: 2.8 ± 2.7). The mean dosage of baclofen at the onset of the first adverse effect was 83 ± 57 mg/day. The most frequent group of adverse effects involved disruption of the wake-sleep cycle and affected 73 patients (63%). Persistent adverse effects occurred in 62 patients (53%). Eight patients (7%) had adverse effects that led them to stop taking baclofen. Their dosages were <90 mg/day at that time. Alertness disorders and depression were the adverse effects that most frequently led to stopping baclofen. Bouts of somnolence and hypomanic episodes were the most potentially dangerous adverse effects. Women reported significantly more adverse effects than men.	High-dose baclofen exposes patients with alcohol disorders to many adverse effects. Generally persistent, some adverse effects appear at low doses and may be dangerous.	
26035194	Sleep problems are common in adults and should be treated to improve overall health and safety. To choose the best treatment for patients with sleep problems, clinicians should understand the sleep-wake cycle and the stages of rapid eye movement and non-rapid eye movement sleep as well as the neurologic pathways of sleep and wake systems. The sleep- and wake-promoting systems are mutually inhibitory, with the predominantly active system determining if a person is awake or asleep. The orexin system also plays an important role in the stabilization of the sleep-wake cycle. 
26035523	To investigate the effect of pregabalin on wake and sleep bout parameters.A post hoc analysis of polysomnography data from a randomized, placebo-controlled, crossover study investigating the effect of pregabalin (150 to 450 mg/d) and placebo on sleep in fibromyalgia (FM). Eligible patients had FM and sleep-maintenance problems, including wake after sleep onset ≥45 minutes and total sleep time (TST) 3.0 to 6.5 hours, but no other sleep/circadian rhythm disorders. Polysomnography was performed for 2 consecutive nights (screening, post-treatment). Wake and sleep bout duration and frequency were derived; a "bout"=consecutive 30-s epochs of sleep or wake.	Of 119 patients randomized (103 [87%] female), data were available for 103 treated with pregabalin and 106 with placebo. Pregabalin versus placebo treatment decreased mean±SD number of wake/sleep bouts (33.24±1.33 vs. 36.85±1.32; difference: -3.61 [95% confidence interval, -6.03, -1.18]; P=0.0039) and increased sleep bout duration (15.25±0.63 vs. 11.58±0.62 min; +3.67 min [2.22, 5.12 min]; P<0.0001). Pregabalin decreased mean duration of wake bouts versus placebo (3.41±0.55 vs. 3.94±0.55 min; -0.53 min [-1.06, -0.002 min]; P=0.0493). An exploratory correlation analysis of treatment effects found stage 1 sleep was negatively correlated with wake and sleep bout duration and positively with wake/sleep bout number; slow wave sleep (%total sleep time) was positively correlated with wake and sleep bout duration and negatively with wake/sleep bout number.	Pregabalin improved sleep parameters characteristic of disturbed sleep in FM, by preventing awakenings and increasing sleep bout duration. These effects are reflected in, and correlated with, a decrease in "light sleep" (stage 1) and an increase in "deep sleep" (slow wave sleep).	
26035521	A significant number of people who experience chronic pain also complain of depression and sleep problems. The comorbidities and bidirectional relationships that exist between these ailments are well recognized clinically. Further, all 3 disorders involve similar alterations in structural and functional neurobiology and share common pathophysiological mechanisms. We sought to comprehensively review the research literature regarding common neurobiological factors associated with these complex clinical disorders in order to better understand how they are related and provide further rationale for future clinical and research efforts to appropriately understand and manage them.A comprehensive review of the existing research literature was conducted in the domains of chronic pain, depression, and sleep.	Although the neurobiological underpinnings of these factors are complex and require further investigation, comparable changes are seen in levels of serotonin (5-hydroxytryptamine), proinflammatory cytokines, brain-derived neurotrophic factor, and other transmitters in these disorders.	This review is unique as it attempts to cast a broader net over the common neurobiological correlates that exist across these 3 conditions. It highlights the complexity of the interrelationships between these disorders and the importance of increasing our understanding of neurobiological factors associated with them.	
26034071	The corticosterone (CORT) level changes along the circadian rhythm. Hippocampus is sensitive to CORT, since glucocorticoid receptors are highly expressed. In rat hippocampus fixed in a living state every 3 h, we found that the dendritic spine density of CA1 pyramidal neurons increased upon waking (within 3 h), as compared with the spine density in the sleep state. Particularly, the large-head spines increased. The observed change in the spine density may be due to the change in the hippocampal CORT level, since the CORT level at awake state (∼30 nM) in cerebrospinal fluid was higher than that at sleep state (∼3 nM), as observed from our earlier study. In adrenalectomized (ADX) rats, such a wake-induced increase of the spine density disappeared. S.c. administration of CORT into ADX rats rescued the decreased spine density. By using isolated hippocampal slices, we found that the application of 30 nM CORT increased the spine density within 1 h and that the spine increase was mediated via PKA, PKC, ERK MAPK, and LIMK signaling pathways. These findings suggest that the moderately rapid increase of the spine density on waking might mainly be caused by the CORT-driven kinase networks. 
26033837	Although sleep disturbance is common in chronic obstructive pulmonary disease (COPD), relatively little is known on the effect of the exacerbation on sleep quality. Accordingly, we longitudinally assessed sleep variables during exacerbations and clinical stability. This is a sub-study of a larger observational analysis. Inclusion criteria were clinically stable COPD and two or more clinical exacerbations in the preceding 12 months. Patients were followed for approximately 6 months and during this time the following were recorded daily: (1) COPD exacerbations, which were determined in two ways, clinically and symptom defined using the exacerbations of chronic pulmonary disease tool (EXACT); (2) daytime sleepiness, which was measured using the Stanford Sleepiness Scale; (3) subjective awakenings, which was measured from a sleep diary; and (4) sleep duration, efficiency, and objective awakenings, which was measured from actigraphy. These variables for exacerbation and non-exacerbation days were compared. Seventeen patients (9 male, age 63 ± 12 years, forced expiratory volume in 1 second 52 ± 20%) entered data over 135 ± 18 days. During this time, 15 patients had 27 symptom-defined exacerbations and 8 had 9 clinically reported exacerbations. Symptom-defined exacerbation days were 26% of the total study days. More daytime sleepiness, decreased total sleep time (TST), and decreased sleep efficiency (SE) were present during exacerbations compared with clinical stability (p < 0.001). These disturbances tended to be greater during clinically reported exacerbations than during unreported events (p < 0.05). Increased daytime sleepiness, less TST, and poorer SE are present during COPD exacerbations. 
26032796	The foods we eat have substantial impact on our health, and excessive food intake is associated with numerous long-term health conditions. It is therefore essential to understand the factors influencing this crucial health behavior. Research has identified sleep problems as one such factor; however, little research has examined how sleep problems impact food intake. Using a multisystemic perspective, this article proposes a variety of ways in which sleep problems likely increase food intake and illustrates the need for research to empirically examine these underlying mechanisms. Such research would have important treatment implications for health conditions often treated with dietary interventions. 
26031911	Among patients with neuromyelitis optica spectrum disorder (NMOSD), fatigue is commonly complained about and is one of the most debilitating symptoms. This study aimed to investigate the incidence of fatigue and explore impacting factors attributed to fatigue in NMOSD.Thirty-three patients with NMOSD and twenty matched healthy controls were enrolled. A battery of self-reported questionnaires was conducted to assess quality of sleep, daytime sleepiness, fatigue, depression, and level of activity of daily life. The structure of sleep was assessed by polysomnography with blood oxygen saturation monitored by noninvasive pulse oximeter. Brain and spinal cord lesions were evaluated by MRIs.	Fatigue was more severe and more prevalent among the patients with NMOSD compared with controls (fatigue score which ranges from 0 to 11 with higher scores indicating more severe fatigue: 6.4 ± 0.6 vs. 3.8 ± 0.4, P = 0.002; incidence, 64% vs. 35%, P = 0.043), and it was negatively associated with daily activity level (r = 0.455, P = 0.008). The patients with fatigue had higher Pittsburgh Sleep Quality Index score, higher Epworth Sleepiness Scale score, lower blood oxygen state, and higher depression score than patients without fatigue; blood oxygen was especially negatively correlated with fatigue (nadir SpO2 , r = -0.558, P = 0.001; mean SpO2 , r = -0.457, P = 0.007); depression was also positively correlated with fatigue (r = 0.599, P < 0.001).	Patients with NMOSD experienced significant fatigue, which had an obvious impact on their daily activity. Fatigue in these patients was related to hypoxemia, sleep disturbances, and depression.	
26031352	To investigate the association between sleep duration and myopia.This population-based, cross-sectional study using a nationwide, systemic, stratified, multistage, clustered sampling method included a total of 3625 subjects aged 12-19 years who participated in the Korean National Health and Nutrition Examination Survey 2008-2012. All participants underwent ophthalmic examination and a standardized interview including average sleep duration (hr/day), education, physical activity and economic status (annual household income). Refractive error was measured by autorefraction without cycloplegia. Myopia and high myopia were defined as ≤-0.50 dioptres (D) and ≤-6.0 D, respectively. Sleep durations were classified into 5 categories: <5, 6, 7, 8 and >9 hr.	The overall prevalence of myopia and high myopia were 77.8% and 9.4%, respectively, and the overall sleep duration was 7.1 hr/day. The refractive error increased by 0.10 D per 1 hr increase in sleep after adjusting for potential confounders including sex, age, height, education level, economic status and physical activity. The adjusted odds ratio (OR) for refractive error was 0.90 (95% confidence interval [CI], 0.83-0.97) per 1 hr increase in sleep. The adjusted OR for myopia was decreased in those with >9 hr of sleep (OR, 0.59; 95% CI, 0.38-0.93; p for trend = 0.006) than in those with <5 hr of sleep. However, high myopia was not associated with sleep duration.	This study provides the population-based, epidemiologic evidence for an inverse relationship between sleep duration and myopia in a representative population of Korean adolescents.	
26031297	Circadian rhythms play a crucial role in our cardiovascular system. Importantly, there has been a recent flurry of clinical and experimental studies revealing the profound adverse consequences of disturbing these rhythms on the cardiovascular system. For example, circadian disturbance worsens outcome after myocardial infarction with implications for patients in acute care settings. Moreover, disturbing rhythms exacerbates cardiac remodelling in heart disease models. Also, circadian dyssynchrony is a causal factor in the pathogenesis of heart disease. These discoveries have profound implications for the cardiovascular health of shift workers, individuals with circadian and sleep disorders, or anyone subjected to the 24/7 demands of society. Moreover, these studies give rise to 2 new frontiers for translational research: (1) circadian rhythms and the cardiac sarcomere, which sheds new light on our understanding of myofilament structure, signalling, and electrophysiology; and (2) knowledge translation, which includes biomarker discovery (chronobiomarkers), timing of therapies (chronotherapy), and other new promising approaches to improve the management and treatment of cardiovascular disease. Reconsidering circadian rhythms in the clinical setting benefits repair mechanisms, and offers new promise for patients. 
26030850	Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly. 
26030698	When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain. 
26030141	Personality is a trait that affects behavior and lifestyle, and sleep quality is an important component of a healthy life. We analyzed the association between personality traits and sleep quality in a cross-section of 1,406 young women (from 18 to 40 years of age) who were not reporting clinically meaningful depression symptoms. Surveys were carried out from December 2011 to February 2012, using the Revised NEO Personality Inventory and the Pittsburgh Sleep Quality Index (PSQI). All analyses were adjusted for demographic and behavioral variables. We considered beta weights, structure coefficients, unique effects, and common effects when evaluating the importance of sleep quality predictors in multiple linear regression models. Neuroticism was the most important contributor to PSQI global scores in the multiple regression models. By contrast, despite being strongly correlated with sleep quality, conscientiousness had a near-zero beta weight in linear regression models, because most variance was shared with other personality traits. However, conscientiousness was the most noteworthy predictor of poor sleep quality status (PSQI ≥ 6) in logistic regression models and individuals high in conscientiousness were least likely to have poor sleep quality, which is consistent with an OR of 0.813, with conscientiousness being protective against poor sleep quality. Personality may be a factor in poor sleep quality and should be considered in sleep interventions targeting young women.
26029988	Melatonin is a neurohormone secreted mainly by the pineal gland that controls circadian rhythm, which is primarily regulated by light. Although melatonin levels are known to be altered in individuals with sleep disorders, melatonin also has modulatory effects on other body systems, including the skeletal and immune systems. In addition, melatonin has been shown to interfere with carbohydrate and lipid metabolism and to have significant antioxidant effects, both directly and via its metabolites. Melatonin levels vary throughout human life and are known to decrease with age but the effects of declining melatonin levels are poorly understood. In women, this age-related decrease in melatonin levels coincides with the menopause. This review aims to summarize the impact of altered melatonin levels in aging women and the outcomes of exogenous replacement therapies. 
26029685	Despite strong evidence linking sleep to developmental outcomes, the longitudinal relationship between sleep and emotional well-being remains largely unknown. To address this gap in our knowledge, the current study examined sleep in infancy, measured via actigraphy, as a predictor of social-emotional problems in toddlers. A total of 47 children (29 males) were included in this longitudinal study. At time one, actigraphy measures of sleep were obtained from 3- to 4-month-old infants. At time two, parents rated their 18- to 24-month-old toddler's social-emotional well-being using the Brief Infant Toddler Social Emotional Assessment. Results indicated that boys tended to have higher levels of externalizing behaviors than did girls. Additionally, boys with longer sleep durations also showed lower sleep efficiency. In girls, sleep duration in infancy was a significant predictor of autism spectrum disorder behaviors and approached significance as a predictor of externalizing problems in toddlerhood. Our findings are the first to show a relationship between sleep measured in infancy and autism spectrum disorder symptomatology measured in early childhood. They suggest that the etiology of social-emotional problems may differ between genders and raise the possibility that sleep/wake cycles may be differentially related to autism spectrum disorder symptoms in girls and boys. 
26029046	Delirium is an acute state marked by disturbances in cognition, attention, memory, perception, and sleep-wake cycle which is common in elderly. Others have shown an association between delirium and increased mortality, length of hospitalization, cost, and discharge to extended stay facilities. Until recently it was not known that after an episode of delirium in elderly, there is a 63% probability of developing dementia at 48 months compared to 8% in patients without delirium. Currently there are no preventive therapies for delirium, thus elucidation of cellular and molecular underpinnings of this condition may lead to the development of early interventions and thus prevent permanent cognitive damage. In this article we make the case for the role of glia in the pathophysiology of delirium and describe an astrocyte-dependent central and peripheral cholinergic anti-inflammatory shield which may be disabled by astrocytic pathology, leading to neuroinflammation and delirium. We also touch on the role of glia in information processing and neuroimaging. 
26027828	The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.
26027596	Dysmenorrhea is a common menstrual disorder experienced by adolescents, and its major symptoms, including pain, adversely affect daily life and school performance. However, little epidemiologic evidence on dysmenorrhea in Japanese adolescents exists. This cross-sectional study aimed to determine the prevalence of and identify factors associated with dysmenorrhea in Japanese female junior high school students. Among 1,167 girls aged between 12 and 15 years, 1,018 participants completed a questionnaire that solicited information on age at menarche, menstruation, and lifestyle, as well as demographic characteristics. Dysmenorrhea was defined based on menstrual pain using a Visual Analog Scale (VAS), with moderate or severe (moderate-severe) dysmenorrhea, which adversely affects daily life, defined as VAS ≥ 4, and severe dysmenorrhea defined as VAS ≥ 7. The prevalence of moderate-severe dysmenorrhea was 476/1,018 (46.8%), and that of severe dysmenorrhea was 180/1,018 (17.7%). Higher chronological and gynecological ages (years after menarche) were significantly associated with a higher prevalence of dysmenorrhea regardless of severity (P for trend < 0.001). In addition, short sleeping hours (< 6/day) were associated with moderate-severe dysmenorrhea (OR = 3.05, 95%CI: 1.06-8.77), and sports activity levels were associated with severe dysmenorrhea (P for trend = 0.045). Our findings suggest that dysmenorrhea that adversely affects daily activities is highly prevalent, and may be associated with certain lifestyle factors in junior high school students. Health education teachers should be made aware of these facts, and appropriately care for those suffering from dysmenorrhea symptoms, absentees, and those experiencing difficulties in school life due to dysmenorrhea symptoms. 
26026580	To investigate the effect of ramelteon on sleep and daytime functioning among individuals with traumatic brain injury (TBI).A double-blind, placebo-controlled study with a crossover design.	A research facility attached to an acute rehabilitation hospital.	Individuals with TBI (N=13) complaining of sleep difficulties with a Pittsburgh Sleep Quality Index score >5.	A nightly dosage of ramelteon (8 mg) was given over a period of 3 weeks.	An actigraph and a daily sleep log were used to measure sleep/wake patterns. Daytime functioning was measured after 3 weeks of treatment using a computer-administrated neuropsychological test battery in conjunction with subjective questionnaires measuring mood, daytime sleepiness, and fatigue.	A significant increase in objectively measured total sleep time and a small increase in sleep latency were observed after 3 weeks of treatment compared with placebo. Treatment also showed a significant increase in standardized neuropsychological test scores, with a particular improvement on an index of executive functioning.	Preliminary evidence for the effectiveness of 8 mg of ramelteon taken nightly over a 3-week period was found in the treatment of sleep difficulties among individuals with TBI. Improvements in total sleep time and some aspects of cognitive functioning are discussed.	
26025785	We assessed the relationship between core temperature (Tc) and sleep rhythms in mice, and examined the effects of ambient temperature and fasting. Tc, electroencephalograms (EEG), electromyograms (EMG), and spontaneous activity in male ICR mice (n=9) were measured by telemetry for 3 days under a 12:12h dark-light cycle. Mice were fed or fasted at an ambient temperature (Ta) of 27°C or 20°C for the final 30h of the experiment. The vigilance state was categorized into a wake state, rapid-eye movement (REM) sleep, and non-REM (NREM) sleep, and the total sleep time (TST) was assessed. Relationships between Tc and TST, NREM periods, and REM sleep were estimated using Pearson's correlation coefficient. During cold exposure, Tc decreased during the dark and light phases, and TST and the periods of NREM and REM sleep decreased during the dark phase. Throughout the fasting period, Tc also decreased during the dark and light phases. Furthermore, the decrease in Tc was augmented when fasting and cold were combined. TST and NREM sleep periods decreased in the light and dark phases, respectively, whereas REM sleep periods decreased in both phases. Negative linear correlations (r=-0.884 to -0.987) were observed between Tc and TST, NREM sleep periods, and REM sleep periods, except for Tc and REM sleep periods where fasting and cold conditions were combined. The correlations between sleep and Tc rhythms were well maintained during cold exposure and fasting. However, when cold and fasting were combined, REM sleep and Tc rhythms were desynchronized.
26024330	Sleep disorders are frequent clinical presentations, especially among active-duty service members. Medications are one factor that can affect sleep in many ways.To determine the effect of increasing numbers of medications on the sleep cycle of active-duty service members.	Medical records for active-duty service members who completed enhanced sleep assessments at the Psychiatry Continuity Service at Walter Reed National Military Medical Center from October 1, 2010, through November 30, 2013, were retrospectively reviewed. Data were collected on home sleep study findings, sleep-related self-report instrument scores, and active medications.	A total of 135 medical records were reviewed. One hundred patients (74.07%) had an active prescription for a psychoactive drug. Among all patients, the mean (SD) number of active medications per participant was 2.52 (2.09), with 118 patients (82.96%) having an active medication for depression or insomnia. As the number of prescribed medications increased, the percentage of the sleep cycle in deep sleep decreased (P=.049), the percentage of light sleep increased (P=.016), the percentage of rapid eye movement sleep decreased (P=.083), and the first episode of deep sleep was delayed (P=.056). An increased number of medications had no significant impact on total sleep time (P&gt;.05).	An increasing number of medications did not influence total sleep time but negatively affected the sleep cycle.	
26022361	Orexins/hypocretins (OXA and OXB) are two hypothalamic peptides involved in the regulation of many physiological processes including the sleep-wake cycle, food intake and arousal. The orexinergic system of the lateral hypothalamus is considered a non-specific peptidergic system, and its nerve fibers innervate numerous brain areas. Among many targets of orexinergic neurons is the intergeniculate leaflet (IGL) of the thalamus - a small but important structure of the mammalian biological clock. In rats, the IGL consists of GABAergic cells which also synthesize different neuropeptides. One group of neurons produces neuropeptide Y (NPY) and sends its axons to the master biological clock known as the suprachiasmatic nuclei. Another neuronal group produces enkephalin and is known to connect contralateral IGLs. This study evaluated the effects of orexins on identified IGL neurons revealing that 58% of the recorded neurons were sensitive to OXA (200nM) and OXB (200nM) administration. Both NPY-positive and -negative neurons were depolarized by these neuropeptides. Experiments using selective orexin receptor antagonists (SB-334867, 10μM and TCS-OX2-29, 10μM) suggested that both orexin receptors participate in the recorded OXA effects. In addition, IGL neurons were either directly depolarized by OXA or their activity was altered by changes in presynaptic inputs. We observed an increase of GABA release onto the investigated IGL neuron after OXA application, consistent with a presynaptic localization of the orexin receptors. An increase in miniature excitatory postsynaptic current frequency was not observed within the IGL. Our findings reinforce the connection between circadian clock physiology and the orexinergic system.
26021838	Recent studies have shown that the peripheral inflammation may cause the up-regulation of central nervous system inflammation and therefore possibly plays a vital role in the pathophysiology of subsequent psychiatric disorders.We explored the relationship between gastroesophageal reflux disease (GERD) and the subsequent development of psychiatric disorders including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders.	We investigated patients who were diagnosed with GERD according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised patients without GERD who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on the diagnoses of psychiatrists.	The GERD cohort consisted of 3813 patients, and the comparison cohort comprised 15,252 matched control patients without GERD. The risks of depressive disorder (HR=3.37, 95% confidence interval [CI]=2.49-4.57), anxiety disorder (HR=2.99, 95% CI=2.12-4.22), and sleep disorder (HR=2.69, 95% CI=1.83-3.94), were higher in the GERD cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive, anxiety, and sleep disorders remained significantly increased in all of the stratified follow-up durations (0-1, ≥1year).	GERD may increase the risks of subsequent depressive, anxiety, and sleep disorders. These psychiatric disorders have a negative effect on people's quality of life. Clinicians should pay a particular attention to psychiatric comorbidities in GERD patients.	
26020963	Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring. 
26019388	La sindrome delle apnee ostruttive durante il sonno è associata ad un aumento della morbilità e mortalità cerebro-cardiovascolare. Si tratta di un fattore di rischio indipendente per aterosclerosi precoce, trombosi vascolare e sindrome metabolica e di recente è stata anche associata ad un aumento dell'incidenza di cancro. Un nesso di causalità tra OSAS ed aterosclerosi è parzialmente fondata ma non completamente chiarita. Una recente ricerca su aterosclerosi precoce in OSAS ha messo in correlazione la tendenza alla trombosi e la viscosità del sangue, fornendo una nuova visione dei meccanismi della malattia. L'ipossia intermittente notturna cronica tipica dell'OSAS insieme alle alterazioni macro e micro strutturali del sonno e la conseguente induzione ematica di stress ossidativo infiammatorio cronico cellulare con alterazioni genetiche possono contemporaneamente allo sviluppo di aterosclerosi precoce, rappresentare anche un meccanismo sottostante a lungo termine che induce atipie cellulari e patogenesi e progressione del cancro.Obstructive sleep apnoea syndrome (OSAS) is associated with severe cerebro-cardiovascular morbidity and mortality. It is an independent risk factor for atherosclerosis, arterial thrombosis and metabolic syndrome, and recently has been associated with an increased incidence of cancer and death. A causal link between OSAS and atherosclerosis has been partially established. Recent research on atherosclerosis in OSAS has focused on thrombotic tendency and blood viscosity, providing new insight into disease mechanisms. Hypoxia is a critical pathophysiological element in OSAS that leads to intensive sympathetic activity, in association with inflammation, oxidative stress and procoagulant activity. Hypoxia and the induction of oxidative stress can simultaneously represent an underlying mechanism in the pathogenesis of cancer development and progression. This mini-review will discuss the latest findings on the association and potential relationship between OSA and pathological vascular sequelae. 	
26019008	Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10 Hz) and sigma (10-15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure. 
26018218	The association between alcohol use and sleep problems is well established and clinically meaningful, particularly as predictors of relapse. This study aims to elucidate the relationship between sleep disturbances and alcohol problems in a non-treatment-seeking community sample using an alcoholism problem severity factor.Participants were problem drinkers (N = 295) from the Los Angeles community who had a breath alcohol content (BrAC) of 0.00 g/dl when they completed an in-person assessment battery comprised of measures of sleep quality, anxiety and depression, cigarette smoking, as well as multiple assessments of alcohol use and alcohol use problems.	A series of hierarchical regressions showed that alcohol problem severity explained a significant amount of variance in sleep disturbance beyond demographic, mood and smoking variables. Alcohol problem severity was predictive of the PSQI global score (B = 1.11, P < 0.001), perceived sleep quality factor (B = 0.18, P < 0.001) and daily disturbance factor (B = 0.28, P < 0.001). However, contrary to study hypothesis, alcohol problem severity was predictive of improved sleep efficiency (B = -0.14, P < 0.05).	In sum, alcohol problem severity may be predictive of sleep disturbances. Given the complex nature of these relationships, further work is needed to develop adequate treatment for sleep disturbance during alcohol recovery. Nonetheless, this study suggests that as alcohol problem severity increases so do sleep problems. Thus, attending to sleep problems at early stages of alcohol problems may be warranted.	
26018095	To examine the association of sleep duration and sleep disorder with red blood cell distribution width (RDW).Data from the 2005-2012 National Health and Nutrition Examination Survey were used, including 17,621 adults. A questionnaire was used to assess sleep duration and sleep disorder, with a blood sample used to assess RDW.	Compared to persons getting 7-8 hours/night of sleep, those getting 5, 9, and ≥ 10 hours/night respectively had a 23%, 29%, and 67% increased odds of having an elevated RDW (p < .05 for all odds ratios). Participants with a physician-diagnosed sleep disorder had a higher RDW (β = 0.08; p = .04).	Sleep duration and sleep disorder are associated with elevated RDW.	
26017904	To develop a symptoms cluster model that can describe factors of fibromyalgia syndrome (FMS) associated with fatigue severity as reported by the sample and to explore FMS clinical symptom subclusters based on varying symptom intensities.FMS individuals (n = 120, 82% ages 31-60 years, 90% women, 59% white) diagnosed with the 1990 or 2010 American College of Rheumatology diagnostic criteria were enrolled. Participants completed multiple validated self-report questionnaires to measure fatigue, pain, depression, anxiety, pain catastrophizing, daytime sleepiness, cognitive function, and FMS-related polysymptomatic distress. Cluster analysis using SPSS 19.0 and structural equation modeling using AMOS 17.0 were used.	Final structural equation modeling the symptoms cluster model showed good fit and revealed that FMS fatigue was associated with widespread pain, symptoms severity, pain intensity, pain interference, cognitive dysfunction, catastrophizing, anxiety, and depression (χ(2)  = 121.72 (98df), P > 0.05, χ(2) /df = 1.242, comparative fit index = 0.982, root mean square error of approximation = 0.045). Two distinct clinical symptom subclusters emerged: subcluster 1 (78% of total subjects), defined by widespread pain, unrefreshed waking, and somatic symptoms, and subcluster 2 (22% of total subjects), defined by fatigue and cognitive dysfunction with pain being a less severe and less widespread occurrence.	Overall, subcluster 1 had more intense symptoms than subcluster 2. FMS symptoms may be categorized into 2 clinical subclusters. These findings have implications for an illness whose diagnosis and management are symptom dependent. A longitudinal study capturing the variability in the symptom experience of FMS subjects is warranted.	
26013634	Catathrenia is a rare sleep disorder characterized by repeated groaning in a protracted expiration preceded by a deep inspiration. This study aimed to explore whether anatomy is one of pathophysiology of catathrenia by investigating the anatomical features associated with catathrenia in the upper airway, craniofacial structures, and dental patterns.Twenty-two patients with catathrenia (7 males, 15 females; age 22 to 69 years) were recruited as well as 66 patients matched by age and gender (matching proportion 1:3) with obstructive sleep apnea syndrome (OSAS). Both groups underwent cephalograms and dental casting, and cephalometric measurements and the Peer Assessment Rating (PAR) index was applied. Differences between the two groups were evaluated and cephalometric measurements in catathrenia group were compared with control values of Chinese patients from previous studies.	As for airway-related measurements, increased PNS-R, PNS-UPW, and H-FH and decreased SPT and TGL were found in catathrenia group compared to normal values. Such trends were found even more evident when compared with the OSAS Group. As for craniofacial parameters, values of U1/NA and U1/SN were found increased in the catathrenia group compared with normal values and values of MP/FH and Y decreased. The differences were more distinct from the OSAS Group. Increased arch lengths and upper inter-first molar widths, and decreased overbite and PAR index, were found in catathrenia group compared with the OSAS Group.	Catathrenia patients present with a broad upper airway, yet protrusive upper incisors and flat mandibular angles. Anatomical characteristics of catathrenia are different from those associated with OSAS, namely a wide airway, large skeleton, and good occlusion.	


26011086	Children with autism spectrum disorder (ASD) may present with multiple medical conditions in addition to ASD symptoms. This study investigated whether there are predictive patterns of medical conditions that co-occur with ASD, which could inform medical evaluation and treatment in ASD, as well as potentially identify etiologically meaningful subgroups. Medical history data were queried in the multiplex family Autism Genetic Resource Exchange (AGRE). Fourteen medical conditions were analyzed. Replication in the Simons Simplex Collection (SSC) was attempted using available medical condition data on gastrointestinal disturbances (GID), sleep problems, allergy and epilepsy. In the AGRE cohort, no discrete clusters emerged among 14 medical conditions. GID and seizures were enriched in unaffected family members, and together with sleep problems, were represented in both AGRE and SSC. Further analysis of these medical conditions identified predictive co-occurring patterns in both samples. For a child with ASD, the presence of GID predicts sleep problems and vice versa, with an approximately 2-fold odds ratio in each direction. These risk patterns were replicated in the SSC sample, and in addition, there was increased risk for seizures and sleep problems to co-occur with GID. In these cohorts, seizure alone was not predictive of the other conditions co-occurring, but behavioral impairments were more severe as the number of co-occurring medical symptoms increased. These findings indicate that interdisciplinary clinical care for children with ASD will benefit from evaluation for specific patterns of medical conditions in the affected child and their family members.
26010113	Nightmares and sleep disturbances are common complaints among military Veterans (Plumb & Zelman, 2009) and may be difficult to eradicate (Forbes, Phelps, & McHugh, 2001). A treatment protocol (Exposure, Relaxation, and Rescription Therapy [ERRT]) targeting nightmares and sleep disturbances, which has been used effectively in civilian populations, was adapted for the military (ERRT-M). A pilot study evaluated the efficacy of ERRT-M in improving sleep quality and quantity and reducing nightmares, symptoms of posttraumatic stress disorder, and depression in a trauma-exposed, Veteran sample (N = 19). At 1 week after treatment, analyses revealed improvements in nightmare frequency and severity, depression, sleep quality, and insomnia severity. Treatment gains were maintained at a 2-month follow-up. Fifty percent of the sample was considered treatment responders (i.e., no nightmares in the previous week). Results of this pilot study suggest that directly targeting sleep and nightmares is successful in alleviating sleep disturbances and related psychopathology in some Veterans.

26007728	In this paper, we propose an energy-efficient transmission technique known as the sleep/wake algorithm for a bicycle torque sensor node. This paper aims to highlight the trade-off between energy efficiency and the communication range between the cyclist and coach. Two experiments were conducted. The first experiment utilised the Zigbee protocol (XBee S2), and the second experiment used the Advanced and Adaptive Network Technology (ANT) protocol based on the Nordic nRF24L01 radio transceiver chip. The current consumption of ANT was measured, simulated and compared with a torque sensor node that uses the XBee S2 protocol. In addition, an analytical model was derived to correlate the sensor node average current consumption with a crank arm cadence. The sensor node achieved 98% power savings for ANT relative to ZigBee when they were compared alone, and the power savings amounted to 30% when all components of the sensor node are considered. The achievable communication range was 65 and 50 m for ZigBee and ANT, respectively, during measurement on an outdoor cycling track (i.e., velodrome). The conclusions indicate that the ANT protocol is more suitable for use in a torque sensor node when power consumption is a crucial demand, whereas the ZigBee protocol is more convenient in ensuring data communication between cyclist and coach. 
26004873	To determine persistent post-surgical pain prevalence after orthopaedic surgery with its impact on patient quality of life and to assess factors related to it.Cross-sectional cohort study.	A questionnaire was mailed to 2100 patients undergoing orthopaedic surgery in our teaching hospital.	Pain prevalence 3 months after surgery, pain intensity, a neuropathic pain component using the DN4 questionnaire and its impact on patient quality of life were assessed.	One thousand two hundred and ninety-two patients answered our questionnaire. Among them, 48% suffered from chronic pain. This pain had a neuropathic component in 43%, which was responsible for analgesic overconsumption and increases in sleep disturbance and sick leave. Arthrodesis, knee arthroplasty and leg fracture were linked to increased chronic post-surgical pain (OR=2.7, OR=1.8, OR=1.9, respectively; P<0.05). Elbow surgery, meniscectomy, amputation and neurolysis were linked to increased neuropathic pain.	Chronic, post-surgical pain is common after orthopaedic surgery, leading to analgesic consumption and sleep disturbance. Patients at high risk for developing chronic post-surgical pain must be identified preoperatively. The development of postoperative pain clinics should be one way to respond to this public health problem.	
26004526	The last decade has witnessed the emergence of new chronopharmacological perspectives. In the case of sleep disorders, the accumulating evidence suggests that even a minor dysfunction in the biological clock can impact broadly upon body physiology causing increases in sleep onset latency, phase delays or advances in sleep initiation, frequent nocturnal awakenings, reduced sleep efficiency, delayed and shortened rapid eye movement sleep and increased periodic leg movements, among others. Thus, restoration of the adequate circadian pattern of proper sleep hygiene, targeted exposure to light and the use of chronobiotic drugs, such as melatonin, which affect the output phase of clock-controlled circadian rhythms, can help to recover the sleep-wake cycle. The optimization of drug effects and/or minimization of toxicity by timing medications with regard to biological rhythms is known as chronotherapeutics. While chronotherapeutical approaches have been particularly successful in the treatment of hypertension, allergies and some forms of cancer, a time-dependent pharmacological approach can be also effective when dealing with sleep disruptions like insomnia. A large proportion of patients under benzodiazepine (BZD)/Z drug treatment fail to achieve a complete and sustained recovery and are left with residual symptoms, like tolerance or dependency, that make relapse or recurrence more likely, and poorer quality of life a reality. Thus the chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. This short review discusses available data on the efficacy of melatonin to reduce chronic BZD use in insomnia patients. 
26004187	Circadian rhythms regulate many aspects of physiology, ranging from sleep-wake cycles and metabolic parameters to susceptibility to infection. The molecular clock, with transcription factor BMAL1 at its core, controls both central and cell-intrinsic circadian rhythms. Using a circadian reporter, we observed dynamic regulation of clock activity in lymphocytes. However, its disruption upon conditional Bmal1 ablation did not alter T- or B-cell differentiation or function. Although the magnitude of interleukin 2 (IL-2) production was affected by the time of bacterial infection, it was independent of cell-intrinsic expression of BMAL1. The circadian gating of the IL-2 response was preserved in Bmal1-deficient T cells, despite a slight reduction in cytokine production in a competitive setting. Our results suggest that, contrary to the prevailing view, the adaptive immune response is not affected by the cell-intrinsic clock but is likely influenced by cell-extrinsic circadian cues operating across multiple cell types.
26004167	Prior studies have documented disparities in short and long sleep duration, excessive daytime sleepiness, and insomnia by educational attainment and race/ethnicity separately. We examined both independent and interactive effects of these factors with a broader range of sleep indicators in a racially/ethnically diverse sample.We analyzed 2012 National Health Interview Survey data from 33,865 adults aged ≥18years. Sleep-related symptomatology included short sleep duration (≤6h), long sleep duration (≥9h), fatigue >3days, excessive daytime sleepiness, and insomnia. Bivariate analyses with chi-square tests and log-linear regression were performed.	The overall age-adjusted prevalence was 29.1% for short sleep duration, 8.5% for long sleep duration, 15.1% for fatigue, 12.6% for excessive daytime sleepiness, and 18.8% for insomnia. Educational attainment and race/ethnicity were independently related to the five sleep-related symptoms. Among Whites, the likelihood of most sleep indicators increased as educational attainment decreased; relationships varied for the other racial/ethnic groups. For short sleep duration, the educational attainment-by-race/ethnicity interaction effect was significant for African Americans (p<0.0001), Hispanics (p<0.0001), and Asians (p=0.0233) compared to Whites. For long sleep duration, the interaction was significant for Hispanics only (p=0.0003).	Our results demonstrate the importance of examining both educational attainment and race/ethnicity simultaneously to more fully understand disparities in sleep health. Increased understanding of the mechanisms linking sociodemographic factors to sleep health is needed to determine whether policies and programs to increase educational attainment may also reduce these disparities within an increasingly diverse population.	
26003945	Sleep is not a uniform phenomenon, but is organized in alternating, fundamentally different states, rapid eye movement sleep and non-rapid eye movement sleep. Zebrafish (Danio rerio) have recently emerged as an excellent model for sleep research. Zebrafish are well characterized in terms of development, neurobiology and genetics. Moreover, there are many experimental tools not easily applied in mammalian models that can be readily applied to zebrafish, making them a valuable additional animal model for sleep research. Sleep in zebrafish is defined behaviorally and exhibits the hallmarks of mammalian sleep (e.g. sleep homeostasis and pressure). To our knowledge no attempts have been made to discern if sleep in zebrafish entails alternations of REM-NREM sleep cycles which are critical for further development of the model. In the current experiment we quantify two key REM sleep components, rapid eye movements and respiratory rates, across sleep-wake cycles. We find no sleep-related rapid eye movements. During sleep respiratory rates, however, are reduced and become less regular, further establishing that the behavioral definition used truly captures a change in the fish's physiology. We thus fail to find evidence for REM-NREM sleep cycles in zebrafish but demonstrate a physiological change that occurs concomitantly with the previously defined behavioral state of sleep. We do not rule out that other phasic REM components (e.g. atonia, cardiac arrhythmias, myoclonic twitches or desynchronized EEG) are coherently expressed during sleep but we conclude that adult zebrafish do not have REM-sleep-related rapid eye movements. 
26003786	Sleep disturbance is a common problem for caregivers. In general, patients with Duchenne muscular dystrophy (DMD) use noninvasive ventilation to maintain quality of life and improve survival.The aim of this study was to evaluate the sleep quality of caregiver-mothers of sons with DMD and factors that are associated with their sleep quality.	We evaluated 32 caregiver-mothers of sons with DMD and 32 mothers of sons without any neuromuscular or chronic disease (control-CTRL group). The evaluation of quality of sleep was made using the Pittsburgh Sleep Quality Index (PSQI).	Caregiver-mothers had poor sleep quality, specifically longer sleep latency and reduced sleep efficiency. The impaired sleep quality of the caregiver-mothers was associated with the length of time of noninvasive ventilation used by their sons.	Our results suggest that caregiver-mothers of sons with DMD have poor quality of sleep, and the length of use of noninvasive ventilation of their sons is associated with better sleep of caregiver-mothers.	
26003420	Sleep-wake patterns are rarely examined in adolescents with borderline personality disorder (BPD) or bipolar disorder (BD). Within a developmental perspective, this study explores the sleep-wake cycle of adolescents aged 12-17 years with BPD or BD and healthy controls (HC) during periods with and without entrainment by school/work schedules. Eighteen euthymic BPD, six euthymic BD, and 20 HC adolescents wore wrist actigraphy during nine consecutive days to assess sleep-wake patterns. During school/work days, BPD adolescents spent more time awake when they were in bed compared to HC and BD adolescents (p = 0.039). On schedule-free days, BPD and BD youths spent more time in bed compared to HC adolescents (p = 0.015). BPD adolescents woke up over 1 h later compared to HC (p = 0.003). Total sleep time was more variable between nights in BPD adolescents compared to the HC group (p = 0.031). Future research should explore if sleep-wake pattern disruptions are a cause or a consequence of BPD symptomatology in adolescents. Addressing sleep-wake pattern during clinical assessment and treatment of BPD adolescents may potentially reduce their symptoms; this therapeutic effect still needs to be evaluated. 
26003285	To explore the presence and types of sleep disorders in chronic patients with severe traumatic brain injury (TBI) undergoing inpatient rehabilitation using formal diagnostic criteria based on the International Classification of Sleep Disorders, 2nd edition.Cross-sectional study.	Inpatient brain injury rehabilitation units.	Chronic inpatients with severe TBI (N=30) were evaluated during rehabilitation.	Not applicable.	Participants wore an actiwatch for 7 days and completed self-report measures on sleep, mood, fatigue, pain, and daytime sleepiness.	Twenty participants (67%) had a sleep-wake cycle disturbance, of which 15 (50%) met diagnostic criteria for a sleep disorder. Diagnosed sleep disorders in the sample were insomnia (26.7%), posttraumatic hypersomnia (6.7%), delayed sleep phase syndrome (10%), irregular sleep-wake pattern disorder (3.3%), and periodic limb movement disorder (3.3%). Sleep quality was estimated by senior clinical staff as interfering with rehabilitation in 36.6% of the sample. Poor sleep quality was associated with greater anxiety, fatigue, and daytime sleepiness.	Consistent with previous studies, the present study showed high levels of sleep-wake cycle disturbances in patients with severe TBI undergoing rehabilitation, which were associated with anxiety, fatigue, and daytime sleepiness. These findings highlight the importance of assessing and treating sleep problems in patients with TBI undergoing rehabilitation.	
26002848	The present study examined multiple indices of sleep as moderators of the association between peer victimization and adjustment among typically developing adolescents. Participants included 252 adolescents (M = 15.79 years; 66 % European American, 34 % African American) and their parents. A multi-method, multi-informant design was employed to address the research questions. Sleep was assessed objectively with actigraphy (sleep minutes and sleep efficiency) and subjectively with self-reports. Adolescents reported on peer victimization and internalizing symptoms. Externalizing behaviors were examined with mother and father reports. Subjective sleep/wake problems moderated the associations between peer victimization and internalizing and externalizing symptoms. A stronger relation emerged between peer victimization and internalizing symptoms among adolescents who reported higher versus lower levels of sleep/wake problems. Adolescents with elevated sleep/wake problems had higher levels of externalizing symptoms across the range of peer victimization. However, for those with fewer sleep/wake problems, a positive relation between peer victimization and externalizing symptoms was observed. Actigraphy-based sleep minutes and sleep efficiency also moderated the relations between peer victimization and internalizing symptoms. Although peer victimization was associated with higher levels of internalizing symptoms for all youth, those who reported the lowest levels of such symptoms had longer and more efficient sleep in conjunction with low levels of peer victimization. Findings are novel and highlight the importance of considering both bioregulatory processes and peer relations in the prediction of adolescents' adjustment.
26001587	Suicide is one of the leading causes of death in postpartum women. Identifying modifiable factors related to suicide risk in mothers after delivery is a public health priority. Our study aim was to examine associations between suicidal ideation (SI) and plausible risk factors (experience of abuse in childhood or as an adult, sleep disturbance, and anxiety symptoms) in depressed postpartum women.This secondary analysis included 628 depressed mothers at 4-6 weeks postpartum. Diagnosis was confirmed with the Structured Clinical Interview for DSM-IV. We examined SI from responses to the Edinburgh Postnatal Depression Scale-EPDS item 10; depression levels on the Structured Interview Guide for the Hamilton Depression Rating Scale, Atypical Depression Symptoms (SIGH-ADS); plus sleep disturbance and anxiety levels with subscales from the EPDS and SIGH-ADS items on sleep and anxiety symptoms.	Of the depressed mothers, 496 (79%) 'never' had thoughts of self-harm; 98 (15.6%) 'hardly ever'; and 34 (5.4%) 'sometimes' or 'quite often'. Logistic regression models indicated that having frequent thoughts of self-harm was related to childhood physical abuse (odds ratio-OR = 1.68, 95% CI = 1.00, 2.81); in mothers without childhood physical abuse, having frequent self-harm thoughts was related to sleep disturbance (OR = 1.15, 95% CI = 1.02, 1.29) and anxiety symptoms (OR = 1.11, 95% CI = 1.01, 1.23).	Because women with postpartum depression can present with frequent thoughts of self-harm and a high level of clinical complexity, conducting a detailed safety assessment, that includes evaluation of childhood abuse history and current symptoms of sleep disturbance and anxiety, is a key component in the management of depressed mothers.	
26000810	The aims of this study were to investigate the clinical effects and safety of botulinum toxin A (BTX-A) in treating trigeminal neuralgia and its influences on accompanied depression, anxiety, sleep disorders, and quality of life.Eighty-seven patients with one-branch classical trigeminal neuralgia were injected with BTX-A in the pain area. The visual analogic scale score, sleep interference score, Hamilton Anxiety Scale score, Hamilton Depression Scale score, and side effects were assessed at 1 week prior to and 8 weeks after treatment, respectively.	The effective rates after 1, 2, 4, and 8 weeks of treatment were 48.28%, 66.67%, 78.16%, and 80.46%, respectively. The effective rates of anxiety and depression were 90.32% and 96.77%, respectively. When compared to that before treatment, the quality of life was significantly better in terms of role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health (all P < 0.01), while physical function was not significantly improved (P = 0.317).	BTX-A treatment can significantly relieve the pain in trigeminal neuralgia patients; improve anxiety, depression, and sleep; and increase the quality of life. BTX-A treatment is a safe and effective method to treat classical trigeminal neuralgia.	
26000551	Sleep problems are prominent after menopause. The aim of our study was to look into the effect of black cohosh on both objective and subjective sleep in early postmenopausal women with sleep complaints.We performed a randomized, double-blind and placebo-controlled research during a 6-month period. Forty-eight postmenopausal women aged 45-60 years with sleep disturbance were enrolled and received daily administration of either black cohosh or placebo. Polysomnography and the Pittsburg Sleep Quality Index (PSQI) were performed at the initiation and termination of the study, as well as the Menopause-specific Quality of Life questionnaire and estradiol and follicle stimulating hormone tests. Liver and renal functions and breast and pelvic ultrasound were set as safety measures, carried out every 3 months.	Seventy-six women were interviewed, of whom 42 women completed the whole trial. Compared with placebo, black cohosh treatment led to significant polysomnographic changes, including increased sleep efficiency and decreased wake after sleep onset (WASO) duration, and tended to improve PSQI with a medium effect size. On average, 15.8% of WASO duration was reduced in the black cohosh group. Vasomotor and physical domains of life quality were improved compared with placebo. Safety measures did not yield any adverse event assigned to black cohosh.	In early postmenopausal women with a major sleep complaint, black cohosh effectively improved sleep and might be a safe measure in managing menopausal sleep disturbance.	

25999004	Data suggest that surgical patients with obstructive sleep apnea (OSA) may be difficult to ventilate and intubate, and may be prone to postoperative complications. This article addresses the identification of patients at risk for OSA, epidemiology of the disorder, and treatment options, as well as the perioperative management of this population. 
25998878	The aim of this study was to describe the overall health-related quality of life (HRQoL) in women five years after the birth of their first child as well as the HRQoL in relation to mode of delivery.545 first-time pregnant women, drawn from a hospital situated in Sweden, consented to be included in a cohort. Five years after the birth of the first child, 372 (68%) women agreed to participate in a follow-up study. HRQoL was measured using the Swedish Health-Related Quality of Life Survey (SWED-QUAL) questionnaire. Socio-demographic background and variables related to pregnancy and childbirth were collected using a self-report questionnaire.	Overall, the HRQoL was perceived to be good. Suboptimal scores were obtained for the three variables: Sleeping problems, Emotional well-being - negative affect and Family functioning - sexual functioning. Women having a vaginal birth, an instrumental vaginal birth or women who underwent caesarean section on maternal request were more likely to report better perceived HRQoL than women who had undergone an emergency caesarean section or caesarean section due to medical indication.	This study demonstrates that the overall HRQoL of the women in the cohort was reported as good. Mode of delivery was associated with differences in HRQoL five years after birth of the first child. Our result suggests that some differences in perceived HRQoL persist in the long term.	
25997766	The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer-peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep-wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence. 
25995669	The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea.A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 ≤ 3.2, 3.2 < DAS28 < 5.1, and DAS28 ≥ 5.1, respectively).	The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 ± 4.19, 38.5%) than in the control subjects (3.57 ± 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI ≤ 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high.	Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.	
25995662	Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus.The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography.	The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood pressure.	Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.	
25995170	The use of melatonin is increasing among Swedish children and adolescents despite deficient knowledge of usage in these groups. The aim of this study was to investigate the use of melatonin in Swedish children and adolescents according to age, gender, dosage, treatment duration, and use of attention deficit hyperactivity disorder (ADHD) medication.Data from the Swedish Prescribed Drug Register was analyzed for children and adolescents 0-19 years old in Sweden during 2006-2013.	The number of new users of melatonin in 2013 was 4296 and 3093 among boys and girls, respectively. Girls started treatment with melatonin in older ages compared to boys. Regular users of melatonin were most common among boys 10-14 years. The average defined daily dose (DDD) per regular user was decreasing from 2.4 DDD in 2006 to 1.7 DDD in 2012. Among girls and boys 5-9 years who were regular users in 2010, over 40 and 50%, respectively, were still regular users in 2013. In the age group 15-19 years, only about 10% were still regular users in 2013. In 2013, 65% of boys and 49% of girls, using melatonin regularly, also used medication for ADHD regularly.	More Swedish boys than girls used melatonin regularly. The boys started treatment earlier and more often combined regular use of melatonin with regular use of medication for ADHD. This indicates that girls and boys partly are prescribed melatonin for different reasons. About half of the younger children stayed on melatonin treatment for several years, while 90% of adolescents (15-19 years) concluded their treatment.	
25992476	Appropriate inhibitory response control is associated with goal-directed behavior. Sleep accelerates the offline consolidation of acquired motor skills that are explicitly predictable; however, the effect of sleep on implicit (unpredictable) motor skills remains controversial. We speculated that a key component of response inhibition skill differentiates between these skill consolidation properties because explicit prediction can minimize the inhibitory efforts in a motor skill. We explored the offline skill learning properties of response inhibition during sleep and wakefulness using auditory Go and Go/Nogo tasks. We attempted to discriminate the possible effects of time elapsed after training (12 or 24 h), post-training sleep/wake state (sleep or wakefulness), and time of day (nighttime or daytime) in 79 healthy human subjects divided into 6 groups that underwent various sleep regimens prior to training and retesting. We found that delayed response inhibition skill improvement was achieved via a simple passage of daytime, regardless of the participants' alertness level. Our results suggest that sleep-independent neuroplasticity occurs during the daytime and facilitates a delayed learning of response inhibition skill.
25991763	A national network of expert centers for bipolar disorders was set up in France to provide support, mainly for psychiatrists, who need help for managing bipolar disorder patients. The aims of this article are to present the main characteristics of the patients referred to an expert center in order to highlight the major disturbances affecting these patients and to understand the most significant difficulties encountered by practitioners dealing with bipolar disorder patients.Patients were evaluated by trained psychiatrists and psychologists, with standardized and systematic assessment using interviews and self-report questionnaires.	All patients (n = 839) met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for bipolar disorder I (48.4%), bipolar disorder II (38.1%) or bipolar disorder-not otherwise specified (13.5%). Mean illness duration was 17 years (±11.3), with 41.9% of patients having a history of suicide attempts. Lifetime comorbidities were 43.8% for anxiety disorders and 32.8% for substance abuse. At the point of inclusion, most patients (76.2%) were not in an acute phase, being considered to have a syndromal remission, but which still required referral to a tertiary system of care. Among these patients, 37.5% had mild to moderate residual depressive symptoms (Montgomery and Asberg Depression Rating Scale ranging from 7 to 19) despite 39% receiving an antidepressant. However, 47.8% were considered to be poorly adherent to medication; 55% showed evidence of sleep disturbances, with half being overweight; 68.1% of patients showed poor functioning (Functioning Assessment Short Test ⩾ 12) with this being linked to residual depressive symptoms, sleep disturbances and increased body mass index.	It appears that bipolar disorder patients referred to an expert center in most cases do not suffer from a severe or resistant illness but they rather have residual symptoms, including subtle but chronic perturbations that have a major impact on levels of functioning. The longitudinal follow-up of these patients will enable a better understanding of the evolution of such residual symptoms.	
25991652	Benzodiazepines are frequently prescribed in patients with Alzheimer's disease. Unfortunately, studies evaluating their benefits and risks in these patients are limited.Clinical trials focusing on the effect of benzodiazepines on cognitive functions, disease progression, behavioral symptoms, sleep disturbances, and the general frequency of benzodiazepine use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology initiative.	Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with benzodiazepine use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in Alzheimer's disease patients. No evidence was found for an improvement of sleep quality using benzodiazepines.	This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer's disease patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area.	
25991187	Consumer sleep tracking devices are widely advertised as effective means to monitor and manage sleep quality and to provide positive effects on overall heath. However objective evidence supporting these claims is not always readily available. The goal of this study was to perform a comprehensive review of available information on six representative sleep tracking devices: BodyMedia FIT, Fitbit Flex, Jawbone UP, Basis Band, Innovative Sleep Solutions SleepTracker, and Zeo Sleep Manager Pro. The review was conducted along the following dimensions: output metrics, theoretical frameworks, systematic evaluation, and FDA clearance. The review identified a critical lack of basic information about the devices: five out of six devices provided no supporting information on their sensor accuracy and four out of six devices provided no information on their output metrics accuracy. Only three devices were found to have related peer-reviewed articles. However in these articles wake detection accuracy was revealed to be quite low and to vary widely (BodyMedia, 49.9±3.6%; Fitbit, 19.8%; Zeo, 78.9% to 83.5%). No supporting evidence on how well tracking devices can help mitigate sleep loss and manage sleep disturbances in practical life was provided. 
25990812	Neurodevelopmental disorders are increasingly believed to originate from intrauterine growth restriction (IUGR). Current reviews exploring the neurodevelopmental effects of IUGR, however, are mostly based on birthweight, an inadequate proxy.We aimed to examine the association between IUGR documented in utero, and neurodevelopmental outcomes during childhood.	Medline, CINAHL, PsycInfo and Scopus were searched for relevant studies published after 1970.	The analysis included studies that identified IUGR in utero, with follow-up assessments between 1 month and 12 years of age.	Data was extracted for cognitive, behavioural, language, motor, hearing, vision or sleep outcomes. Studies were summarised separately for children born at <35 and ≥35 weeks gestation.	Of 28 876 titles identified, 38 were suitable for inclusion. IUGR children born ≥35 weeks gestation scored on average 0.5 SD lower than non-IUGR children across all neurodevelopmental assessments. IUGR children born <35 weeks of gestation scored approximately 0.7 SD lower than non-IUGR children across all neurodevelopmental assessments. IUGR children with evidence of fetal circulatory redistribution (preferential perfusion of the brain) had more severe neurodevelopmental impairments than those born IUGR alone.	IUGR increases the risk of neurodevelopmental impairment during childhood differentially across domains. IUGR children born preterm or with evidence of fetal circulatory redistribution are more severely affected.	IUGR is associated with an overall risk for neurodevelopmental delay in a range of neurodevelopmental domains.	
25989071	Obsessive-compulsive (OC) symptoms and repetitive negative thinking (RNT) are associated with poor inhibitory control. Sleep disruptions may partially mediate these relations and/or act as a "second hit" to individuals with OC symptoms and RNT. Models including habitual (past month) hours slept and bedtimes were tested.We employed a go/no-go task that allowed us to examine the relation between sleep and inhibition with various task contingencies. Sixty-seven unselected individuals were recruited from the participant pool at a public university.	Bias-corrected bootstrap estimates did not show that sleep disruption mediated the relation between OC symptoms and response inhibition nor the relation between RNT and response inhibition. Multiple linear regression analyses found significant interactions between hours slept and OC symptom severity and between RNT and hours slept to predict poor response inhibition. Hours slept significantly negatively predicted commission errors when OC symptoms and RNT levels were relatively heightened but not when OC symptoms and RNT levels were relatively low. These effects were present in blocks where task contingencies were designed to shape a no-go bias. No significant relations were found with habitual bedtimes.	The cross-sectional study design precludes testing the temporal precedence of symptoms in the "second hit" model. The unselected sample also limits generalization to clinical samples.	These findings support a "second hit" model of interaction between sleep disruption and perseverative thoughts and behaviors. Further research on the mechanisms of the relation between sleep disruption and perseverative thought symptoms (OC and RNT) is warranted.	
25989046	To evaluate the antinociceptive and hypnotic effects of pregabalin, we established a neuropathic pain-like model in mice using partial sciatic nerve ligation (PSNL), and examined thermal hyperalgesia, mechanical allodynia, electroencephalogram, rota-rod testing, and c-Fos expression in the anterior cingulate cortex. Gabapentin was used as a reference drug in the study. Pregabalin administered i.g. at 12.5 and 25mg/kg prolonged the duration of thermal latencies by 1.4- and 1.6-fold and increased the mechanical threshold by 2.2- and 3.1-fold 3h after administration, respectively, but did not affect motor coordination in PSNL mice, compared with vehicle control. Pregabalin (12.5 and 25mg/kg) given at 6:30 increased the amount of non-rapid eye movement sleep in a 4-h period by 1.3- and 1.4-fold, respectively, in PSNL mice. However, pregabalin (25mg/kg) given at 20:30 did not alter the sleep pattern in normal mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of anterior cingulate cortex by 2.1-fold, which could be reversed by pregabalin. These results indicate that pregabalin is an effective treatment for both neuropathic pain and sleep disturbance in PSNL mice. 
25988561	The aim of the present study was to evaluate the influence of sleep duration on cardiovascular risk factors in obese children.Cross-sectional analysis of 90 obese children ages 7 to 16 years. Anthropometric and clinical evaluation with specification of dietary and lifestyle habits was carried out during an office visit. Sleep duration was evaluated by the BEARS (B = bedtime issues, E = excessive daytime sleepiness, A = night awakening, R = regularity and duration of sleep, S = snoring) questionnaire on children's sleep characteristics. Sleep time adequacy by age was assessed according to the criteria of the National Sleep Foundation. Biochemical blood variables indicative of metabolic risk (glucose, lipid profile, and insulin) were obtained. Emergent new factors of metabolic risk, including high-sensitive C-reactive protein, γ-glutamyltranspeptidase, homocysteine, retinol-binding protein 4 (RBP4), thyroid-stimulating hormone (TSH), inflammatory markers, and the adipokines leptin, adiponectin, and ghrelin were also evaluated. The relations between the duration of sleep and these variables were analyzed by general lineal model analysis. Significant variables were introduced in logistic regression analysis to determine the odds ratio (OR) and 95% confidence interval (CI) of cardiometabolic factors with respect to sleep.	Children who slept for short duration were significantly more at risk of severe central obesity. In the regression model, the mean arterial pressure (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.17, P = 0.008), homocysteine (OR 1.41, 95% CI 1.08-1.84, P = 0.013), RBP4 (OR 1.78, 95% CI 1.15-2.78, P = 0.010), and TSH (OR 2.01, 95% CI 1.21-3.34, P = 0.007) remain as significant independent predictors related to short sleep duration. We did not find any association between sleep duration and inflammatory markers or adipokines.	Short sleep duration increases the severity of obesity and is related to cardiovascular risk factors in children.	

25986444	Chronic neuropathic pain is a neuro-immune disorder, characterised by allodynia, hyperalgesia and spontaneous pain, as well as debilitating affective-motivational disturbances (e.g., reduced social interactions, sleep-wake cycle disruption, anhedonia, and depression). The role of the immune system in altered sensation following nerve injury is well documented. However, its role in the development of affective-motivational disturbances remains largely unknown. Here, we aimed to characterise changes in the immune response at peripheral and spinal sites in a rat model of neuropathic pain and disability.Sixty-two rats underwent sciatic nerve chronic constriction injury (CCI) and were characterised as either Pain and disability, Pain and transient disability or Pain alone on the basis of sensory threshold testing and changes in post-CCI dominance behaviour in resident-intruder interactions. Nerve ultrastructure was assessed and the number of T lymphocytes and macrophages were quantified at the site of injury on day six post-CCI. ATF3 expression was quantified in the dorsal root ganglia (DRG). Using a multiplex assay, eight cytokines were quantified in the sciatic nerve, DRG and spinal cord.	All CCI rats displayed equal levels of mechanical allodynia, structural nerve damage, and reorganisation. All CCI rats had significant infiltration of macrophages and T lymphocytes to both the injury site and the DRG. Pain and disability rats had significantly greater numbers of T lymphocytes. CCI increased IL-6 and MCP-1 in the sciatic nerve. Examination of disability subgroups revealed increases in IL-6 and MCP-1 were restricted to Pain and disability rats. Conversely, CCI led to a decrease in IL-17, which was restricted to Pain and transient disability and Pain alone rats. CCI significantly increased IL-6 and MCP-1 in the DRG, with IL-6 restricted to Pain and disability rats. CCI rats had increased IL-1β, IL-6 and MCP-1 in the spinal cord. Amongst subgroups, only Pain and disability rats had increased IL-1β.	This study has defined individual differences in the immune response at peripheral and spinal sites following CCI in rats. These changes correlated with the degree of disability. Our data suggest that individual immune signatures play a significant role in the different behavioural trajectories following nerve injury, and in some cases may lead to persistent affective-motivational disturbances.	
25986436	Population-based studies have linked measures of sleep disordered breathing to nocturnally occurring atrial fibrillation (AF) episodes. Whether measures of sleep disordered breathing and sleep quality are associated with prevalent AF has not been studied in an unselected population. We investigated the cross-sectional association with prevalent AF of objectively collected prespecified measures of overnight sleep breathing disturbances, sleep stage distributions, arousal and sleep duration.AF prevalence, defined by diagnosis codes, study electrocardiography and sleep study were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent polysomnography in the MESA Sleep Study (n=2048).	Higher apnoea hypopnoea index (AHI) was associated with increased odds of AF, although the significance was attenuated after full adjustment for covariates including prevalent cardiovascular disease (OR: 1.22 (0.99 to 1.49) per SD (17/h), p=0.06). Analyses of sleep architecture measures and AF revealed significantly lower odds of AF associated with longer duration of slow wave sleep (OR: 0.66 (0.5 to 0.89) per SD (34 min), p=0.01) which persisted after additionally adjusting for AHI (OR: 0.68 (0.51 to 0.92), p=0.01). Higher sleep efficiency was significantly associated with lower likelihood of AF but the significance was lost when adjusted for AHI. No significant association was present between sleep duration and AF. In a model including AHI and arousal index, the association between AHI and AF was strengthened (AHI: OR 1.49 (1.15 to 1.91) per SD, p=0.002) and a significant inverse association between arousal index and AF was observed (OR 0.65 (0.50 to 0.86) per SD (12/h), p=0.005).	In a study of a large multiethnic population, AF was associated with AHI severity, and was more common in individuals with poor sleep quality as measured by reduced slow wave sleep time, a finding that was independent of AHI.	
25986199	Epileptic encephalopathy with electrical status epilepticus during slow sleep (ESES) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies.In this retrospective study we assess the efficacy and tolerability of the KD in patients with ESES syndrome.	Between March 1, 1990 and April 1, 2013, 65 patients who met diagnostic criteria of ESES syndrome were seen at our department. Twelve of them were placed on the KD and followed for a minimum of 18 months.	The children had previously received a mean of 5.5 different AEDs and were on a mean of 3 AEDs when the diet was started. Eighteen months after initiating the diet, seven of the initial patients (58%) remained on the diet; one patient (8.3%) had become seizure free, one (8.3%) had a 75-99% decrease in seizures, two (16.6%) had a 50-74% decrease in seizures, and the remaining three children (24.9%) had a <50% decrease in seizures. In the patient who had become seizure free and in the one who had a 75-99% seizure decrease AEDs were reduced.	The KD is a well-tolerated treatment option for patients with ESES syndrome, not only for structural cases but also for those with an unknown etiology. The diet should be considered in the management of this syndrome.	
25985889	Dopamine plays a key role in the regulation of sleep-wake states, as revealed by the observation that dopamine-releasing agents such as methylphenidate have wake-promoting effects. However, the precise mechanisms for the wake-promoting effect produced by the enhancement of dopamine transmission are not fully understood. Although dopamine D1, D2, and D3 receptors are known to have differential effects on sleep architecture, the role of D4 receptors (D4Rs), and particularly the influence of D4R activation on the sleep-wake state, has not been studied so far. In this study, we investigated for the first time the effects of two structurally different D4R agonists, Ro 10-5824 and A-412997, on the sleep-wake states in rats. We found that both D4R agonists generally increased waking duration, and conversely, reduced non-rapid eye movement (NREM) sleep duration in rats. The onset of NREM sleep was also generally delayed. However, only the A-412997 agonist (but not the Ro 10-5824) influenced rapid eye movement sleep onset and duration. Furthermore, these effects were accompanied with an enhancement of EEG spectral power in the theta and the gamma bands. Our results suggest the involvement of dopamine D4R in the regulation of sleep-wake states. The activation of the D4R could enhance the arousal states as revealed by the behavioral and electrophysiological patterns in this study. Dopamine D4R may contribute to the arousal effects of dopamine-releasing agents such as methylphenidate. 
25982992	Noise generated by wind turbines has been reported to affect sleep and quality of life (QOL), but the relationship is unclear. Our objective was to explore the association between wind turbine noise, sleep disturbance and quality of life, using data from published observational studies. We searched Medline, Embase, Global Health and Google Scholar databases. No language restrictions were imposed. Hand searches of bibliography of retrieved full texts were also conducted. The reporting quality of included studies was assessed using the STROBE guidelines. Two reviewers independently determined the eligibility of studies, assessed the quality of included studies, and extracted the data. We included eight studies with a total of 2433 participants. All studies were cross-sectional, and the overall reporting quality was moderate. Meta-analysis of six studies (n=2364) revealed that the odds of being annoyed is significantly increased by wind turbine noise (OR: 4.08; 95% CI: 2.37 to 7.04; p<0.00001). The odds of sleep disturbance was also significantly increased with greater exposure to wind turbine noise (OR: 2.94; 95% CI: 1.98 to 4.37; p<0.00001). Four studies reported that wind turbine noise significantly interfered with QOL. Further, visual perception of wind turbine generators was associated with greater frequency of reported negative health effects. In conclusion, there is some evidence that exposure to wind turbine noise is associated with increased odds of annoyance and sleep problems. Individual attitudes could influence the type of response to noise from wind turbines. Experimental and observational studies investigating the relationship between wind turbine noise and health are warranted. 
25982882	Epilepsy is one of the most common neurological diseases and has many detrimental effects on the patients' well-being as well as sleep quality. The aim of this study was to assess the subjective quality of sleep and influencing factors on subjective sleep quality in patients with partial epilepsy using a combined retrospective and prospective study design.We conducted a combined retrospective and prospective study in patients with partial epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17 female, 15 male; mean age: 40.41 ± 12.67 years, range: 20-64) with partial epilepsy (mean duration of epilepsy diagnosis: 18.31 ± 13.26 years) and 32 healthy gender-matched and age-matched controls. All patients filled out a seizure diary for 90 days, which included the number, duration, and type (partial vs. secondary generalized) of epileptic seizures and intake of antiepileptic and sleep medications. At baseline, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI score of ≥ 5.	Twenty-three patients (72%) reported 15.17 ± 25.54 seizures in the previous three months, and nine (28%) patients reported being seizure-free. During the 90-day diary period, twenty-two patients (69%) documented a total of 319 epileptic seizures, while ten patients (31%) reported that they were seizure-free. The mean PSQI score of all patients was 4.88 ± 2.92 (range: 1-14) and the mean ESS score was 5.25 ± 2.98 (range: 0-10). The mean PSQI score of the control group was 3.25 ± 1.57 (range: 1-6), and their mean ESS score was 6.72 ± 3.48 (range: 0-14). The comparison of the two groups showed a significantly higher PSQI score in the patient group (t = 2.778, p = 0.008), but no statistically significant difference regarding their ESS score (t = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers showed a significantly lower PSQI (2.69 ± 1.08 vs. 7.06 ± 2.49; p < 0.001) and BDI scores (2.38 ± 2.50 vs. 9.63 ± 7.63; p < 0.002) than poor sleepers. Linear regression analysis showed that the BDI score was the significant predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS score (estimate: 0.2251; p = 0.0321).	In patients with partial epilepsy, a higher depression score was the best predictor for a poor subjective sleep quality and increased daytime sleepiness.	
25982568	Chronotherapeutics such as wake therapy and bright light therapy are well-established methods in treating adults with depressive disorders and are additionally beneficent for sleep regulation. Few studies concerning chronotherapeutics in juvenile depression exist, though the established treatments are insufficient and sleep disorders often co-occur. In this study, we investigate the impact of two types of chronotherapeutics on depressive symptoms and sleep behavior in a juvenile setting. Juvenile inpatients (n = 62) with moderate to severe depressive symptoms took part in either a combined setting consisting of one night wake therapy followed by 2 weeks bright light therapy or in a setting of bright light therapy alone. Depressive symptoms, general psychopathology, clinical impression and sleep behavior were measured before (T1), directly after (T2) and 2 weeks after intervention (T3). Depressive symptoms decreased while sleep quality increased in both groups. The bright light therapy alone group showed further improvement at T3 in regards to depressive symptoms. Correlation analyses indicated significant negative correlations between sleep quality and awaking after restorative sleep with the depressive symptoms. However, only awaking after restorative sleep had a predictive impact on treatment outcome. The present study provides first evidence for a positive impact of chronotherapeutic interventions on treatment outcome in depressed juvenile inpatients. Bright light therapy seems to stabilize and further enhance reduction of depressive symptoms during follow-up, whereas one night wake therapy does not have an additional long-lasting impact on depressive symptoms and sleep parameters.

25979721	Primary Sjögren syndrome (pSS) is a chronic autoimmune disease. A clear temporal causal relationship between pSS and psychiatric disorders has not been well established. We used a nationwide population-based retrospective cohort study to explore the relationship between pSS and the subsequent development of psychiatric disorders.We identified subjects who were newly diagnosed with pSS between January 1, 2000, and December 31, 2008, in the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed for patients without pSS. There were 2686 patients with pSS and 10,744 matched controls observed until diagnosed with psychiatric disorders or until death, withdrawal from the NHI system, or December 31, 2009. The Institutional Review Board of Taipei Veterans General Hospital approved this study (2012-12-013BC).	The adjusted HR of depressive disorder, anxiety disorder, and sleep disorder in subjects with pSS were significantly higher at 1.829, 1.856, and 1.967 than those of the controls during the followup. We found that pSS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder that may impair life quality.	Our findings highlight the need for psychiatric evaluation and intervention for patients with pSS.	

25976874	The quality of social relationships and social support appears to be associated with physical health outcomes and sleep quality. Almost all previous research in this area focuses on positive aspects of relationships.The present study thus intended to examine the links between supportive, aversive, ambivalent, and indifferent network ties and sleep quality.	Relationship data, Pittsburgh Sleep Quality Index (PSQI)-assessed sleep quality, and depression were examined in 175 middle-aged and older adults.	Consistent with hypotheses, supportive ties were positively related to sleep quality, while aversive ties predicted worse sleep quality, associations that were primarily seen for close relationships. Ambivalent and indifferent ties were not significant predictors of sleep quality. Importantly, depression was found to mediate the link between relationship quality and sleep quality.	These data suggest the more specific types of social relationships that may be linked to poor sleep quality and that depression appears to underlie these associations.	
25976571	To characterise sleep quality and assess degree of daytime sleepiness among medical students of Karachi.The cross-sectional study was conducted between August and December 2013 and subjects were recruited from five haphazardly selected medical colleges in Karachi. A convenience sample of medical students underwent two validated self-administered questionnaires i.e. Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. SPSS 17 was used for statistical analysis.	Of the 650 students approached, 504(77.5%) subjects completely filled out the questionnaires. Of them, 300(59.5%) were females and 204(40.5%) were males. Overall mean age was 20±1.4 years. Of them, 199(39.5%) were classified as "Poor Sleepers". Poor sleep quality was associated with female gender (p <0.05), excessive daytime sleepiness (p <0.05), total hours slept (p <0.001) and sleep disturbances (p <0.001). Bed-timing analysis showed 365(72%) students went to bed after midnight.	Sleep quality among Pakistani medical students was significantly poor. Efforts must be directed towards proper sleep hygiene education.	
25975657	Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy. 

25974623	Two-thirds of adolescents with chronic musculoskeletal pain report a concurrent sleep problem. Both musculoskeletal pain and sleep problems can have deleterious effects on physiological and psychological well-being. We explored the prevalence of sleep problems and musculoskeletal pain, using data on 3568 adolescents from the Avon Longitudinal Study of Children.A comprehensive battery of questionnaires was administered to derive clinical phenotypes of musculoskeletal pain. Adolescents with single symptoms were compared with those reporting both musculoskeletal pain and sleep problems. Linear and logistic regression analyses were used to compare groups on pain-related variables and psychological complaints. The association between sociodemographic variables and comorbid musculoskeletal pain and sleep problems was assessed using logistic regression.	Over half the sample was female (n=2076, 58.2%) and the majority of European ancestry (n=3174, 97.7%). Only 5.5% (n=196) of participants were identified as having a pain condition, while 21.2% (n=749) reported a significant sleep problem, and 2.8% (n=99) reported comorbid musculoskeletal pain and sleep problems. Adolescents with comorbid problems experienced greater pain intensity and pain-related anxiety. Other psychological complaints were also higher in those who experienced concurrent problems, including depression, fatigue, concentration, and overall severity of psychological symptoms.	Comorbid sleep and pain problems were associated with a higher incidence of pain-related and psychological symptoms. Sleep problems may therefore be an important modifiable risk factor for alleviating distress in adolescents with musculoskeletal pain.	
25974056	This study aimed to examine the association between sleep disturbance and attempted suicide in rural China. The study group included 409 suicide attempters from six rural counties in Shandong Province, China and an equal number of controls matched on age, sex, and residency. Sleep disturbance was assessed by the item "sleep restless" in the Center for Epidemiologic Studies Depression Scale. Sleep disturbance was reported more frequently in suicide attempters than in controls (1-2 days/week, 9.0% vs. 4.4%; 3-4 days/week, 11.5% vs. 2.4%; ≥5 days/week, 30.3% vs. 7.5%, χ 2= 128.72, p < 0.001). Suicide risk was significantly associated with increased frequency of sleep disturbance (OR = 3.98, 95% CI = 1.62-9.74 for 1-2 days/week; OR = 3.28, 95% CI = 1.21-8.84 for 3-4 days/week; OR = 2.41, 95% CI = 1.26-4.60 for ≥5 days/week) even after adjusting for potential psychosocial confounding factors and mental disorders. This finding may have important implications for early intervention and prevention of suicide.
25971368	Concussion literature and treatment guidelines are inconclusive regarding the role of sex in symptom reporting at baseline and post-concussion. Although empirical evidence is lacking, it is generally regarded that females have a more severe symptomatic presentation than males at all time-points on the concussion spectrum.Our objective was to determine whether differences exist between males and females at baseline (pre-season/before concussion) or post-concussion for self-reported (1) prevalence of individual symptoms and (2) total symptom scores in high school and college athletes.	Systematic review and meta-analysis of observational cohort studies; level of evidence, 1.	A computerized search of the PubMed, SPORTDiscus, CINAHL, and Scopus databases was performed. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Criteria for inclusion were (1) self-report of symptoms at any time within the concussion spectrum, including baseline and after concussion, (2) study sample included high school and/or collegiate athletes aged 12-26 years, (3) concussions occurred during participation in sport, and (4) symptom reporting was separated by sex. The Quality Assessment Tool for Cohort Studies, Q-Coh, was utilized for quality assessment.	Twenty-one studies met the criteria for inclusion: seventeen had good quality and four, acceptable quality. At baseline, females had significantly higher odds than males of reporting the individual symptoms of vision/hearing problems, headache/migraine, difficulty concentrating, energy/sleep disturbances, and emotional disturbances. Post-concussion, only one symptom demonstrated significant differences between males and females, with females demonstrating lower odds of reporting confusion than males. Statistically, at baseline and post-concussion, females had significantly higher total symptom scores on the Post-Concussion Scale (PCS) and the Sport Concussion Assessment Tool 2 (SCAT2), but when the standard mean difference was interpreted after back-transformation, these results were clinically insignificant.	The symptomatic presentation of males and females, most notably the prevalence of specific symptoms, is very divergent. Females had higher total symptom scores at baseline and post-concussion, however, clinically this cannot be interpreted as a meaningful difference. It is possible that these differences can be explained by normal hormonal changes associated with the menstrual cycle. The implications of these findings are that symptomatic presentation during an individual female's menstrual cycle needs to be taken into consideration post-concussion when making return-to-play decisions, as returning to a completely asymptomatic level may not be a reasonable expectation.	
25970699	Light, noise, and interruptions from hospital staff lead to frequent awakenings and detrimental changes to sleep quantity and quality for children who are hospitalized and their parents who stay with them overnight. An understanding of nurses' views on how care affects sleep for the hospitalized child and parent is crucial to the development of strategies to decrease sleep disturbance in hospital. The purpose of this descriptive qualitative study was to gain an understanding of nurses' views on their role in and influence on sleep for families; perceived barriers and facilitators of patient and parent sleep at night; strategies nurses use to preserve sleep; the distribution, between parent and nurse, of care for the child at night; views of the parent as a recipient of nursing care at night; and the nature of interactions between nurses and families at night. Thirty registered nurses from general pediatric and critical care units participated in one of four semi-structured focus groups. Four main influences on sleep were identified: child factors; environmental factors; nurse-parent interaction factors; and nursing care factors. Some of these restricted nurses' ability to optimize sleep, but many factors were amenable to intervention. Balancing strategies to preserve sleep with the provision of nursing assessment and intervention was challenging and complicated by the difficult nature of work outside of usual waking hours. Nurses highlighted the need for formal policy and mentoring related to provision of nursing care at night in pediatric settings.
25970525	Studies suggest a tight relationship between protein kinase C (PKC) and circadian clock. However, the role of PKC in sleep-wake regulation remains unclear. The present study was conducted to investigate the role of PKC signaling in sleep-wake regulation in the rat. Our results showed that the phosphorylation level of PKC in dorsal raphe nucleus (DRN) was decreased after 6h sleep deprivation, while no alterations were found in ventrolateral preoptic nucleus (VLPO) or locus coeruleus (LC). Microinjection of a pan-PKC inhibitor, chelerythrine chloride (CHEL, 5 or 10nmol), into DRN of freely moving rats promoted non rapid eye movement sleep (NREMS) without influences on rapid eye movement sleep (REMS). Especially, CHEL application at 5nmol increased light sleep (LS) time while CHEL application at 10nmol increased slow wave sleep (SWS) time and percentage. On the other hand, microinjection of CaCl2 into DRN not only increased the phosphorylation level of PKC, but also reduced NREMS time, especially SWS time and percentage. While CHEL abolished the inhibitory effect of CaCl2 on NREMS and SWS. These data provide the first direct evidence that inhibition of intracellular PKC signaling in DRN could increase NREMS time including SWS time and percentage, while activation of PKC could suppress NREMS and reduce SWS time and percentage. These novel findings further our understanding of the basic cellular and molecular mechanisms of sleep-wake regulation. 
25970104	We measured the illuminance exposure for 3 days in winter of a convenience sample of 44 elderly people certified as requiring support in Japan's Hokuriku region. We calculated the illuminance ratio per minute during activity and while in bed and analyzed the relationship between illuminance, subjective sleep quality, and psychosomatic health. There was a significant negative correlation between illuminance and 15-item Geriatric Depression Scale scores. Multiple regression analysis indicated that depression scores were significantly related to age, level of required support, and illuminance. The findings suggest that environments without light and dark cycles increase depression scores in frail elderly people. 
25969504	Changes in health-related behaviour may be a key mechanism linking impaired sleep to poor health, but evidence on this is limited. In this study, we analysed observational data to determine whether onset of impaired sleep is followed by changes in health-related behaviours.We used data from 37,508 adults from the longitudinal Finnish Public Sector Study. In analysis of 59 152 person-observations on duration and quality of sleep and health-related behaviours (alcohol consumption, smoking, physical activity and weight control), data were treated as a series of non-randomized pseudo-trials with strict predefined criteria for data inclusion and temporality.	Smokers who experienced onset of short sleep were less likely to quit smoking than those with persistent normal sleep [odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.64-0.97]. Onset of short sleep also predicted initiating high-risk alcohol consumption (OR = 1.17, 95% CI: 1.00-1.37). Onset of disturbed sleep was associated with changes in all assessed health-related behaviours: initiation of high-risk alcohol consumption (OR = 1.23, 95% CI: 1.05-1.45), quitting smoking (OR = 0.80, 95% CI: 0.63-1.00), becoming physically inactive (OR = 1.17, 95% CI: 1.06-1.30) and becoming overweight or obese (OR = 1.12, 95% CI: 1.01-1.23).	Findings suggest that the onset of short or disturbed sleep are risk factors for adverse changes in health-related behaviours. These findings highlight potential pathways linking impaired sleep to the development of lifestyle-related morbidity and mortality.	
25969172	Two studies were carried out to explore the relationship between circadian typology and the Alternative Five-Factor Model of personality. In the first study, 379 participants (232 females) were administered the reduced version of the Morningness-Eveningness Questionnaire and the Zuckerman-Kuhlman Personality Questionnaire. Evening types reported higher impulsive sensation-seeking scores than morning and intermediate types, whereas morning types scored higher than evening types on activity factor. In the second study, the association between morningness and activity personality factor was verified through the objective-actigraphic monitoring of the rest-activity cycle. Actigraphy allowed us to operationalise both circadian typology, through the computing of midpoint of sleep (early values, expressed in hours and minutes, correspond to an advanced phase of the sleep/wake cycle), and activity factor by the means of motor activity recording. Fifty-one individuals (30 females) wore an actigraph on the nondominant wrist continuously for 1 week. A negative correlation was observed between midpoint of sleep and mean diurnal motor activity, demonstrating that an early phase of the sleep/wake cycle (i.e. morningness preference) was related to higher diurnal motor activity. Assessed both subjectively and objectively, the results of both studies highlight a significant relationship between morningness and activity personality factor. 
25968449	Pain has been found to be associated with poor sleep quality, awakenings, and shorter sleep time. There is a need to understand the relationship of pain and sleep over time to adequately manage the pain disorder and its consequences. The objectives of this study were to establish the prevalence of sleep disturbance in patients with acute or persistent low back pain (LBP), to investigate the correlation between pain and sleep disturbance and to explore the influence of pain on sleep disturbance.Data from a prospective observational study of 233 patients with acute and persistent LBP were used. Twenty-six weekly pain reports and monthly (weeks 2, 6, 10, 14, 18, 22, and 26) sleep reports were collected with text messages. The prevalence of sleep disturbance, the correlation of pain and sleep disturbance, and the risk of reporting disturbed sleep after experiencing LBP were calculated.	Sleep disturbance was reported by 67% of the sample. Among patients with acute and persistent LBP, the prevalence was 55% and 76%, respectively. Measures of pain and sleep disturbance were significantly correlated. Compared with being pain free, the risk of reporting sleep disturbance after experiencing pain the previous week was significantly increased (relative risk=2.1 to 5.8), and a dose-response between the number of days with pain and the risk of sleep disturbance was found.	This study used repeated measures of both pain and sleep disturbance. The results were in line with previous research, confirming that sleep disturbance was found in the majority of patients with LBP. Pain and sleep measures were significantly correlated, and there was an increased risk of reporting sleep disturbance after experiencing LBP.	
25965811	Sleep and epilepsy have a close relationship. About 20% of patients suffer seizures only during the night, approximately 40% only during the day and approximately 35% during the day and night. In certain epilepsy syndromes, the occurrence of seizures is strongly related to sleep or awakening. Infantile spasms appear predominately on awakening, and hypsarrhythmia is sometimes visible only in sleep. Children with Panayiotopoulos syndrome or benign epilepsy with centrotemporal spikes (BECTS) have seizures mostly when asleep, and in both syndromes interictal spike waves are markedly accentuated in slow wave sleep. Electrical status epilepticus during slow sleep/continuous spike wave discharges during sleep (ESES/CSWS), atypical benign partial epilepsy, and Landau-Kleffner syndrome are epileptic encephalopathies with substantial behavioral and cognitive deficits, various seizures, and continuous spike-wave activity during non-rapid eye movement (NREM) sleep. The hallmark of juvenile myoclonic epilepsy and grand mal seizures on awakening are seizure symptoms within 2 hours after awakening, often provoked by sleep deprivation. Nocturnal frontal lobe epilepsy is sometimes mistaken for parasomnia. Differentiation is possible when the clinical symptoms and the frequency of the paroxysmal events per night and month are carefully observed and nocturnal video electroencephalography (EEG) performed. Sleep EEG recordings may be helpful in patients with suspected epilepsy and nonconclusive awake EEG. Depending on the clinical question, sleep recordings should be performed during nap (natural sleep or drug induced), during the night, or after sleep deprivation. 

25961599	Several methods are used to evaluate sleep in infants, children, and adolescents including: Questionnaires and diaries, actigraphy, polysomnography, and electroencephalography which are well established. Novel approaches such as high-density electroencephalography, simultaneous electroencephalography-functional magnetic resonance imaging and nonpharmacological methods aiming for a modulation of sleep are currently only used for research. These approaches might become valuable methods for clinical application in the future. The purpose of this review is to present an overview of current methods and their respective fields of application and to report available rules and recommendations for their use. 
25961116	"Positive health," defined as a state beyond the mere absence of disease, was used as a model to examine factors for enhancing health despite extreme trauma. The study examined the United States' longest detained American prisoners of war, those held in Vietnam in the 1960s through early 1970s. Positive health was measured using a physical and a psychological composite score for each individual, based on 9 physical and 9 psychological variables. Physical and psychological health was correlated with optimism obtained postrepatriation (circa 1973). Linear regressions were employed to determine which variables contributed most to health ratings. Optimism was the strongest predictor of physical health (β = -.33, t = -2.73, p = .008), followed by fewer sleep complaints (β = -.29, t = -2.52, p = .01). This model accounted for 25% of the variance. Optimism was also the strongest predictor of psychological health (β = -.41, t = -2.87, p = .006), followed by Minnesota Multiphasic Personality Inventory-Psychopathic Deviate (MMPI-PD; McKinley & Hathaway, 1944) scores (β = -.23, t = -1.88, p = .07). This model strongly suggests that optimism is a significant predictor of positive physical and psychological health, and optimism also provides long-term protective benefits. These findings and the utility of this model suggest a promising area for future research and intervention.
25959075	Testosterone level follows a circadian rhythm. However, whether sleep duration and disturbances can affect testosterone level, muscle mass, and strength remains unknown.To examine the relationship of sleep duration and disturbances to testosterone level, muscle mass, muscle strength, and walking speed.	We recruited 1274 community-dwelling men older than 65 years of age. Their early morning testosterone level was assayed by mass spectrometry. A sleep questionnaire was administered to enquire about their reported sleep duration, prolonged sleep latency (>0.5 hour), and subjective insomnia complaint. Muscle mass was measured by dual-energy x-ray absorptiometry. Testosterone level, muscle mass, handgrip strength, and walking speed were tested against sleep duration and disturbances.	Testosterone increased with increasing sleep duration up to 9.9 hours, after which it decreased, giving rise to an inverted U-shaped relationship (P for quadratic trend <.05). A similar inverted U-shaped relationship occurred between sleep duration and muscle mass and function. Earlier go-to-bed time, despite being associated with a higher testosterone level (P < .05), was associated with weaker grip strength (P < .05). Earlier wake-up time was associated with higher muscle mass (P < .05) but neither grip strength nor walking speed. Neither prolonged sleep latency nor insomnia was associated with testosterone levels. However, prolonged sleep latency was associated with lower muscle mass (P < .05), weaker grip strength (P < .05), and slower walking speed (P < .001). Insomnia, on the other hand was associated with weaker grip strength (P < .05) and slower walking speed (P < .001) but not muscle mass.	Sleep duration and disturbances can affect testosterone level, muscle mass, and its function. Whether optimization of sleep can ameliorate age-associated decline in sex hormone and muscle performance warrants further studies.	
25959021	Sleep disorders are common among the patients undergoing dialysis in end stage renal disease (ESRD). Although variable, their prevalence has been reported to be higher when compared to the general population. The most frequently reported complaints are insomnia, restless leg syndrome (RLS), sleep-disordered breathing and excessive daytime sleepiness (EDS). The aim of this study was to assess the prevalence of sleep disorders in end stage renal disease patients on regular hemodialysis (group I with 30 patients) and CKD patients (group II with 30 patients) in comparison to 30 normal population (control group). In addition to laboratory investigations which included creatinine clearance using Cockroft and Gault formula, hemoglobin level (Hb), blood urea, serum creatinine, serum albumin, serum calcium and phosphorus and lipid profile, all subjects underwent one night of laboratory-based polysomnography (PSG) consisting of a standard montage of electroencephalography (EEG) (C3/A1 and O2/C3 or O1/C4), monopolar left and right electrooculography (EOG) referenced to the opposite mastoid, surface mentalis electromyography (EMG), respiratory airflow (measured by thermistor) and effort (piezoelectric sensors), electrocardiography (ECG), anterior tibialis EMG and pulse oximetry. For hemodialysis subjects, this study was performed on a night immediately following hemodialysis treatment. The results showed that patients on hemodialysis have sleep disorders, and that sleep disorders are common in group I and II than control group. The percentage of sleep disorders in hemodialysis patients were as follows: insomnia (69%), followed by obstructive sleep apnea syndrome OSAS (24%), RLS and periodic limb movement PLM (18%), nightmares (13%), EDS (12%), sleepwalking (2%), possible rapid eye movement behavior disorders RED (2%), possible narcolepsy (1.4%). While the percentage of sleep disorders in CKD patients were as follows: insomnia (54%), followed by RLS (19%), PLM (12%), OSAS (16%), nightmares (15%), EDS (15%), sleepwalking (4%), possible RBD (3%), possible narcolepsy (1%). There was inverse correlation between sleep disorders and Hb, albumin and creatinine clearance; also there was positive correlation between sleep disorder and phosphorus. We concluded that the sleep disorders are common in CKD patients either on conservative management or on regular hemodialysis. Treatment of anemia, hyperphosphatemia and hypoalbuminemia may improve sleep disorders among those patients. 
25958936	We aimed to assess the prevalence of sleep disturbance in a cardiac patient population over a 12-month period and assess its relationship with treatment adherence, self-efficacy, anxiety and depression. A total of 134 patients consecutively admitted to two Australian hospitals after acute myocardial infarction (31%), or to undergo bypass surgery (29%) or percutaneous coronary intervention (40%) were interviewed at six weeks and four and 12 months. Sleep disturbance was measured using a recode of the Beck Depression Inventory (v.2) item 16. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale. Sleep disturbance was highly prevalent (69%) at 6 weeks but was not associated with 12-month psychological outcomes. Path analysis revealed that sleep disturbance at 4 months was, however, associated with reduced treatment adherence and self-efficacy, and higher anxiety and depression scores at 12 months. The high prevalence of sleep disturbance in this study and its association with psychological outcomes may have adverse prognostic implications and possibly impede cardiac rehabilitation efforts.

25958234	This study aimed to investigate symptom experience and identify the predictors of symptom experience in cancer patients undergoing chemotherapy.This study was a cross-sectional and descriptive design. A total of 167 participants were recruited from the outpatient department of a university hospital in South Korea. Symptom experience (symptom prevalence, severity, and interference with daily activities), physiological factors (absolute neutrophil count, hemoglobin), psychological factors (depression, fighting spirit), and a situational factor (social support), based on the Theory of Unpleasant Symptoms, were measured. Descriptive statistics and multiple regression analyses were performed.	Symptom prevalence ranged from 74.3% to 98.8% of patients. The five most severe symptoms were fatigue, numbness/tingling, dry mouth, sleep disturbance, and drowsiness. General activity and work were the most affected areas of daily life. Symptom experience was significantly related to hemoglobin, depression, fighting spirit, and social support. In the multiple regression analysis, higher level of depression and lung cancer accounted for 20.2% of the variance in symptom severity. Higher level of depression, lower level of fighting spirit and third or fourth-line chemotherapy accounted for 31.0% of the variance in symptom interference.	Attention is drawn to developing a comprehensive approach which considers relevant physiological, psychological and social factors in assessment and management of concurrent symptoms in cancer patients undergoing chemotherapy. Health care professionals need to play a key role in helping patients deal with depressive mood and promote fighting spirit, particularly in patients with lung cancer or patients treated with higher-line chemotherapy, for controlling their symptom experience.	
25958105	Spina bifida is a congenital defect of the neural tube resulting in motor and sensory disruption. Persons with spina bifida can also experience executive function impairments. Secondary conditions are physical, medical, cognitive, emotional, or psychosocial consequences to which persons with disabilities are more susceptible. Our experience suggested clinicians underappreciate the presence and impact of secondary conditions in adults with spina bifida because they do not specifically ask for this information.Describe the presence and impact of secondary conditions on daily life, as perceived by adults with spina bifida.	A clinic-based sample was recruited from the active patient population of an adult specialty center for spina bifida-related care. All subjects were verbally administered a survey developed through literature review and clinical experience of the researchers. The survey measured the presence and perceived impact of secondary conditions. Recruitment and survey data collection occurred over a 6-month period to maximize age representation. Survey data were stratified by age, gender and lesion level for analysis.	Seventy-two respondents completed the survey. Pain was commonly reported, along with pressure ulcers, bowel & bladder concerns, depression, sleep disturbance, and limited social and community participation. No significant relationships were found between the presence or perceived impact of secondary conditions and age, gender or level of lesion.	Secondary conditions in spina bifida are present by early adulthood. Identifying these conditions during clinical encounters requires specific rather than general questions. Future study should evaluate earlier initiation of preventative measures by pediatric providers.	
25957987	The genetic background of autism spectrum disorder (ASD) is considered a multi-genetic disorder with high heritability. Autistic children present with a higher prevalence of sleep disorders than has been observed in children with normal development. Some circadian-relevant genes have been associated with ASD (e.g., PER1, PER2, NPAS2, MTNR1A, and MTNR1B).We analyzed 28 ASD patients (14 with sleep disorders and 14 without) and 23 control subjects of Japanese descent. The coding regions of 18 canonical clock genes and clock-controlled genes were sequenced. Detected mutations were verified by direct sequencing analysis, and additional control individuals were screened.	Thirty-six base changes with amino acid changes were detected in 11 genes. Six missense changes were detected only in individuals with ASD with sleep disturbance: p.F498S in TIMELESS, p.S20R in NR1D1, p.R493C in PER3, p.H542R in CLOCK, p.L473S in ARNTL2, and p.A325V in MTNR1B. Six missense changes were detected only in individuals with ASD without sleep disturbance: p.S1241N in PER1, p.A325T in TIMELESS, p.S13T in ARNTL, p.G24E in MTNR1B, p.G24E in PER2, and p.T1177A in PER3. The p.R493C mutation in PER3 was detected in both groups. One missense change, p.P932L in PER2, was detected only in the control group. Mutations in NR1D1, CLOCK, and ARNTL2 were detected only in individuals with ASD with sleep disorder. The prevalence of the mutations detected only single time differed significantly among all ASD patients and controls (p=0.003). Two kinds of mutations detected only in individuals with ASD with sleep disorder, p.F498S in TIMELESS and p.R366Q in PER3, were considered to affect gene function by three different methods: PolyPhen-2, scale-invariant feature transform (SIFT) prediction, and Mutation Taster (www.mutationtaster.org). The mutations p.S20R in NR1D1, p.H542R in CLOCK, p.L473S in ARNTL2, p.A325T in TIMELESS, p.S13T in ARNTL, and p.G24E in PER2 were diagnosed to negatively affect gene function by more than one of these methods.	Mutations in circadian-relevant genes affecting gene function are more frequent in patients with ASD than in controls. Circadian-relevant genes may be involved in the psychopathology of ASD.	
25957618	The objective of this study is to examine the association between sleep quality and obesity status.A cross-sectional study of 3225 Chinese participants aged 18 to 65 years was conducted in Beijing in 2007. Body mass index (BMI) was classified according to the Working Group on Obesity in China, and sleep quality was assessed by the modified Pittsburg Sleep Quality Index questionnaire. Logistic regression models were applied to estimate the odds ratios (OR) and 95 % CIs of obesity by sleep quality adjusted for potential confounders. Two sets of potential confounders were used in the adjusted models. Model 1 was adjusted for sex and age. Model 2 was further adjusted for education level, occupation, marriage status, smoking, alcohol consumption, body pain, and health status.	Poor sleep quality was significantly negatively associated with overweight/obesity in men but not in women. Additional adjustment for education level, occupation, marriage status, smoking, alcohol consumption, body pain, and health status did not attenuate the association (OR = 1.41 with 95 % CI 1.03-1.93; P < 0.05) among men. The adjusted OR per sleep quality score hour was 1.07 (1.01-1.14) for overweight/obesity, suggesting that for one score increase in sleep quality, obesity/overweight risk increased by 7 % in men.	Sleep quality was negatively associated with overweight/obesity in Chinese men but not in women.	
25957617	Sleep disturbances such as insomnia, nocturnal awakenings, restless legs syndrome, habitual snoring, and excessive daytime sleepiness are frequent during pregnancy, and these have been linked to adverse maternal and fetal outcomes.A prospective observational study was performed in high-risk Indian pregnant women. We used modified Berlin questionnaire (MBQ), Pittsburgh sleep quality index (PSQI), International Restless Legs Syndrome Study Group 2011 criteria, and Epworth sleepiness scale to diagnose various sleep disorders, such as symptomatic OSA, poor sleep quality and insomnia, RLS, and excessive daytime sleepiness, respectively, in successive trimesters of pregnancy. Outcome variables of interest were development of gestational hypertension (GH), gestational diabetes mellitus (GDM), and cesarean delivery (CS); the Apgar scores; and low birth weight (LBW). The relationship between sleep disorders and outcomes was explored using logistic regression analysis.	Outcome data were obtained in 209 deliveries. As compared to nonsnorers, women who reported snoring once, twice, and thrice or more had odds ratios for developing GH-4.0 (95 % CI 1.3-11.9), 1.5 (95 % CI 0.5-4.5), and 2.9 (95 % CI 1.0-8.2) and for undergoing CS-5.3 (95 % CI 1.7-16.3), 4.9 (95 % CI 1.8-13.1), and 5.1 (95 % CI 1.9-14.9), respectively. Pregnant women who were persistently positive on MBQ had increased odds for GH and CS.	Snoring and high-risk MBQ in pregnant women are strong risk factors for GH and CS. In view of the significant morbidity and health care costs, simple screening of pregnant women with questionnaires such as MBQ may have clinical utility.	
25957245	Dementia is characterized by cognitive and also behavioral and psychological symptoms of dementia (BPSD). The most prominent BPSD are depression and apathy but sleep disorders also complicate the clinical course of dementia. These symptoms are a severe burden for patients and caregivers and are difficult to treat partly due to comorbidities. Common sleep disorders in dementia are insomnia, hypersomnia, circadian rhythm alterations and aberrant nocturnal motor behavior. Sleep duration and rapid eye movement (REM) sleep are reduced. The diagnostic assessment of sleep disorders should include an evaluation of the underlying risk factors and a detailed sleep history for which several assessment instruments are available. The therapy of sleep disorders of dementia is primarily nonpharmacological: sleep counseling, sleep hygiene regulation, relaxation and psychotherapy techniques are given priority. Pharmacological treatment often has severe side effects in this elderly, vulnerable population and can only be considered if other nonpharmacological options have been unsuccessful. The application of medication should be limited in time and dosage. The pharmacological therapeutic options are critically discussed in detail. 
25956251	Sleep disruption, which includes a loss of sleep as well as poor quality fragmented sleep, frequently follows traumatic brain injury (TBI) impacting a large number of patients each year in the United States. Fragmented and/or disrupted sleep can worsen neuropsychiatric, behavioral, and physical symptoms of TBI. Additionally, sleep disruption impairs recovery and can lead to cognitive decline. The most common sleep disruption following TBI is insomnia, which is difficulty staying asleep. The consequences of disrupted sleep following injury range from deranged metabolomics and blood brain barrier compromise to altered neuroplasticity and degeneration. There are several theories for why sleep is necessary (e.g., glymphatic clearance and metabolic regulation) and these may help explain how sleep disruption contributes to degeneration within the brain. Experimental data indicate disrupted sleep allows hyperphosphorylated tau and amyloid β plaques to accumulate. As sleep disruption may act as a cellular stressor, target areas warranting further scientific investigation include the increase in endoplasmic reticulum and oxidative stress following acute periods of sleep deprivation. Potential treatment options for restoring the normal sleep cycle include melatonin derivatives and cognitive behavioral therapy. 

25953512	The orexin/hypocretin receptors are a family of G protein-coupled receptors and consist of orexin-1 (OX1) and orexin-2 (OX2) receptor subtypes. Orexin receptors are expressed throughout the central nervous system and are involved in the regulation of the sleep/wake cycle. Because modulation of these receptors constitutes a promising target for novel treatments of disorders associated with the control of sleep and wakefulness, such as insomnia, the development of orexin receptor antagonists has emerged as an important focus in drug discovery research. Here, we report the design, synthesis, characterization, and structure-activity relationships (SARs) of novel orexin receptor antagonists. Various modifications made to the core structure of a previously developed compound (-)-5, the lead molecule, resulted in compounds with improved chemical and pharmacological profiles. The investigation afforded a potential therapeutic agent, (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006), an orally active, potent orexin antagonist. The efficacy was demonstrated in mice in an in vivo study by using sleep parameter measurements. 
25952066	Sleep patterns share common pathways with nociceptive stimuli. Several important factors are reviewed in considering connections between sleep and pain. Causes for sleep fragmentation include sleep disordered breathing; abnormal leg movements, including restless legs syndrome and periodic limb movements; and underlying mood disorder, which may be exacerbated by physical symptoms. Identification and management of insomnia includes the definition of the condition, pharmacologic interventions, the role of circadian rhythms and clock adjustments, and the use of cognitive behavior therapy for insomnia. 
25951784	Headaches and sleep disorders are associated in a complex manner. Both the disorders are common in the general population, but the relationship between the two is more than coincidental. Sleep disorders can exacerbate headache sand the converse is also true. Treatment of sleep disorders can have a positive impact on the treatment of headaches. Screening for sleep disorders should be considered in all patients with headaches. This can be accomplished with brief screening tools. Those who screen positively can be further evaluated or referred to asleep specialist.
25951489	To determine (a) the incidence of restless legs syndrome (RLS) in patients with Crohn's disease (CD), (b) whether and how the occurrence and severity of RLS is related to severity of CD, and (c) how RLS influences the quality of life of CD patients.We carried out a cross-sectional questionnaire study in a random selection of 144 CD patients and 80 controls. Differences were calculated using a χ-test (categorical data), an independent T-test (continuous data, normal distribution), or a Mann-Whitney U-test (continuous data, non-normal distribution). Logistic regression analysis was carried out to establish the relation between CD and RLS after adjusting for risk factors.	The prevalence of RLS was 25.7% (37/144) in CD patients compared with 12.5% (10/80) in the control group (P=0.02). CD patients using caffeine and patients with arthralgias had a higher risk for RLS. A higher score on the modified Harvey Bradshaw Index and CD-related surgery were also associated with a higher risk for RLS. CD-related surgery was also associated with a more severe course of RLS. Patients and controls with RLS had a lower score on 'physical functioning', one of the subcategories of the RAND-36 quality-of-life questionnaire.	RLS occurs more frequently in patients with CD compared with healthy individuals. A more severe course of CD seems to be associated with a higher risk for RLS. The presence of RLS has a negative influence on quality of life, mainly interfering with physical activities of daily life.	
25948448	Patients with coronary diseases admitted to special care unit often suffer from sleep disorders, which may cause physiological changes and adversely affect patient's health. The relationship between sleep disorders and obesity is an important factor in studies on sleep disorders and other chronic diseases in all groups, including cardiovascular diseases. Understanding this relationship may increase the chance of progress in effective medical interventions in sleep disorders and obesity. This study was designed to evaluate the association between short sleep and Body Mass Index (BMI), hypertension among acute coronary syndrome patients.In this descriptive analytical study, 221 coronary patients admitted to coronary care unit and general wards were investigated. Data were collected through a researcher-made questionnaire whose validity and reliability had been confirmed. Data were analyzed with SPSS-16 software.	A total of 221 patients with acute coronary diseases (including myocardial infarction and angina pectoris) with a mean age of 61.27 years were studied, of whom 61.5% were male and 38.5% were female. A significant association was observed between short sleep and higher BMI (P=0.000). About half the patients (49.3%) had a history of hypertension, and sleep disorders were also significantly related to hypertension (P=0.006).	In this study, sleep disorders were patients' main complaint. Researchers found that patients with less than 5 hours or more than 9 hours sleep at night were more likely to have hypertension compared to patients that slept 7-8 hours. Lack of sleep affects metabolism, and daily energy expenditure reduces with increased immobility. In this study, a significant relationship was observed between BMI and sleep duration among hospitalized patients in coronary care unit (P=0.000), and sleep disorders increased with higher BMI. Short of sleep increases sympathetic tonus, cortisol level, and activation of inflammatory pathways, impairing glucose metabolism and contributing to overweigh, increased visceral fat.	Our findings suggest that poor sleep quality, is related to higher BMI and hypertension among acute coronary syndrome patients.	
25947281	While Emil Kraepelin's comprehensive psychiatric oeuvre has attracted researchers' attention, his studies on sleep disorders and their treatment as well as on the interconnections between sleep and mental disorders so far seem to have been neglected.This article identifies and analyzes Kraepelin's sporadic contributions on the pathology of sleep, the comorbidities and treatment made between 1883 and 1924 in textbooks and isolated papers as well as in a presentation that was also published and compares them with current opinions in sleep research.Kraepelin never published a dedicated work on sleep, apart from a summary of the different narcotics; however, his occasional statements reveal astonishing insights and in particular his clear etiologically oriented classification of sleep disorders is captivating. Similar to the current classification, Kraepelin conceptualized sleep disorders as symptoms or rather a complex of symptoms and also identified associated diseases which once again are very near to current opinion. Apart from this his recommendations on sleep hygiene and, in a second step, pharmacological treatment of pathological sleep patterns are still clinically relevant. As early as the end of the nineteenth century Kraepelin laid down an algorithm of treatment which is very similar to the current clinical guidelines. At Kraepelin's time it seemed impossible to reach an agreement on classification and treatment issues of sleep disturbances and even though there has been an ongoing discussion until the present day, an agreement at least about guidelines could be reached. Against this background Kraepelin's contributions can still be regarded as a proposal for best practice. 
25946052	Sleep disorders are common in patients with Alzheimer dementia and affect the quality of life of patients and of their caregivers. Despite the rising number of studies in the area, almost all of them are about non-pharmacological treatment. Our objective was to review the literature concerning pharmacological and non-pharmacological approaches to treat sleep disorders of elderly patients with Alzheimer dementia in the ambulatory setting. The treatments revised consisted of sleep hygiene and/or use of intense light coupled or not with use of melatonin, cholinesterase inhibitors, antipsychotics, hypnotics or antidepressants. In addition to the non-pharmacological measures, there is evidence that the use of trazodone may aid the treatment of sleep disorders of older individuals with Alzheimer dementia. More studies are necessary to examine the non-pharmacological and pharmacological treatments revised herein. 
25945942	Psoriasis is a common dermatological disorder with psychiatric comorbidity. Psoriasis is associated with a variety of psychological problems, including poor self-esteem, sexual dysfunction, sleep disturbances, anxiety, depression, and suicidal ideation.We aimed to investigate general psychiatric symptoms, quality of sleep, and coping strategies in patients with psoriasis vulgaris.	A total of 79 subjects (37 patients with psoriasis vulgaris and 42 control subjects) were enrolled in the study. Coping strategies were measured using the Coping Orientations to Problems Experienced (COPE) Scale. General psychopathological status was assessed using the Symptom Checklist-90-R (SCL90R), and sleep quality and disturbances were assessed using the Pittsburgh Sleep Quality Index (PSQI).	The mean age of the patients was 39.18 ± 16.85 years. The mean age of control subjects was 39.33 ± 11.61 years. The mean score on the Psoriasis Area and Severity Index (PASI) was 7.56 ± 3.66. There were no significant differences in scores on the SCL90R and COPE subscales between the patient and control groups. However, significant differences between the groups emerged on the PSQI subscales for subjective sleep quality and habitual sleep efficiency (Z = -1.964, P = 0.049, and Z = -2.452, P = 0.014, respectively).	The present study found no significant differences in general psychiatric symptoms and coping strategies between the psoriasis patients and the control group, by contrast with findings reported elsewhere in the literature. We think that the low PASI scores of our patients, which indicate the low severity of disease in the present group, is the main reason for this finding. However, sleep quality is lower in psoriasis vulgaris patients than in healthy controls. This may be associated with the itch and pain caused by lesions. Further experimental studies are required to explain these findings.	
25945557	This study investigates the effects of seasonality and altitude on sleep in extreme Antarctic conditions.During summer and winter periods, 24 h of actimetric recordings were obtained at two different research stations, Dumont d'Urville (sea level altitude) and Concordia (corrected altitude 12,467 ft or 3800 m).	During daytime, there were no altitude- or season-related differences in time spent at work, energy expenditure, or number of walking steps. During the nighttime however, total sleep time was longer (m = 427.4; SD = 42.4), sleep efficiency higher (m = 90; SD = 4.8), and wake after sleep onset shorter (m = 42.2; SD = 28.7) at sea level. Additionally, sleep fragmentation episodes and energy expenditure were higher during summer than winter periods.	Our results show that dramatic variations in light exposure are not the only main factor affecting sleep quality in Antarctica, as altitude also markedly impacted sleep in these conditions. The effect of altitude-induced hypoxia should be taken into account in future investigations of sleep in extreme environments.	
25944985	Mediators of inflammation, oxidative stress, and chemoattractants drive the hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the hypoxic stimuli for oxidative stress, culminating in systemic inflammation and generalized vascular endothelial damage. Comorbidities like pulmonary hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary vasoconstriction contribute to chronic hypoxemia leading to the release of proinflammatory cytokines that may propagate clinical deterioration and alter the pulmonary fibrotic pathway. Tissue inhibitor of metalloproteinase (TIMP-1), interleukin- (IL-) 1α, cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β), lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG-1), macrophage inflammatory protein- (MIP-) 1α, MIP-3α, and nuclear factor- (NF-) κB appear to mediate disease progression. Adipocytes may induce hypoxia inducible factor (HIF) 1α production; GERD is associated with increased levels of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and tumor necrosis factor alpha (TNF-α); pulmonary artery myocytes often exhibit increased cytosolic free Ca2+. Protein kinase C (PKC) mediated upregulation of TNF-α and IL-1β also occurs in the pulmonary arteries. Increased understanding of the inflammatory mechanisms driving hypoxemia in pulmonary fibrosis and obstructive sleep apnea may potentiate the identification of appropriate therapeutic targets for developing effective therapies. 
25944510	In Parkinson's disease (PD), sleep disorders (SD) occur as a result of the neurochemical changes in sleep centres, neurodegenerative changes in dopaminergic neurons, and other factors. The most common SD include excessive daytime sleepiness, insomnia, restless legs syndrome and nocturia. The aim of the study was to compare quality of sleep, as a factor that greatly impacts quality of life (QoL), between PD patients and a control group and to further examine SD in the PD group with focus on incidence and SD types as well as on effects various factors (age, sex, PD characteristics, medication usage) have on these disorders. The study included 110 patients who met the criteria for the diagnosis of PD and 110 age-matched healthy controls. We used the Pittsburgh Sleep Quality Index, PD Sleep Scale, Epworth Sleepiness Scale, PD QoL Questionnaire-8 and PD Questionnaire-39 (items 30 and 33). In the group with PD, we considered the duration of the disease, the stage of disease according to the Hoehn and Yahr scale, medications and their impact on the SD. The average duration of the disease was 6 years and the mean stage was 2.44. The result showed significant differences in the sleep quality between groups. In the PD group, SD differences were also found according to gender, duration of the disease and medication usage. The most common SD were fragmented sleep, insomnia and nocturia. To improve the QoL of PD patients, it is necessary to pay more attention to detecting and solving SD. 
25944135	The aim of the present study was to determine the effects of perceived pain on quality of sleep and life in patients hospitalized in a pain clinic.Population of the present descriptive study composed of patients (>18 years old) treated as inpatients in the algology clinic of a university located at the city center of Sivas, who consented to participate in the study (122 patients). Data were collected through Personal Information Form, Visual Analog Scale (VAS), Pittsburg Sleep Quality Index (PSQI) and Short Form 36. Data were analyzed using independent t-test, Mann Whitney U test, Kruskal Wallis test and Pearson correlation test. Statistical significance level was set at p<0.05.	A moderate negative correlation was found between VAS and three dimensions of SF-36, namely Physical Functioning, Role-Physical and Role-Emotional. VAS was weakly and negatively correlated to Vitality and Mental Health. There was a good linear correlation between VAS and quality of life (QoL), pain score while there was a moderate linear correlation between VAS and the total sleep score. It was found that quality of life was not statistically significantly correlated to General Health and Social Functioning.	There is a relationship between pain, sleep quality and quality of life. Quality of sleep and life was found to decrease as the level of pain increased, and quality of life was affected negatively when the quality of sleep was poor. Applications towards resolving pain would have a positive effect on the quality of sleep and life.	
25944011	Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may develop after exposure to a life-threatening trauma. As veterans and armed forces may deal with diverse health problems compared with civilians, they have a greater risk for psychiatric disorders, including PTSD, than civilians, even if the disorder may be also frequent in the general population. PTSD is associated with significant comorbidity, especially with mood disorders and substance abuse. Moreover, the suicide risk is higher in PTSD patients than in the general population. Selective Serotonin Reuptake Inhibitors (SSRIs), atypical antipsychotics and benzodiazepines are commonly employed in the management of PTSD, but often these treatments fail or are discontinued due to adverse effects. It has been demonstrated that high noradrenergic activity may be associated with hyperarousal, trauma nightmares and sleep disturbances in PTSD subjects, probably through the stimulation of α -1 adrenergic receptors in the brain prefrontal cortex. The α -1 adrenoreceptor antagonist prazosin decreases noradrenaline effects at brain α-1 adrenoreceptors and may be a promising agent in the treatment of PTSD, as some studies have found it effective and well tolerated. Therefore, the present review is aimed to examine the role of noradrenergic system in the pathophysiology of PTSD. Moreover, we conducted a systematic review to evaluate the effectiveness and tolerability of prazosin in PTSD patients. Meta-analysis was used to combine data from multiple studies and better estimate the effect of prazosin on specific outcomes. We found prazosin to be significantly more efficacious than placebo in reducing distressing dreams in PTSD patients, even though our results should be interpreted with caution due to the small number of studies included in our quantitative synthesis. 
25941148	A 2011 study at one U.S. dental school found that patients were not routinely screened by dental students for obstructive sleep apnea and/or other related sleep disorders, nor were students being trained to screen. Consequently, the medical history questionnaire used in the clinic was updated to include five specific screening questions. The aim of this two-year follow-up study was to determine whether screening had improved at the school. A retrospective chart review of all patients (age 14-70+) in the third- and fourth-year dental clinics in 2012 and 2013 searched for "YES" responses to the five questions. Of 5,931 patients, 38% reported they snore or were told they snore. By age 50-59, their reports of snoring increased to 50%. About 5% reported incidents waking up choking. By age 50, between one-fifth and one-quarter indicated they woke up frequently during the night. One in six frequently felt overly tired during the daytime, often falling asleep. This problem was evenly reported by all age groups between ages 30 and 69. About half the patients reporting sleep problems also had hypertension and cardiovascular problems with an equal distribution between males and females. The results showed that updating the medical history form had dramatically improved screening for sleep-disordered breathing by these dental students. Though screening is neither a definitive diagnosis nor an attempt to distinguish among sleep disorders, the results correlate with national statistics. Screening is an important step to increase student awareness of this serious health trend as it prepares students to engage more constructively in its management and referral. 
25941141	According to the National Research Council, 70 million Americans chronically suffer from approximately 60 medically recognized sleep disorders. With most clinicians unaware of these disorders, many individuals remain undiagnosed. To effectively address this issue, health care professionals must work collaboratively to educate, identify, and treat patients with sleep disorders. However, medical and dental clinicians do not receive adequate education in sleep medicine. On the frontline regarding prevention and counseling, dental hygienists play an important role in patient education, screening, and management of sleep disorders. The aim of this study was to assess the amount of sleep medicine content in U.S. dental hygiene programs. An electronic survey was emailed to all 334 accredited U.S. dental hygiene programs. The 18-question survey assessed the sleep medicine content presented during the 2012-13 academic year. A total of 35.3% (n=118) of the programs responded. The mean number of hours devoted to sleep medicine in their curricula was 1.55 hours (SD=1.37). Although 69% (n=79) of the responding programs reported spending time on sleep bruxism (mean=1.38 hours, SD=0.85), only 28% (n=32) reported spending time on other topics such as snoring and obstructive sleep apnea (mean=1.39 hours, SD=0.72). These results suggest that sleep medicine is included in the majority of U.S. dental hygiene programs, but the content is limited and focused on sleep bruxism. This level of training is inadequate to prepare dental hygienists for their potential role in patient education, screening, and management of sleep-related breathing disorders. 
25938708	Although melatonin is increasingly used for sleep disturbances in children with neurodevelopmental disorders, evidence on effective dose and impact on specific types of sleep disturbance is limited.We assessed 45 children (35 males, mean age: 6.3 ± 1.7 years) with neurodevelopmental disorders (n = 29: intellectual disability; n = 9: autism spectrum disorder; n = 7: attention-deficit/hyperactivity disorder) and sleep disturbances, treated with melatonin (mean duration: 326 days) with doses increased according to response.	Thirty-eight percent of children responded to low (2.5-3 mg), 31% to medium (5-6 mg) and 9% to high doses (9-10 mg) of melatonin, with a significant increase in total hours of sleep/night, decreased sleep onset delay and decreased number of awakenings/night (all: p = 0.001), as measured with sleep diaries. No serious adverse events were reported.	Melatonin is generally effective and safe in children with neurodevelopmental conditions. Increasing above 6 mg/night adds further benefit only in a small percentage of children.	
25938536	Sleep disturbances regularly co-occur with clinical psychotic disorders and dimensions of psychotic-like experiences (PLEs). One possible explanation for this, which has yet to be tested, is that similar genetic or environmental influences underlie sleep disturbances and vulnerability to PLEs. We conducted a twin study to test this possibility in relation to sleep disturbances and six specific PLEs in adolescence in the general population. Approximately 5,000 16-year-old twin pairs completed the Pittsburgh Sleep Quality Index and Insomnia Severity Index. PLEs were assessed using the Specific PLEs Questionnaire, comprising five self-report subscales (Paranoia, Hallucinations, Cognitive Disorganization, Grandiosity, and Anhedonia) and one parent-report subscale (Negative Symptoms). The associations between these measures were tested using structural equation twin model fitting. Paranoia, Hallucinations, and Cognitive Disorganization displayed moderate and significant correlations with both sleep measures (0.32-.42), while Negative Symptoms, Anhedonia, and Grandiosity showed lower correlations (0.01-0.17). Genetic and environmental influences significantly overlapped across PLEs (Paranoia, Hallucinations, Cognitive Disorganization) and both types of sleep disturbance (mean genetic and nonshared environmental correlations = 0.54 and 0.24, respectively). These estimates reduced, yet remained significant, after controlling for negative affect. The association between PLEs with sleep disturbances in adolescence is partly due to genetic and environmental influences that are common to them both. These findings indicate that the known neurobiology of sleep disturbance may provide clues regarding the causes of PLEs in adolescence.
25936158	This paper reviews the sleep habit and sleep problems in Japanese women. Some nationwide surveys in Japan showed that average sleep duration of Japanese women has been decreasing in these years. Insomnia related with menopause, restless legs syndrome and sleep related breathing disorder are recognized in middle-aged women. Recent studies have provided evidence that these sleep disorders increase the occurrence of cardiovascular events or other comorbid physical disorders. It is important to promote health education on sleep hygiene and provide early interventions for insomnia.
25935315	To date, no study has investigated the effects of avalanches on survivor's health beyond the first years. The aim of this study was to examine long-term health status 16 years after exposure to avalanches using a matched cohort design. Mental health, sleep quality and somatic symptoms among avalanche survivors (n=286) and non-exposed controls (n=357) were examined. Results showed that 16% of survivors currently experience avalanche-specific PTSD symptoms (PDS score>14). In addition, survivors presented with increased risk of PTSD hyperarousal symptoms (>85th percentile) (aRR=1.83; 98.3% CI [1.23-2.74]); sleep-related problems (PSQI score>5) (aRR=1.34; 95% CI [1.05-1.70]); PTSD-related sleep disturbances (PSQI-A score≥4) (aRR=1.86; 95% CI [1.30-2.67]); musculoskeletal and nervous system problems (aRR 1.43; 99% CI 1.06-1.93) and gastrointestinal problems (aRR 2.16; 99% CI 1.21-3.86) compared to the unexposed group. Results highlight the need for treatment for long-term PTSD symptoms and sleep disruption in disaster communities. 
25934608	Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features. 
25934538	Hypertension and inflammation may contribute to the increased risk of cardiovascular disease in individuals with suboptimal sleep, but large prospective studies are lacking. This study tested whether sleep duration and disturbance were predictive of incident hypertension and inflammation four years later.Participants were men and women aged 50 years and older from the English Longitudinal Study of Ageing. Sleep was assessed by self-report, incident hypertension (N = 3068) was defined by clinical examination and C-reactive protein and fibrinogen (N = 3768) were measures of inflammation.	Both men (odds ratio, OR:1.73, confidence interval, C.I. 1.08-2.76) and women (OR: 1.44, C.I. 1.00-2.07) reporting short sleep at baseline had increased odds of incident hypertension 4 years later, after adjustment for covariates. Age-stratified analyses revealed that short sleep was predictive of incident hypertension in men (OR: 2.27, C.I. 1.01-5.11) and women (OR: 2.10, C.I. 1.08-4.09) younger than 60 years but not in older people. Disturbed sleep also predicted incident hypertension in men (OR: 1.20, C.I. 1.02-1.41). In women, disturbed sleep was associated with elevated C-reactive protein (B = 0.030, C.I. 0.00-0.06) and fibrinogen (B = 0.030, C.I. 0.01-0.05) at follow-up controlling for baseline inflammation and other covariates. Sleep duration was unrelated to inflammatory markers in either sex.	This study of older men and women adds to growing evidence that aberrant sleep patterns may increase the risk of cardiovascular outcomes through its adverse impact on blood pressure and inflammation.	
25934527	To explore the interactions of sleep quality and sleep duration on the development of type 2 diabetes mellitus (DM2) in Chinese adults.We randomly selected 11,842 Chinese subjects from the Xuzhou community of China and obtained self-reported quality and duration of sleep by questionnaire. DM2 was assessed by fasting blood glucose. Sleep quality was categorized as good, common, or poor. Sleep duration was measured by average hours of sleep per night. We evaluated interaction, relative excess risk of interaction (RERI), the attributable proportion (AP), and the synergy index (S) using a logistic regression model.	The relative risk for the development of DM2 was higher in subjects with short sleep duration (1.67 [1.34-2.16]) or poor sleep quality (1.91 [1.31-2.74]) or long sleep duration (1.45 [1.02-1.77]). DM2 occurred more frequently with poor sleep quality combined with short sleep duration (odds ratio: 6.21; 95% confidence interval (CI): 2.78-11.81). RERI, AP, and S values (and their 95% CI) were 3.99 (1.41-7.76), 0.64 (0.45-0.76), and 5.15 (3.74-7.89) for the interaction between poor sleep quality and short sleep duration. In subjects with poor sleep quality combined with long sleep duration, the RERI, AP, and S values (and 95% CI) were 0.13 (-0.19 to 0.66), 0.07 (-0.35 to 0.18), and 1.19 (0.85-2.11).	Interactions between poor sleep quality and short sleep duration were additive. Preventive measures should focus on short sleep duration and poor sleep quality.	
25931180	To investigate the effect of sleep disturbances on functional and social outcomes after mild traumatic brain injury.Outpatient traumatic brain injury clinic in a tertiary trauma center.	A total of 374 mild traumatic brain injury patients were assessed within 3 months of injury and followed up every 3 months for 1 year.	Analysis of a historical cohort in a naturalistic clinical setting.	At each visit, symptoms of concussion and psychological distress and indices of functional and social outcomes were measured with the Rivermead Postconcussion Questionnaire, 28-item General Health Questionnaire, and Rivermead Head Injury Follow-up Questionnaire, respectively. Changes in outcome scores over time were explored using repeated measures analysis of variance and compared between subjects with persistent (SD) and recovered (SR) sleep disturbances. Predictors of functional/social outcome were determined using linear regression.	The percentages of subjects reporting sleep disturbances at each time point were 71.9%, 57.2%, 55.1%, and 53.7%, respectively. For functional and social outcomes, significant effects of time (F3,315 = 9.54; P < .001), group (SD vs SR) F1,317 = 5.32; P = .022, and time X group interaction F3,315 = 4.14; P = .007 were found. Persistent sleep disturbance (P = 0.011) and higher symptom burden at 6 months postinjury (P < .0001) were independent predictors of poorer outcome.	Sleep disturbance, independent of psychological distress, is an important prognostic factor of functional and social outcomes after mild traumatic brain injury.	

25930074	We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02-1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM. 

25925983	To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls.Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains.	Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures-University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory-effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89-0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI: 0.89-0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI: 0.86-0.95).	Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls.	
25924933	The Veterans Health Administration (VHA) represents one of the largest integrated health-care systems in the country. In 2012, the Veterans Affairs Sleep Network (VASN) sought to identify available sleep resources at VA medical centers (VAMCs) across the country through a national sleep inventory.The sleep inventory was administered at the annual 2012 VA Sleep Practitioners meeting and by email to sleep contacts at each VAMC. National prosthetics contacts were used to identify personnel at VAMCs without established sleep programs. Follow-up emails and telephone calls were made through March 2013.	One hundred eleven VA medical centers were included for analysis. Thirty-nine programs did not respond, and 10 were considered "satellites," referring all sleep services to a larger neighboring VAMC. Sleep programs were stratified based on extent of services offered (i.e., in-lab and home testing, sleep specialty clinics, cognitive behavioral therapy for insomnia (CBT-i)): 28 % were complex sleep programs (CSPs), 46 % were intermediate (ISPs), 9 % were standard (SSPs), and 17 % offered no formal sleep services. Overall, 138,175 clinic visits and 90,904 sleep testing encounters were provided in fiscal year 2011 by 112.1 physicians and clinical psychologists, 100.4 sleep technologists, and 115.3 respiratory therapists. More than half of all programs had home testing and CBT-i programs, and 26 % utilized sleep telehealth.	The 2012 VA sleep inventory suggests considerable variability in sleep services within the VA. Demand for sleep services is high, with programs using home testing, sleep telehealth, and a growing number of mid-level providers to improve access to care.	
25923855	Principal components analysis applied to the Delirium Rating Scale-Revised-98 contributes to understanding the delirium construct. Using a multisite pooled international delirium database, the authors applied confirmatory factor analysis to Delirium Rating Scale-Revised-98 scores from 859 adult patients evaluated by delirium experts (delirium, N=516; nondelirium, N=343). Confirmatory factor analysis found all diagnostic features and core symptoms (cognitive, language, thought process, sleep-wake cycle, motor retardation), except motor agitation, loaded onto factor 1. Motor agitation loaded onto factor 2 with noncore symptoms (delusions, affective lability, and perceptual disturbances). Factor 1 loading supports delirium as a single construct, but when accompanied by psychosis, motor agitation's role may not be solely as a circadian activity indicator. 
25921948	Our previous study reported that a dried bonito broth known in Japan as 'dashi' improved or ameliorated mood states, including fatigue, during the daily lives of human subjects. Histidine is an amino acid that is present in dried bonito broth, and we sought to evaluate whether histidine would affect feelings of fatigue in humans. We investigated the effects of histidine intake on the feeling of fatigue, mood states and mental task performance by performing a placebo-controlled, double-blind crossover trial. Twenty subjects with high fatigue and sleep disruption scores were asked to ingest histidine or a placebo every day for two weeks. The subjects' mood states were evaluated using the Profile of Mood States (POMS) scale and a visual analog scale (VAS) for eight feelings (fatigue, depression, carelessness, drowsiness, clear thinking, motivation, attentiveness and concentration). We also measured subjects' cognitive performance using the CogHealth test battery. The fatigue T-scores on the POMS test decreased significantly following histidine ingestion compared to placebo ingestion (p<0.05). After two weeks of histidine ingestion, the reaction time for the working memory task in the CogHealth test battery was significantly shorten compared to placebo ingestion. The VAS scores for clear thinking and for attentiveness were increased significantly following histidine ingestion compared to placebo ingestion (p<0.05). These results suggest that daily ingestion of histidine may ameliorate feelings of fatigue, increase performance during working memory tasks, and improve the clear thinking and attentiveness. 

25918987	This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families. 
25917940	To examine the reliability and validity of a modified Chinese version of the uraemic pruritus scale for measurement of different degrees of itching, as well as to identify the predictors for the severity of uraemic pruritus among long-term dialysis patients.Long-term dialysis patients (n = 110) were recruited for a cross-sectional study from a medical centre in Taiwan. A modified Chinese version of the uraemic pruritus scale was used to evaluate sleep disturbance and the severity, frequency and distribution of itching. Reliability was evaluated using item-total correlations, Cronbach's α, and intra-class correlation. Validity was evaluated by the content validity index, predictive and discriminative validity. Multiple linear regression was used on the predictors for the severity of uraemic pruritus.	After optimization for reliability, the scale retained seven items. The Cronbach's α was 0.86, and the results showed that the scale had predictive and discriminative validity. High intact-parathyroid hormone and creatinine clearance rate were important predictors for the severity of uraemic pruritus. The severity of uraemic pruritus was the important predictor for the sleeping disturbance.	The modified uraemic pruritus scale can discriminate between patients with a total pruritus score of ≥11 and those with a score of 0 points. The modified Chinese scale is a useful tool for clinically assessing the various degrees of itching among long-term dialysis patients. Our study validates that it could apply to clinical practice in assessment of uraemic pruritus.	
25917816	The primary purpose of this study was to establish the feasibility of a couple-based Vivekananda Yoga (VKC) intervention in lung cancer patients and caregivers. Secondly, we examined preliminary efficacy regarding quality of life (QOL) outcomes.In this single-arm feasibility trial, patients with lung cancer undergoing radiotherapy and their caregivers participated in a 15-session VKC program that focused on the interconnectedness of the dyad. We assessed pre-and post-intervention levels of fatigue, sleep disturbances, psychological distress, overall QOL, spirituality, and relational closeness. We tracked feasibility data, and participants completed program evaluations.	We approached 28 eligible dyads of which 15 (53%) consented and 9 (60%) completed the intervention. Patients (mean age = 73 years, 63% female, all stage III) and caregivers (mean age = 62 years, 38% female, 63% spouses) completed a mean of 10 sessions and 95.5% of them rated the program as very useful. Paired t tests revealed a significant increase in patients' mental health (d = 0.84; P = .04) and a significant decrease in caregivers' sleep disturbances (d = 1.44; P = .02). Although not statistically significant, for patients, effect sizes for change scores were medium for benefit finding and small for distress (d = 0.65 and 0.37, respectively). For caregivers, medium effects were found for improvement in physical functioning (d = 0.50).	This novel supportive care program appears to be safe, feasible, acceptable, and subjectively useful for lung cancer patients and their caregivers and lends support for further study.	
25917768	To determine if several multisystem comorbid conditions occur more frequently in subjects with tilt-table defined postural tachycardia syndrome (POTS) compared with those without.Retrospective chart review of 67 subjects aged 6-24 years, referred to a tertiary care neurogastroenterology and autonomic disorders clinic for a constellation of functional gastrointestinal, chronic pain, and autonomic complaints. All patients underwent formal autonomic testing, Beighton scores assessment for joint hypermobility (0-9), and fibromyalgia tender points (0-18) (43 subjects).	Twenty-five subjects (37%) met tilt table criteria for POTS. The median age of 16 years (range, 12-24 years) in the POTS group differed from 15 years (range, 6-21 years) in the no-POTS group (P = .03). Comorbidities including chronic fatigue, sleep disturbances, dizziness, syncope, migraines, functional gastrointestinal disorders, chronic nausea, fibromyalgia, and joint hypermobility did not differ between groups. All subjects with fibromyalgia by tender point-examination had a Beighton score ≥ 4 (P = .002).	Comorbid conditions are equally prevalent in children and young adults with and without tilt-table defined POTS, suggesting that POTS itself is not a cause of the other comorbidities. Instead, POTS likely reflects another comorbid condition in children with functional disorders. Dizziness and syncope, classically associated with POTS, are not predictive of a diagnosis of POTS by tilt table, a test that is still required for formal diagnosis. These results suggest a paradigm shift in the concept of POTS as the physiological basis of many functional symptoms.	
25915171	Sleep problems exert a negative impact on youths and their families. Parent and child mental health represent 2 posited, yet understudied, risk factors for sleep problems in youths. As such, this study sought to examine the role that parental psychopathology may play in mediating the relationship between child anxiety and sleep problems utilizing Internet sampling procedures.Parents (n = 83; 90.4% female) answered questions about their own mental health, and about their child's (n = 83; 77.1% female) anxiety and sleep.	Analyses found that parent anxiety and stress mediated the relationship between child anxiety and sleep problems.	This is the first study to examine the joint roles of parent psychopathology and child anxiety in explaining sleep problems in youths. Limitations notwithstanding, these results suggest that both parent- and child-level variables are important for developing a more comprehensive understanding of child sleep problems. Future areas of research are discussed.	

25913575	Patients suffering from narcolepsy type 1 show altered skin temperatures, resembling the profile that is related to sleep onset in healthy controls. The aim of the present study is to investigate the effects of sodium oxybate, a widely used drug to treat narcolepsy, on the 24-h profiles of temperature and sleep-wakefulness in patients with narcolepsy and controls. Eight hypocretin-deficient male narcolepsy type 1 patients and eight healthy matched controls underwent temperature measurement of core body and proximal and distal skin twice, and the sleep-wake state for 24 h. After the baseline assessment, 2 × 3 g of sodium oxybate was administered for 5 nights, immediately followed by the second assessment. At baseline, daytime core body temperature and proximal skin temperature were significantly lower in patients with narcolepsy (core: 36.8 ± 0.05 °C versus 37.0 ± 0.05 °C, F = 8.31, P = 0.01; proximal: 33.4 ± 0.26 °C versus 34.3 ± 0.26 °C, F = 5.66, P = 0.03). In patients, sodium oxybate administration increased proximal skin temperature during the day (F = 6.46, P = 0.04) to a level similar as in controls, but did not affect core body temperature, distal temperature or distal-proximal temperature gradient. Sodium oxybate administration normalised the predictive value of distal skin temperature and distal-proximal temperature gradient for the onset of daytime naps (P < 0.01). In conclusion, sodium oxybate administration resulted in a partial normalisation of the skin temperature profile, by increasing daytime proximal skin temperature, and by strengthening the known relationship between skin temperature and daytime sleep propensity. These changes seem to be related to the clinical improvement induced by sodium oxybate treatment. A causal relationship is not proven. 
25913551	Since 1972, the World Health Organization (WHO) has declared noise as a pollutant. Over the last decades, the quality of the urban environment has attracted the interest of researchers due to the growing urban sprawl, especially in developing countries. The objective of this study was to evaluate the effects of noise exposure in six urban soundscapes: Areas with high and low levels of noise in scenarios of leisure, work, and home. Cross-sectional study. The study was conducted in two steps: Evaluation of noise levels, with the development of noise maps, and health related inquiries. 180 individuals were interviewed, being 60 in each scenario, divided into 30 exposed to high level of noise and 30 to low level. Chi-Square test and Ordered Logistic Regression Model (P < 0,005). 70% of the interviewees reported noticing some source of noise in the selected scenarios and it was observed an association between exposure and perception of some source of noise (P < 0.001). 41.7% of the interviewees reported some degree of annoyance, being that this was associated with exposure (P < 0.001). There was also an association between exposure in different scenarios and reports of poor quality of sleep (P < 0.001). In the scenarios of work and home, the chance of reporting annoyance increased when compared with the scenario of leisure. We conclude that the use of this sort of assessment may clarify the relationship between urban noise exposure and health. 
25912597	Poor sleep is common among patients with medical disorders. Sleep disturbances can be a cause of fatigue and poor quality of life for patients suffering from sarcoidosis. Studies on subjective sleep quality or prevalence of insomnia have not been reported so far.The aim of this study was to investigate the subjectively reported sleep quality and its relation to psychological and physical factors in sarcoidosis patients.	1197 patients from Germany diagnosed with sarcoidosis were examined using the Pittsburgh Sleep Quality Index (PSQI), the Medical Research Council (MRC) dyspnea scale, the Hospital Anxiety and Depression Scale (HADS) and the Multidimensional Fatigue Inventory (MFI).	802 patients (67%) had PSQI global scores >5, indicating subjectively poor quality of sleep. The mean PSQI score was 7.79 ± 4.00. Women reported a significantly inferior individual quality of sleep than men. The subjective quality of sleep was lowered significantly with increasing dyspnea for men and women. 294 patients (25%) had PSQI global scores >10 usually found in patients with clinically relevant insomnia. In this group 86% had high values for fatigue, 69% for anxiety, and 59% for depression. The prevalence of known sleep apnea was 8.7% and 15.7% for restless legs.	Poor subjective sleep quality in sarcoidosis patients is about twice as common as in the general population and is associated with fatigue, anxiety, depression and dyspnea. Questions about sleep complaints should therefore be included in the management of sarcoidosis.	
25912293	Bipolar disorder (BD) and cluster headache (CH) are distinct conditions with important similarities such as a temporal pattern of disturbances, dysregulation of the sleep-wake cycle, and response to lithium treatment in a proportion of patients. Aiming to identify common transcription signatures in these two disorders, we carried out an exploratory microarray gene expression analysis in lymphoblasts from 8 CH and 10 BD I patients selected for positive response to lithium and 10 healthy controls (CO). Gene expression levels of BD and CH were compared with CO to create two lists of differentially expressed genes. We then matched the two lists and focus on genes showing statistically significant difference and same change direction in both disorders. RNA binding motif protein 3 (RBM3) was the most significantly altered gene in the list (3.17 × 10(-13) in BD, 9.44 × 10(-14) in CH). Pathway analysis identified protein processing in endoplasmic reticulum as the most significantly enriched. For validation with quantitative reverse transcription PCR (qRT-PCR) using the same samples, we selected seven genes. Among these, we were able to validate the RBM3, nuclear receptor subfamily 1, group D, member 1 (NR1D1), and tryptophan hydroxylase 1 (TPH1). These genes encode for elements involved in circadian rhythm regulation (RBM3 and NR1D1) and in serotonin synthesis (TPH1), processes previously involved in both disorders, and in the mechanism of action of lithium.
25912096	Previous studies demonstrated conflicting results about the association of sleep duration and hypertension. Given the potential relationship between sleep quality and hypertension, this study aimed to investigate the interaction of self-reported sleep duration and sleep quality on hypertension prevalence in adult Chinese males.We undertook a cross-sectional analysis of 4144 male subjects. Sleep duration were measured by self-reported average sleep time during the past month. Sleep quality was evaluated using the standard Pittsburgh Sleep Quality Index. Hypertension was defined as blood pressure level ≥140/90 mm Hg or current antihypertensive treatment. The association between hypertension prevalence, sleep duration, and sleep quality was analyzed using logistic regression after adjusting for basic cardiovascular characteristics.	Sleep duration shorter than 8 hours was found to be associated with increased hypertension, with odds ratios and 95% confidence intervals (CIs) of 1.25 (95% CI, 1.03-1.52) for 7 hours, 1.41 (95% CI, 1.14-1.73) for 6 hours, and 2.38 (95% CI, 1.81-3.11) for <6 hours. Using very good sleep quality as the reference, good, poor, and very poor sleep quality were associated with hypertension, with odds ratios of 1.20 (95% CI, 1.01-1.42), 1.67 (95% CI, 1.32-2.11), and 2.32 (95% CI, 1.67-3.21), respectively. More importantly, further investigation of the association of different combinations of sleep duration and quality in relation to hypertension indicated an additive interaction.	There is an additive interaction of poor sleep quality and short sleep duration on hypertension prevalence. More comprehensive measurement of sleep should be performed in future studies.	
25908646	Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas under field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlations between clinical observations and melatonin secretion, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions depend also on the melatonin signal, for instance immune, antioxidant defences, haemostasis and glucose regulation. The difference between physiological and pharmacological effects of melatonin is not always clear but is based upon consideration of dose and not of duration of the hormone message. It is admitted that a "physiological" dose provides plasma melatonin levels in the same order of magnitude as a nocturnal peak. Since the regulating system of melatonin secretion is complex, following central and autonomic pathways, there are many pathophysiological situations where melatonin secretion can be disturbed. The resulting alteration could increase the predisposition to disease, add to the severity of symptoms or modify the course and outcome of the disorder. Since melatonin receptors display a very wide distribution in the body, putative therapeutic indications of this compound are multiple. Great advances in this field could be achieved by developing multicentre trials in a large series of patients, in order to establish efficacy of melatonin and absence of long-term toxicity. 
25907704	Fibromyalgia is a common cause of chronic widespread pain, characterized by reduced pressure pain thresholds with hyperalgesia and allodynia. In addition to pain, common symptoms include nonrestorative sleep, fatigue, cognitive dysfunction, stiffness and mood disturbances. The latest research indicates that the dominant pathophysiology in fibromyalgia is abnormal pain processing and central sensitization. Neuroimaging studies have shown that patients with fibromyalgia have similar neural activation to healthy age-matched and gender-matched individuals; however, they have a lower pressure-pain threshold. Polysomnography data has demonstrated that these patients have reduced short-wave sleep and abnormal α-rhythms, suggestive of wakefulness during non-REM (rapid eye movement) sleep. Sleep deprivation in healthy individuals can cause symptoms of fibromyalgia, including myalgia, tenderness and fatigue, suggesting that sleep dysfunction might be not only a consequence of pain, but also pathogenic. Epidemiological studies indicate that poor sleep quality is a risk factor for the development of chronic widespread pain among an otherwise healthy population. Mechanistically, sleep deprivation impairs descending pain-inhibition pathways that are important in controlling and coping with pain. Clinical trials of pharmacological and nonpharmacological therapies have shown that improving sleep quality can reduce pain and fatigue, further supporting the hypothesis that sleep dysfunction is a pathogenic stimulus of fibromyalgia. 
25905723	Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four 'disability-specific' genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure, transcription or translation). We suggest that these patterns of gene expression lead to either the expression of disability, or to resilience and recovery, by modifying local spinal circuitry at the origin of ascending supraspinal pathways. 
25905530	To use the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II and additional pain-related and psychosocial variables to identify subtypes of TMD patients in a primary health care setting based on pain-related disability.Consecutive TMD pain patients (n = 399) seeking treatment in a primary care setting completed a multidimensional pain questionnaire. Subtyping was based on the Graded Chronic Pain Scale (GCPS), and the patients were divided into a no-disability group (0 disability points), lowdisability group (1-2 disability points), and high-disability group (3-6 disability points). Psychosocial variables included RDC/TMD Axis II variables, anxiety, tension and stress, worry, catastrophizing, coping ability, general health, and other pain problems. Subtype differences were analyzed with t test, Wilcoxon rank-sum test, ANOVA, or Kruskal-Wallis test. A further analysis with multivariable logistic model was applied. All P values from pairwise comparisons were Bonferroni adjusted.	Most (61%) of the patients belonged to the no-disability group, 27% to the low-disability group, and 12% to the high-disability group. When subtypes were compared, patients in the no-disability group appeared psychosocially well-functioning, with fewer symptoms related to psychosocial distress, better ability to control pain, and fewer jaw functional limitations and other pain problems. Patients in the high-disability group reported the highest levels of symptoms of depression and somatization, sleep dysfunction, worry, and catastrophizing thoughts. The low-disability patients formed an intermediate group between the no-disability and high-disability groups.	The results suggest that GCPS-related disability scoring can be used as a simple screening instrument in primary care settings to identify individuals with different, clinically relevant psychosocial subtypes.	
25905349	In mammals and man, historical investigation suggests that early recognition for a role of the hypothalamus as a site for integration of endocrine, autonomic and behavioral responses can be dated to the 2nd -18th centuries A.D. Although the hypothalamus comprises only 2% of the total brain volume, it is a key regulator of pituitary function and homeostatic balance. In this chapter, we provide an overview of the historical landmarks, embryologic, gross, microscopic and functional anatomy of the mammalian and human hypothalamus and pituitary, and how the hypothalamus relates to the rest of the brain and responds to peripheral signals. In particular, we show that its rostral, nuclear portion exerts prominent regulation of homeostatic behaviors related to energy balance and reproduction. The two caudal portions are primarily involved in ensuring adequate metabolic resources for defensive and exploratory behaviors and responses to sudden changes in endogenous and exogenous stimuli. In addition, we discuss how its network of neurons is made of cells with different functions (neurosecretory, autonomic, motor), how they interact, and how these neural circuitries are woven into a complex architecture of conduits for the movement of intercellular fluids (vasculature, glymphatic channels, meningeal lymphatic vessels). Finally, we focus on the hypothalamic mechanisms involved in the regulation of anterior and posterior pituitary secretion (hypothalamic tuberoinfundibular and neurohypophysial systems), as well those involved in food and fluid intake, lactation, thermoregulation, circadian rhythmicity and the sleep-wake cycle. For complete coverage of all related areas of Endocrinology, please see our online FREE web-book, www.endotext.org.
25903199	We describe a case of a 48-year-old woman who underwent a resection of a tectal pilocytic astrocytoma complicated by a sequence of fluctuating consciousness, psychosis with complex hallucinations and lasting sleeping disturbances in which she vividly acts out her dreams. Based on the clinical and anatomical evidence of this case, we propose the term locus coeruleus syndrome to describe this association of iatrogenic symptoms. Along with those of the locus coeruleus, lesions of the dorsal raphe nucleus, ventral tegmentum, substantia nigra pars compacta, the superior colliculus and other peduncular lesions (such as peduncular hallucinosis) are involved in the regulation of sleep-wake/arousal, behaviour, sleeping disorders and rapid eye movement atonia. However, iatrogenic lesion of the locus coeruleus could explain the complications on all levels in our patient. 
25902831	Although in the past decade occidental countries have increasingly recognized the personal and societal burden of migraine, it remains poorly understood in Africa. No study has evaluated the impact of sleep disturbances and the quality of life (QOL) in sub-Saharan Africans with migraine.This was a cross-sectional study evaluating adults, ≥ 18 years of age, attending outpatient clinics in Ethiopia. Standardized questionnaires were utilized to collect demographic, headache, sleep, lifestyle, and QOL characteristics in all participants. Migraine classification was based on International Classification of Headache Disorders (ICHD)-II criteria. The Pittsburgh Sleep Quality Index (PSQI) and the World Health Organization Quality of Life (WHOQOL-BREF) questionnaires were utilized to assess sleep quality and QOL characteristics, respectively. Multivariable logistic regression models were fit to estimate adjusted odds ratio (OR) and 95% confidence intervals (95% CI).	Of 1,060 participants, 145 (14%) met ICHD-II criteria for migraine. Approximately three-fifth of the study participants (60.5%) were found to have poor sleep quality. After adjustments, migraineurs had over a two-fold increased odds (OR = 2.24, 95% CI 1.49-3.38) of overall poor sleep quality (PSQI global score >5) as compared with non-migraineurs. Compared with non-migraineurs, migraineurs were also more likely to experience short sleep duration (≤7 hours) (OR = 2.07, 95% CI 1.43-3.00), long sleep latency (≥30 min) (OR = 1.97, 95% CI 1.36-2.85), daytime dysfunction due to sleepiness (OR = 1.51, 95% CI 1.12-2.02), and poor sleep efficiency (<85%) (OR = 1.93, 95% CI 1.31-2.88). Similar to occidental countries, Ethiopian migraineurs reported a reduced QOL as compared to non-migraineurs. Specifically Ethiopian migraineurs were more likely to experience poor physical (OR = 1.56, 95% CI 1.08-2.25) and psychological health (OR = 1.75, 95% CI 1.20-2.56), as well as poor social relationships (OR = 1.56, 95% CI 1.08-2.25), and living environments (OR = 1.41, 95% CI 0.97-2.05) as compared to those without migraine.	Similar to occidental countries, migraine is highly prevalent among Ethiopians and is associated with poor sleep quality and a lower QOL. These findings support the need for physicians and policy makers to take action to improve the quality of headache care and access to treatment in Ethiopia.	
25902807	Sleepwalking is a disorder characterized by arousal specifically from slow wave sleep with dissociated brain activity that may be related to lower nociceptive state. Our objectives were to assess the frequency of chronic pain, headache, and migraine in sleepwalkers compared to controls, examine the impact and determinants of pain in sleepwalkers, and report analgesia frequency during injurious parasomnia episodes.Cross-sectional case-control study.	Data were collected at the Sleep Disorders Center, Montpellier, France.	One hundred patients with sleepwalking were assessed for disease characteristics, sleep (polysomnography, sleepiness, and insomnia), pain (chronic pain, multidimensional pain inventory, headache, and migraine), depressive symptoms, and quality of life compared to 100 adult controls. Pain perception was retrospectively assessed during injurious parasomnia episodes.	Raw association data showed that lifetime headache, migraine, and chronic pain at time of study were significantly associated with sleepwalking (also called somnambulism). Compared to controls, sleepwalkers reported more frequent daytime sleepiness, and depressive and insomnia symptoms. After adjustments, sleepwalking was associated with increased risk for headache and migraine only. Compared to pain-free sleepwalkers, sleepwalkers with chronic pain were more likely to be older and to have greater daytime sleepiness, insomnia, and depressive symptoms, with no difference in polysomnography assessment. Of the 47 sleepwalkers with at least one previous violent parasomnia episode, 78.7% perceived no pain during episodes, allowing them to remain asleep despite injury.	Our results highlight the clinical enigma of pain in sleepwalking patients with complaints of frequent chronic pain, migraine, and headache during wakefulness but who report retrospectively experience of analgesia during severe parasomnia episodes, suggesting a relationship between dissociated brain activity and nociceptive dysregulation.	
25898321	Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness. 
25896523	A novel line of research has emerged, suggesting that daily feeding-fasting schedules that are synchronized with sleep-wake cycles have metabolic implications that are highly relevant to breast cancer. We examined associations of nighttime fasting duration with biomarkers of breast cancer risk among women in the 2009-2010 U.S. National Health and Nutrition Examination Survey.Dietary, anthropometric, and HbA1c data were available for 2,212 women, and 2-hour postprandial glucose concentrations were available for 1,066 women. Nighttime fasting duration was calculated using 24-hour food records. Separate linear regression models examined associations of nighttime fasting with HbA1c and 2-hour glucose concentrations. Logistic regression modeled associations of nighttime fasting with elevated HbA1c (HbA1c ≥ 39 mmol/mol or 5.7%) and elevated 2-hour glucose (glucose ≥ 140 mg/dL). All models adjusted for age, education, race/ethnicity, body mass index, total kcal intake, evening kcal intake, and the number of eating episodes per day.	Each 3-hour increase in nighttime fasting (roughly 1 SD) was associated with a 4% lower 2-hour glucose measurement [β, 0.96; 95% confidence interval (CI), 0.93-1.00; P < 0.05], and a nonstatistically significant decrease in HbA1c. Logistic regression models indicate that each 3-hour increase in nighttime fasting duration was associated with roughly a 20% reduced odds of elevated HbA1c (OR, 0.81; 95% CI, 0.68-0.97; P < 0.05) and nonsignificantly reduced odds of elevated 2-hour glucose.	A longer nighttime duration was significantly associated with improved glycemic regulation.	Randomized trials are needed to confirm whether prolonged nighttime fasting could improve biomarkers of glucose control, thereby reducing breast cancer risk.	
25896348	This is a cross-sectional survey.The objective of this study was to evaluate the subjective sleep disturbances and quality of life in chronic tetraplegia.	This study was conducted in a community sample from Victoria, Australia.	People with tetraplegia were mailed a survey battery including the following: demographic questions; Karolinska Sleepiness Scale (KSS); Basic Nordic Sleepiness Questionnaire; Functional Outcomes of Sleep Questionnaire (FOSQ); Multivariate Apnoea Prediction Index and Assessment of Quality of Life (AQoL) Questionnaire. Scores were compared with the best available normative data.	A total of 163 of 424 (38%) surveys were returned (77% male; 39% sensory and motor complete; mean age±s.d.=46±14 years; mean years since injury=11±8 years). The AQoL health utility score (0.31±0.29) was significantly lower than published population norms. FOSQ total (17.55±2.57) and KSS (3.93±2.27) scores were no different from the best available population data. People with tetraplegia reported worse sleep habits, symptoms and quality than a normal population, as indicated on 17 of 21 questions on the Basic Nordic Sleep Questionnaire. Multivariate analysis found that greater injury severity (coefficient (95% CI)=0.14 (0.10, 0.18)), increasing age (-0.004 (-0.008, -0.001)) and worse sleep symptoms (-0.005 (-0.009, -0.0003)) were all significantly associated with reduced quality of life.	People with chronic tetraplegia experience more subjective sleep problems and worse quality of life than their able-bodied counterparts. Quality of life is related to injury severity, age and sleep symptoms. Treating the sleep disorders experienced by people living with tetraplegia has the potential to improve their health and well-being.	
25895933	Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.
25895575	Sleep disorders are a pervasive problem throughout all patient populations but represent an especially important health problem for the elderly. Alterations in sleep architecture that occur as a part of normal aging will contribute to sleep problems as we grow older. Other contributing factors-including comorbid medical conditions, changes in lifestyle and schedule, altered circadian rhythm, among a host of others-can have detrimental effects on the health of the elderly. Coupled with a number of sleep disorders that either emerge or exacerbate with age, the effects of poor sleep often result in an overall worsening of quality of life. Treatment options can be unique in this population and often more difficult due to the effects of normal aging, as well as polypharmacy and possible medication interactions. The following article will focus on the common sleep disorders that can besiege this population, symptoms to aid in diagnosis, and specific treatment options to help improve quality of life in the elderly. 
25894573	Conventional scoring of sleep provides little information about the process of transitioning between vigilance states. We applied the state space technique (SST) using frequency band ratios to follow normal maturation of different sleep/wake states, velocities of movements, and transitions between states of juvenile (postnatal day 34, P34) and young adult rats (P71).24-h sleep recordings of eight P34 and nine P71 were analyzed using conventional scoring criteria and SST one week following implantation of telemetric transmitter. SST is a non-categorical approach that allows novel quantitative and unbiased examination of vigilance-states dynamics and state transitions. In this approach, behavioral changes are described in a 2-dimensional state space that is derived from spectral characteristics of the electroencephalography.	With maturation sleep intensity declines, the duration of deep slow wave sleep (DSWS) and light slow wave sleep (LSWS) decreases and increases, respectively. Vigilance state determination, as a function of frequency, is not constant; there is a substantial shift to higher ratio 1 in all vigilance states except DSWS. Deep slow wave sleep decreases in adult relative to juvenile animals at all frequencies. P71 animals have 400% more trajectories from Wake to LSWS (p = 0.005) and vice versa (p = 0.005), and 100% more micro-arousals (p = 0.021), while trajectories from LSWS to DSWS (p = 0.047) and vice versa (p = 0.033) were reduced by 60%. In both juvenile and adult animals, no significant changes were found in sleep velocity at all regions of the 2-dimensional state space plot; suggesting that maturation has a partial effect on sleep stability.	Here, we present novel and original evidence that SST enables visualization of vigilance-state intensity, transitions, and velocities that were not evident by traditional scoring methods. These observations provide new perspectives in sleep state dynamics and highlight the usefulness of this technique in exploring the development of sleep-wake activity.	
25894359	Sleep disturbances are among the most commonly endorsed symptoms of post-traumatic stress disorder (PTSD). Treatment modalities that are effective for the waking symptoms of PTSD may have limited efficacy for post-traumatic sleep problems. The aim of this review is to summarize the evidence for empirically supported and/or utilized psychotherapeutic and pharmacological treatments for post-traumatic nightmares and insomnia. While there are few controlled studies of the applicability of general sleep-focused interventions to the management of the sleep disturbances in PTSD, evidence is growing to support several psychotherapeutic and pharmacological treatments. Future investigations should include trials that combine treatments focused on sleep with treatments effective in managing the waking symptoms of PTSD. 
25894326	Metabolic acidosis is a common feature in chronic renal failure patients, worsening progressively as renal function declines. There are conflicting data in hemodialysis (HD) patients with regard to acidosis, alkalosis and mortality. In HD patients, cognitive impairment, depression, sleep disorders and impaired quality of life are very common. Besides, these conditions are related with increased morbidity and mortality. However, no previous study investigated the relationship between pH, venous bicarbonate and anion gap with depression, sleep problems and cognitive function in HD patients. In this study we investigated these relationships. In total, 65 HD patients were included. The demographic parameters and laboratory parameters including bicarbonate, pH and anion gap was measured for all patients. Depressive symptoms, sleep quality and cognitive function, were measured by Beck depression inventory, The Pittsburgh Sleep Quality Index and by Mini Mental State Examination, respectively. We found that, sleep quality but not cognitive function or depression was independently related with venous pH and bicarbonate. Anion gap has no independent relationship with sleep quality, cognitive function and depression. In conclusion, metabolic acidosis and bicarbonate levels were independently related with sleep quality in HD patients. However, there was no association between metabolic acidosis and bicarbonate levels with cognitive function and depression. 
25892993	The objective of this review was to investigate the impact of shift and night work on metabolic processes and the role of alterations in the sleep-wake cycle and feeding times and environmental changes in the occurrence of metabolic disorders. The literature review was performed by searching three electronic databases for relevant studies published in the last 10 years. The methodological quality of each study was assessed, and best-evidence synthesis was applied to draw conclusions. The literature has shown changes in concentrations of melatonin, cortisol, ghrelin, and leptin among shift workers. Melatonin has been implicated for its role in the synthesis and action of insulin. The action of this hormone also regulates the expression of transporter glucose type 4 or triggers phosphorylation of the insulin receptor. Therefore, a reduction in melatonin can be associated with an increase in insulin resistance and a propensity for the development of diabetes. Moreover, shift work can negatively affect sleep and contribute to sedentarism, unhealthy eating habits, and stress. Recent studies on metabolic processes have increasingly revealed their complexity. Physiological changes induced in workers who invert their activity-rest cycle to fulfill work hours include disruptions in metabolic processes. 
25892375	Our study presents pain-related interference rates in a sample of community-dwelling, older adults and determines factors associated with these restrictions. Participants were 9506 respondents to the Biopsychosocial Religion and Health Study (66.8% female and 33.2% male; average age = 62.3 years). In this sample, 48.2% reported no pain-related interference, whereas 37.7% reported moderate and 14.1% reported severe interference. As hypothesized, older age, female gender, lower education, financial strain, traumatic experiences, worse health, increased body mass index, poor sleep, and depressive symptoms all were associated with higher pain interference ratings (ordered logistic regression/three-level pain criterion; odds ratios p < 0.05). Our findings are similar to those from younger adults, and they suggest enduring effects of trauma on health and reveal the complexity of chronic pain in community-dwelling, older adults. 
25891946	Sleep-wake disturbances (SWD) after traumatic brain injury (TBI) are frequently reported and can persist several years post-injury. The adult literature covering this topic is exhaustive; numerous robust studies using objective measures of sleep and advanced methodologies support the presence of SWD post-TBI. Despite being the leading cause of morbidity in children and adolescents, however, relatively few studies exist investigating SWD and symptoms of fatigue after pediatric TBI. We undertook a systematic search of the literature in PsycINFO, MEDLINE, CINAHL, and Web of Science databases with the aim of documenting persistent fatigue and SWD after pediatric TBI. Terms and keywords pertaining to TBI, children/adolescents, and sleep/fatigue were used, and of the 461 articles initially identified, 24 studies met our inclusion criteria. According to the results of the literature search, SWD and fatigue are common after pediatric TBI. The methodologies used in the studies reported varied widely, however, and were mainly subjective (e.g., questionnaires and interviews with caregivers). Moreover, no study targeted preschool children despite the fact that there is evidence regarding the critical importance of sleep for appropriate cognitive development, especially in high-order cognitive functioning. In sum, the results of the studies analyzed were consistent with the presence of SWD and fatigue after pediatric TBI, but there is a lack of information concerning this relationship in younger children. The use of more objective measures, such as actigraphy, could bring better insight to the impact of TBI on the quality of children's sleep. 
25891543	Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep-wake disorder.Three totally blind males (63.0 ± 7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48 h every 1-2 weeks. Participants completed daily sleep-wake logs, and rated their alertness and mood using nine-point scales every ~2-4 h while awake on urine sampling days. Caffeine capsules (150 mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period τ and compared to placebo (n = 2) or no treatment (n = 1) in a single-masked manner.	Non-24-h aMT6s rhythms were confirmed in all three participants (τ range = 24.32-24.57 h). Daily administration of 150 mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p <0.0001) but did not decrease the occurrence of daytime naps compared with placebo.	Although caffeine was able to improve daytime alertness acutely and may therefore provide temporary symptomatic relief, the inability of caffeine to correct the underlying circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep-Wake Disorder in the blind appropriately.	
25891358	Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet. 
25890785	We investigated effects of NREM and REM predominant sleep periods on sleepiness and psychomotor performances measured with visual analog scales and the psychomotor vigilance task, respectively. After one week of stable sleep-wake rhythms, 18 healthy sleepers slept 3hours of early sleep and 3hours of late sleep, under polysomnographic control, spaced by two hours of sustained wakefulness between sleep periods in a within subjects split-night, sleep interruption protocol. Power spectra analysis was applied for sleep EEG recordings and sleep phase-relative power proportions were computed for six different frequency bands (delta, theta, alpha, sigma, beta and gamma). Both sleep periods presented with similar sleep duration and efficiency. As expected, phasic NREM and REM predominances were obtained for early and late sleep conditions, respectively. Albeit revealing additive effects of total sleep duration, our results showed a systematic discrepancy between psychomotor performances and sleepiness levels. In addition, sleepiness remained stable throughout sustained wakefulness during both conditions, whereas psychomotor performances even decreased after the second sleep period. Disregarding exchanges for frequency bands in NREM or stability in REM, correlations between outcome measures and EEG power proportions further evidenced directional divergence with respect to sleepiness and psychomotor performances, respectively. Showing that the functional correlation pattern changed with respect to early and late sleep condition, the relationships between EEG power and subjective or behavioral outcomes might however essentially be related to total sleep duration rather than to the phasic predominance of REM or NREM sleep. 
25890781	The identification of biological markers that allow the early diagnosis, or even the prevention of age-related diseases, is an important goal that is being actively pursued in the research community. Sleep is one of the physiological processes that is most affected by aging, and there is a strong relationship between age-related sleep alterations and diseases. Changes in cellular senescence and the linked changes in telomere length might be potential markers of age-related sleep changes. In this review, we present some of the most recent evidence showing that telomere length has been associated with sleep loss and sleep disturbances in cross-sectional and case-control studies. We also present insights into the cellular senescence mechanisms relating to changes in telomere length, and we suggest that this field lacks basic and clinical research studies, especially long-term longitudinal studies, which may bring opportunities to sleep researchers to investigate this relationship in more depth. 
25889207	Efavirenz (EFV) therapeutic response and toxicity are associated with high inter-individual variability attributed to variation in its pharmacokinetics. Plasma concentrations below 1 μg/ml may result in virologic failure and above 4 μg/ml, may result in central nervous system adverse effects. This study used population pharmacokinetics modeling to explore the influence of demographic and pharmacogenetic factors including efavirenz-rifampicin interaction on EFV pharmacokinetics, towards safer dosing of EFV.Patients receiving an EFV-based regimen for their antiretroviral therapy and a rifampicin-containing anti-TB regimen were recruited. EFV plasma concentrations were measured by HPLC and genomic DNA genotyped for variants in the CYP2B6, CYP2A6 and ABCB1 genes. All patients were evaluated for central nervous system adverse effects characterised as sleep disorders, hallucinations and headaches using the WHO ADR grading system. A pharmacokinetic model was built in a forward and reverse procedure using nonlinear mixed effect modeling in NONMEM VI followed by model-based simulations for optimal doses.	CYP2B6*6 and *18 variant alleles, weight and sex were the most significant covariates explaining 55% of inter-individual variability in EFV clearance. Patients with the CYP2B6*6TT genotype had a 63% decrease in EFV clearance despite their CYP2B6*18 genotypes with females having 22% higher clearance compared to males. There was a 21% increase in clearance for every 10 kg increase in weight. The effect of TB/HIV co-treatment versus HIV treatment only was not statistically significant. No clinically relevant association between CYP2B6 genotypes and CNS adverse effects was seen, but patients with CNS adverse effects had a 27% lower clearance compared to those without. Model- based simulations indicated that all carriers of CYP2B6*6 TT genotype would be recommended a dose reduction to 200 mg/day, while the majority of extensive metabolisers may be given 400 mg/day and still maintain therapeutic levels.	This study showed that screening for CYP2B6 functional variants has a high predictability for efavirenz plasma levels and could be used in prescribing optimal and safe EFV doses.	
25889117	Particularly in Asia, dense, traffic-intense, and usually high-rise cities are increasingly the norm. Is existing knowledge on exposure to road traffic noise, and on people's response to such exposure, garnered primarily from western cities, equally applicable in these?Hong Kong has high population and traffic density and a high-rise building form. Road traffic noise exposure was estimated, and residents' responses to traffic noise measured, for a sample of 10,077 dwellings. Noise level estimates were based on three-dimensional modelling. Best international survey practice measured self-reported annoyance and sleep-disturbance. Benchmark estimates of exposure, and of annoyance and self-reported sleep disturbance, are provided. We compare Hong Kong exposure with those of European cities, and the exposure-response relationship for annoyance in Hong Kong to those reported from elsewhere - based on the tolerance limits of previous syntheses. Exposure-response for self-reported sleep disturbance is also compared.	The distribution of exposures of dwellings in high-rise, high-density, Hong Kong is different from those reported from Europe, but not at the higher noise levels. The exposure-annoyance relationship for road traffic noise was from the same population of exposure-response relationships, being well within the tolerance limits, of studies used to generate the synthesized Miedema and Oudshoorn curves. The exposure-response curve for self-reported sleep disturbance was parallel to that of Miedema and Vos but slightly lower.	The proportion of the Hong Kong population exposed to high levels (>70 dB) is similar to that found in Europe. However, a much higher proportion, compared to European cities, is exposed to Lden levels of 60-64 dB, and a much lower proportion to lower levels (<55 dB). There is no evidence that the exposure-response relationships for annoyance and self-reported sleep disturbance in Hong Kong are different from relationships synthesized from earlier studies - despite the western bias and temperate-climate bias in the studies available in the syntheses. This is an important finding for urban planning and traffic noise management of the growing mega-cities in the world whose built forms can be expected to reflect that of Hong Kong more than of cities in the west.	
25888026	Patients with precapillary pulmonary hypertension (PH) have been reported to suffer from poor sleep quality, however, if this is related to physical exercise performance has not yet been thoroughly investigated.Clinically stable out-patients with idiopathic pulmonary arterial hypertension (IPAH, n = 52) and chronic thromboembolic PH (CTEPH, n = 64) in NYHA classes II and III were prospectively enrolled. 54 healthy volunteers matched for anthropometric variables served as a control group. The Pittsburgh Sleep Quality Index (PSQI) was used to rate subjective sleep quality. In the PH patients, six-minute walk tests (6MWT) were performed to assess exercise capacity.	Poor sleep quality (i.e. a PSQI score > 5) occurred more frequently in PH (IPAH: n = 25 [48.1%], CTEPH: n = 39 [60.9%], controls: n = 10 [18.5%]; p < 0.01 when compared to controls). In addition, poor vs. good sleepers had significantly higher average NYHA class (IPAH: 2.6 ± 0.1 vs. 2.3 ± 0.1, CTEPH: 2.8 ± 0.1 vs. 2.3 ± 0.2; p < 0.01) and shorter 6MWT distances (IPAH: 338 ± 23 vs. 441 ± 29 m, CTEPH: 355 ± 15 vs. 413 ± 26 m; p < 0.05).	Self-reported poor sleep quality is more common in PH than in healthy controls. Furthermore, it is related to reduced physical exercise capacity.	

25886830	Posttraumatic stress disorder (PTSD) is associated with indicators of poor physical health and sleep disturbance. This study investigated the relationship between PTSD and metabolic risk factors and examined the role of sleep duration in medically healthy and medication-free adults.Participants with PTSD (n = 44, mean age = 30.6 years) and control participants free of lifetime psychiatric history (n = 50, mean age = 30.3 years) recorded sleep using sleep diary for 10 nights and actigraphy for 7 nights. We assessed metabolic risk factors including fasting triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol, as well as abdominal fat using dual-energy x-ray absorptiometry.	PTSD was associated with shorter sleep duration (based on self-report, not actigraphy) and higher metabolic risks (controlling for body fat percentage), including increased triglycerides (p = .03), total cholesterol (p < .001), LDL cholesterol (p = .006), very low density lipoprotein cholesterol (p = .002), and cholesterol/high-density lipoprotein ratio (p = .024). In addition, sleep duration was associated with metabolic risks in PTSD (significant correlations ranged from r = -0.20 to r = -0.40) but did not fully account for the association between PTSD and metabolic measures.	Metabolic risk factors are associated with PTSD even in early adulthood, which highlights the need for early intervention. Future longitudinal research should assess whether sleep disturbance in PTSD is a mechanism that contributes to heightened metabolic risk to elucidate the pathway from PTSD to higher rates of medical disorders such as obesity, diabetes, and heart disease.	
25885066	Sleep disturbance is bi-directionally related to mood de-stabilization in bipolar disorder (BD), and sleep quality differs in men and women. We aimed to determine whether perception of poor sleep quality would have a different effect on mood outcome in men versus women.We assessed association between sleep quality (Pittsburgh Sleep Quality Index (PSQI)) at study intake and mood outcome over 2 years in subjects from the Prechter Longitudinal Study of Bipolar Disorder (N=216; 29.6% males). The main outcome measure was the severity, variability, and frequency of mood episodes measured by self-report over 2 years of follow-up. Multivariable linear regression models stratified by sex examined the relationship between PSQI with mood outcomes, while age, stressful life events, mood state and neuroticism at baseline were controlled.	In women, poor sleep quality at baseline predicted increased severity (B=0.28, p<0.001) and frequency of episodes (B=0.32, p<0.001) of depression, and poor sleep quality was a stronger predictor than baseline depression; poor sleep quality predicted increased severity (B=0.19, p<0.05) and variability (B=0.20, p<0.05) of mania, and frequency of mixed episodes (B=0.27, p<0.01). In men, baseline depression and neuroticism were stronger predictors of mood outcome compared to poor sleep quality.	We measured perception of sleep quality, but not objective changes in sleep.	In a longitudinal study of BD, women reported poorer perceived sleep quality than men, and poor sleep quality predicted worse mood outcome in BD. Clinicians should be sensitive to addressing sleep complaints in women with BD early in treatment to improve outcome in BD.	
25884573	Illicit drug use/dependence has been recognized as a major problem. Clinical studies demonstrate that poor sleep quality is associated with increased frequency of drug use and relapse. However, few studies have addressed the issue of sleep quality among illicit drug dependent subjects.This cross-sectional study explored sleep quality in drug dependent subjects in China. We studied 2178 illicit drug dependent subjects from drug rehabilitation centres in Changsha and 2236 non-drug-using subjects, all of whom completed the self-report Pittsburgh Sleep Quality Index (PSQI).	We found that the prevalence of sleep disturbance was much higher in drug users (68.5%, PSQI >5; specifically, 80.24% in heroin users, 54.16% in methamphetamine users and 81.98% in ketamine users with PSQI >5) than non-users (26.4%, PSQI >5). Drug users had approximately twice the sleep latency than nondrug users (37.7 minutes V.S 18.4 minutes). Although drug users and non-users reported similar sleep duration (about 7.4 hours), drug users showed poorer subjective sleep quality and habitual sleep efficiency. They reported more sleep disturbance and need for sleep medications, more daytime dysfunction and poorer subjective sleep quality compared with nondrug users. The total PSQI score positively correlated with the duration of drug use (rp = 0.164, p < 0.001). We also found a link between sleep problems and cigarette smoking, alcohol drinking, and duration of drug use.	Poor sleep quality is common among illicit drug dependent subjects. Long-term substance users had more sleep problems. Future research aiming at quantifying the benefits of treatment interventions should not neglect the influence of sleep problems. Gaining more insight into the impact of sleep quality on the addiction treatment could also help to target future intervention measures more effectively.	
25884538	Since chronic fatigue syndrome (CFS) and fibromyalgia (FM) often co-exist, some believe they reflect the same process, somatization. Against that hypothesis are data suggesting FM but not CFS was common in patients with sleep-disordered breathing (SDB). The presence of discrete case definitions for CFS and FM allowed us to explore rates of CFS alone, CFS with FM, and FM alone in SDB patients compared to those with sleep complaints that fulfilled criteria for insomnia.Participants were 175 sequential patients with sleep-related symptoms (122 had SDB and 21 had insomnia) and 39 healthy controls. Diagnoses were made by questionnaires, tender point count, and rule out labs; sleepiness was assessed with Epworth Sleepiness Scale and mood with Beck Depression Inventory.	Rates of CFS, FM or CFS + FM were high: 13% in SDB and 48% in insomnia. CFS occurred frequently in SDB and insomnia, but FM occurred frequently only in insomnia. SDB patients with CFS and/or FM had higher daytime sleepiness than those without these disorders.	CFS patients should complete Epworth scales, and sleep evaluation should be considered for those with scores ≥ 16 before receiving the diagnosis of CFS; the coexistence of depressed mood in these patients suggests some may be helped by treatment of their depression. That FM was underrepresented in SDB suggests FM and CFS may have different underlying pathophysiological causes.	

25879643	The American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force acknowledged the multi-faceted nature of asthma in its recent definition of asthma control as a summary term capturing symptoms, reliever use, frequency/severity of exacerbations, lung function, and future risk and the Global Initiative for Asthma (GINA) defines the clinical manifestations (well established markers of asthma severity) of asthma to include symptoms, sleep disturbances, limitations of daily activity, impairment of lung function, and use of rescue medications. The objectives of this qualitative work were to identify symptoms and markers of symptom severity relevant to patients with moderate to severe asthma and to evaluate the content validity of the asthma symptom diary (ASD).A qualitative interview study was conducted using a purposive sample of symptomatic adult and adolescent (≥12 years) subjects with asthma. Concept elicitation (CE) interviews (n = 50) were conducted to identify core asthma symptoms and symptom-related clinical markers, followed by cognitive interviews (n = 24) to ensure patient comprehension of the items, instructions and response options. CE interviews were coded using ATLAS.ti for content analysis.	The study sample had a diverse range of symptom severity, level of symptom control, sociodemographic and socioeconomic status. The most frequently reported symptoms in adults were chest tightness (n = 33/34; 97.1%), wheezing (n = 31; 91.2%), coughing (n = 30; 88.2%), and shortness of breath (n = 25; 73.5%); in adolescents they were wheezing (n = 14/16; 87.5%), coughing (n = 13; 81.3%), and chest tightness (n = 11; 68.8%). Adults identified chest tightness followed by shortness of breath as their most severe symptoms; while adolescents reported coughing and chest tightness as their most severe symptoms. Sleep awakenings and limitations in day-to-day activities were frequent symptom-related clinical markers. Day-to-day variability and differences between daytime and nighttime symptom experiences reported by subjects resulted in the need for the ASD to be administered twice daily. Cognitive interviews indicated that subjects found the revised ASD items clear and easy to understand.	This study supports the content validity of the revised ASD, showing it to be consistent with patient experiences and ready for further psychometric testing.	
25879416	Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA.PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time.	Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC.	Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit.	
25877032	To evaluate the sleep quality and explore the manifestations of sleep disorders for 62 essential tremor (ET) patients, 60 normal controls and 62 Parkinson's disease (PD) patients.A total of 62 ET patients, 60 normal controls and 62 PD patients from June 2009 to December 2013 were recruited. All of them were outpatients at Second Affiliated Hospital, Soochow University and Hospital of Changshu Hospital of Traditional Chinese Medicine. Sleep was assessed with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS).	The global PSQI score was 4.7 ± 2.5 in controls, 6.0 ± 4.0 in ET cases and 7.4 ± 3. 7 in PD cases. PD cases had the highest PSQI score, followed by ET (intermediate) and lowest scores in controls (F = 9.022, P = 0.000). A poor quality of sleep was observed in normal controls (23/62, 38.3%) compared to ET cases (34/62, 54.8%) and PD cases (40/62, 64.5%) (χ² = 8.555, P = 0.014 when comparing all three groups and χ² = 1.206, P = 0.272 when ET vs PD). The ESS score increased from normal controls (4.4 ± 2.5) to ET cases (6.3 ± 4.8) and PD cases (8.2 ± 4.2). An ESS score ≥ 10 (an indicator of greater than normal levels of daytime sleepiness) was observed in 6 (10.0%) normal controls, compared to ET cases (16, 25.8%) and PD cases (20, 32.3%) (χ² = 9.047, P = 0.011 when comparing all three groups and χ² = 0.626, P = 0.429 when ET vs PD). For normal controls, ET and PD patients, the factor scores of subjective sleep were 0.6 ± 0.7, 0.8 ± 0.8 and 1.1 ± 0.7; the factor scores of quality sleep latency 0.6 ± 0.7, 0.9 ± 0.9 and 1.1 ± 1.0; the factor scores of sleep duration 0.6 ± 0.8, 0.7 ± 1.0 and 1.0 ± 0.9; the factor scores of sleep efficiency 0.6 ± 0.8, 0.9 ± 0.9 and 1.0 ± 1.0; the factor scores of sleep disturbances 1.2 ± 0.6, 1.2 ± 0.5 and 1.7 ± 0.7; the factor scores of daytime dysfunction 1.2 ± 1.0, 1.3 ± 1.0 and 2.0 ± 1.1 respectively. There were inter-group statistical differences in subjective sleep (F = 7.709, P = 0.001), quality sleep latency (F = 4.414, P = 0.013), sleep duration (F = 4.464, P = 0.013), sleep efficiency (F = 3.201, P = 0.043), sleep disturbances (F = 12.594, P = 0.000) and daytime dysfunction (F = 9.022, P = 0.000) . However, no inter-group statistical differences existed in use of sleeping medication (F = 1.200, P = 0.304). There were statistical differences in subjective sleep (P < 0.05), sleep efficiency (P < 0.05) and daytime dysfunction (P < 0.05) between ET and PD patients.	Some sleep scores in ET are intermediate between those of PD cases and normal controls. And it suggests that a mild form of sleep dysregulation may be present in ET.	
25874578	This pooled analysis investigated the effects of gabapentin enacarbil (GEn) on clinical correlates of sleep disturbance in adults with moderate-to-severe primary restless legs syndrome (RLS) and no-to-moderate or severe-to-very severe baseline sleep disturbance.Co-primary end-points were mean change from baseline to week 12 in International Restless Legs Scale (IRLS) total score and proportion of responders ('much'/'very much' improved) on the investigator-rated Clinical Global Impression-Improvement (CGI-I) scale (week 12). Pain, mood, individual IRLS items, and safety were assessed.	The modified intent-to-treat population was 671 adults randomized to GEn 600 mg (n = 161), GEn 1200 mg (n = 266), or placebo (n = 244). GEn significantly improved least squares mean change in IRLS total score from baseline versus placebo for no-to-moderate (GEn 600 mg,- 12.3; 1200 mg, - 11.3; placebo, - 7.7) and severe-to-very severe (- 16.6; - 17.0; - 12.7) groups (all P < 0.01). Significantly more GEn-treated patients (both doses) were CGI-I responders (week 12) versus placebo in both sleep subgroups (all P < 0.01). GEn substantially improved mood and pain scores for both sleep subgroups versus placebo. The most frequent treatment-emergent adverse events were somnolence and dizziness.	GEn (600 mg and 1200 mg) was effective and well tolerated in adults with moderate-to-severe primary RLS regardless of baseline sleep disturbance level.	
25873295	Cancer survivors experience high levels of distress, associated with a host of negative psychological states, including anxiety, depression, and fear of recurrence, which often lead to sleep problems and reduction in quality of life (QOL) and well-being. As a neuropeptide hormone associated with affiliation, calmness, and well-being, oxytocin may be a useful biological measure of changes in health outcomes in cancer survivors. In this exploratory study, which comprised a subset of participants from a larger study, we evaluated (a) the feasibility and reliability of salivary oxytocin (sOT) levels in cancer survivors and (b) the effects of 2 sleep-focused mind-body interventions, mind-body bridging (MBB) and mindfulness meditation (MM), compared with a sleep hygiene education (SHE) control, on changes in sOT levels in 30 cancer survivors with self-reported sleep disturbance. Interventions were conducted in 3 sessions, once per week for 3 weeks. Saliva samples were collected at baseline, postintervention (~1 week after the last session), and at the 2-month follow-up. In this cancer survivor group, we found that intra-individual sOT levels were fairly stable across the 3 time points, of about 3 months' duration, and mean baseline sOT levels did not differ between females and males and were not correlated with age. Correlations between baseline sOT and self-report measures were weak; however, several of these relationships were in the predicted direction, in which sOT levels were negatively associated with sleep problems and depression and positively associated with cancer-related QOL and well-being. Regarding intervention effects on sOT, baseline-subtracted sOT levels were significantly larger at postintervention in the MBB group as compared with those in SHE. In this sample of cancer survivors assessed for sOT, at postintervention, greater reductions in sleep problems were noted for MBB and MM compared with that of SHE, and increases in mindfulness and self-compassion were observed in the MBB group compared with those in SHE. The findings in this exploratory study suggest that sOT may be a reliable biological measure over time that may provide insight into the effects of mind-body interventions on health outcomes in cancer survivors. 
25873294	Cancer patients frequently suffer from poor sleep quality. Bryophyllum pinnatum is a herbal medication used in anthroposophic medicine, which has been shown to be associated with improvements in sleep quality during pregnancy with only few and minor or moderate side-effects reported. In this study, the sleep quality of cancer patients during treatment with B pinnatum was investigated.In this prospective, observational study, cancer patients suffering from sleep problems were treated with B pinnatum (350 mg tablets, corresponding to 50% of leaf pressed juice [Weleda AG, Arlesheim, Switzerland], dosage at physician's consideration, but most frequently 2 tablets with evening meal and 2 before going to bed).	Sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daily sleepiness (Epworth Sleeping Scale [ESS]), and fatigue (Fatigue Severity Scale [FSS]) were assessed at the beginning of the treatment and after 3 weeks. Possible adverse drug reactions perceived by the patients during the treatment were recorded. From the 28 recruited patients, 20 completed both questionnaires and were considered in the present analysis. Data are expressed as mean ± standard deviation.	Patients were 61 ± 10.4 years old and the majority were female (17 out of 20). During treatment with B pinnatum, the PSQI decreased from 12.2 ± 3.62 to 9.1 ± 3.61 (P < .01), and ESS changed from 8.4 ± 3.18 to 7.1 ± 3.98 (P < .05). There was no change in FSS. The treatment was well tolerated by the majority of patients, with only 6 patients reporting discomfort that might have been caused by B pinnatum (fatigue n = 3, dry throat n = 1, agitation n = 1, difficult digestion n = 1). No serious adverse drug reactions were detected.	B pinnatum may be a suitable treatment for sleep problems of cancer patients. Controlled, randomized clinical trials of the use of B pinnatum in sleep disorders are urgently needed.	
25873292	Current research examining the effect of exercise on immune responses in cancer survivors is limited.The aim of this pilot study was to examine the effect of 1 bout of intermittent exercise on natural killer (NK) cell numbers in breast cancer survivors.	A total of 9 women with stage I to III invasive breast cancer who were 3 to 6 months posttreatment and 9 sedentary women without a history of cancer completed 10 three-minute intervals of aerobic exercise on the cycle ergometer at 60% of VO2peak (peak oxygen uptake). Whole blood samples were taken pre-exercise, immediately postexercise, and at 2 hours and 24 hours postexercise. NK cell counts were assessed using flow cytometry.	In both groups, NK cell counts significantly increased immediately postexercise compared with pre-exercise (P = .004-.008) and returned to near pre-exercise levels during recovery (P = .129-.547). Absolute NK cell counts were significantly lower in breast cancer survivors immediately postexercise when compared with controls (P = .046).	The breast cancer survivor group exhibited NK cell responses to 30 minutes of moderate-intensity intermittent aerobic exercise that were comparable with that in the group of physically similar women without a history of cancer. Immune changes related to cancer treatments may be related to the lower absolute NK cell counts observed in the breast cancer survivor group. Although the results of this study are preliminary in nature, they suggest that this type of exercise does not disrupt this aspect of innate immunity in recent breast cancer survivors, thereby supporting current exercise recommendations for this population.	
25872975	The aim of this study was to assess energy intake, resting metabolic rate (RMR), appetite sensations, eating behaviours and sleep duration and quality in obese women resistant to body weight loss when subjected to a diet-based weight-reducing programme. A pooled cohort of obese women (n = 75; aged 39 ± 8 years; body mass index: 33 ± 4 kg m(-2)) participated in a 12-16-week diet-based weight loss programme targeting a daily energy deficit of 500-700 kcal d(-1). Women were classified in tertiles a posteriori based on the response of their body weight to dietary supervision (high, moderate and low responders). Post-intervention, mean weight loss was 3.3 ± 2.8 kg and explained by the 2.9 ± 2.6 kg reduction in fat mass. Mean weight loss was 6.2 ± 1.6, 3.4 ± 0.6 and 0.2 ± 1.4 kg in participants classified in the high, middle and low tertiles, respectively. Women in the low tertile reduced their daily energy intake and susceptibility to hunger during the programme to a lesser extent than those in the high tertile and had higher fasting hunger in response to the dietary intervention. Women in the high tertile maintained their RMR, which was in contrast to the significant decrease predicted by their weight loss. They also reported a significant improvement in sleep quality and an increase in sleep duration compared with other tertiles. The differences in the response of body weight to dietary supervision may be explained, in part, by variations in energy intake, eating behaviours, appetite sensations and sleep duration and quality.
25872556	Understanding factors affecting post-operative recovery is of great importance to efforts at reducing morbidity and mortality after general surgery. Post-operatively, most patients suffer from objectively and subjectively measurable reduced sleep quality. We aimed to review the available literature on post-operative sleep in patients undergoing colorectal surgery.This systematic review was conducted according to the PRISMA guidelines, searching the electronic data-bases PubMed, Embase and the Cochrane Library. All articles were evaluated according to pre-defined inclusion criteria.	Five studies were included in the review. Sleep quality was affected by type of surgery (open or laparoscopic), the administration/mode of application of analgesics (epidural analgesia or continuous wound infusion) and the level of pain. Patients who listened to new age music and a "relaxing text" had better quality of post-operative sleep than controls. Overall, pain interfered with subjective, post-operative sleep quality and adequate treatment of pain improved subjective sleep quality.	Sleep quality is sensitive to various factors in the perioperative period, and impairment of sleep quality can be prevented by simple improvements in perioperative care.	
25872265	The article presents results of individual evaluation of coefficient of oxidative stress as an integral indicator of balance of the system "lipids peroxidation-antioxidant defense" in women with sleep disturbances in post menopause conditions. The condition of the system "lipids peroxidation-antioxidant defense" was evaluated using analysis of content of substrates of oxidation of processes of lipid peroxidation with conjugated double bonds, diene conjugates, ketodienes and conjugated trienes, TBC-active products of retinol α-tokoferol, reduced and oxidized glutathione, activity of superoxiddismutase in blood. The application of coefficient of oxidative stress permitted to demonstrate differences in processes of lipids peroxidation in women with the same diagnosis and use it as a justification of individual approach under prescription of antioxidant therapy.
27560526	To analyze the relationship between the severity of pain and sleep disorder using wrist actigraphy in patients with cervical disc herniation (CDH).Fifty patients with the diagnosis of CDH underwent subjective tests and actigraphic analysis in preoperative period, and at the end of postoperative first week and postoperative first month. The data of the subjective tests and actigraphic analysis were compared.	There was a strong and statistically significant negative correlation between the subjective tests of Visual Analog Scale (VAS) for Pain 0-1-2 and the objective parameters of Sleep Onset Latency (SOL) 0-1-2 (rs= -0.798, p=0.009 - rs= - 0.832, p=0.006 - rs=- 0.710, p=0.004). There was a positive correlation between the subjective tests of VAS for Pain 0-1-2 and the objective parameters of Sleep Efficiency (SEF) 0-1-2 (rs=0.721, p=0.006 - rs= 0.768, p=0.001 - rs= 0.748, p=0.001).	Actigraphy may be used for the evaluation of cervical disc surgery, as an alternative and objective test for sleep disorders.	
25871014	Sleep disturbances among family caregivers (FCs) are common in advanced cancer. The comprehensive factors for sleep disturbances among the FCs of patients with cancer have not been investigated in Taiwan. The purposes of this study were to investigate the sleep disturbances among the FCs of patients with advanced cancer and to determine predictors of sleep disturbance.A descriptive, cross-sectional study was conducted among 172 FCs. Data were collected using the Pittsburgh Sleep Quality Index and wrist actigraphy. A linear regression model was used to identify the predictive factors for sleep quality.	Seventy-six percent of the FCs experienced some sleep disturbances. Female gender, more fatigue, greater depression, more caregiving burden, and spending over 16 h per day on caregiving tasks were risk factors for sleep disturbances in caregivers.	Sleep disturbances were common among the Taiwanese FCs of patients with advanced cancer. FCs with risk factors for sleep disturbances should be identified and provided assistance.	
25871005	The purpose of this study was to identify clusters of midlife women by sleep-related symptoms in multiethnic groups and to examine racial/ethnic differences in the clusters.This secondary analysis was conducted on data from 1,054 midlife women who participated in two cross-sectional descriptive national Internet surveys. The instruments included questions on background characteristics, health, and menopause status, and the Sleep Index for Midlife Women. The data were analyzed using hierarchical clustering methods, χ2 test, analysis of variance, and multinomial logistic regression analyses.	A four-cluster solution was adopted: cluster 1 (low total symptoms group), cluster 2 (moderate physical and psychosomatic symptoms group), cluster 3 (moderate psychological symptoms group), and cluster 4 (high total symptoms group). There were significant differences in education, employment status, family income, social support, country of birth, race/ethnicity, body mass index, perceived general health, diagnosed disease, access to health care, and menopause status among clusters (P < 0.05). In cluster 1 only, there were significant racial/ethnic differences in the total number of total severity scores for physical symptoms (P < 0.01). When racial/ethnic differences in individual symptoms in each cluster were determined, there were no consistent racial/ethnic differences.	Researchers need to consider that racial/ethnic differences could be prominent in midlife women with low sleep-related symptoms.	
25870289	Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show--by using two 8-d laboratory protocols--in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.
25868869	We investigated the percentage of women with poor sleep quality and its related factors among mainland Chinese women. Sleep quality and menopausal status were self-reported. We explored the contribution of possible risk factors, including sociodemographic characteristics, comorbidities, lifestyle, psychological status, stressful life events, and vasomotor symptoms. We found that 38.6% of midlife Chinese women were poor sleepers. This percentage was higher in comparison with women from other Asian countries. Our multiple logistic regression showed that anxiety, comorbidities, perceived stress, and vasomotor symptoms were risk factors for poor sleep quality. 
25868673	Biologically active peptides are widely expressed throughout in human bodies. For example, endothelin-1 and adrenomedullin are expressed in almost all types of cells, including neurons, glial cells, fibroblasts, macrophages, cardiomyocytes, vascular endothelial cells, epithelial cells and cancer cells of various origins. Expression of both these peptides is induced by stimuli, such as hypoxia and inflammatory cytokines. They have a variety of biological functions, such as effects on brain function, hormone secretion, the cardiovascular system and cell proliferation. By contrast, orexins (hypocretins) and melanin-concentrating hormone (MCH) are specifically expressed in the hypothalamus, particularly in the lateral hypothalamus, although very low concentrations of these peptides are found in the peripheral tissues. Orexins and MCH play coordinated, but distinct physiological roles in the regulation of sleep-wake cycle, appetite, emotion and other brain functions. The cardiovascular system is regulated by cardiovascular peptides, such as natriuretic peptides, endothelins and angiotensin II. The renin-angiotensin system (RAS) is one of the most classical regulatory systems on blood pressure, electrolytes and kidney. (Pro)renin receptor is a novel member of the RAS and may be related to the pathophysiology of microvascular complications of hypertension and diabetes mellitus. Moreover, (pro)renin receptor forms a functional complex with vacuolar-type H(+)-ATPase, which plays an important physiological role in maintaining the acidic environment of intracellular compartments including secretory vesicles. Perhaps, the complex of (pro)renin receptor and vacuolar-type H(+)-ATPase may be important for the post-translational processing and secretion of many biologically active peptides. 
25866391	Ambient light affects multiple physiological functions and behaviors, such as circadian rhythms, sleep-wake activities, and development, from flies to mammals. Mammals exhibit a higher body temperature when exposed to acute light compared to when they are exposed to the dark, but the underlying mechanisms are largely unknown. The body temperature of small ectotherms, such as Drosophila, relies on the temperature of their surrounding environment, and these animals exhibit a robust temperature preference behavior. Here, we demonstrate that Drosophila prefer a ∼1° higher temperature when exposed to acute light rather than the dark. This acute light response, light-dependent temperature preference (LDTP), was observed regardless of the time of day, suggesting that LDTP is regulated separately from the circadian clock. However, screening of eye and circadian clock mutants suggests that the circadian clock neurons posterior dorsal neurons 1 (DN1(p)s) and Pigment-Dispersing Factor Receptor (PDFR) play a role in LDTP. To further investigate the role of DN1(p)s in LDTP, PDFR in DN1(p)s was knocked down, resulting in an abnormal LDTP. The phenotype of the pdfr mutant was rescued sufficiently by expressing PDFR in DN1(p)s, indicating that PDFR in DN1(p)s is responsible for LDTP. These results suggest that light positively influences temperature preference via the circadian clock neurons, DN1(p)s, which may result from the integration of light and temperature information. Given that both Drosophila and mammals respond to acute light by increasing their body temperature, the effect of acute light on temperature regulation may be conserved evolutionarily between flies and humans.
25865216	Resource constraints may inhibit the provision of appropriate interventions for children with neurodisabilities presenting with behavioural sleep problems. Telephone calls (TC), as opposed to home visits (HV), may be a more resource efficient means of supporting these families.To conduct a preliminary investigation exploring the feasibility and acceptability of replacing HV with TC to support parents implementing sleep management strategies and to gather evidence to inform the design and methods of a full trial.	Parents referred to a sleep management intervention routinely delivered by a community paediatric team were alternately allocated to receive implementation support via HV (n = 7) or TC (n = 8). Activity logs recorded the frequency, duration and mode of support. Parents and practitioners were interviewed about their experiences of receiving/delivering the intervention.	Intervention drop-out was low, the frequency, number of contacts and intervention duration appeared comparable. Parents allocated TC received less contact time. Parents valued implementation support irrespective of delivery mode and practitioners reported that despite initial reservations, implementation support via TC appeared to work well.	TC appears an acceptable and convenient mode of delivering sleep support, valued by both parents and practitioners. We recommend a full-scale trial to investigate effectiveness.	
25863826	Anxiety disorders constitute the most common mental health disturbance experienced by youth. Sleep-related problems (SRPs) are highly prevalent among anxious youth and encompass a variety of problems including nighttime fears, insomnia, and refusal to sleep alone. Given that chronic sleep disturbance is associated with a range of behavioral and physical problems in youth and predicts future psychopathology, it is important to elucidate the nature of SRPs in anxious youth. The present study investigated the relationship between sleep problems and anxiety sensitivity in a sample of 101 anxious youth, ages 6-17. Heightened anxiety sensitivity significantly predicted prolonged sleep onset latency across the sample, even after accounting for severity of anxiety, depression, and age. Results support previous research indicating that SRPs are common among anxious youth and suggest that anxiety sensitivity may play a particularly important role in sleep onset latency. 
25862571	The main Zeitgeber, the day-night cycle, synchronizes the central oscillator which determines behaviors rhythms as sleep-wake behavior, body temperature, the regulation of hormone secretion, and the acquisition and processing of memory. Thus, actions such as acquisition, consolidation, and retrieval performed in the hippocampus are modulated by the circadian system and show a varied dependence on light and dark. To investigate changes in the hippocampus' cellular mechanism invoked by the day and night in a diurnal primate, this study analyzed the expression of PER2 and the calcium binding proteins (CaBPs) calbindin, calretinin and parvalbumin in the hippocampus of Sapajus apella, a diurnal primate, at two different time points, one during the day and one during the dark phase. The PER2 protein expression peaked at night in the antiphase described for the suprachiasmatic nucleus (SCN) of the same primate, indicating that hippocampal cells can present independent rhythmicity. This hippocampal rhythm was similar to that presented by diurnal but not nocturnal rodents. The CaBPs immunoreactivity also showed day/night variations in the cell number and in the cell morphology. Our findings provide evidence for the claim that the circadian regulation in the hippocampus may involve rhythms of PER2 and CaBPs expression that may contribute to the adaptation of this species in events and activities relevant to the respective periods. 
25858174	To use the pupillary light reflex and polysomnography to evaluate the function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to correlate this function with structural damage in glaucoma.Cross-sectional study.	A study was conducted on both eyes of 45 participants (32 patients with glaucoma and 13 healthy subjects).	For the pupillary reflex evaluation, patients were tested in the dark using a Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter was measured with an eye tracker system. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors, we used a 1-second 640-nm flash with a luminance of 250 cd/m(2). All of the subjects underwent polysomnography. Subjects underwent standard automated perimetry and optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA).	Correlations between ipRGC activity, as measured by the pupillary light reflex, and polysomnography parameters, and correlations between retinal nerve fiber layer (RNFL) thickness and the pupillary light reflex and polysomnography parameters.	The mean patient ages in the healthy and glaucoma groups were 56.8±7.8 years and 61.5±11.6 years, respectively (P = 0.174). Patients with glaucoma had significantly lower average total sleep time, sleep efficiency, and minimum oxyhemoglobin saturation compared with the healthy subjects (P  = 0.008, P = 0.002, and P = 0.028, respectively). Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements (P = 0.002 and P = 0.045, respectively). There was an inverse correlation between the rapid eye movement latency and the peak of the pupillary response to the blue flash (P = 0.004). The total arousals were inversely correlated with the sustained blue flash response (P = 0.029). The RNFL thickness was associated with the peak and sustained responses to the blue flash (P  <  0.001 for both comparisons); however, RNFL thickness was only associated with the mean oxygen desaturation index among the polysomnography parameters (P = 0.023).	This study demonstrated that decreased ipRGC function caused by glaucoma affected pupillary response and sleep quality.	
25857269	Chemotherapeutic resistance, particularly to doxorubicin (Dox), represents a major impediment to successfully treating breast cancer and is linked to elevated tumor metabolism and tumor over-expression and/or activation of various families of receptor- and non-receptor-associated tyrosine kinases. Disruption of circadian time structure and suppression of nocturnal melatonin production by dim light exposure at night (dLEN), as occurs with shift work, and/or disturbed sleep-wake cycles, is associated with a significantly increased risk of an array of diseases, including breast cancer. Melatonin inhibits human breast cancer growth via mechanisms that include the suppression of tumor metabolism and inhibition of expression or phospho-activation of the receptor kinases AKT and ERK1/2 and various other kinases and transcription factors. We demonstrate in tissue-isolated estrogen receptor alpha-positive (ERα+) MCF-7 human breast cancer xenografts, grown in nude rats maintained on a light/dark cycle of LD 12:12 in which dLEN is present during the dark phase (suppressed endogenous nocturnal melatonin), a significant shortening of tumor latency-to-onset, increased tumor metabolism and growth, and complete intrinsic resistance to Dox therapy. Conversely, a LD 12:12 dLEN environment incorporating nocturnal melatonin replacement resulted in significantly lengthened tumor latency-to-onset, tumor regression, suppression of nighttime tumor metabolism, and kinase and transcription factor phosphorylation, while Dox sensitivity was completely restored. Melatonin acts as both a tumor metabolic inhibitor and circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to Dox and drive tumor regression, indicating that dLEN-induced circadian disruption of nocturnal melatonin production contributes to a complete loss of tumor sensitivity to Dox chemotherapy. 
25856540	The association between sleep disturbances and cardiometabolic diseases has been understudied in blacks with metabolic syndrome.This study is a cross-sectional analysis of the Metabolic Syndrome Outcome Study (MetSO) trial. We assessed insomnia symptoms, sleep duration, and risk for sleep apnea. Multivariate logistic regression models evaluated the association between sleep disturbances with diabetes mellitus (DM) and the combined outcomes of DM and hypertension as well as DM and dyslipidemia.	The sample consisted of 1,013 participants, mean age of 62 ± 14 years and 61% female. DM was diagnosed in 60% of the sample. Sleep apnea risk was observed in 48% of the sample, while 10% had insomnia symptoms and 65% reported short sleep duration (< 6 hours). Sleep apnea risk, but not insomnia or sleep duration, was associated with DM (OR 1.66; 95% CI 1.21-2.28), adjusting for age, sex, income, obesity (BMI ≥ 30 kg/m(2)), tobacco use, alcohol use, hypertension, dyslipidemia, and depression. In fully adjusted models, sleep apnea risk was associated with the combined outcome of DM-hypertension (OR 1.95; 95% CI 1.42-2.69), but not with diabetes-dyslipidemia.	We observed a strong association between sleep apnea risk and diabetes mellitus among blacks with metabolic syndrome.	
25855969	Despite substantial progress in the study of diabetes, important questions remain about its comorbidities and clinical heterogeneity. To explore these issues, we develop a framework allowing for the first time to quantify nation-wide risks and their age- and sex-dependence for each diabetic comorbidity, and whether the association may be consequential or causal, in a sample of almost two million patients. This study is equivalent to nearly 40,000 single clinical measurements. We confirm the highly controversial relation of increased risk for Parkinson's disease in diabetics, using a 10 times larger cohort than previous studies on this relation. Detection of type 1 diabetes leads detection of depressions, whereas there is a strong comorbidity relation between type 2 diabetes and schizophrenia, suggesting similar pathogenic or medication-related mechanisms. We find significant sex differences in the progression of, for instance, sleep disorders and congestive heart failure in diabetic patients. Hypertension is a highly sex-sensitive comorbidity with females being at lower risk during fertile age, but at higher risk otherwise. These results may be useful to improve screening practices in the general population. Clinical management of diabetes must address age- and sex-dependence of multiple comorbid conditions. 
25855040	To examine the effect of physical activity on the physical and psychosocial symptoms of lung cancer survivors.A longitudinal design was used in this study. Participants were recruited from the chest and surgical departments of medical centers in Taiwan. The instruments used were the Godin Leisure-Time Exercise Questionnaire and the Taiwanese version of the M.D. Anderson Symptom Inventory.	In total, 185 survivors were followed up for 6 months (response rate 66%). Disturbed sleep was the most prevalent symptom in the participants. A generalized estimating equation (GEE) method was employed to analyze the relationships among intensity of physical activity, symptom severity, and symptom interference in the daily life of the participants. Regarding symptom severity, significant differences were observed in fatigue, drowsiness, and disturbed sleep between the participants who engaged in moderate physical activity and those who did not engage in any physical activity. Regarding symptom interference, the participants who engaged in light physical activity experienced a significantly lower level of symptom interference than did those with a sedentary lifestyle.	This is the first study to explore the role of physical activity in alleviating symptoms in lung cancer survivors by using the GEE method. The results suggest that physical activity plays an essential role in alleviating the physical and psychological symptoms of lung cancer survivors.	
25854650	Narcolepsy is a severe, incurable, neurological disorder that is treated by pharmacological management of its symptoms. The main symptoms are excessive daytime sleepiness (EDS) and cataplexy, although addition symptoms that may require treatment include sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. Sodium oxybate and modafinil/armodafinil are the first-line treatments for EDS, and sodium oxybate for cataplexy. Sodium oxybate treats all the symptoms of narcolepsy, whereas modafinil is effective for EDS only. Alternative medications for EDS include methylphenidate or amphetamines such as dextroamphetamine, lisdexamfetamine, methamphetamine, or combination amphetamine salts. Non-FDA approved medications for cataplexy include norepinephrine reuptake inhibitors such as venlafaxine or atomoxetine. Combination therapy can be more effective for sleepiness such as sodium oxybate and modafinil/armodafinil. Medication for narcolepsy is generally well tolerated and usually required life-long although does not eliminate all symptoms of narcolepsy.
25852644	Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock, and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g., obesity) involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small molecules (CEMs) identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep, and metabolism will also have far-reaching implications for various chronic human diseases and aging. 
25852578	Advanced video technology is available for sleep-laboratories. However, low-cost equipment for screening in the home setting has not been identified and tested, nor has a methodology for analysis of video recordings been suggested.We investigated different combinations of hardware/software for home-videosomnography (HVS) and established a process for qualitative and quantitative analysis of HVS-recordings. A case vignette (HVS analysis for a 5.5-year-old girl with major insomnia and several co-morbidities) demonstrates how methodological considerations were addressed and how HVS added value to clinical assessment.	We suggest an "ideal set of hardware/software" that is reliable, affordable (∼$500) and portable (=2.8 kg) to conduct non-invasive HVS, which allows time-lapse analyses. The equipment consists of a net-book, a camera with infrared optics, and a video capture device. (1) We present an HVS-analysis protocol consisting of three steps of analysis at varying replay speeds: (a) basic overview and classification at 16× normal speed; (b) second viewing and detailed descriptions at 4-8× normal speed, and (c) viewing, listening, and in-depth descriptions at real-time speed. (2) We also present a custom software program that facilitates video analysis and note-taking (Annotator(©)), and Optical Flow software that automatically quantifies movement for internal quality control of the HVS-recording. The case vignette demonstrates how the HVS-recordings revealed the dimension of insomnia caused by restless legs syndrome, and illustrated the cascade of symptoms, challenging behaviors, and resulting medications.	The strategy of using HVS, although requiring validation and reliability testing, opens the floor for a new "observational sleep medicine," which has been useful in describing discomfort-related behavioral movement patterns in patients with communication difficulties presenting with challenging/disruptive sleep/wake behaviors.	
25852234	Mild traumatic brain injury (mTBI) has been widely studied and the effects of injury can be long term or even lifelong. This research aims to characterize the sleep problems of patients following acute mTBI.A total of 171 patients with mTBI within one month and 145 non-mTBI controls were recruited in this study. The questionnaire, Pittsburgh Sleep Quality Index (PSQI), was used to evaluate seven aspects of sleep problems. A propensity score method was used to generate a quasirandomized design to account for the background information, including gender, age, Beck's Anxiety Index, Beck's Depression Index, and Epworth Sleepiness Scale. The effect was evaluated via cumulative logit regression including propensity scores as a covariate.	Before adjustment, about 60% mTBI patients and over three quarters of control subjects had mild sleep disturbance while one third mTBI patients had moderate sleep disturbance. After adjusting by the propensity scores, the scores of sleep quality and duration were significant between mTBI and control groups.	Our study supports that sleep problem is common in mTBI group. After adjusting the confounders by propensity score, sleep duration and subjective sleep quality are the most frequently reported problems in mTBI patients within one month after the injury.	
25851828	To examine the association between sleep complaints, use of sleep-promoting medications, and persistent severe fatigue (PSF).Analysis of data from the National Health Aging Trends Study.	Contiguous United States.	A representative sample of Medicare beneficiaries aged 65 and older.	Difficulty initiating sleep, difficulty staying asleep, use of sleep-promoting medications, demographic characteristics, presence of pain, use of pain medications, depression, chronic medical disease, physical activity level, and Short Physical Performance Battery score measured at baseline. The outcome of interest was PSF (fatigue that limits daily activities reported at baseline and 12-month follow-up).	Of 8,245 participants at baseline, 7,075 completed 12-month follow-up; 31% reported severe fatigue at baseline and 31% at follow-up, and 19% reported PSF. In a logistic regression model, difficulty staying asleep some nights (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.08-1.60) and most nights or every night (OR = 1.40, 95% CI = 1.09-1.79) and use of sleep-promoting medications most nights or every night (OR = 1.35, 95% CI = 1.08-1.67) independently predicted PSF.	The results indicate greater risk of PSF in older adults with difficulty staying asleep and those who use sleep-promoting medications. These findings underscore the significance of sleep problems and present potential targets for interventional studies that aim to improve fatigue in older adults.	
25851638	Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl] propanamide), a novel dual melatonin receptor agonist that demonstrates specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2 receptors), is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly absorbed, with a mean absolute bioavailability of approximately 38%, and is extensively metabolized primarily by oxidation at multiple sites, mainly by cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro studies and confirmed by the results of clinical drug-drug interactions presented here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2 and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans. Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin pretreatment resulted in a decrease in tasimelteon's exposure of approximately 89%. 
25850902	Bipolar patients have a high prevalence of comorbid alcohol use and abuse disorders, while chronic alcohol drinking may increase the presence and severity of certain symptoms of bipolar disorder. As such, there may be many individuals that are prescribed lithium to alleviate the manic symptoms of bipolar disorder, but also drink alcohol concurrently. In addition, both alcoholics and individuals with bipolar disorder often exhibit disruptions to their sleep-wake cycles and other circadian rhythms. Interestingly, both ethanol and lithium are known to alter both the period and the phase of free-running rhythms in mammals. While lithium is known to lengthen the period, ethanol seems to shorten the period and attenuate the responses to acute light pulses. Therefore, the present study aimed to determine whether ethanol and lithium have opposing effects on the circadian pacemaker when administered together. C57BL/6J mice were provided drinking solutions containing lithium, alcohol, or both, and their free-running rhythms along with their response to photic phase shifts were investigated. Mice treated with lithium displayed period lengthening, which was almost completely negated when ethanol was added. Moreover, ethanol significantly attenuated light-induced phase delays while the addition of lithium partially restored this response. These results indicate that alcohol and lithium have opposing effects on behavioral circadian rhythms. Individuals with bipolar disorder who are prescribed lithium and who drink alcohol might be inadvertently altering their sleep and circadian cycles, which may exacerbate their symptoms.
25850879	In 2 large-scale, placebo-controlled trials, pregabalin improved both pain and pain-related sleep interference in patients with neuropathic pain due to spinal cord injury (SCI). In both trials, pregabalin found statistically significant improvement compared with placebo after 1 week of treatment. However, the effects of pregabalin in the days immediately after initiation of treatment are unknown. The purpose of the present analysis was to determine timing of pregabalin's therapeutic effect in the days after initiation of treatment.Data were derived from 2 trials of pregabalin in patients with SCI-related neuropathic pain. Each day patients rated severity of pain and pain-related sleep interference over the past 24 hours on a scale from 0 to 10, with higher scores indicating greater severity. To quantify timing of therapeutic effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related sleep interference scores over the first 14 days of treatment. Significant improvement was defined as the first day, of ≥2 consecutive days, that pregabalin significantly (P < 0.05) reduced mean scores compared with placebo. To further quantify timing of therapeutic effect, each treatment group was examined to determine the time required to achieve a ≥1-point improvement in pain and pain-related sleep interference score among patients with a clinically meaningful and sustained response (≥30% improvement from baseline to end point) by using a time-to-event analysis method. Kaplan-Meier analyses were used to estimate the median (or 25th quartile) time (in days) required to achieve a ≥1-point improvement, among these responders, in pain and pain-related sleep interference scores. Comparisons between pregabalin and placebo were made with a log-rank test.	In both trials, significant improvement of pain and pain-related sleep interference occurred within 2 days of initiating treatment with pregabalin. Among patients reporting a clinically meaningful and sustained response to treatment (patients with ≥30% improvement from baseline to end point), the time to a ≥1-point improvement of pain and pain-related sleep interference occurred significantly earlier among pregabalin-treated patients than among placebo-treated patients. Finally, the timing of pregabalin's effect on pain and pain-related sleep interference was unaffected by the use of concomitant medications that were allowed for treatment of neuropathic pain in both trials.	Treatment with pregabalin results in rapid time to significant improvement in both pain and pain-related sleep interference in patients with neuropathic pain due to SCI. These findings should only be used as a guide to physicians and patients as to when clinical response to pregabalin may be expected.	
25850114	We aimed to build upon the state of knowledge about the impacts of sleep disruption into the domain of complex cognitive task performance for three types of sleep disruption: total sleep deprivation, sleep restriction, and circadian cycle.Sleep disruption affects human performance by increasing the likelihood of errors or the time it takes to complete tasks, such as the Psychomotor Vigilance Task. It is not clear whether complex tasks are affected in the same way. Understanding the impact of sleep disruption on complex cognitive tasks is important for, and in some instances more relevant to, professional workers confronted with unexpected, catastrophic failures following a period of disrupted sleep.	Meta-analytic review methods were applied to each of the three different areas of sleep disruption research.	Complex cognitive task performance declines over consecutive hours of continuous wakefulness as well as consecutive days of restricted sleep, is worse for severely restricted sleep (4 or fewer hours in bed), is worse during the circadian nadir than apex, and appears less degraded than simple task performance.	The reviews suggest that complex cognitive task performance may not be impacted by disrupted sleep as severely as simple cognitive task performance.	Findings apply to predicting effects of sleep disruption on workers in safety-critical environments, such as health care, aviation, the military, process control, and in particular, safety-critical environments involving shiftwork or long-duration missions.	

25848287	Individual patients with depression present with unique symptom clusters - before, during, and even after treatment. The prevalence of persistent, unresolved symptoms and their contribution to patient functioning and disease progression emphasize the importance of finding the right treatment choice at the onset and the utility of switching medications based on suboptimal responses. Our primary goal as clinicians is to improve patient function and quality of life. In fact, feelings of well-being and the return to premorbid levels of functioning are frequently rated by patients as being more important than symptom relief. However, functional improvements often lag behind resolution of mood, attributed in large part to persistent and functionally impairing symptoms - namely, fatigue, sleep/wake disturbance, and cognitive dysfunction. Thus, patient outcomes can be optimized by deconstructing each patient's depressive profile to its component symptoms and specifically targeting those domains that differentially limit patient function. This article will provide an evidence-based framework within which clinicians may tailor pharmacotherapy to patient symptomatology for improved treatment outcomes. 
25847544	The aim of this study was to explore the relationship between sleep, including both qualitative and quantitative aspects, and delinquent behaviour while controlling for psychopathic features of adolescents and parental supervision at bedtime. We analysed data from a nationally representative sample of 4855 Finnish adolescents (mean age 15.3 years, 51% females). Sleep problems, hours of sleep and delinquency were evaluated via self-report. Psychopathic features were measured with the Antisocial Process Screening Device - Self-Report. In negative binomial regressions, gender and sleep-related variables acted as predictors for both property and violent crime after controlling for psychopathic features and parental supervision at bedtime. The results suggest that both sleep problems (at least three times per week, at least for a year) and an insufficient amount of sleep (less than 7 h) are associated with property crime and violent behaviour, and the relationship is not explained by gender, degree of parental supervision at bedtime or co-occurring psychopathic features. These results suggest that sleep difficulties and insufficient amount of sleep are associated with delinquent behaviour in adolescents. The significance of addressing sleep-related problems, both qualitative and quantitative, among adolescents is thus highlighted. Implications for a prevention technique of delinquent behaviour are discussed. 
25847085	To determine the prevalence of restless legs syndrome (RLS) in Chinese children and adolescents as well as the impact of the disorder on 8-11 and 12-17 years old. This population-based study was conducted in five primary schools and seven high schools, which were randomly selected in Henan province, China. A total of 6792 students aged 8-17 years old were given a questionnaire that included the adult diagnostic criteria of RLS proposed by the International Restless Legs Study Group. Subjects who answered "yes" to all four questions were selected for a face-to-face interview to confirm RLS diagnosis. Individuals with definite RLS were then administered another questionnaire to survey RLS symptoms and perceived consequences. The prevalence of definite RLS in Chinese children and adolescents was 2.2 % (141/6437), with a prevalence of 1.8 % in the 8-11 years old age group and 2.4 % in the 12-17 years old age group. RLS was found to be more prevalent in females (2.7 %) than in males (1.7 %) (P = 0.008), and the prevalence of RLS was determined to increase with age. Sleep disturbance was the most common symptom of RLS in children and adolescents. Various consequences were attributed to RLS, with participants reporting that they dreaded the arrival of evening/night most frequently, followed by the description that RLS had a negative impact on mood. These data suggest that RLS is prevalent in Chinese children and adolescents, and that those affected by this disorder suffer from disruptions to sleep and daytime function.
25845902	We sought to evaluate the construct validity and factor structure of the Spanish-language version of the Pittsburgh Sleep Quality Index (PSQI) among pregnant Peruvian women.A cohort of 642 women were interviewed at ≤ 16 weeks of gestation. During interview, we ascertained information about lifestyles, demographics, sleep characteristics, and mood symptoms. Stress induced sleep disturbance, depressive symptoms, and anxiety symptoms were evaluated using the Ford Insomnia Response to Stress Test (FIRST), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) assessment scales, respectively. Consistency indices, exploratory and confirmatory factor analyses, correlations, and logistic regressions were used.	Both exploratory and confirmatory factor analyses indicated a three-factor solution: sleep quality, sleep efficiency, and sleep medication. We observed significantly positive correlations of the PSQI with the FIRST (0.42), the PHQ-9 (0.49), and the GAD-7 (0.46). Poor sleepers (PSQI global score > 5) had significantly increased odds of experiencing stress-induced sleep disturbance (odds ratio, OR = 3.57; 95% CI: 2.40, 5.31), depression (OR = 5.48; 95% CI: 3.58, 8.37), and generalized anxiety disorder (OR = 4.57; 95% CI: 3.08, 6.76).	The Spanish-language version of the PSQI instrument was found to have good construct validity among pregnant Peruvian women. Consistent with some other studies, the PSQI was found to have a three-factor structure. Further assessment and validation studies are needed to determine whether the three, factor-specific scoring of the PSQI is favored over the PSQI global score in diverse populations.	
25845895	Caffeine, a commonly consumed psychoactive substance, can have significant effects on sleep. Caffeine intake among children is increasing, mainly in the form of sodas. However, adolescent caffeine consumers may lack knowledge about the caffeine content in common beverages. If true, this very fact may hamper the assessment of the effects of caffeine consumption on sleep in children if such assessments are a priori dependent on responders being able to reliably distinguish between caffeinated and noncaffeinated beverages. This preliminary study investigated adolescents' caffeine knowledge and intake at a Cleveland-area public middle school.Seventh- and eighth-grade students were surveyed using: (1) the Caffeine Literacy and Sleep Study (CLASS), a 15-question pilot instrument designed to assess caffeine knowledge and intake by type, quantity and timing, as well as sleep habits; and (2) the Cleveland Adolescent Sleepiness Questionnaire (CASQ), a validated survey measuring excessive daytime sleepiness in adolescents. These questionnaires were distributed and collected during a specified class period.	Of the 635 seventh- and eighth-grade students who attended school on the day of the study, 555 (87%) participated. Lack of knowledge about caffeine content of particular drinks was noted in seventh and eighth graders of both sexes with nearly 29% unaware that their favorite drinks contain caffeine and more than 50% unable to correctly identify the drinks with the most caffeine. A low percentage of students correctly identified light-colored sodas lacking caffeine: 7-Up (24.1%), Sierra Mist (38.9%), ginger ale (39.8%), Sprite (39.8%), and Fresca (53.7%). The percentages of students correctly identifying caffeinated light-colored beverages were: Arizona Green Tea (43.5%), Mello Yellow (50.9%), and A&W cream soda (67.6%). However, Mountain Dew was correctly identified by most (93.5%) as caffeinated.	Students were not consistently able to identify caffeine content or lack thereof in some common beverages. The results of this pilot study show that caffeine literacy in adolescents warrants further investigation and educational intervention.	

25845891	Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve both sleep and depressive symptoms, but predictors of depression outcome following CBT-I have not been well examined. This study investigated how chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency (SE) were related to changes in depressive symptoms among recipients of CBT-I.Included were 419 adult insomnia outpatients from a sleep disorders clinic (43.20% males, age mean ± standard deviation = 48.14 ± 14.02). All participants completed the Composite Scale of Morningness and attended at least 4 sessions of a 6-session group CBT-I. SE was extracted from sleep diary; depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior to (Baseline), and at the end (End) of intervention.	Multilevel structural equation modeling revealed that from Baseline to End, SE increased and BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline, stronger evening chronotype and less improvement in SE significantly and uniquely predicted less reduction in BDI from Baseline to End. Chronotype did not predict improvement in SE.	In an insomnia outpatient sample, SE and depressive symptoms improved significantly after a CBT-I group intervention. All chronotypes benefited from sleep improvement, but those with greater eveningness and/or less sleep improvement experienced less reduction in depressive symptom severity. This suggests that evening preference and insomnia symptoms may have distinct relationships with mood, raising the possibility that the effect of CBT-I on depressive symptoms could be enhanced by assessing and addressing circadian factors.	
25845698	To evaluate the sleep pattern and the motor activity during sleep in a cohort of patients affected by Huntington disease (HD).Cross-sectional cohort study.	Sleep laboratory.	Thirty HD patients, 16 women and 14 men (mean age 57.3 ± 12.2 y); 30 matched healthy controls (mean age 56.5 ± 11.8 y).	Subjective sleep evaluation: Epworth Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical evaluation: disease duration, clinical severity (unified Huntington disease motor rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video-polysomnography (V-PSG).	The duration of the disease was 9.4 ± 4.4 y, UHMDRS score was 55.5 ± 23.4, CAG repeats were 44.3 ± 4.1. Body mass index was 21.9 ± 4.0 kg/m(2). No patients or caregivers reported poor sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS score ≥ 9. Eight patients had high risk of obstructive sleep apnea. At the RBD questionnaire, two patients had a pathological score. HD patients, compared to controls, showed shorter sleep, reduced sleep efficiency index, and increased arousals and awakenings. Four patients presented with sleep disordered breathing (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all patients. No episode of RBD was observed in the V-PSG recordings, and no patients showed rapid eye movement (REM) sleep without atonia. The disease duration correlated with ESS score (P < 0.02). UHMDRS correlated positively with the ESS score (P < 0.005), and negatively with the percentage of REM sleep.	Patients with Huntington disease showed a severe sleep disruption and a high prevalence of periodic limb movements, but no evidence of sleep disordered breathing or REM sleep behavior disorder.	
25845697	While actigraphy is considered objective, the process of setting rest intervals to calculate sleep variables is subjective. We sought to evaluate the reproducibility of actigraphy-derived measures of sleep using a standardized algorithm for setting rest intervals.Observational study.	Community-based.	A random sample of 50 adults aged 18-64 years free of severe sleep apnea participating in the Sueño sleep ancillary study to the Hispanic Community Health Study/Study of Latinos.	N/A.	Participants underwent 7 days of continuous wrist actigraphy and completed daily sleep diaries. Studies were scored twice by each of two scorers. Rest intervals were set using a standardized hierarchical approach based on event marker, diary, light, and activity data. Sleep/wake status was then determined for each 30-sec epoch using a validated algorithm, and this was used to generate 11 variables: mean nightly sleep duration, nap duration, 24-h sleep duration, sleep latency, sleep maintenance efficiency, sleep fragmentation index, sleep onset time, sleep offset time, sleep midpoint time, standard deviation of sleep duration, and standard deviation of sleep midpoint. Intra-scorer intraclass correlation coefficients (ICCs) were high, ranging from 0.911 to 0.995 across all 11 variables. Similarly, inter-scorer ICCs were high, also ranging from 0.911 to 0.995, and mean inter-scorer differences were small. Bland-Altman plots did not reveal any systematic disagreement in scoring.	With use of a standardized algorithm to set rest intervals, scoring of actigraphy for the purpose of generating a wide array of sleep variables is highly reproducible.	
25845696	The ventrolateral preoptic area (VLPO) and the orexin/hypocretin neuronal system are key regulators of sleep onset, transitions between vigilance states, and energy homeostasis. Reciprocal projections exist between the VLPO and orexin/hypocretin neurons. Although the importance of the VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are involved in energy balance. The purpose of these studies was to determine if the VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO modulates behaviors (sleep and wakefulness, feeding, spontaneous physical activity [SPA]) to increase energy expenditure.Sleep, wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae targeting the VLPO. We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively.	Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep with no effect on food intake. Pretreatment with DORA blocked the increase in wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R antagonist reduced SPA stimulated by orexin-A.	These data show the ventrolateral preoptic area is a site of action for orexin-A, which may promote negative energy balance by modulating sleep/wakefulness and stimulating spontaneous physical activity and energy expenditure.	
25845695	The CACNA1C gene encodes the alpha 1C (α1C) subunit of the Cav1.2 voltage-dependent L-type calcium channel (LTCC). Some of the other voltage-dependent calcium channels, e.g., P-/Q-type, Cav2.1; N-type, Cav2.2; E-/R-type, Cav2.3; and T-type, Cav3.3 have been implicated in sleep modulation. However, the contribution of LTCCs to sleep remains largely unknown. Based on recent genome-wide association studies, CACNA1C emerged as one of potential candidate genes associated with both sleep and psychiatric disorders. Indeed, most patients with mental illnesses have sleep problems and vice versa.To investigate an impact of Cav1.2 on sleep-wake behavior and electroencephalogram (EEG) activity, polysomnography was performed in heterozygous Cacna1c (HET) knockout mice and their wild-type (WT) littermates under baseline and challenging conditions (acute sleep deprivation and restraint stress).	HET mice displayed significantly lower EEG spectral power than WT mice across high frequency ranges (beta to gamma) during wake and rapid eye movement (REM) sleep. Although HET mice spent slightly more time asleep in the dark period, daily amounts of sleep did not differ between the two genotypes. However, recovery sleep after exposure to both types of challenging stress conditions differed markedly; HET mice exhibited reduced REM sleep recovery responses compared to WT mice.	These results suggest the involvement of Cacna1c (Cav1.2) in fast electroencephalogram oscillations and REM sleep regulatory processes. Lower spectral gamma activity, slightly increased sleep demands, and altered REM sleep responses found in heterozygous Cacna1c knockout mice may rather resemble a sleep phenotype observed in schizophrenia patients.	
25845691	The aim of this study was to investigate trajectories of sleep quality and associations with mood in the perinatal period. Although it is commonly accepted that subjective sleep quality declines during pregnancy and the transition to parenthood, some women may follow qualitatively distinct trajectories.Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age [GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based semiparametric mixture model was used to estimate patterns of sleep quality throughout the perinatal period.	Four trajectory groups were identified, including patterns defined by high sleep quality throughout (21.5%), mild decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%) and a group with poor sleep quality throughout (6.7%). Women who had the worst sleep quality at Time 1 and those who experienced significant increases in sleep problems throughout pregnancy were also the groups who reported the highest levels of anxiety and depressive symptoms in early pregnancy and the lowest levels of social support. After controlling for covariates, the groups with worst subjective sleep quality during pregnancy were also the most likely to experience high symptoms of depression in the postpartum period.	Most of the women in our sample reported mild sleep disturbances through the perinatal period. A subgroup of women reported a significant decline in sleep quality from early to late pregnancy and another reported poor subjective sleep quality throughout pregnancy; these groups had the greatest risk of experiencing high symptoms of depression in the postpartum period.	
25844033	Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms. While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood. Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011. Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week. Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met. Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures. Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels. Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom. Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms. Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without. Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. 
25842346	This analysis examined the influence of quantifiable parameters of daily sleep continuity, primarily sleep duration and sleep fragmentation, on daily pain in adults with sickle cell disease. Seventy-five adults with sickle cell disease completed baseline psychosocial measures and daily morning (sleep) and evening (pain) diaries over a 3-month period. Mixed-effect modeling was used to examine daily between- and within-subjects effects of sleep continuity parameters on pain, as well as the synergistic effect of sleep fragmentation and sleep duration on pain. Results revealed that nights of shorter sleep duration and time in bed, increased fragmentation, and less efficient sleep (relative to one's own mean) were followed by days of greater pain severity. Further, the analgesic benefit of longer sleep duration was attenuated when sleep fragmentation was elevated. These results suggest that both the separate and combined effects of sleep duration and fragmentation should be considered in evaluating pain in adults with sickle cell disease.Subjective parameters of sleep continuity (eg, sleep duration, fragmentation, and efficiency) predict clinical pain in individuals with sickle cell disease. Additionally, sleep duration should not be considered in isolation, and its association with pain may be qualified by sleep fragmentation. Research and practice should include assessments of both when addressing pain severity.	
25842028	Nocturnal shoulder pain resulting in poor sleep quality is a common finding in patients with shoulder disease. The purpose of this paper was to describe and to compare the sleep quality, pain, and function in adult subjects who have been diagnosed with rotator cuff disorders, osteoarthritis, or adhesive capsulitis (AC).Patients completed a clinical assessment and comprehensive questionnaire regarding their current medical health history, shoulder symptoms, and impact of their symptoms on activities of daily living and quality of sleep.	The study analyzed 343 patients with an average age of 57.4 years. The mean Single Assessment Numeric Evaluation score for AC was 34%, which was significantly lower than the score for the subacromial impingement syndrome group of 53% (P = .007). The mean American Shoulder and Elbow Surgeons scale score for AC was 38, which was also significantly lower than the score for the subacromial impingement syndrome group of 51 (P = .007). There were no significant differences in pain, with mean scores ranging from 4.90 to 5.82 for diagnostic subgroups on a visual analog scale (P = .28). Sleep quality was significantly poorer in the AC group (P = .008), with a mean Pittsburgh Sleep Quality Index score of 12.07. Specific subcomponents of the Pittsburgh Sleep Quality Index that had a significant impact on sleep interruption included sleep quality, sleep duration, and habitual sleep efficiency in the AC group (P < .05).	This study shows that whereas many patients with shoulder disease may have sleep-related issues, patients with adhesive capsulitis are particularly vulnerable to reduced sleep quality.	
25840445	To characterize the health-related quality of life (HRQoL) of children with eosinophilic esophagitis (EoE) as well as generate novel hypotheses for future research in this pediatric population.A literature review was completed using PubMed and the keywords below.	Research has shown that for children with EoE and their parents, symptom experiences and recommended treatments can have a negative impact on HRQoL. However, studies have yet to adequately address mechanisms that may help explain why this is. Areas of interest include sleep quality and disturbances, the experience of pain, and the presence of internalizing symptoms, all of which have the potential to uniquely and synergistically impact HRQoL.	With greater understanding of the associations among sleep, pain, internalizing symptoms, and HRQoL in children with EoE may come enhanced therapies that substantially improve the quality of their health care.	
25840384	Sleep disturbances are recognized as a side effect of cancer treatment, affecting physiological and psychological functioning. Sleep disturbances can persist through treatment and survivorship, and are increasingly prevalent among breast cancer survivors (BCSs).The purpose of this review is to summarize current research on subjective and objective measures of sleep disturbances, the association between subjective and objective measures, and interventions used to manage sleep disturbances among BCSs after the completion of treatment.	Articles published from 2003-2013 were retrieved using PubMed, Web of Science, and ScienceDirect. Key search terms included breast cancer, sleep actigraphy, and sleep disturbances. Articles assessing sleep subjectively and objectively in the post-treatment period were included.	Twelve studies met the inclusion criteria.	
25839208	Since there is less movement during sleep than during wake, the recording of body movements by actigraphy has been used to indirectly evaluate the sleep-wake cycle. In general, most actigraphic devices are placed on the wrist and their measures are based on acceleration detection. Here, we propose an alternative way of measuring actigraphy at the level of the arm for joint evaluation of activity and body position. This method analyzes the tilt of three axes, scoring activity as the cumulative change of degrees per minute with respect to the previous sampling, and measuring arm tilt for the body position inference. In this study, subjects (N = 13) went about their daily routine for 7 days, kept daily sleep logs, wore three ambulatory monitoring devices and collected sequential saliva samples during evenings for the measurement of dim light melatonin onset (DLMO). These devices measured motor activity (arm activity, AA) and body position (P) using the tilt sensing of the arm, with acceleration (wrist acceleration, WA) and skin temperature at wrist level (WT). Cosinor, Fourier and non-parametric rhythmic analyses were performed for the different variables, and the results were compared by the ANOVA test. Linear correlations were also performed between actimetry methods (AA and WA) and WT. The AA and WA suitability for circadian phase prediction and for evaluating the sleep-wake cycle was assessed by comparison with the DLMO and sleep logs, respectively. All correlations between rhythmic parameters obtained from AA and WA were highly significant. Only parameters related to activity levels, such as mesor, RA (relative amplitude), VL5 and VM10 (value for the 5 and 10 consecutive hours of minimum and maximum activity, respectively) showed significant differences between AA and WA records. However, when a correlation analysis was performed on the phase markers acrophase, mid-time for the 10 consecutive hours of highest (M10) and mid-time for the five consecutive hours of lowest activity (L5) with DLMO, all of them showed a significant correlation for AA (R = 0.607, p = 0.028; R = 0.582, p = 0.037; R = 0.620, p = 0.031, respectively), while for WA, only acrophase did (R = 0.621, p = 0.031). Regarding sleep detection, WA showed higher specificity than AA (0.95 ± 0.01 versus 0.86 ± 0.02), while the agreement rate and sensitivity were higher for AA (0.76 ± 0.02 versus 0.66 ± 0.02 and 0.71 ± 0.03 versus 0.53 ± 0.03, respectively). Cohen's kappa coefficient also presented the highest values for AA (0.49 ± 0.04) and AP (0.64 ± 0.04), followed by WT (0.45 ± 0.06) and WA (0.37 ± 0.04). The findings demonstrate that this alternative actigraphy method (AA), based on tilt sensing of the arm, can be used to reliably evaluate the activity and sleep-wake rhythm, since it presents a higher agreement rate and sensitivity for detecting sleep, at the same time allows the detection of body position and improves circadian phase assessment compared to the classical actigraphic method based on wrist acceleration. 
25838043	The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging.Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment.	Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022).	Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging.	
25835421	Sleep disorders are frequently reported in Alzheimer's disease (AD), with a significant impact on patients and caregivers and a major risk factor for early institutionalization. Although changes in sleep organization are a hallmark of the normal aging processes, sleep macro- and micro-architectural alterations are more evident in patients affected by AD. Degeneration of neural pathways regulating sleep-wake patterns and sleep architecture may contribute to sleep alterations. In return, several recent studies suggested that common sleep disorders may precede clinical symptoms of dementia and represent risk factors for cognitive decline, through impairment of sleep-dependent memory consolidation processes. Thus, a close relationship between sleep disorders and AD has been largely hypothesized. Here, sleep alterations in AD and its pre-dementia stage, mild cognitive impairment, and their complex interactions are reviewed.
25829994	This article looks at the issues of excessive daytime sleepiness and unintended sleep episodes in patients with Parkinson's disease (PD) and explores the reasons why patients might suffer from these symptoms, and what steps could be taken to manage them. During the last decade, understanding of sleep/wake regulation has increased. Several brainstem nuclei and their communication pathways in the ascending arousing system through the hypothalamus and thalamus to the cortex play key roles in sleep disorders. Insomnia is the most common sleep disorder in PD patients, and excessive daytime sleepiness is also common. Excessive daytime sleepiness affects up to 50% of PD patients and a growing body of research has established this sleep disturbance as a marker of preclinical and premotor PD. It is a frequent and highly persistent feature in PD, with multifactorial underlying pathophysiology. Both age and disease-related disturbances of sleep-wake regulation contribute to hypersomnia in PD. Treatment with dopamine agonists also contribute to excessive daytime sleepiness. Effective management of sleep disturbances and excessive daytime sleepiness can greatly improve the quality of life for patients with PD. 
25828678	The state of sleep consists of different phases that proceed in successive, tightly regulated order through the night forming a physiological program, which for each individual is different but stabile from one night to another. Failure to accomplish this program results in feeling of unrefreshing sleep and tiredness in the morning. The pro- gram core is constructed by genetic factors but regulated by circadian rhythm and duration and intensity of day time brain activity. Many environmental factors modulate sleep, including stress, health status and ingestion of vigilance-affecting nutrients or medicines (e.g. caffeine). Knowledge of the factors that regulate the spontaneous sleep-wake cycle and factors that can affect this regulation forms the basis for diagnosis and treatment of the many common disorders of sleep. 
25828559	Fatigue is the most common symptom in oncology patients during chemotherapy. Little is known about the predictors of interindividual variability in initial levels and trajectories of morning fatigue severity in these patients.An evaluation was done to determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of morning fatigue and to compare findings with our companion paper on evening fatigue.	A sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (n = 586) completed demographic and symptom questionnaires a total of six times over two cycles of chemotherapy. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling was used to answer the study objectives.	A large amount of interindividual variability was found in the morning fatigue trajectories. A piecewise model fit the data best. Patients with higher body mass index, who did not exercise regularly, with a lower functional status, and who had higher levels of state anxiety, sleep disturbance, and depressive symptoms reported higher levels of morning fatigue at enrollment. Variations in the trajectories of morning fatigue were predicted by the patients' ethnicity and younger age.	The modifiable risk factors that were associated with only morning fatigue were body mass index, exercise, and state anxiety. Modifiable risk factors that were associated with both morning and evening fatigue included functional status, depressive symptoms, and sleep disturbance. Using this information, clinicians can identify patients at higher risk for more severe morning fatigue and evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors.	
25827799	Asymptomatic reflux esophagitis (RE) is simply regarded as RE without the typical reflux symptoms, but it is unknown whether patients with asymptomatic RE have atypical symptoms. The aim of this study was to examine the clinical characteristics and health-related quality of life (HRQOL) of patients with asymptomatic RE.Consecutive patients with RE were enrolled during January 2010 to August 2012, and of them, 41 who had taken acid-suppressing drugs were excluded, leaving 280 patients as the study group. The patients' symptoms were evaluated using a self-completed questionnaire (modified Frequency Scale for the Symptoms of gastroesophageal reflux disease [FSSG]), as well as an HRQOL questionnaire (SF-8). We defined the typical symptoms of RE as heartburn and regurgitation. Asymptomatic RE was defined if the total symptom score was 0 or the minimum (1 point) for typical reflux symptoms in the modified FSSG.	Of the 280 RE patients, 71.8% (n = 201) were symptomatic and 28.2% (n = 79) were asymptomatic. The atypical symptom scores were significantly lower in asymptomatic RE (2.2 ± 2.2) than in symptomatic RE patients (6.9 ± 5.2) (P < 0.0001), and the HRQOL scores were significantly higher in asymptomatic RE than in symptomatic RE (P < 0.0001). Sleep was significantly less disturbed and chronic cough less frequent in asymptomatic RE than in symptomatic RE.	Frequency and severity of atypical symptoms in patients with asymptomatic RE were significantly less than in patients with symptomatic RE, and the HRQOL score was significantly higher in those patients. These observations suggest a specific patient cohort that is truly unlikely to manifest symptoms.	
25827402	A novel series of 3,4-diaza-bicyclo[4.1.0]hept-4-en-2-ones were designed and synthesized as H3R analogs of irdabisant 6. Separation of the isomers, assignment of the stereochemistry by crystallography, and detailed profiling of diastereomers 25 and 26 led to the identification of (1R,6S)-5-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)propoxy]phenyl}-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one 25 as a potential second generation H3R candidate. Diastereomer 25 had high H3R binding affinity, excellent selectivity, displayed potent H3R functional antagonism and robust wake-promoting activity in vivo, and showed acceptable pharmacokinetic and pharmaceutical profiles for potential further development. 
25825756	Sleep in Drosophila shares many features with mammalian sleep, but it remains unknown whether spontaneous and evoked activity of individual neurons change with the sleep/wake cycle in flies as they do in mammals. Here we used calcium imaging to assess how the Kenyon cells in the fly mushroom bodies change their activity and reactivity to stimuli during sleep, wake, and after short or long sleep deprivation. As before, sleep was defined as a period of immobility of >5 min associated with a reduced behavioral response to a stimulus. We found that calcium levels in Kenyon cells decline when flies fall asleep and increase when they wake up. Moreover, calcium transients in response to two different stimuli are larger in awake flies than in sleeping flies. The activity of Kenyon cells is also affected by sleep/wake history: in awake flies, more cells are spontaneously active and responding to stimuli if the last several hours (5-8 h) before imaging were spent awake rather than asleep. By contrast, long wake (≥29 h) reduces both baseline and evoked neural activity and decreases the ability of neurons to respond consistently to the same repeated stimulus. The latter finding may underlie some of the negative effects of sleep deprivation on cognitive performance and is consistent with the occurrence of local sleep during wake as described in behaving rats. Thus, calcium imaging uncovers new similarities between fly and mammalian sleep: fly neurons are more active and reactive in wake than in sleep, and their activity tracks sleep/wake history. 
25824597	Fibromyalgia (FM) and rheumatoid arthritis (RA) are associated with sleep disturbance and daytime sleepiness. We sought to determine whether sleep homeostatic mechanisms are blunted in FM by assessing the effects of reduced time in bed (4h) on next day sleepiness and recovery sleep.Fifty women (18 with FM, 16 with RA, and 16 HC) had a baseline 8h time-in-bed (TIB) and Multiple Sleep Latency Test (MSLT) the following day, and 3-7 days later bedtime was reduced (4h) followed by MSLT and an 8h TIB recovery night.	Following reduced bedtime the MSLT was reduced relative to baseline in the FM group by an amount (4.3+/-4.8 min) similar to that of the RA (3.1+/-5.2 min) and HC (4.8 +/-3.1 min) groups. Relative to the baseline on the recovery night the FM group showed increased sleep efficiency (83.7+/-7.8 to 88.1+/-9.2%) relative to the RA (83.9+/-8.6 to 80.9+/-13.3%) and HC (90.1+/-5.0 to 87.4+/-7.6%) groups due primarily to reduced wake after sleep onset. The groups did not differ in recovery night sleep stages with the exception that the FM group showed REM rebound (21.6+/-6.5 to 25.2+/-6.0%), which was not found in the RA (20.4+/-7.4 to 17.8+/-6.5%) or HC (16.6+/-6.6 to 17.5+/-6.0%) groups.	Compared to RA and HC, people with FM responded to reduced bedtime with a comparable increase in sleepiness and greater recovery sleep efficiency, suggesting that homeostatic sleep mechanisms are functional in FM. People with FM uniquely showed REM rebound on recovery from reduced bedtime suggesting underlying REM pressure.	
25822517	Research evidence is limited regarding developmentally appropriate care. Variations exits with respect to test procedure type, infant age at testing, and test relatedness.To assess developmental continuity using multiple developmental measures from birth to 12 months in a single cohort of term infants.	A secondary analysis, longitudinal, correlational design was used to assess developmental continuity in a single cohort of infants (n 27). Measures included: sleep, using the Motility Monitoring System (first 48 hours of life); temperament, using the Infant Characteristics Questionnaire (ICQ, 6 months) and the Revised Infant Temperament Questionnaire (RITQ, 12 months); problem-solving, using the Willatts Infant Planning Test (PS, 9 and 12 months); and the Fagan Test of Infant Intelligence (FTII, 6 and 9 months).	Using Spearmen correlation, significant correlations included: (1) Sleep and ICQ: transitional sleep and "unpredictable" (r 0.455, P .017), "unadaptable" (r 0.420, P .026), and "dull" (r 0.416, P .028); (2) ICQ and FTII 6 months (r -0.512, P .008); (3) RITQ "approachability" and quiet sleep (r 0.662, P .005); (4) arousals in active sleep and PS at 9 months (r -0.528, P .016).	Given our reported continuity between early sleep and later developmental measures, sleep-wake state should be considered in caregiving and environmental control to support sleep. Parental education on facilitating sleep-wake regulation in the home environment is essential.	These data support the existence of continuity between early sleep and later developmental milestones warranting a larger-scale investigation. Specific focus on development of care strategies for facilitating sleep immediately following birth is warranted.	
25820491	This study explores the state dependence of the hypercapnic ventilatory reflex (HCVR). We simulated an instantaneous increase or decrease of central chemoreceptor activity by activating or inhibiting the retrotrapezoid nucleus (RTN) by optogenetics in conscious rats. During quiet wake or non-REM sleep, hypercapnia increased both breathing frequency (fR ) and tidal volume (VT ) whereas, in REM sleep, hypercapnia increased VT exclusively. Optogenetic inhibition of RTN reduced VT in all sleep-wake states, but reduced fR only during quiet wake and non-REM sleep. RTN stimulation always increased VT but raised fR only in quiet wake and non-REM sleep. Phasic RTN stimulation produced active expiration and reduced early expiratory airflow (i.e. increased upper airway resistance) only during wake. We conclude that the HCVR is highly state-dependent. The HCVR is reduced during REM sleep because fR is no longer under chemoreceptor control and thus could explain why central sleep apnoea is less frequent in REM sleep.Breathing has different characteristics during quiet wake, non-REM or REM sleep, including variable dependence on PCO2. We investigated whether the retrotrapezoid nucleus (RTN), a proton-sensitive structure that mediates a large portion of the hypercapnic ventilatory reflex, regulates breathing differently during sleep vs. wake. Electroencephalogram, neck electromyogram, blood pressure, respiratory frequency (fR ) and tidal volume (VT ) were recorded in 28 conscious adult male Sprague-Dawley rats. Optogenetic stimulation of RTN with channelrhodopsin-2, or inhibition with archaerhodopsin, simulated an instantaneous increase or decrease of central chemoreceptor activity. Both opsins were delivered with PRSX8-promoter-containing lentiviral vectors. RTN and catecholaminergic neurons were transduced. During quiet wake or non-REM sleep, hypercapnia (3 or 6% FI,CO2 ) increased both fR and VT whereas, in REM sleep, hypercapnia increased VT exclusively. RTN inhibition always reduced VT but reduced fR only during quiet wake and non-REM sleep. RTN stimulation always increased VT but raised fR only in quiet wake and non-REM sleep. Blood pressure was unaffected by either stimulation or inhibition. Except in REM sleep, phasic RTN stimulation entrained and shortened the breathing cycle by selectively shortening the post-inspiratory phase. Phasic stimulation also produced active expiration and reduced early expiratory airflow but only during wake. VT is always regulated by RTN and CO2 but fR is regulated by CO2 and RTN only when the brainstem pattern generator is in autorhythmic mode (anaesthesia, non-REM sleep, quiet wake). The reduced contribution of RTN to breathing during REM sleep could explain why certain central apnoeas are less frequent during this sleep stage.	
25819463	To examine the relationship between postpartum sleep disturbance and postpartum depression and describe the characteristics and demographics of the samples.Electronic databases Medline, PubMed, Cochrane, EPOC, CINAHL, ProQuest, and Psych INFO. In addition, hand searches of bibliographies supplemented the electronic search.	English language primary studies on the relationship between postpartum sleep disturbance and postpartum depression were included. Thirteen observational studies met the inclusion criteria.	Data that specified the relationship between sleep disturbance and postpartum depression were extracted from the studies. The data were organized per author, year, participants, setting, country, demographics, design, sample size, outcomes, evidence, and effect size.	The effect size indicating the relationship between sleep disturbance and postpartum depression across the studies ranged between 0.4 and 1.7. There was evidence of a strong relationship between sleep disturbance and postpartum depression; however, the participants in the 13 studies were predominantly educated, middle class, older than age 30 years, and White. Likewise, the definition and measurement of postpartum sleep varied across the studies, which increased the possibility of bias.	Further research within the postpartum period involving underserved, younger women and samples with more diversity in race and ethnicity are needed.	
25819418	The aim of this study was to evaluate whether high-frequency heart rate variability (HF-HRV) during waking restfulness and during worry predicts increases in sleep disturbances in response to a stressful life event.A longitudinal study following up 22 individuals from well-defined periods of lower and higher stress was conducted. HF-HRV during waking restfulness and in response to a worry induction was measured during a low-stress period. Sleep disturbances were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) during low-stress and high-stress periods.	During both the low- and high-stress periods, lower HF-HRV during worry was associated with greater PSQI scores. Importantly, lower HF-HRV during the worry induction prospectively predicted greater increases in the PSQI score from the low-stress to the high-stress periods.	HF-HRV during worry might represent an index of vulnerability to stress-induced sleep disturbances.	
25819416	The objective of this study was to investigate the role of obesity and weight gain in the development of sleep problems in a population-based cohort.A population-based sample of men (n = 1896, aged 40-79 years) and women (n = 5116, age ≥20 years) responded to questionnaires at baseline and follow-up after 10-13 years. Sleep problems were assessed through questions about difficulties initiating sleep (DIS), difficulties maintaining sleep (DMS), excessive daytime sleepiness (EDS), and insomnia. Body mass index (BMI) was calculated from self-reported weight and height at both baseline and follow-up, while confounding factors (physical activity, tobacco and alcohol use, somatic disease, and snoring) were based on responses at baseline.	Although overweight and obese subjects reported more sleep problems at baseline, there was no independent association between BMI level at baseline and development of new sleep problems. Subjects in the quartile with the highest rise in BMI with a weight gain exceeding 2.06 kg/m2 had a higher risk of developing DMS [adjusted odds ratio (OR) 1.58; 95% confidence interval (CI) 1.25-2.01), EDS (2.25; 1.65-3.06], and insomnia (2.78; 1.60-4.82). Weight gain was not associated with the development of DIS.	Weight gain is an independent risk factor for developing several sleep problems and daytime sleepiness. The presence of overweight and weight gain should be considered when treating patients with sleep problems.	
25818627	Sleep disturbance is prevalent among patients with psychosis, yet little is known about sleep health during the ultra high-risk (UHR) period. This study used actigraphy to evaluate sleep in healthy control (HC) and UHR adolescents to examine the relationship between sleep disturbance and psychosis symptoms at baseline and 12-month follow-up, as well as comparisons between objective and subjective measurements of sleep functioning in UHR youth.Thirty-six UHR and 31 HC youth participated in a baseline evaluation including 5 nights of actigraphy, subjective measurement of sleep health (Pittsburgh Sleep Quality Index; PSQI), and clinical interviews. Clinical measures were repeated with UHR youth (N=23) at a 12-month follow-up.	The actigraphy data indicated that UHR youth displayed increased wake time after onset (WASO), increased movements during sleep, and decreased efficiency compared to HC, and several markers of sleep disturbance including decreased efficiency, increased WASO, number of awakenings, and increased movements were associated with symptomatology in the UHR group. Interestingly, there were associations between actigraph and self-report indices of sleep duration and efficiency (at the trend level) but not awakenings. Several objective measures of sleep disturbance and one self-reported measure (disrupted continuity) predicted the longitudinal course of symptoms over 12 months in the UHR group.	Taken together, the results suggest a potential role for sleep problems in the etiology of schizophrenia, and highlight sleep health as a possible target for prevention/intervention efforts. Additionally, actigraphy represents an inexpensive, sensitive measurement providing unique information not captured by self-report, and may be an informative adjunct to UHR assessments.	
25817615	Modern lifestyle and job requirements have changed the sleep habits of most of the adult population. Various population-based studies have associated an increase in mortality with either shortened sleep or long sleep duration. Thus a U-shaped relationship between sleep duration and all-cause mortality in both men and women has been suggested. Several studies have found an association between sleep duration and risk of cardiovascular diseases also. Efforts to understand the etiology of stroke have indicated an association between sleep and stroke too. Obstructive sleep apnea, a sleep-related disorder, has been reported to significantly increase the risk of stroke. Moreover, many studies have shown that both short and long sleep durations are related to increased likelihood of diabetes and hypertension, which themselves are risk factors for stroke. Therefore, this review focuses on the correlation between sleep duration and risk of stroke based on the experimental and epidemiologic studies. Although a few experimental studies have reported that partial sleep deprivation may reduce stroke incidence and severity, yet, most experimental and observational studies have indicated a strong association between short/long sleep durations and higher risk of stroke. 
25815329	The prevalence of HIV (human immunodeficiency virus) associated neurocognitive disorders (HAND) will undoubtedly increase with the improved longevity of HIV-infected persons. HIV infection, itself, as well as multiple physiologic and psychosocial factors can contribute to cognitive impairment and neurologic complications. These comorbidities confound the diagnosis, assessment, and interventions for neurocognitive disorders. In this review, we discuss the role of several key comorbid factors that may contribute significantly to the development and progression of HIV-related neurocognitive impairment, as well as the current status of diagnostic strategies aimed at identifying HIV-infected individuals with impaired cognition and future research priorities and challenges. 
25811755	Disordered sleep and myopia are increasingly prevalent among Chinese children. Similar pathways may be involved in regulation of both sleep cycles and eye growth. We therefore sought to examine the association between disordered sleep and myopia in this group.Urban primary school children participating in a clinical trial on myopia and outdoor activity underwent automated cycloplegic refraction with subjective refinement. Parents answered questions about children's sleep duration, sleep disorders (Children's Sleep Habits Questionnaire [CSHQ]), near work and time spent outdoors.	Among 1970 children, 1902 (96.5%, mean [standard deviation SD] age 9.80 [0.44] years, 53.1% boys) completed refraction and questionnaires. Myopia < = -0.50 Diopters was present in both eyes of 588 (30.9%) children (1329/3804 = 34.9% of eyes) and 1129 children (59.4%) had abnormal CSHQ scores (> 41). In logistic regression models by eye, odds of myopia < = -0.50D increased with worse CSHQ score (Odds Ratio [OR] 1.01 per point, 95% Confidence Interval [CI] [1.001, 1.02], P = 0.014) and more night-time sleep (OR 1.02, 95% CI [1.01, 1.04, P = 0.002], while male sex (OR 0.82, 95% CI [0.70, 0.95], P = 0.008) and time outdoors (OR = 0.97, 95% CI [0.95, 0.99], P = 0.011) were associated with less myopia. The association between sleep duration and myopia was not significant (p = 0.199) for total (night + midday) sleep.	Myopia and disordered sleep were both common in this cohort, but we did not find consistent evidence for an association between the two.	
25809806	The prevalence of subjective sleep and cognitive complaints increases with age. The purpose of this study was to investigate the link between subjective cognitive and sleep complaints in a population aged 65.analysis of a cohort of 1011 subjects aged 65 years old at time of inclusion.	Older people underwent a cognitive tests battery and a nocturnal polygraphy recording. Subjective cognitive difficulties were scored on the McNair and Kahn Scale. Subjective sleep complaints were evaluated according to the St. Mary's Hospital Sleep Questionnaire and the Epworth Sleepiness Scale score.	In a 65 years old population, an association between subjective cognitive difficulties and poor sleep quality was observed. This remained significant after adjustment on gender, depression score, anxiety, educational level, medication intake, Apnea/Hypopnea index, Body Mass Index and Mini-Mental State Examination (OR = 2.1; p = 0.0002). Similar significant association was demonstrated between subjective cognitive difficulties and daytime sleepiness (OR = 2.6; p = 0.0007).	There was a significant association between subjective cognitive and sleep complaints, and daytime sleepiness in our population of older people.	


25808396	Sleep disturbances are extremely common in alcohol recovery. Systematic research into the relationship between alcohol relapse and sleep disturbances using validated scales and accounting for potential confounders is lacking.Patients admitted to a 1-month residential addiction treatment program were administered the Pittsburg Sleep Quality Index (PSQI) at admission/discharge. In addition, the Alcohol Use Disorders Identification Test (AUDIT), Patient Health Questionnaire-9 (PHQ-9), and Pennsylvania Alcohol Craving Scale (PACS) were administered. Patients were contacted every 3 months over 1 year following discharge. Associations of clinical factors with time until relapse were examined using univariate Cox proportional hazard models.	One-hundred and nineteen patients with alcohol use disorders met inclusion criteria (mean age 50.6 ± 13.2 years, 57% male), relapse data were available for 81 patients. Eighty percent of subjects had other psychiatric diagnoses, 66.3% had sleep disturbances at the time of admission, and 57.1% were using hypnotics; 49.1% of patients had sleep disturbances at discharge. Sleep disturbances at admission and discharge were not associated with alcohol relapse at 12 months (OR = 1.00, 95% CI = 0.89-1.13; p = 0.95 and OR = 0.97, 95% CI = 0.86-1.09; p = 0.61). The PSQI sub-scale scores were also not associated with relapse at 12 months. The use of alcohol to help fall asleep (OR = 3.26, 95% CI = 1.33-7.95; p = 0.008), hypnotic use at admission (OR = 4.03, 95% CI = 1.63-9.97; p = 0.002) and age (OR = 1.03, 95% CI = 1.00-1.06; p = 0.035) were associated with relapse over 12 months.	In patients completing a residential treatment program, sleep disturbances as measured by the PSQI were not associated with alcohol relapse at 12 months. Alcohol use as a hypnotic and hypnotic use at admission were associated with subsequent relapse.	
25806502	Due to the increasing flexibilisation of the European labour market, new forms of atypical work organisation have been arising. Atypical employment may cause negative health effects similar to unemployment. Considering the health-promoting relevance of sleep for work productivity, we investigate if different forms of atypical employment are associated with difficulties falling and maintaining asleep among middle-aged male and female employees.Data were retrieved from the 1(st) wave of the lidA study, a nation-wide survey among employees in Germany in 2011. According to the Integrated Employment Biography (IEB) of the Institute of Employment Research (IAB), participants were born in 1959 or 1965 and subject to mandatory social insurance contributions on 31.12.11. Our analysis is based on 4 544 participants. Using logistic regression models separately for men and women, difficulties falling and maintaining asleep were modelled to depend on years mostly spent in full-time, part-time, in marginal employment or in unemployment during the period from 1999-2010 as well as on years in the current position, fixed-term employment contract, organisational restructuring and dismissals at time of the survey in 2011.	Women (9%) were more affected by difficulties falling and maintaining asleep than men (5%). Among women, past years mostly spent in full-time, part-time, marginal employment or in unemployment were not associated with sleep disturbances. Men who had mostly worked part-time or unemployment were more likely to report difficulties falling and maintaining asleep. Likewise, in men a fixed-term contract was linked with a higher risk of sleep disturbances. In women, witnessed dismissal in the working environment was a significant influencing factor.	Atypical employment can be related to difficulties falling and maintaining asleep. In future research gender-specific reasons for atypical employment as well as adverse working conditions should be taken into account. Changes between different forms of atypical employment as well as cumulative measures of these employment exposures in employees' biographies should be included in future studies.	
25803668	This study aims to elicit midlife women's heuristics about symptom clusters they were experiencing, as identified by the Computerized Symptom Capture Tool for Menopause (C-SCAT M).Women aged 40 to 60 years who were experiencing symptoms that they associated with menopause were recruited through flyers posted on campus and in clinics. Women completed the C-SCAT M application (app), using an iPad, by identifying and drawing symptom clusters they experienced during the last 24 hours, indicating relationships among symptoms, prioritizing the clusters and symptoms within them, making causal attributions, and identifying exacerbating and ameliorating factors. They were asked to prioritize the clusters and a symptom within each cluster. While women were completing the app, they were asked to "think aloud" about their experience using the app. Data generated from the C-SCAT M app were transmitted securely to an Amazon Web Services account and saved as screen images and Excel files to preserve both graphical images and text elicited from the app. Qualitative data were saved in verbatim phrases. Conventional content analysis was used to analyze qualitative data.	Thirty women completed the app. Most women (77%) stated that the final diagrams were very/extremely accurate in depicting their symptoms and their connections. Women reported between 1 and 22 symptoms (median, 11). Hot flashes, waking up during the night, night sweats, and early morning awakening were the most commonly reported symptoms. Women rated hot flashes as their most bothersome symptom, followed by waking up during the night and fatigue. They reported more than 300 different bivariate relationships between their symptoms and more than 150 unique causal paths. They believed that hot flashes caused several symptoms, especially sleep disruption, and most could describe the time order of their symptoms. Women reported clusters consisting of 2 to 18 symptoms. Women also named each cluster based on their response to their symptoms ("really annoying"), time of occurrence ("night problem"), and symptoms included in the cluster ("hot flash"). They attributed their clusters to menopause, life demands, and other symptoms, among other causes. Management strategies that women used included over-the-counter preparations, sleep, rest, and other lifestyle changes. Some women requested for a copy of their final symptom cluster diagram to discuss with their healthcare providers.	Use of the C-SCAT M affords women an opportunity to depict their symptoms and clusters and the relationships between them and to provide narrative data about their heuristics. Women's unsolicited comments about using the cluster diagram to facilitate conversations (about their symptoms) with their healthcare providers suggest the potential value of modifying the C-SCAT M and evaluating its use in a healthcare setting.	
25803007	In cases of burnout, chronic fatigue, depression, somatization, overtaxation, or impairment in wellbeing and work capacity, the cause can be sleep problems. Goal of the present study was to estimate the prevalence of sleep problems in psychosomatic inpatients.Included were 1325 unselected patients from a psychosomatic rehabilitation hospital. They filled in the SCL-90, the PSQI and were assessed in respect to their clinical, social and occupational status.	At admission 13.4% of patients had a PSQI score of 5 at maximum (no sleep problem), 34.6% 6 to 10 (moderate sleep problem) und 52.1% over 10 (severe sleep problem). At discharge there was a reduction of sleep problems with 32.7% of patients over 10. Sleep problems were significantly associated with more severe mental problems, older age, women, lower socioeconomic status, and also incapacity to work or early retirement.	Mental disorders can cause sleep problems and sleep problems mental disorders and incapacity to work, with a negative interaction. The high rate of severe sleep problems in rehabilitation patients shows that this problem is in need of special diagnostic and therapeutic attention. Also, the equipment of hospitals and the qualification of therapists should allow adequate care.	
25801728	Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed significant sleep disturbance, meanwhile, the glucocorticoid receptor (GR) level was notably lowered in locus coeruleus (LC). We further discovered the activation of noradrenergic neuron in LC, the suppression of GABAergic neuron in ventrolateral preoptic area (VLPO), the remarkable elevation of norepinephrine in LC, VLPO and hypothalamus, as well as increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO after CORT treatment. Microinjection of GR antagonist RU486 into LC reversed the CORT-induced sleep changes. These results suggest that GR in LC may play a key role in stress-related sleep disorders and support the hypothesis that repeated CORT treatment may decrease GR levels and induce the activation of noradrenergic neurons in LC, consequently inhibit GABAergic neurons in VLPO and result in sleep disorders. Our findings provide novel insights into the effect of stress-inducing agent CORT on sleep and GRs' role in sleep regulation. 
25801248	This nationwide population-based cohort study evaluated the effect of nonapnea sleep disorders (NSDs) on the subsequent development of a migraine.We identified 46,777 patients aged 20 years and older who were diagnosed with an NSD (ICD-9-CM: 307.4 or 780.5) and without coding for apnea-sleep disorders (ICD-9-CM: 780.51, 780.53, or 780.57) between 2000 and 2002 as the sleep disorder (SD) cohort. A comparison cohort of 93,552 people was enrolled. We calculated the adjusted hazard ratio (aHR) for developing a migraine (ICD-9-CM: 346) after adjusting for age, sex, comorbidity, and drug use. A Kaplan-Meier analysis was used to measure the cumulative incidence of a migraine between 2 curves until the end of 2011.	The cumulative incidence of a migraine was significantly higher in the SD cohort. The aHR for developing a migraine in the SD cohort was 3.52 (95% CI=3.28-3.79). The risk of developing a migraine with an NSD was higher in men (aHR=4.31) than in women (aHR=3.35). The age-stratified effect of an NSD on developing a migraine was highest among patients aged 55 years and younger. Higher risks of developing a migraine were observed among the participants without any comorbidity and without any drug treatment for their insomnia.	The findings of this population-based cohort study indicate a higher risk of developing a subsequent migraine in patients with an NSD, which could be considered an independent, predisposing factor for developing subsequent a migraine in adulthood.	
25799940	Corticosteroids, which are a mainstay in the treatment of acute lymphoblastic leukemia (ALL), have a well-documented adverse effect on sleep. We sought to characterize the effects of dexamethasone on sleep over an entire 28-day treatment cycle using actigraphy, an objective measure of sleep.The sleep of 25 children aged 2-9 years (mean 4.5 years) with ALL treated with dexamethasone were evaluated during maintenance chemotherapy using a within-subject experimental design, actigraphy, and standardized questionnaires to assess sleep, sleep problems, and fatigue.	During the five days of dexamethasone treatment, sleep time increased during the night (535 vs. 498 min; p = 0.004) and daytime napping increased the following day (14 vs. 0 min; p = 0.002), and the number of wake episodes during the night was lower (14 vs. 20; p =  ≤ 0.001). However, when assessed individually, sleep-onset time, efficiency, and wake after sleep onset during the night were unchanged during dexamethasone treatment; when the cumulative effect of all of these factors was assessed, there was a statistically and clinically significant increase in nighttime sleep duration during dexamethasone treatment.	During the five days of treatment with dexamethasone, an increase in nighttime sleep as well as daytime napping was observed in young children with ALL. The increases in sleep duration return to baseline one day after the discontinuation of dexamethasone.	
25798510	Currently, the dominant paradigm for infant sleep from birth to 6 months is behavioral sleep interventions that aim to entrain the infant's biological patterns of sleep using techniques such as delayed response to cues, feed-play-sleep routines, sleep algorithms, and education of parents about "tired cues" and "overstimulation." A recent systematic literature review has identified that while behavioral sleep interventions may modestly increase the length of time an infant sleeps at night without signaling, they are not associated with improved infant or maternal outcomes and may have unintended negative consequences (Douglas & Hill, 2013). This article reviews the empirical literature on behavioral infant sleep interventions, sleep regulation, and sleep disturbance. Based on the available scientific literature, a new paradigm for infant sleep intervention, from birth to 6 months of age, is proposed. This new approach, the Possums Sleep Intervention, integrates interdisciplinary knowledge from developmental psychology, medical science, lactation science, evolutionary science, and neuroscience with third-wave contextual behaviorism, acceptance and commitment therapy, to create a unique, new intervention that supports parental flexibility, cued care, and the establishment of healthy biopsychosocial rhythms. 
25796476	To examine how self-reported sleep quality and daytime symptoms are associated with selected domains of cognitive function among individuals with heart failure (HF).HF patients suffer from poor sleep quality and cognitive decline. The relationship between sleep and cognition has not been well documented among individuals with HF.	In this descriptive, cross-sectional study, 68 individuals with HF (male: 63%, mean age = 72 years, SD = 11) completed sleep questionnaires and a neuropsychological battery.	Participant had mean Pittsburgh Sleep Quality Index score of 5.04 (SD = 2.8). Regression analyses demonstrated neither sleep quality or excessive daytime sleepiness (EDS) were related to cognitive function, but daytime dysfunction was related to lower letter fluency and attention index.	Contrary to some earlier reports, subjective sleep and EDS in this group of individuals was not associated with cognitive decline.	
25795516	MPS IIIA is an inherited neurodegenerative lysosomal storage disorder characterized by cognitive impairment, sleep-wake cycle disturbance, speech difficulties, eventual mental regression and early death. Neuropathological changes include accumulation of heparan sulfate and glycolipids, neuroinflammation and degeneration. Pre-clinical animal studies indicate that replacement of the deficient enzyme, sulfamidase, via intra-cerebrospinal fluid (CSF) injection is a clinically-relevant treatment approach, reducing neuropathological changes and improving symptoms. Given that there are several routes of administration of enzyme into the CSF (intrathecal lumbar, cisternal and ventricular), determining the effectiveness of each injection strategy is crucial in order to provide the best outcome for patients. We delivered recombinant human sulfamidase (rhSGSH) to a congenic mouse model of MPS IIIA via each of the three routes. Mice were euthanized 24h or one-week post-injection; the distribution of enzyme within the brain and spinal cord parenchyma was investigated, and the impact on primary substrate levels and other pathological lesions determined. Both ventricular and cisternal injection of rhSGSH enable enzyme delivery to brain and spinal cord regions, with the former mediating large, statistically significant decreases in substrate levels and reducing microglial activation. The single lumbar CSF infusion permitted more restricted enzyme delivery, with no reduction in substrate levels and little change in other disease-related lesions in brain tissue. While the ventricular route is the most invasive of the three methods, this strategy may enable the widest distribution of enzyme within the brain, and thus requires further exploration. 
25795266	"Sleep sex," also known as sexsomnia, is a sleep disorder characterized by sexual behaviors committed while asleep. There has recently been increased interest in sexsomnia due to controversies arising in legal trials that have been widely publicized in the social and public media. This article attempts to marshal the current information about sexsomnia from the forensic literature and provides an overview of sexsomnia including common features, precipitating factors, prevalence rates, diagnostic procedures, and treatment. As sexsomnia represents a condition in which sexual acts are committed without awareness or intention, this paper also reviews the development of sexsomnia as a legal defense and summarizes Canadian case law on the topic. It provides an overview of the hurdles presented to defense attorneys attempting to utilize the defense and examines popular public notions surrounding the legitimacy of sexsomnia and the possibility of malingering. We conclude that sexsomnia is a legitimate sleep disorder for which case law now exists to support its use in legal defenses based on automatism. The question of whether it is an example of "sane" or "insane" automatism remains to be determined by the courts. Regardless of whether or not sexsomnia is determined to be a mental disorder by the courts, it is now a recognized and well-described sleep disorder that can be safely treated and managed by knowledgeable clinicians.
25794635	To determine whether a diagnosis of sleep disturbance is associated with dementia in older veterans.For this retrospective cohort study, we obtained medical record data from the Department of Veterans Affairs National Patient Care Database for 200,000 randomly selected veterans aged 55 years and older. Prevalent cases of dementia from the baseline period (2000-2003) were excluded, leaving an analytic sample of 179,738 male veterans. Follow-up took place from 2004 to 2011. The primary outcome was all-cause dementia, ascertained using International Classification of Disease, Ninth Revision codes. Sleep disturbance, the primary predictor, was also ascertained using these codes.	After adjusting for potential confounders, those with sleep disturbance had a 27% increased risk of dementia (hazard ratio: 1.27; 95% confidence interval: 1.20-1.34).	Sleep disturbance was associated with increased risk of dementia among a large cohort of older, primarily male veterans.	
25793596	Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans have high rates of posttraumatic stress disorder (PTSD), depression, and sleep problems. Identifying potential contributing factors to these mental health problems is crucial for improving treatments in this population. Rumination, or repeated thoughts about negative experiences, is associated with worse PTSD, depression, and sleep problems in nonveterans. Therefore, we hypothesized that rumination would be associated with worse sleep problems, PTSD, and depressive symptoms in OIF/OEF veterans. Additionally, we proposed a novel hypothesis that sleep problems are a mechanism by which rumination contributes to depressive and PTSD symptoms. In this cross-sectional study, 89 OIF/OEF veterans completed measures of trait rumination, sleep problems, and PTSD and depressive symptoms. Analyses confirmed that greater rumination was associated with worse functioning on all mental health measures. Moreover, greater global sleep problems statistically mediated the association between higher rumination and more PTSD and depressive symptoms. Specifically, sleep disturbance and daytime somnolence but not sleep quantity emerged as significant mediators. Although it is impossible with the current nonexperimental data to test causal mediation, these results support the idea that rumination could contribute to impaired sleep, which in turn could contribute to psychological symptoms. We suggest that interventions targeting both rumination and sleep problems may be an effective way to treat OIF/OEF veterans with PTSD or depressive symptoms.
25792719	For some decades, after the introduction of the head-up tilt test into clinical practice, the clinical presentation of vasovagal syncope (VVS) has been classified as typical (or classical) and atypical (or non-classical). Some clinical features and recent data suggest that even unexplained falls and syncope during sleeping hours may be possible clinical presentations of VVS. In recent studies, tilt testing and carotid sinus massage by means of the 'method of symptoms' were performed in one group of patients with unexplained falls and in another group with unexplained syncope (presence of prodromal symptoms). Overall, tilt testing and carotid sinus massage displayed a high positivity rate in the group of patients with unexplained falls (about 60%), which was similar to that of the unexplained syncope group. These new data seem to indicate that some unexplained falls could be cases of atypical VVS/carotid sinus syncope with retrograde amnesia. Some clinical features suggest that syncope during sleeping hours is a form of VVS with a different clinical presentation: high prevalence of autonomic prodromes, of diurnal episodes of typical VVS and specific phobias, and of positive tilt testing with severe cardioinhibition. 
25792540	Sleep problems are more prevalent and severe among children with intellectual disabilities and autism compared to typically developing children. Training parents in behavioural approaches to manage sleep problems is advocated. However, delivering such interventions via groups is novel. This article reports the findings from a preliminary evaluation of a group-delivered intervention routinely delivered by a Child and Adolescent Mental Health Service Learning Disability team in England. For this purpose, parents (n = 23) of children with intellectual disabilities were recruited. The Children's Sleep Habits Questionnaire, Parents' Sense of Competence Scale and parent-set goals captured outcomes at pre-intervention, post-intervention and 3- and 6-month follow-up. Intervention delivery costs were collected. Take-up was high (86%), and no parent dropped out. Statistically significant improvements in night wakings, parent-set goals and parents' sense of efficacy were observed. The estimated mean cost of delivering each intervention was British (GBP) £1570. Findings suggest the intervention is a low-cost, acceptable service warranting further evaluation. 
25791123	Sleep-related problems are often documented in children with Autism Spectrum Disorders (ASD). This study examined physical activity as a variable that might influence sleep quality in children with ASD. Ten children, ages 9-16 years, were asked to wear accelerometer devices for 7 days in order to track objective measures of activity and sleep quality. Parents of the children also completed the Child's Sleep Habits Questionnaire and maintained a daily sleep log while their child wore the device. This study demonstrated that though over half of the children were identified as having at least one sleep-related problem, their activity levels were significantly related to their sleep patterns. Specifically, the more physically active children had overall higher sleep quality.
25789439	Concussion after a force to the head is called mild traumatic brain injury (mTBI). Approximately 1 in 5 patients with mTBI will develop chronic pain (headache and widespread pain, possibly of central origin) and/or sleep problems (insomnia, disordered breathing, periodic limb movements). However, the predisposing mechanisms for chronic pain in patients with mTBI are unknown. Mild traumatic brain injury is a rare model to prospectively assess the risk factors and mechanisms for pain chronification from the injury onset in the absence of pretrauma comorbidity or medication. In the acute phase, headaches and sleep disturbances seem to predict the poorest long-term cognitive and mood outcomes. Although recent studies suggest that certain brain biomarkers and mood alterations (eg, anxiety, depression) contribute, the causality of chronic pain remains unclear. In mTBI patients with pain, poor sleep quality was correlated with fast beta and gamma electroencephalographic activity in frontal, central, and occipital electroencephalographic (EEG) derivations in all sleep stages. Sleep recuperative function seems to be disturbed by persistent wake EEG activity, corroborating patient complaints such as feeling awake when asleep. Pain and sleep management in mTBI is not yet evidence-based. Treatments include cognitive behavioral and light therapies, medications, and continuous positive airway pressure (CPAP) or oral appliances for disordered sleep breathing. Customized approaches are indicated for mTBI, pain, and sleep complaints. Further studies in pediatric, sport, and transportation populations are needed to prevent TBI chronification. Improvements are emerging in biomarker sensitivity and specificity and management strategies for TBI, pain, and sleep comorbidities. 
25786444	Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although treatment with proton pump inhibitors (PPIs) helps to improve GERD symptoms and subjective sleep parameters, the effects of PPI therapy on objective sleep parameters are conflicting. The aim of this study was to examine the effects of esomeprazole treatment on GERD symptoms and sleep parameters assessed using actigraphs and questionnaires.Thirteen patients with GERD received 20 mg of esomeprazole once daily for two weeks. The patients wore actigraphs from three days before the initiation of PPI treatment to the end of therapy. They were also asked to answer the following self-reported questionnaires: Frequency Scale for the Symptoms of GERD (FSSG), Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Objective sleep parameters were evaluated using actigraphy.	Treatment with esomeprazole significantly decreased the total FSSG score, including the scores for reflux and dysmotility, as well as the ESS score, although it had no effect on the PSQI score. After the second week of treatment, esomeprazole significantly decreased the wake time (from 47.5±39.6 min to 36.0±27.1 min) and sleep latency period (from 19.5±19.8 min to 9.9±10.2 min) and increased the percentage of sleep time (from 89.1±8.8% to 91.9±6.3%); however, improvements were not noted in all objective parameters.	Esomeprazole treatment significantly improves various objective sleep parameters in Japanese patients with GERD. Further placebo-controlled randomized trials are needed to obtain detailed results.	
25786045	To examine the agreement between objective (accelerometer) and subjective measures of sleep in fibromyalgia women (FW) and healthy women (HW). To identify explanatory variables of the discrepancies between the objective and subjective measures in FW and in HW.127 diagnosed FW and 53 HW filled the Fibromyalgia Impact Questionnaire (FIQ) and wore the SenseWear Pro Armband (SWA) for 7 days in order to assess sleep over the last week. Participants completed the Pittsburgh Sleep Quality Index (PSQI) when the SWA was returned.	The SWA showed greater total duration (74 vs. 88 min/day) and average duration (7 vs. 9 min) of wake after sleep onset in FW compared with HW. The PSQI showed poorer sleep quality in all the variables studied in FW than in HW (all, p<0.001), except time in bed. There was a lack of inter-method agreement for total sleep time, sleep time without naps and sleep latency in FW. Age and educational status explained the inter-method mean difference in sleep time in FW. High discrepancy in sleep time between the SWA and the PSQI was related to higher FIQ scores (p<0.05).	The objective measure only showed higher frequency and average duration of wake after sleep onset in FW compared with HW. The agreement between the SWA and the PSQI measures of sleep were poor in the FW group. Age, educational level and the impact of fibromyalgia might be explanatory variables of the inter-method discrepancies in FW.	

25786030	To test the independent and interactive associations of physical activity (PA) and screen time (ST) with self-reported mental health and sleep quality among Chinese college students.Data were collected in October, 2013. The gender, age, residential background, body mass index (BMI), perceived family economy and perceived study burden were obtained from a total of 4747 college students (41.6% males and 58.4% females). The outcomes were self-reported PA status, ST, anxiety, depression, psychopathological symptoms and sleep quality. Analyses were conducted with logistic regression models.	Overall, 16.3%, 15.9% and 17.3% of the students had psychological problems, such as anxiety, depression and psychopathological symptoms, respectively. The prevalence of poor sleep quality was 9.8%. High ST was significantly positively associated with anxiety (OR=1.38, 95%CI: 1.15-1.65), depression (OR=1.76, 95%CI: 1.47-2.09), psychopathological symptoms (OR=1.69, 95%CI: 1.43-2.01) and poor sleep quality (OR=1.32, 95%CI: 1.06-1.65). High PA was insignificantly negatively associated with anxiety, depression, psychopathological symptoms and poor sleep. Low PA and high ST were independently and interactively associated with increased risks of mental health problems and poor sleep quality (p<0.05 for all).	Interventions are needed to reduce ST and increase PA in the lifestyles of young people. Future research should develop and measure the impacts of interventions and their potential consequences on sleep, health, and well being.	
25785893	Optimal sleep is integral to health but is commonly not obtained. Despite its wide-ranging public health impact, sleep health is considered only rarely by policy makers, employers, schools, and others whose policies and structures can adversely affect sleep. An inadequate duration of sleep and poor-quality sleep are prevalent in minority and low-income populations, and may be fundamental to racial and socioeconomic status inequities that contribute to a range of health conditions, including cardiovascular disease (CVD). This review examines the relationship between sleep and disparities in CVD. We describe the public health importance of sleep and the role of sleep duration, as well as the two most common disorders (sleep apnea and insomnia) as risk factors for a number of chronic diseases. We use a multilevel model focused on population health and health disparities, which is based on the notion that individual behaviors, such as sleep, are influenced by complex and dynamic interrelations among individuals and their physical and social environments. We also describe modifiable factors that contribute to insufficient sleep and circadian misalignment, propose potential interventions in various sectors (e.g., neighborhoods, schools, workplaces) that can address social structures that contribute to disparities, and recommend areas for future research. Integrating sleep into public health research will identify novel approaches for closing gaps in health disparities. 

25783155	To describe the sleep patterns and problems in children aged between 12 and 36 mo of age.This cross sectional survey was collected over a span of 1 y in Advanced Pediatric Centre, PGIMER, Chandigarh and crèches of Chandigarh. Children in the age group of 12 to 36 mo were included in study. Children with chronic illness, developmental delay, seizure disorder and lack of consent were excluded. A total of 368 children were enrolled. Main outcome measures were sleep duration over 1 to 3 y of life; sleep behavior at onset, during and waking of sleep and parent reported sleep problems and their predictors.	The average duration of sleep was 12.5 h (S.D = 1.9). The mean total sleep duration and mean day time sleep duration decreased, while mean night time sleep increased as the age advanced from 12 to 36 mo. Following were the frequency of sleep habits seen in the index study; bed time routine was seen only in 68(18.5 %), a regular bed time ritual was seen in 281(76.4 %), 329(89.4 %) children frequently required 0-20 min time to fall asleep, 11(3 %) parents used sleep inducing drugs. Night waking (1 to 3 times a night) was seen in 297(80.7 %) and its frequency declined with age. Parent reported sleep problems were seen in 12.8 % (47/368). Lack of co-sleeping and night waking were considered as strongest predictors of parent reported sleep problems.	Toddlers' sleep duration, night waking behavior, and day time naps decrease as the age progress while night time sleep duration increases with age. Lack of co-sleeping and night waking are considered as strongest predictors of parent reported sleep problems.	
25782921	Since sympathovagal imbalance influences clinical phenomena, such as hypertension, diabetes mellitus, chronic kidney disease (CKD) and sleeping problems, there should be correlations between these conditions. We hypothesized that sleep quality would be correlated with estimated glomerular filtration rate (eGFR), blood pressure and the presence of diabetes.We included 303 CKD patients in this study. We employed the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI) and Short Form 36 Quality of Life Health Survey Questions (SF-36) to screen sleeping disturbances, depression and quality of life, respectively. A chart review was performed for the patients' demographics, diagnoses and certain laboratory parameters--including blood glucose, hemoglobin, albumin, calcium, phosphate, parathyroid hormone and eGFR. Multivariate logistic regression models were employed to estimate odds ratios with 95% confidence intervals.	We included 303 patients in this cross-sectional study. A total of 101 patients were on dialysis. In the univariate models, gender, calcium and mental component summary scores (MCS) reached a significant level of 0.1, and those covariates were included in the multivariate analysis. The reduced models included gender and MCS categories. Female gender increases the risk for poor sleep quality. In our report, evidence suggests MCS domain scores are inversely related to the risk for impaired sleep.	Our results indicated a high burden of sleep disturbances in kidney patients. In addition, female gender and having low MCS scores may influence sleep quality in kidney patients.	
25782721	To explore sleep-related problems reported by patients with cancer prior to undergoing radiotherapy, and to analyse the effect of cancer severity, history of treatment and psychosomatic symptomatology on these problems.A descriptive cross-sectional study was conducted. One hundred and five patients with cancer were evaluated prior to radiotherapy. The primary endpoint was the sleep problem score measured by a self-rated version of the Oviedo Sleep Questionnaire. Secondary variables were impact of pain on sleep, anxiety and asthenia.	Patients reported important levels of insomnia and hypersomnia. Insomnia-related problems were significantly higher in patients with more-severe disease (P < 0.05), and led to higher levels of hypnotic drug intake. Prior chemotherapy was significantly associated with hypersomnia-related problems (P < 0.05). Anxiety was significantly associated with both sleep-related problems.	Sleep problems are significant among patients with cancer prior to undergoing radiotherapy, and were found to be associated with progression of cancer, prior treatments and other psychosomatic symptoms (e.g. anxiety). Sleep problems within this context must be explored to provide adequate guidelines to palliate their effects on quality of life.	
25782283	In representatives of class of birds (pigeons Columba livia) using electrophysiological methods for the first time there was performed analysis of effects of microinjections into the hypothalamic ventrolateral preoptical area (VLPA) of antagonists of the adenosine A(2A) type receptors on the sleep-wale cycle under natural conditions and on realization of somnogenic effect of Heat shock protein 70 kDa (Hsp70). The following has been established: 1) microinjections of adenosine A(2A) receptors antagonist (8-(3-Chlorostyryl) caffeine (ChC)) into VLPA at the beginning of inactive phase of the 24-h period dose-dependently increase wakefulness and suppress sleep; 2) microinjections of Hsp70 into VLPA produce somnogenic effect manifested as an increase of the total time of slow sleep (SS) and enhancement of mechanisms of initiation and maintenance of SS; 3) block of adenosine A(2A) receptors by ChC suppresses the Hsp70-induced SS. The obtained data indicate participation of adenosine A(2A) receptors located in VLPA in modulation of the sleep-wake cycle under natural conditions and in realization of somnogenic effect of Hsp70 in pigeons. A hypothesis is put forward that the somnogenic action of Hsp70 is mediated by modulating effect of this chaperone on function of adenosine proteins-receptors.
25780233	Over the past 3 billion years, an endogenous circadian rhythmicity has developed in almost all life forms in which daily oscillations in physiology occur. This allows for anticipation of sunrise and sunset. This physiological rhythmicity is kept at precisely 24 h by the daily cycle of sunlight and dark. However, since the introduction of electric lighting, there has been inadequate light during the day inside buildings for a robust resetting of the human endogenous circadian rhythmicity, and too much light at night for a true dark to be detected; this results in circadian disruption and alters sleep/wake cycle, core body temperature, hormone regulation and release, and patterns of gene expression throughout the body. The question is the extent to which circadian disruption compromises human health, and can account for a portion of the modern pandemics of breast and prostate cancers, obesity, diabetes and depression. As societies modernize (i.e. electrify) these conditions increase in prevalence. There are a number of promising leads on putative mechanisms, and epidemiological findings supporting an aetiologic role for electric lighting in disease causation. These include melatonin suppression, circadian gene expression, and connection of circadian rhythmicity to metabolism in part affected by haem iron intake and distribution.
25779967	Disturbances in the sleep/wake cycle are prevalent in patients with Rett syndrome (RTT). We sought to determine whether the circadian system is disrupted in a RTT model, Mecp2(-/y) mice. We found that MeCP2 mutants showed decreased strength and precision of daily rhythms of activity coupled with extremely fragmented sleep. The central circadian clock (suprachiasmatic nucleus) exhibited significant reduction in the number of neurons expressing vasoactive intestinal peptide (VIP) as well as compromised spontaneous neural activity. The molecular clockwork was disrupted both centrally in the SCN and in peripheral organs, indicating a general disorganization of the circadian system. Disruption of the molecular clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice were vulnerable to circadian disruption as chronic jet lag accelerated mortality. Our finds suggest an integral role of MeCP2 in the circadian timing system and provides a possible mechanistic explanation for the sleep/wake distrubances observed in RTT patients. The work raises the possibility that RTT patients may benefit from a temporally structured environment. 
25779719	Fatigue is a major concern for individuals with rheumatoid arthritis (RA). However, in order to treat fatigue adequately, its sources need to be identified.Data were collected during a single home visit (number of participants = 158). All participants had physician-diagnosed RA. Assessments of self-reported sleep quality, depression, physical activity, RA disease activity, muscle strength, functional limitations, and body composition were made. Information on demographics, medications, and smoking was collected. The Fatigue Severity Inventory (FSI; measuring average fatigue over the past 7 days) was used as the primary outcome. Analyses were first conducted to evaluate bivariate relationships with fatigue. Correlations among risk factors were examined. Multivariate analyses identified independent predictors of fatigue.	The mean ± SD age was 59 ± 11 years, the mean ± SD disease duration was 21 ± 13 years, and 85% of subjects were female. The mean ± SD FSI rating was 3.8 ± 2.0 (range 0-10). In multivariate analyses, self-reported disease activity, poor sleep, depression, and obesity were independently associated with fatigue. Physical inactivity was correlated with poor sleep, depression, and obesity. Mediation analyses indicated that physical inactivity had an indirect association with fatigue, mediated by poor sleep, depression, and obesity.	This cross-sectional study suggests that fatigue may not be solely a result of RA disease activity, but may result from a constellation of factors that includes RA disease activity or pain, but also includes inactivity, depression, obesity, and poor sleep. The results suggest new avenues for interventions to improve fatigue in individuals with RA, such as increasing physical activity or addressing depression or obesity.	
25778497	To investigate the prevalence, severity and relation to fluid retention of self-reported pregnancy-related carpal tunnel syndrome (CTS) symptoms in a large sample of pregnant women.A prospective longitudinal cohort study.	Dutch women who became pregnant between January 2013 and January 2014 in the southeast of The Netherlands.	A total of 639 Dutch pregnant women.	Baseline characteristics were assessed at 12 weeks' gestation. CTS symptoms were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ) at 32 weeks and during the first postpartum week regarding the last weeks of pregnancy. Fluid retention, sleeping problems and depressive symptoms (using the Edinburgh Depression Scale) were assessed at several time points during pregnancy.	BCTQ scores, fluid retention and sleeping problems.	Of the 639 women, 219 (34%) reported CTS symptoms during pregnancy. Total mean scores on the BCTQ were significantly higher after 32 weeks' than up to 32 weeks' gestation. Most women experienced mild to moderate symptoms. Pregnant women with CTS symptoms reported significantly higher levels of fluid retention during gestation compared with pregnant women without CTS symptoms [F = 60.6, df (1598), P < 0.001], adjusted for body mass index (BMI), age, parity, and depression scores. Higher scores on fluid retention throughout the pregnancy were significantly related to CTS (OR = 1.8, 95%CI 1.5, 2.1, P < 0.001). Finally, the occurrence of CTS was independently related to sleeping problems.	Although the severity of symptoms and functional impairment of CTS were relatively mild, health care professionals should be aware of the high prevalence. The occurrence of CTS symptoms is significantly higher in women who report fluid retention during gestation and it can contribute to sleeping problems.	
25777522	The purpose of the study was to evaluate the influences of cholinesterase inhibitors on sleep pattern and sleep disturbance. A total of 87 mild to moderate stage dementia patients who were not on cholinesterase enzyme inhibitor and memantine treatment were included in the study. The dementia patients were treated with donepezil, galantamine or rivastigmine, depending on the preference of the clinician. Fifty-five dementia patients (63.2 %) completed the study. Twenty-three elderly subjects, who had normal cognitive functions, were included in the study as the control group. The Pittsburgh Sleep Quality Index was used for evaluating the sleep quality at the beginning and at the final assessment. The improvement in sleep quality was better with regard to changes in Pittsburgh Sleep Quality Index scores with galantamine treatment compared to the donepezil and the control groups. A significant decrease in Pittsburgh Sleep Quality Index scores was detected in the galantamine group after treatment. Although statistically not significant, rivastigmine decreased and donepezil increased the Pittsburgh Sleep Quality Index scores after treatment. Dementia patients who had a poor sleep quality (n: 36), the rate of improvement in sleep disturbance was 81.8 % in the galantamine group, 75 % in the rivastigmine, and 50 % in the donepezil group. Galantamine may be the first choice of cholinesterase inhibitor in mild to moderate dementia patients in terms of improving sleep quality.
25777485	Adverse childhood experiences (ACEs) represent substantial threats to public health and affect about 58% of youth in the US. In addition to their acute effects such as injury and physical trauma, ACEs are associated with an increased risk of several negative health outcomes throughout the life course. Emerging evidence suggests that sleep disorders may be one such outcome, but existing studies have not been systematically reviewed and summarized. We conducted a systematic review to summarize the evidence concerning the relationship between ACEs and sleep disorders and disturbances, with a focus on adult women. Original publications were identified through searches of the electronic databases MEDLINE, Embase, and Web of Science using the keywords "childhood," "adversity," "abuse," and "sleep" as well as searches of the reference lists of eligible studies. Studies evaluating ACEs that occurred before 18 years of age and sleep outcomes that were assessed at 18 years or older were adjudicated and included. A total of 30 publications were identified. Of the 30 studies, 28 were retrospective analyses and there was vast heterogeneity in the types of ACEs and sleep outcomes measured. The majority of retrospective studies (N = 25 of 28) documented statistically significant associations between sleep disorders including sleep apnea, narcolepsy, nightmare distress, sleep paralysis, and psychiatric sleep disorders with a history of childhood adversity. In many studies, the strengths of associations increased with the number and severity of adverse experiences. These associations were corroborated by the two prospective studies published to date. Notably, investigators have documented statistically significant associations between family conflict at 7-15 years of age and insomnia at 18 years of age (odds ratio, OR = 1.4; 95% confidence interval, CI = 1.2-1.7) and between childhood sexual abuse and sleep disturbances 10 years later in adult women (β = 0.24, p <0.05). There is a growing scientific body of knowledge suggesting an association between ACEs and multiple sleep disorders in adulthood. The available evidence indicates the need to develop treatment strategies such as trauma-informed care for survivors of abuse who suffer from sleep disorders and disturbances. Further, longitudinal studies among diverse populations are needed to improve the overall understanding of this association and to investigate potential gender and racial/ethnic disparities in the strength of the association. 
25777484	To examine the association of socioeconomic status (SES) with subjective and objective sleep disturbances and the role of socio-demographic, behavioural and psychological factors in explaining this association.Analyses are based on 3391 participants (53% female, aged 40-81 years) of the follow-up of the CoLaus study (2009-2012), a population-based sample of the city of Lausanne, Switzerland. All participants completed a sleep questionnaire and a sub-sample (N = 1569) underwent polysomnography.	Compared with men with a high SES, men with a low SES were more likely to suffer from poor sleep quality [prevalence ratio (PR) for occupational position = 1.68, 95% Confidence Interval (CI): 1.30-2.17], and to have long sleep latency (PR = 4.90, 95%CI: 2.14-11.17), insomnia (PR = 1.47, 95% CI: 1.12-1.93) and short sleep duration (PR = 3.03, 95% CI: 1.78-5.18). The same pattern was observed among women (PR = 1.29 for sleep quality, 2.34 for sleep latency, 2.01 for daytime sleepiness, 3.16 for sleep duration, 95%CIs ranging from 1.00 to 7.51). Use of sleep medications was not patterned by SES. SES differences in sleep disturbances were only marginally attenuated by adjustment for other socio-demographic, behavioural and psychological factors. Results from polysomnography confirmed poorer sleep patterns among participants with low SES (p <0.05 for sleep efficiency/stage shifts), but no SES differences were found for sleep duration.	In this population-based sample, low SES was strongly associated with sleep disturbances, independently of socio-demographic, behavioural, and psychological factors. Further research should establish the extent to which social differences in sleep contribute to socioeconomic differences in health outcomes.	
25776185	Sleep disturbance is a common complaint of patients with a rotator cuff tear. Inadequate and restless sleep, along with pain, is often a driving symptom for patients to proceed with rotator cuff repair. To date, no studies have examined sleep disturbance in patients undergoing rotator cuff repair, and there is no evidence that surgery improves sleep disturbance.Sleep disturbance is prevalent in patients with a symptomatic rotator cuff tear, and sleep disturbance improves after arthroscopic rotator cuff repair.	Case series; Level of evidence, 4.	A total of 56 patients undergoing arthroscopic rotator cuff repair for full-thickness tears were enrolled in a prospective study. Patients were surveyed preoperatively and postoperatively at intervals of 2, 6, 12, 18, and 24 weeks. Patient outcomes were scored using the Pittsburgh Sleep Quality Index (PSQI), Simple Shoulder Test (SST), visual analog scale for pain (VAS), and single assessment numeric evaluation (SANE). Demographic and surgical factors were also collected for analysis.	Preoperative PSQI scores indicative of sleep disturbance were reported in 89% of patients. After surgery, a statistically significant improvement in PSQI was achieved at 3 months (P = .0012; 91% follow-up) and continued through 6 months (P = .0179; 93% follow-up). Six months after surgery, only 38% of patients continued to have sleep disturbance. Multivariable linear regression of all surgical and demographic factors versus PSQI was performed and demonstrated that preoperative and prolonged postoperative narcotic use negatively affected sleep.	Sleep disturbance is common in patients undergoing rotator cuff repair. After surgery, sleep disturbance improves to levels comparable with those of the general public. Preoperative and prolonged postoperative use of narcotic pain medication negatively affects sleep.	

25774609	The mandate of the International Commission on Biological Effects of Noise (ICBEN) is to promote a high level of scientific research concerning all aspects of noise-induced effects on human beings and animals. In this review, ICBEN team chairs and co-chairs summarize relevant findings, publications, developments, and policies related to the biological effects of noise, with a focus on the period 2011-2014 and for the following topics: Noise-induced hearing loss; nonauditory effects of noise; effects of noise on performance and behavior; effects of noise on sleep; community response to noise; and interactions with other agents and contextual factors. Occupational settings and transport have been identified as the most prominent sources of noise that affect health. These reviews demonstrate that noise is a prevalent and often underestimated threat for both auditory and nonauditory health and that strategies for the prevention of noise and its associated negative health consequences are needed to promote public health. 
25773787	Exploding head syndrome is characterized by the perception of loud noises during sleep-wake or wake-sleep transitions. Although episodes by themselves are relatively harmless, it is a frightening phenomenon that may result in clinical consequences. At present there are little systematic data on exploding head syndrome, and prevalence rates are unknown. It has been hypothesized to be rare and to occur primarily in older (i.e. 50+ years) individuals, females, and those suffering from isolated sleep paralysis. In order to test these hypotheses, 211 undergraduate students were assessed for both exploding head syndrome and isolated sleep paralysis using semi-structured diagnostic interviews: 18.00% of the sample experienced lifetime exploding head syndrome, this reduced to 16.60% for recurrent cases. Though not more common in females, it was found in 36.89% of those diagnosed with isolated sleep paralysis. Exploding head syndrome episodes were accompanied by clinically significant levels of fear, and a minority (2.80%) experienced it to such a degree that it was associated with clinically significant distress and/or impairment. Contrary to some earlier theorizing, exploding head syndrome was found to be a relatively common experience in younger individuals. Given the potential clinical impacts, it is recommended that it be assessed more regularly in research and clinical settings. 
25773686	Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. 
25773672	Sleep-related complaints are common among breast cancer survivors. However, the risk factors underlying sleep disturbances in this population are not completely understood. Some studies have shown that maintaining normal weight can result in a reduced risk of cancer-related symptoms, including sleep problems; however, data from published studies are not consistent. This study examined the associations between body mass index (BMI) and sleep-related complaints in breast cancer survivors.Self-reported survey data from 861 breast cancer survivors at a single institution were analyzed. BMI was calculated based on self-reported weight and height at the time of the survey. Daytime sleepiness was assessed using the Epworth Sleepiness Scale. Average sleep duration was calculated based on the reported hours of sleep on a typical weekday and weekend. Associations between BMI and the sleep outcomes were estimated using multivariable logistic regression.	In adjusted models, BMI was not significantly associated with either excessive daytime sleepiness or "short" sleep pattern (≤ 6 h) in our sample of breast cancer survivors. Younger age, presence of strong acute pain, and lower level of education were independent risk factors for excessive daytime sleepiness. African American race, presence of strong acute pain, and lower level of education were independent risk factors for being a short sleeper.	Findings from this study indicate that BMI is not independently associated with sleep-related outcomes among breast cancer survivors. More research is needed to identify cancer survivors who are at increased risk for sleep disturbances as well as the mechanisms that underlie such disturbances.	
25773523	This study examined cross-sectional time trends in health complaints among adolescents living in Switzerland, including differences between population subgroups and sources of differential response to items.Swiss data were analysed from the Health Behaviour in School-aged Children (HBSC; including 11-15 years old) from 1994 (n = 7008), 1998 (n = 8296), 2002 (n = 9066) and 2006 (n = 9255). Structural equation modelling was used to assess (1) the structure of the HBSC Symptom Checklist (HBSC-SCL; questionnaire, which asks about the frequency of eight health complaints) and (2) associations between the HBSC-SCL with year of data collection and demographic characteristics of the participants.	Two correlated factors fitted the data better than a single factor. The psychological factor included the items 'feeling low,' 'irritability and bad temper,' 'nervousness' and 'difficulties in getting to sleep,' and the somatic factor the items 'headache', 'backache', 'stomach ache' and 'dizziness'. Relative to 1994, lower levels of psychological health complaints were experienced in 1998, 2002 and 2006. However, the changes were only minor. In contrast, somatic health complaints increased monotonically over the years of the survey. Experiencing psychological and somatic health complaints was more pronounced with age among females relative to males and was associated with living in particular language regions of Switzerland.	Different cross-sectional time trends were identified for the psychological and somatic latent variables, indicating that both factors should be investigated when studying period effects.	
25773067	We followed the impact of healthy aging on cortical drive during sleep in rats by using the corticomuscular coherence (CMC). We employed the chronic electrodes implantation for sleep recording in adult, male Wistar rats, and followed the aging impact during sleep from 3 to 5.5 months age. We have analyzed the sleep/wake states architecture, and the sleep/wake state related EEG microstructure and CMCs. We evidenced the topographically distinct impact of aging on sleep/wake states architecture within the sensorimotor (SMCx) vs. motor cortex (MCx) from 4.5 to 5.5 months age. Healthy aging consistently altered only the SMCx sleep/wake states architecture, and increased the delta and beta CMCs through both cortical drives during Wake, but only through the MCx drive during REM. According to the delta and beta CMCs values, aging impact through the SMCx drive was opposite, but it was convergent through the MCx drive during Wake vs. REM, and there was a dual and inverse mode for the motor control during REM.
25773000	Sleep disorders are common in patients with multiple sclerosis (MS) and play a crucial role in health and quality of life; however, they are often overlooked. The most important sleep disorders in this context are as follows: insomnia, restless legs syndrome, periodic limb movement disorders, and sleep-related breathing disorders (SRBD). It is unclear if MS-related processes (lesions, brain atrophy) can cause symptomatic forms of sleep apnea. MS-related narcolepsy-like symptoms are described in the literature and, in some cases, have resolved with methylprednisolone pulse therapy. Similarly, REM sleep behavior disorder (RBD) is very rare in MS, but it can be an initial sign of MS where cortisone therapy may be helpful and can be taken into account in this specific context. Independent diagnosis and treatment is required for all of the abovementioned conditions. Treating physicians and neurologists should be aware of these comorbidities and initiate specific therapy. Highly fatigued or sleepy MS patients should have polysomnography in order not to overlook these diagnoses. 
25772847	The power of the application of bioinformatics across multiple publicly available transcriptomic data sets was explored. Using 19 human and mouse circadian transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme-responsive nuclear receptors are the most rhythmic transcripts across sleep conditions and tissues suggesting that they are at the core of circadian rhythm generation. Analyzes of human transcriptomic data show that a core set of transcripts related to processes including immune function, glucocorticoid signalling, and lipid metabolism is rhythmically expressed independently of the sleep-wake cycle. We also identify key transcripts associated with transcription and translation that are disrupted by sleep manipulations, and through network analysis identify putative mechanisms underlying the adverse health outcomes associated with sleep disruption, such as diabetes and cancer. Comparative bioinformatics applied to existing and future data sets will be a powerful tool for the identification of core circadian- and sleep-dependent molecules. 
25772446	Sleep loss and circadian disruption-a state of misalignment between physiological functions and imposed sleep/wake behavior-supposedly play central roles in the etiology of shift work-related pathologies [1-4]. Circadian entrainment is, however, highly individual [5], resulting in different chronotypes [6, 7]. Chronotype in turn modulates the effects of working times: compared to late chronotypes, earlier ones sleep worse and shorter and show higher levels of circadian misalignment during night shifts, while late types experience more sleep and circadian disruption than early types when working morning shifts [8]. To promote sleep and reduce the mismatch between circadian and working time, we implemented a chronotype-adjusted (CTA) shift schedule in a factory. We abolished the most strenuous shifts for extreme chronotypes (i.e., mornings for late chronotypes, nights for early ones) and examined whether sleep duration and quality, social jetlag [9, 10], wellbeing, subjective stress perception, and satisfaction with leisure time improved in this schedule. Intermediate chronotypes (quartiles 2 and 3) served as a control group, still working morning (6:00-14:00), evening (14:00-22:00), and night (22:00-6:00) shifts, with two strenuous shifts (out of twelve per month) replaced by evening ones. We observed a significant increase of self-reported sleep duration and quality, along with increased wellbeing ratings on workdays among extreme chronotypes. The CTA schedule reduced overall social jetlag by 1 hr, did not alter stress levels, and increased satisfaction with leisure time (early types only). Chronotype-based schedules thus can reduce circadian disruption and improve sleep; potential long-term effects on health and economic indicators need to be elucidated in future studies. 
25770043	An increasing body of literature indicates that discrimination has a negative impact on health; poor sleep may be an underlying mechanism. The primary objective of this review was to examine existing studies on the relationship between discrimination and sleep to clarify (a) the potential role of discrimination in shaping population patterns of sleep and sleep disparities, and (b) the research needed to develop interventions at individual and institutional levels. We identified articles from English-language publications in PubMed and EBSCO databases from inception through July 2014. We employed a broad definition of discrimination to include any form of unfair treatment and all self-reported and objectively assessed sleep outcomes, including duration, difficulties, and sleep architecture. Seventeen studies were identified: four prospective, 12 cross-sectional, and one that utilized a daily-diary design. Fifteen of the 17 studies evaluated interpersonal discrimination as the exposure and the majority of studies included self-reported sleep as the outcome. Only four studies incorporated objective sleep assessments. All 17 studies identified at least one association between discrimination and a measure of poorer sleep, although studies with more detailed consideration of either discrimination or sleep architecture revealed some inconsistencies. Taken together, existing studies demonstrate consistent evidence that discrimination is associated with poorer sleep outcomes. This evidence base can be strengthened with additional prospective studies that incorporate objectively measured aspects of sleep. We outline important extensions for this field of inquiry that can inform the development of interventions to improve sleep outcomes, and consequently promote well-being and reduce health inequities across the life course.
25767461	Identifying the neuronal circuits and dynamics of sleep-to-wake transition is essential to understanding brain regulation of behavioral states, including sleep-wake cycles, arousal, and hyperarousal. Recent work by different laboratories has used optogenetics to determine the role of individual neuromodulators in state transitions. The optogenetically driven data do not yet provide a multi-dimensional schematic of the mechanisms underlying changes in vigilance states. This work presents a modeling framework to interpret, assist, and drive research on the sleep-regulatory network. We identify feedback, redundancy, and gating hierarchy as three fundamental aspects of this model. The presented model is expected to expand as additional data on the contribution of each transmitter to a vigilance state becomes available. Incorporation of conductance-based models of neuronal ensembles into this model and existing models of cortical excitability will provide more comprehensive insight into sleep dynamics as well as sleep and arousal-related disorders. 
25767129	To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials.Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios.	Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov.	Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded.	In the 39 randomised controlled trials (10,761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other).	This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however, are already well recognised.	PROSPERO 2014:CRD42014009224.	
25767060	Sleep disturbance is a common and disturbing symptom in military personnel, with many individuals progressing to the development of insomnia, which is characterized by increased arousals, wakefulness after sleep onset, and distorted sleep architecture. The molecular mechanisms underlying insomnia remain elusive, limiting future therapeutic development to address this critical issue. We examined whole gene expression profiles associated with insomnia. We compared subjects with insomnia (n = 25) to controls (n = 13) without insomnia using microarray gene expression profiles obtained from peripheral samples of whole blood obtained from military personnel. Compared to controls, participants with insomnia had differential expression of 44 transcripts from 43 identified genes. Among the identified genes, urotensin 2 was downregulated by more than 6 times in insomnia participants, and the fold-change remained significant after controlling for depression, posttraumatic stress disorder, and medication use. Urotensin 2 is involved in regulation of orexin A and B activity and rapid eye movement during sleep. These findings suggest that differential expression of these sleep-regulating genes contributes to symptoms of insomnia and, specifically, that switching between rapid eye movement and nonrapid eye movement sleep stages underlies insomnia symptoms. Future work to identify therapeutic agents that are able to regulate these pathways may provide novel treatments for insomnia.
25766719	Several inexpensive, readily available smartphone apps that claim to monitor sleep are popular among patients. However, their accuracy is unknown, which limits their widespread clinical use. We therefore conducted this study to evaluate the validity of parameters reported by one such app, the Sleep Time app (Azumio, Inc., Palo Alto, CA, USA) for iPhones.Twenty volunteers with no previously diagnosed sleep disorders underwent in-laboratory polysomnography (PSG) while simultaneously using the app. Parameters reported by the app were then compared to those obtained by PSG. In addition, an epoch-by-epoch analysis was performed by dividing the PSG and app graph into 15-min epochs.	There was no correlation between PSG and app sleep efficiency (r = -0.127, p = 0.592), light sleep percentage (r = 0.024, p = 0.921), deep sleep percentage (r = 0.181, p = 0.444) or sleep latency (rs = 0.384, p = 0.094). The app slightly and nonsignificantly overestimated sleep efficiency by 0.12% (95% confidence interval [CI] -4.9 to 5.1%, p = 0.962), significantly underestimated light sleep by 27.9% (95% CI 19.4-36.4%, p < 0.0001), significantly overestimated deep sleep by 11.1% (CI 4.7-17.4%, p = 0.008) and significantly overestimated sleep latency by 15.6 min (CI 9.7-21.6, p < 0.0001). Epochwise comparison showed low overall accuracy (45.9%) due to poor interstage discrimination, but high accuracy in sleep-wake detection (85.9%). The app had high sensitivity but poor specificity in detecting sleep (89.9% and 50%, respectively).	Our study shows that the absolute parameters and sleep staging reported by the Sleep Time app (Azumio, Inc.) for iPhones correlate poorly with PSG. Further studies comparing app sleep-wake detection to actigraphy may help elucidate its potential clinical utility.	A commentary on this article appears in this issue on page 695.	
25766714	Children and adolescents with chronic fatigue syndrome (CFS) frequently report sleep disturbances. However, little is known about the nature and severity of sleep disturbance and factors associated with sleep problems in pediatric CFS. The purpose of this review was to synthesize and critically appraise existing literature relating to sleep disturbances in pediatric CFS.Embase, CINAHL, PsychINFO, PubMed. and Medline databases were searched to retrieve all studies that included an assessment of sleep in pediatric CFS. Two reviewers independently assessed eligibility, extracted data, and systematically assessed reporting quality.	Six studies were included and these were mostly case-controlled designs. Findings varied across studies; however, most studies found that children and adolescents with CFS had significantly more sleep disturbances when compared to healthy controls. Significant methodological variations and limitations were apparent.	This review suggests that children and adolescents with CFS experience sleep disturbances. However, results need to be interpreted cautiously given the limited evidence available and its overall low quality. More research is required to elucidate the nature and extent of sleep disturbance in pediatric CFS and should focus on (1) identifying the specific types, causes, and severity of sleep disturbances; (2) the specific consequences of sleep disturbances; and (3) the most effective interventions for sleep problems in this population.	
25766713	To evaluate the effects of noninvasive ventilation (NIV) on sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous titration with polysomnography (PSG).In this prospective observational study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were used to assess subjective sleep quality and quality of life (QoL). Patients were readmitted after one month.	In the total group, slow wave sleep and REM sleep increased and the arousal-awakening index improved. The group without bulbar involvement (non-bulbar) showed the same improvements, together with an increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved in the total and non-bulbar group. Except for oxygen saturation during REM sleep, no improvement in respiratory function or sleep structure was found in bulbar patients. However, these patients showed less room for improvement. Patient-reported outcomes showed improvement in sleep quality and QoL for the total and non-bulbar group, while bulbar patients only reported improvements in very few subscores.	This study shows an improvement of sleep architecture, carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and after one month of NIV in ALS patients. More studies are needed to identify the appropriate time to start NIV in bulbar patients. Our results suggest that accurate titration of NIV by PSG improves sleep quality.	A commentary on this article appears in this issue on page 511.	
25766709	Sleep duration and quality are associated with negative neuropsychological and psychosocial outcomes in children and adolescents. However, community awareness of this is low and sleep education programs in schools are attempting to address this issue. Several studies now exist assessing the efficacy of these sleep education programs for improving sleep knowledge, sleep hygiene and sleep patterns. This paper presents these sleep education programs, most particularly, it presents the strengths and weaknesses of the current available studies in the hope that this can identify areas where future sleep education programs can improve.A systematic search of all school-based sleep education studies in adolescents was undertaken. Studies were scrutinized for author, teacher and participant comment regarding strengths and limitations of each study, which were then extracted and summarized.	Two specific types of sleep education programs emerged from the review, those that sought to change sleep behavior and those that sought simply to disseminate information. Issues that dictated the strength or weakness of a particular study including who delivers the program, the theoretical basis, the tools utilized to measure sleep patterns, the content, and their capacity to engage students were assessed. Sleep education was considered important by teachers, students and parents alike.	Future sleep education programs need to take into account lessons learned from previous sleep education efforts in order to maximize the potential for sleep education programs to improve the sleep health of our young people.	A commentary on this article appears in this issue on page 595.	
25766678	Dravet Syndrome (DS) is caused by heterozygous loss-of-function mutations in voltage-gated sodium channel NaV1.1. Our mouse genetic model of DS recapitulates its severe seizures and premature death. Sleep disturbance is common in DS, but its mechanism is unknown. Electroencephalographic studies revealed abnormal sleep in DS mice, including reduced delta wave power, reduced sleep spindles, increased brief wakes, and numerous interictal spikes in Non-Rapid-Eye-Movement sleep. Theta power was reduced in Rapid-Eye-Movement sleep. Mice with NaV1.1 deleted specifically in forebrain interneurons exhibited similar sleep pathology to DS mice, but without changes in circadian rhythm. Sleep architecture depends on oscillatory activity in the thalamocortical network generated by excitatory neurons in the ventrobasal nucleus (VBN) of the thalamus and inhibitory GABAergic neurons in the reticular nucleus of the thalamus (RNT). Whole-cell NaV current was reduced in GABAergic RNT neurons but not in VBN neurons. Rebound firing of action potentials following hyperpolarization, the signature firing pattern of RNT neurons during sleep, was also reduced. These results demonstrate imbalance of excitatory vs. inhibitory neurons in this circuit. As predicted from this functional impairment, we found substantial deficit in homeostatic rebound of slow wave activity following sleep deprivation. Although sleep disorders in epilepsies have been attributed to anti-epileptic drugs, our results show that sleep disorder in DS mice arises from loss of NaV1.1 channels in forebrain GABAergic interneurons without drug treatment. Impairment of NaV currents and excitability of GABAergic RNT neurons are correlated with impaired sleep quality and homeostasis in these mice. 
25766617	Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep-wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep-wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD. 
25766262	Childhood sleep problems are prevalent and relate to a wide range of negative psychological outcomes. However, it remains unclear how biological processes, such as HPA activity, may predict sleep problems over time in childhood in the context of certain parenting environments. Fifty-one mothers and their 18-20 month-old toddlers participated in a short-term longitudinal study assessing how shared variance among morning levels, diurnal change, and nocturnal change in toddlers' cortisol secretion predicted change in sleep problems in the context of maternal overprotection and critical control. A composite characterized by low variability in, and, to a lesser extent, high morning values of cortisol, predicted increasing sleep problems from age 2 to age 3 when mothers reported high critical control. Results suggest value in assessing shared variance among different indices of cortisol secretion patterns and the interaction between cortisol and the environment in predicting sleep problems in early childhood.
25765292	Sleep disturbance, common among children with ADHD, can contribute to cognitive and behavioral dysfunction. It is therefore challenging to determine whether neurobehavioral dysfunction should be attributed to ADHD symptoms, sleep disturbance, or both. The present study examined parent-reported sleep problems (Children's Sleep Habits Questionnaire) and their relationship to neuropsychological function in 64 children, aged 4-7 years, with and without ADHD. Compared to typically developing controls, children with ADHD were reported by parents to have significantly greater sleep disturbance--including sleep onset delay, sleep anxiety, night awakenings, and daytime sleepiness--(all p ≤ .01), and significantly poorer performance on tasks of attention, executive control, processing speed, and working memory (all p < .01). Within the ADHD group, total parent-reported sleep disturbance was significantly associated with deficits in attention and executive control skills (all p ≤ .01); however, significant group differences (relative to controls) on these measures remained (p < .01) even after controlling for total sleep disturbance. While sleep problems are common among young children with ADHD, these findings suggest that inattention and executive dysfunction appear to be attributable to symptoms of ADHD rather than to sleep disturbance. The relationships among sleep, ADHD symptoms, and neurobehavioral function in older children may show different patterns as a function of the chronicity of disordered sleep.
25763660	The circadian clock plays a vital role in physiology and behavior such as the sleep-wake cycle and blood pressure and hormone levels. Immune responses also display circadian rhythmicity and particularly pineal melatonin contributes to immunological processes. Little attention, however, is given to mechanisms underlying rhythmic neutrophil responses to the injury. Here, we used a transgenic Tg(lyz:EGFP) zebrafish tail fin transection model to investigate whether the recruitment of neutrophils toward the injured site is regulated by the circadian clock. We found that migrating neutrophils display robust rhythmicity, peaking at darkness. Melatonin positively regulates rhythmic neutrophil migration, as evidenced that treatment with melatonin at low dosage can significantly enhance neutrophil recruitment toward the injured site, which is attenuated by luzindole treatment and in pinealectomized fish. Furthermore, using a transgenic zebrafish eyeball model, we observed that melatonin enhances secretion of two cytokines, TNF-α and IL-8, both of which markedly enhance neutrophil migration. Taken together, these results highlight a positive role of melatonin in rhythmic neutrophil migration and help obtain a better understanding of circadian regulation in immunology. 
25762221	Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development.


25760719	Atencion a pacientes con estados alterados de conciencia en un hospital de pacientes cronicos y larga estancia.Introduccion. Un 30-40% de los pacientes con daño cerebral presenta alteraciones del nivel de conciencia, y algunos casos, estados alterados de conciencia: sindrome de vigilia sin respuesta (SVSR) o estado de minima conciencia (EMC). La recuperacion es variable y la supervivencia esta amenazada por multiples complicaciones. Objetivos. Presentar la metodologia de trabajo del Hospital La Pedrera (HLP) para pacientes en SVSR o EMC y analizar las caracteristicas clinicas de los pacientes atendidos, la evolucion, y la situacion funcional y cognitiva en el momento del alta. Pacientes y metodos. Estudio descriptivo prospectivo de pacientes atendidos en el HLP durante el periodo 2009-2013, con diagnostico de SVSR o EMC. Resultados. El HLP trabaja mediante el metodo gestion de caso, ofreciendo una atencion integral por un equipo multidisciplinar. Los pacientes se clasifican segun objetivos asistenciales. Los pacientes con SVSR o EMC se incluyen en el programa de cuidados integrales y adaptacion. Se atendio a 23 pacientes (86,9% varones), con una edad media de 54,9 años. Etiologia: hemorragia cerebral, 30,4%; encefalopatia anoxica, 26,6%; encefalopatia metabolica, 17,3%; y otras causas, 17,3%. El 73,9% ingreso en SVSR y el resto en EMC. Evolucion: el 43,4% mejoro su situacion cognitiva inicial y el 88,8% presentaba una situacion de dependencia total en el momento del alta. Las complicaciones mas frecuentes fueron infecciones respiratorias y urinarias (53,6%). El 65,2% de los casos fueron exitus. Conclusiones. La asistencia en SVSR o EMC es compleja y precisa cuidados multidisciplinares. Casi la mitad de los pacientes mejoro su situacion cognitiva, lo que justifica una actitud proactiva que intente mejorar la calidad de vida de los pacientes y sus familias.	Between 30% and 40% of patients with brain damage present alterations in their level of consciousness and, in some cases, altered states of consciousness: unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). Recovery varies and survival is threatened by a number of complications.	The purpose of this study is to present the working methodology used at the Hospital La Pedrera (HLP) for patients in UWS or MCS and to analyse the clinical characteristics of the patients attended to, their progress, and the functional and cognitive situation at the time of their discharge from hospital.	The work consisted in a prospective descriptive study of patients seen at the HLP over the period 2009-2013, who had been diagnosed with UWS or MCS.	The HLP uses the case management method, offering integrated care dispensed by a multidisciplinary team. Patients are classified according to healthcare goals. Patients with UWS or MCS are included in the integrated care and adaptation programme. A total of 23 patients (86.9% males) were attended to, the mean age being 54.9 years. Aetiology: brain haemorrhage, 30.4%; anoxic encephalopathy, 26.6%; metabolic encephalopathy, 17.3%; and other causes, 17.3%. Altogether 73.9% were admitted in UWS and the rest in MCS.	43.4% improved their initial cognitive situation and 88.8% presented a situation of total dependence at the time of discharge. The most frequent complications were respiratory and urinary infections (53.6%). Death occurred in 65.2% of cases.	Medical attention in UWS or MCS is complex and requires multidisciplinary care. Almost half of the patients improved their cognitive situation, which justifies a proactive attitude that attempts to improve the quality of life of both patients and their families.	
25759571	Many patients with chronic obstructive pulmonary disease (COPD) suffer from poor sleep quality. We hypothesized that poor sleep quality in otherwise stable patients predicted exacerbations in these patients.This is a secondary analysis of the results of a previously published randomized trial of azithromycin in 1,117 patients with moderate to severe COPD who were clinically stable on enrollment. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Other quality of life indices included the Medical Outcome Study 36-item Short Form Health Survey and the St Georges Respiratory Questionnaire. Outcomes included time to first exacerbation and exacerbation rate.	Sleep quality was "poor" (Pittsburgh Sleep Quality Index >5) in 53% of participants but was not related to age or severity of airflow obstruction. Quality of life scores were worse in "poor" sleepers than in "good" sleepers. Major classes of comorbid conditions, including psychiatric, neurologic, and musculoskeletal disease, were more prevalent in the "poor" sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days) and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor sleepers, but no differences were observed after adjusting for medications and comorbid conditions associated with poor sleep.	Poor sleepers had greater exacerbation rates than did good sleepers. This appeared to be due largely to them having more, or more severe, concomitant medical conditions and taking more medications.	
25759004	Sleep deprivation is associated with an elevated risk of various diseases and leads to a poor quality of life and negative socioeconomic consequences. Sleep inducers such as drugs and herbal medicines may often lead to dependence and other side effects. L-Theanine (γ-glutamylethylamide), an amino acid naturally found abundant in tea leaves, has anxiolytic effects via the induction of α brain waves without additive and other side effects associated with conventional sleep inducers. Anxiolysis is required for the initiation of high-quality sleep. In this study, we review the mechanism(s), safety, and efficacy of L-theanine. Collectively, sleep studies based on an actigraph, the obstructive sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO) and automatic nervous system (ANS) assessment, sympathetic and parasympathetic nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the administration of 200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis. Because L-theanine does not induce daytime drowsiness, it may be useful at any time of the day. The no observable adverse effect level (NOAEL) for the oral administration of L-theanine was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS: Sleep deprivation-associated morbidity is an increasing public health concern posing a substantial socioeconomic burden. Chronic sleep disorders may seriously affect quality of life and may be etiological factors in a number of chronic diseases such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep inducers are sedatives and are often associated with addiction and other side effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis. This review suggests that L-theanine is a safe natural sleep aid.

25757828	Sleep problems are among the most common non-motor symptoms of Parkinson's disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the original PDSS by adding more items on different aspects of sleep problems, making it a more robust tool to evaluate the severity of sleep disturbances. However, previous studies on deep brain stimulation (DBS) have not used the PDSS-2.To determine if the PDSS-2 could detect improvement reliably in sleep problems after bilateral subthalamic nucleus DBS for PD.	In this prospective study, 25 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were specifically measured by PDSS-2.	Total score of MDS-UPDRS improved from 81 (median, interquartile-range: 63-103) to 55 points (median, IQR: 46-75, p <  0.001). Health-related quality of life, measured by PDQ-39, also improved from 29 (IQR: 18-40) to 15 (IQR: 9-28) points (p = 0.002). Most domains of NMSS also improved. At baseline 13 patients reported sleep problems, but 1 year after DBS implantation only 3 did (p = 0.012). Although only 6 out of 15 items showed a significant decrease after DBS implantation, the total score of PDSS-2 decreased from 24 (IQR: 17-32) to 10 (IQR: 7-18) points (P <  0.001).	Based on our results, PDSS-2 can detect improvements in sleep quality reliably after DBS implantation.	

25754383	Meta-analyses and other previous reviews have identified distinct ethnic/racial differences in the quantity, quality, and propensity for sleep disorders between black and white adults. The present article reviews the meta-analytic evidence along with recent epidemiological, community, and clinical studies to clarify what is known and not known about sleep differences between these two groups. Black individuals tend to have poorer sleep continuity and quality, excessively short or long sleep duration, greater sleep variability, and greater risk of sleep apnea than white individuals. The data suggest that these differences are attenuated yet persist in the face of several relevant confounders such as socioeconomic status, occupational factors, neighborhood context, and comorbidities. However, little is known about the mechanisms that explain ethnic disparities in sleep. We propose a conceptual model of potential mediators for future testing as well as other questions in need of investigation.
25754191	The regulation of wakefulness is important for high-order organisms. Its dysregulation is involved in the pathomechanism of several psychiatric disorders. Thus, a tool for its objective but little time-consuming assessment would be of importance. The Vigilance Algorithm Leipzig allows the objective measurement of sleep propensity, based on a single resting state electroencephalogram. To compare the Vigilance Algorithm Leipzig with the standard for objective assessment of excessive daytime sleepiness, a four-trial Multiple Sleep Latency Test in 25 healthy subjects was conducted. Between the first two trials, a 15-min, 25-channel resting electroencephalogram was recorded, and Vigilance Algorithm Leipzig was used to classify the sleep propensity (i.e., type of vigilance regulation) of each subject. The results of both methods showed significant correlations with the Epworth Sleepiness Scale (ρ = -0.70; ρ = 0.45, respectively) and correlated with each other (ρ = -0.54). Subjects with a stable electroencephalogram-vigilance regulation yielded significant increased sleep latencies compared with an unstable regulation (multiple sleep latency 898.5 s versus 549.9 s; P = 0.03). Further, Vigilance Algorithm Leipzig classifications allowed the identification of subjects with average sleep latencies <6 min with a sensitivity of 100% and a specificity of 77%. Thus, Vigilance Algorithm Leipzig provides similar information on wakefulness regulation in comparison to the much more cost- and time-consuming Multiple Sleep Latency Test. Due to its high sensitivity and specificity for large sleep propensity, Vigilance Algorithm Leipzig could be an effective and reliable alternative to the Multiple Sleep Latency Test, for example for screening purposes in large cohorts, where objective information about wakefulness regulation is needed.
25754117	Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses such as anxiety disorder. To identify promising behavioral targets for pediatric anxiety disorder therapy, we investigated the associations between specific sleep and behavioral problems.We conducted retrospective reviews of 105 patients aged 4-12 years who met the DSM-IV criteria for primary diagnosis of generalized anxiety disorder (n = 33), separation anxiety disorder (n = 23), social phobia (n = 21), or obsessive compulsive disorder (n = 28). Sleep problems were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and behavioral problems by the Spence Children's Anxiety Scale, Oppositional Defiant Behavior Inventory (ODBI), and Depression Self-Rating Scale for Children.	Depressive behavior was weakly correlated with CSHQ subscores for sleep onset delay and night waking but not with total sleep disturbance. Anxiety was correlated with bedtime resistance, night waking, and total sleep disturbance score. Oppositional defiance was correlated with bedtime resistance, daytime sleepiness, sleep onset delay, and most strongly with total sleep disturbance. On multiple regression analysis ODBI score had the strongest positive association with total sleep disturbance and the strongest negative association with total sleep duration.	Sleep problems in children with anxiety disorders are closely related to anxiety and oppositional defiant symptoms.	
25751193	Fear of cancer recurrence (FCR) and sleep disturbance are identified as top psychosocial concerns in cancer survivorship, yet few studies have explored the association between these two factors. Using data from a study of 67 cancer survivors, hierarchical logistic regression models examined the relationships between socio-demographic characteristics, FCR, and sleep disturbance. More than half of survivors reported poor sleep quality; those with some college education and those with higher levels of FCR were at greater risk for poor sleep. These findings provide formative data for oncology social workers to implement interventions that target FCR as a strategy for improving sleep. 
25750600	Bipolar disorder is a severe and chronic disorder, ranked in the top 10 leading causes of disability worldwide. Sleep disturbances are strongly coupled with interepisode dysfunction and symptom worsening in bipolar disorder. Experimental studies suggest that sleep deprivation can trigger manic relapse. There is evidence that sleep deprivation can have an adverse impact on emotion regulation the following day. The clinical management of the sleep disturbances experienced by bipolar patients, including insomnia, hypersomnia delayed sleep phase, and irregular sleep-wake schedule, may include medication approaches, psychological interventions, light therapies and sleep deprivation.
25750599	Humans spend approximately one-third of their lives asleep. Whether due to evolutionary or ontogenetic factors, sleep and psychiatric disorders change with age. Although much of sleep remains an enigma, sleep research is experiencing an exponential increase in its understanding of the causes, correlates, and consequences of sleep disturbances. Although the relationship between age-related sleep and psychiatric conditions is a common clinical observation, empirical investigations remain scarce. Thus, treating patients with symptoms of sleep disorders in the context of psychiatric conditions remains a challenge. This article reviews the state-of-the-science of sleep disorders in the context of psychiatric conditions in late-life.
25747335	Sleep complaints are common after mild traumatic brain injury (mTBI). While recent findings suggest that sleep macro-architecture is preserved in mTBI, features of non-rapid eye movement (NREM) sleep micro-architecture including electroencephalography (EEG) spectral power, slow waves (SW), and sleep spindles could be affected. This study aimed to compare NREM sleep in mTBI and healthy controls, and explore whether NREM sleep characteristics correlate with sleep complaints in these groups.Thirty-four mTBI participants (mean age: 34.2 ± 11.9 yrs; post-injury delay: 10.5 ± 10.4 weeks) and 29 age-matched controls (mean age: 32.4 ± 8.2 yrs) were recruited for two consecutive nights of polysomnographic (PSG) recording. Spectral power was computed and SW and spindles were automatically detected in three derivations (F3, C3, O1) for the first three sleep cycles. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI).	mTBI participants reported significant poorer sleep quality than controls on the PSQI and showed significant increases in beta power during NREM sleep at the occipital derivation only. Conversely, no group differences were found in SW and spindle characteristics. Interestingly, changes in NREM sleep characteristics were not associated with mTBI estimation of sleep quality.	Compared to controls, mTBI were found to have enhanced NREM beta power. However, these changes were not found to be associated with the subjective evaluation of sleep. While increases in beta bands during NREM sleep may be attributable to the occurrence of a brain injury, they could also be related to the presence of pain and anxiety as suggested in one prior study.	
25744440	Sleep disorders occur commonly in Parkinson's disease and are often under-recognized and under treated in clinical practice.To determine the quality of sleep in patients with Young onset Parkinson's disease (YOPD) and to note whether there is any difference in quality of sleep from those patients with older onset Parkinson's disease (OOPD).	One hundred and fifty six patients with Parkinson's disease (YOPD-51, OOPD-105) were clinically examined and quality of sleep was determined using Pittsburgh sleep quality index (PSQI), Parkinson's disease Sleep Scale (PDSS) and Epworth Sleep Scale (ESS). Other scales included Unified Parkinson's Disease Rating Scale -part III (UPDRS-III), Hoehn & Yahr Stage, Mini Mental Status Examination, Hamilton anxiety rating scale and Hamilton depression rating scale.	The frequency of insomnia was higher in OOPD (55.2%) as compared to YOPD (27.5%) group (p = 0.001). The frequency of nightmares was lower in YOPD (7.8%) when compared to OOPD (24.8%) group (p = 0.012). The mean hours of actual sleep per night were higher in YOPD patients. Global PSQI score was better in YOPD indicating good overall sleep quality in YOPD patients. The total ESS score was significantly lower in YOPD (p = 0.019). The total PDSS score was significantly better in YOPD patients (p = 0.018).	Patients with YOPD had an overall better quality of sleep with lesser incidence of insomnia, nightmares, daytime sleepiness and restlessness during sleep.	

25743324	In 2013, the National Heart, Lung, and Blood Institute assembled a working group on epidemiology and population sciences from its Advisory Council and Board of External Experts. The working group was charged with making recommendations to the National Heart, Lung, and Blood Advisory Council about how the National Heart, Lung, and Blood Institute could take advantage of new scientific opportunities and delineate future directions for the epidemiology of heart, lung, blood, and sleep diseases. Seven actionable recommendations were proposed for consideration. The themes included 1) defining the compelling scientific questions and challenges in population sciences and epidemiology of heart, lung, blood, and sleep diseases; 2) developing methods and training mechanisms to integrate "big data" science into the practice of epidemiology; 3) creating a cohort consortium and inventory of major studies to optimize the efficient use of data and specimens; and 4) fostering a more open, competitive approach to evaluating large-scale longitudinal epidemiology and population studies. By building on the track record of success of the heart, lung, blood, and sleep cohorts to leverage new data science opportunities and encourage broad research and training partnerships, these recommendations lay a strong foundation for the transformation of heart, lung, blood, and sleep epidemiology. 
25741949	Sleep problems such as difficulties in sleep initiation, nighttime awakening, and shortened sleep time are often subjectively reported in children with autism spectrum disorder (ASD). However, results of objective studies have been mixed. Our goal was to evaluate the existing data from objective measures using a systematic approach to identify and describe the differences in sleep parameters by comparing total sleep time (TST), sleep latency (SL), and sleep efficiency (SE) in children with ASD with those of typically developing (TD) peers.Studies that used objective measures such as actigraphy or polysomnography (PSG) to describe the sleep parameters of TST, SL, and SE in children with ASD compared with children with TD were identified. A meta-analysis was performed for the 10 studies that met inclusion criteria with evaluation of differences in means using random effects models. A total of 343 children with ASD and 221 children with TD were included. Assessments for sources of heterogeneity and publication bias were undertaken.	TST for children with ASD was on average 32.8 minutes less per day (95% confidence interval [CI]: 16.6-49.0 minutes) than their TD peers. Average SL was 10.9 minutes longer (95% CI: 6.7-15.0 minutes), and average SE was 1.9% less (95% CI: 0.7%-3.1%) than their TD peers. Notable heterogeneity was found within studies for TST, and mild heterogeneity was found for SE. Concurrent intellectual disability was a moderator of TST. Children with ASD and normal intelligence had a small and nonsignificant decrease in TST as compared with TD peers, whereas those with ASD and intellectual disability (ID) had a significant decrease in TST as compared with TD peers. The magnitude of the difference in mean SL and SE increased as compared with TD peers as age increased. Studies that used PSG and those that did not include children on medications were more likely to report mean decreases in SE.	Children with ASD have small but measurable objective differences in their sleep parameters that are consistent with subjective reporting. Children with ASD have shorter TST, longer SL periods, and decreased SE as compared with TD peers. Concurrent ID, medication use, method of data collection, and age of subjects significantly moderated these results. The decrease in TST in children with ASD and normal intelligence was not significant as compared with TD peers, suggesting that ID may help explain the shortened TST in children with ASD.	

25741253	Short-term interval timing i.e., perception and action relating to durations in the seconds range, has been suggested to display time-of-day as well as wake dependent fluctuations due to circadian and sleep-homeostatic changes to the rate at which an underlying pacemaker emits pulses; pertinent human data being relatively sparse and lacking in consistency however, the phenomenon remains elusive and its mechanism poorly understood. To better characterize the putative circadian and sleep-homeostatic effects on interval timing and to assess the ability of a pacemaker-based mechanism to account for the data, we measured timing performance in eighteen young healthy male subjects across two epochs of sustained wakefulness of 38.67 h each, conducted prior to (under entrained conditions) and following (under free-running conditions) a 28 h sleep-wake schedule, using the methods of duration estimation and duration production on target intervals of 10 and 40 s. Our findings of opposing oscillatory time courses across both epochs of sustained wakefulness that combine with increasing and, respectively, decreasing, saturating exponential change for the tasks of estimation and production are consistent with the hypothesis that a pacemaker emitting pulses at a rate controlled by the circadian oscillator and increasing with time awake determines human short-term interval timing; the duration-specificity of this pattern is interpreted as reflecting challenges to maintaining stable attention to the task that progressively increase with stimulus magnitude and thereby moderate the effects of pacemaker-rate changes on overt behavior. 
25735218	Aging impairs the function of the suprachiasmatic nucleus (SCN, the central mammalian clock), leading to a decline in the circadian rhythm of many physiological processes, including sleep-wake rhythms. Recent studies have found evidence of age-related changes in the circadian regulation of potassium currents; these changes presumably lead to a decrease in the SCN's electrical rhythm amplitude. Current through large-conductance Ca(2+)-activated K(+) (BK) channels promote rhythmicity in both SCN neuronal activity and behavior. In many neuron types, changes in BK activity are correlated with changes in intracellular Ca(2+) concentration ([Ca(2+)]i). We performed patch-clamp recordings of SCN neurons in aged mice and observed that the circadian modulation of BK channel activity was lost because of a reduction in BK currents during the night. This reduced current diminished the afterhyperpolarization, depolarized the resting membrane potential, widened the action potential, and increased [Ca(2+)]i. These data suggest that reduced BK current increases [Ca(2+)]i by altering the action potential waveform, possibly contributing to the observed age-related phenotype.
25733538	Major depression has multiple comorbidities, in particular drug use disorders, which often lead to more severe and difficult-to-treat illnesses. However, the mechanisms linking these comorbidities remain largely unknown.We investigated how a depressive-like phenotype modulates cocaine-related behaviors using a genetic model of depression: the Helpless H/Rouen (H) mouse. We selected the H mouse line for its long immobility duration in the tail suspension test when compared to non-helpless (NH) and intermediate (I) mice. Since numerous studies revealed important sex differences in drug addiction and depression, we conducted behavioral experiments in both sexes.	All mice, regardless of phenotype or sex, developed a similar behavioral sensitization after 5 daily cocaine injections (10 mg/kg). Male H and NH mice exhibited similar cocaine-induced conditioned place preference scores that were only slightly higher than in I mice, whereas female H mice strikingly accrued much higher preferences for the cocaine-associated context than those of I and NH mice. Moreover, female H mice acquired cocaine-associated context learning much faster than I and NH mice, a facilitating effect that was associated to a rapid increase in striatal and accumbal brain-derived neurotrophic factor levels (BDNF; up to 35% 24 h after cocaine conditioning). Finally, when re-exposed to the previously cocaine-associated context, female H mice displayed greater Fos activation in the cingulate cortex, nucleus accumbens, and basolateral amygdala.	Our data indicate that neurobiological mechanisms such as alterations in associative learning, striato-accumbal BDNF expression, and limbic-cortico-striatal circuit reactivity could mediate enhanced cocaine vulnerability in female depressive-like mice.	
25733101	Both sleep disturbance and social isolation increase the risk for morbidity and mortality. Systemic inflammation is suspected as a potential mechanism of these associations. However, the complex relationships between sleep disturbance, social isolation, and inflammation have not been examined in a population-based longitudinal study. This study examined the longitudinal association between sleep disturbance and systemic inflammation, and the moderating effects of social isolation on this association. The CARDIA study is a population-based longitudinal study conducted in four US cities. Sleep disturbance - i.e., insomnia complaints and short sleep duration - was assessed in 2962 African-American and White adults at baseline (2000-2001, ages 33-45years). Circulating C-reactive protein (CRP) was measured at baseline and follow-up (2005-2006). Interleukin-6 (IL-6) and subjective and objective social isolation (i.e., feelings of social isolation and social network size) were measured at follow-up. Sleep disturbance was a significant predictor of inflammation five years later after full adjustment for covariates (adjusted betas: 0.048, P=0.012 for CRP; 0.047, P=0.017 for IL-6). Further adjustment for baseline CRP revealed that sleep disturbance also impacted the longitudinal change in CRP levels over five years (adjusted beta: 0.044, P=0.013). Subjective social isolation was a significant moderator of this association between sleep disturbance and CRP (adjusted beta 0.131, P=0.002). Sleep disturbance was associated with heightened systemic inflammation in a general population over a five-year follow-up, and this association was significantly stronger in those who reported feelings of social isolation. Clinical interventions targeting sleep disturbances may be a potential avenue for reducing inflammation, particularly in individuals who feel socially isolated. 
25731881	Behavioral and psychological symptoms of dementia include agitation, depression, apathy, repetitive questioning, psychosis, aggression, sleep problems, wandering, and a variety of inappropriate behaviors. One or more of these symptoms will affect nearly all people with dementia over the course of their illness. These symptoms are among the most complex, stressful, and costly aspects of care, and they lead to a myriad of poor patient health outcomes, healthcare problems, and income loss for family care givers. The causes include neurobiologically related disease factors; unmet needs; care giver factors; environmental triggers; and interactions of individual, care giver, and environmental factors. The complexity of these symptoms means that there is no "one size fits all solution," and approaches tailored to the patient and the care giver are needed. Non-pharmacologic approaches should be used first line, although several exceptions are discussed. Non-pharmacologic approaches with the strongest evidence base involve family care giver interventions. Regarding pharmacologic treatments, antipsychotics have the strongest evidence base, although the risk to benefit ratio is a concern. An approach to integrating non-pharmacologic and pharmacologic treatments is described. Finally, the paradigm shift needed to fully institute tailored treatments for people and families dealing with these symptoms in the community is discussed. 
25730677	The pedunculopontine nucleus (PPN) is a part of the reticular activating system and one of the main sources of the cholinergic fibers in the midbrain, while it is also subject to cholinergic modulation. This nucleus is known to be a structure that controls sleep-wake cycles, arousal, and locomotion. Neurons of the PPN are targets of several neuromodulatory mechanisms, which elicit heterogeneous pharmacological responses including hyperpolarization and depolarization, whereas lack of response can also be observed. In agreement with previous findings, we found that PPN neurons respond to the muscarinic agonist carbachol in a heterogeneous manner: they were depolarized and showed increased firing rate, decreased firing frequency, and were hyperpolarized, or showed no response. The heterogeneity of the muscarinic activation was similar to our previous observations with type 1 cannabinoid (CB1) receptor agonists; therefore, we investigated whether muscarinic and endocannabinoid modulatory mechanisms elicit the same action on a certain neuron. To achieve this, whole-cell patch clamp experiments were conducted on midbrain slices containing the PPN. Carbachol was applied first and, after recording the changes in the membrane potential and the firing frequency and achieving washout, the CB1 receptor agonist arachidonyl-2'-chloroethylamide (ACEA) was applied. A marked but not full overlap was observed: all neurons depolarized by carbachol were depolarized by the CB1 receptor agonist ACEA, and all neurons lacking response to carbachol lacked response to ACEA as well. However, neurons hyperpolarized by carbachol were depolarized, hyperpolarized, or not affected by the ACEA. These results indicate that endocannabinoid and muscarinic modulatory effects involve similar mechanisms of action. 
25728396	Sleep disturbances are common in chronic fatigue syndrome (CFS), and one of the key symptom complaints, yet it has been neglected by previous qualitative research. The aim was to explore the specific role of sleep in patients' experience of their illness.A qualitative semi-structured interview format facilitated a detailed and open exploration of sleep, and the extent to which its management and problems were linked to the lived experience of CFS.	Eleven semi-structured interviews were conducted with individuals with CFS. Data were transcribed verbatim and analysed thematically, to explore and describe patients' experience of their sleep, and its impact on their condition.	Sleep emerged as a key aspect of the illness experience, and its management and effect on daytime functioning was a central pre-occupation for all 11 participants; all of them saw sleep as playing a critical role in their illness through either maintaining or exacerbating existing symptoms. Exploration of individual experiences presented three overarching themes: (1) sleep pattern variability over illness course and from day to day; (2) effect of sleep on daytime functioning; and (3) attempts at coping and sleep management.	Each patient with CFS has a unique experience of sleep. Despite the differing narratives regarding the role of sleep in CFS, all participants held the belief that sleep is a vital process for health and well-being which has had a direct bearing on the course and progression of their CFS. Also, every participant regarded their sleep as in some way 'broken' and in need of management/repair. Patients' insights demonstrate sleep-specific influences on their CFS, and the impact of disturbed sleep should be a consideration for clinical and research work.	What is already known on this subject? Sleep disturbances are common in CFS, and one of the key symptom complaints, yet it has been neglected by previous qualitative research. Ontology of CFS is a matter of dispute, with models ranging from the biological to the psychological competing to explain symptomatology in this illness. A qualitative study has the potential to add some clarity to the debate by making the patients' lived experience of the condition, and their own understanding of it, the focus of research. What this study adds? Coping and attempts at managing sleep problems in CFS adds to the 'illness burden' experienced by patients. Disturbed sleep is universally seen by patients with CFS as impacting on other daytime symptoms. Broken sleep may contribute to a biopsychosocial cycle that serves to maintain this illness.	
25727766	A considerable proportion of subjects with obsessive-compulsive disorder (OCD) have shown resistance or an incomplete response to the standard first-line treatment of serotonin reuptake inhibitors. In particular, patients often continue to show disrupted circadian rhythms with related sleep disturbances and comorbidity with bipolar spectrum disorders.This paper discusses the possible role of agomelatine in the treatment of motivational aspects and dysregulated circadian rhythms of OCD. In particular, the article highlights the pharmacokinetics and pharmacodynamics of agomelatine. Additionally, the article highlights its clinical efficacy, safety and tolerability and provides perspectives on its future development as a potential therapy for the treatment of OCD.	Agomelatine offers the effective resynchronization of circadian rhythm with an improvement in patients' reward mechanism, incentive motivation and general OCD symptoms. Indeed, the authors believe that agomelatine could be a valid alternative drug in treatment-resistant OCD patients, particularly those suffering with bipolar spectrum comorbidity and related sleep disturbances.	
25727101	The present study aimed to assess the prognostic value of early amplitude-integrated electroencephalogram (aEEG) in late preterm infants who were born at a gestational age between 34 0/7 and 36 6/7 weeks for the prediction of neurobehavioral development. Late preterm infants (n = 170) with normal, mild, and severe asphyxia underwent continuous recording of aEEG for 4-6 h starting 6-8 h after delivery. The recordings were analyzed for background pattern, sleep-wake cycle (SWC), and seizures. Survivors were assessed at 18 months by neurological examination and Bayley Scales of Infant Development II. The incidence of adverse neurological outcome in the asphyxia group was significantly higher than in the normal group. For late preterm infants in the asphyxia group, abnormal aEEG pattern had a predictive potential of neurological outcomes with sensitivity of 78.57% (specificity, 87.80%; positive predictive value [PPV], 68.75%; negative predictive value [NPV], 92.31%; power, 85.45%). Non-SWC and intermediate SWC significantly were increased (25.45 and 52.73%, respectively) in the asphyxia group vs. the normal group. SWC pattern had neurological prognosis value in the asphyxia group with sensitivity of 64.29% (specificity, 87.80%; PPV, 64.29%; NPV, 87.80%; power, 81.82%).Early aEEG patterns are important determinants of long-term prognosis of neurodevelopmental outcome in asphyxiated late preterm infants.	
25726988	Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs.This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression.	We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.	
25726892	To review the psychometric properties of the questionnaires commonly filled in by children and adolescents to measure circadian preference.We examined the Morningness-Eveningness Questionnaire for Children and Adolescents (MEQ-CA), the Morningness-Eveningness Scale for Children (MESC) and the Composite Scale of Morningness (CSM). We critically analyzed the reliability, in term of internal consistency (through the Cronbach's alpha) and test-retest reliability (through the correlation coefficient), and the type of validation against external criteria (objective assessment of the sleep/wake cycle, body temperature, hormones and other questionnaires). Fifty studies that reported these data were included in the review: 7 studies used the MEQ-CA, 28 used the MESC and 15 used the CSM.	The percentage of studies reporting at least acceptable levels of internal consistency was high and similar between the three questionnaires. Evidence for test-retest reliability was scant, since only 3 studies were available; it was at least acceptable for the MESC (two studies with a time interval of 1 month), not acceptable for the MEQ-CA (one study with a time interval of 6 months), while no information was available for the CSM. As regards the validation evidence, the MEQ-CA has been validated by the highest number of external criteria (actigraphy, oral body temperature and other questionnaires), followed by the CSM (cortisol sampling and other questionnaires). The MESC has been validated only against self-report measures.	The present state of the art would suggest the use of the MEQ-CA to assess circadian preference in children and adolescents.	
25726855	Several organisms irrespective of their complexity in structure and function have an inbuilt circadian rhythm. Zebrafish could be used as an alternate model animal in sleep research as it exhibits similar sleep-wake dynamics as mammals and Drosophila. In this study, we have analysed the adult zebrafish brain for its differential proteome and gene expression during perturbed light/dark cycle. A total of 53 and 25 proteins including sncb, peroxiredoxins and TCR alpha were identified based on two-dimensional gel electrophoresis Fourier transform mass spectrometer/ion trap tandem mass spectrometer and differential in-gel electrophoresis MALDI TOF MS/MS analysis, respectively, with at least 1.5-fold changes between the control and experimental brains. Real time-polymerase chain reaction revealed that many circadian pathway-associated genes, such as per1b, bmal1b, cry1b, bmal2 and nr1d2, were differentially regulated during continuous light/dark exposures. It is hypothesized that the differential regulation of these genes might lead to the discovery of potential diagnostic markers for gaining insight into the light/dark-associated stress in humans. 
25724467	Musculoskeletal pain is one of the most common causes of sickness absence. Sleep disturbances are often co-occurring with pain, but the relationship between sleep and pain is complex. Little is known about the importance of self-reported sleep, when predicting sickness absence among persons with musculoskeletal pain. This study aims to study the association between self-reported sleep quality and sickness absence 5 years later, among individuals stratified by presence of lower back pain (LBP) and neck and shoulder pain (NSP).The cohort (n = 2286) in this 5-year prospective study (using data from the MUSIC-Norrtälje study) was stratified by self-reported pain into three groups: no LBP or NSP, solely LBP or NSP, and concurrent LBP and NSP. Odds ratios (ORs) for the effect of self-reported sleep disturbances at baseline on sickness absence (> 14 consecutive days), 5 years later, were calculated.	Within all three pain strata, individuals reporting the most sleep problems showed a significantly higher OR for all-cause sickness absence, 5 years later. The group with the most pronounced sleep problems within the concurrent LBP and NSP stratum had a significantly higher OR (OR 2.00; CI 1.09-3.67) also for long-term sickness absence (> 90 days) 5 years later, compared to the group with the best sleep. CONCLUSIONS Sleep disturbances predict sickness absence among individuals regardless of co-existing features of LBP and/or NSP. The clinical evaluation of patients should take possible sleep disturbances into account in the planning of treatments.	

25721246	Numerous studies have reported the relationship between sleep duration and obesity in elderly adults; however, little is known about the relationship of sleep duration and sarcopenia.We examined the relationship of sleep duration with obesity and sarcopenia in community-dwelling older adults.	A total of 488 community-dwelling adults (224 men and 264 women) aged ≥65 years were included in the analysis. Self-reported sleep duration and anthropometric data were collected. Skeletal muscle mass was estimated using the predicted equation from a bioelectrical impedance analysis measurement. Obesity and sarcopenia were defined according to the body mass index and the skeletal muscle mass index, respectively.	The association between sleep duration and sarcopenia exhibited a U shape in older adults. Compared to adults with 6-8 h of sleep, adults with <6 h of sleep had a nearly 3-fold increased likelihood of sarcopenia (odds ratio, OR: 2.76, 95% confidence interval, CI: 1.28-5.96), while adults with ≥8 h of sleep had a nearly 2-fold increased risk of sarcopenia (OR: 1.89, 95% CI: 1.01-3.54). Older adults with a sleep duration <6 h were more prone to obesity (OR: 2.15, 95% CI: 1.08-4.30). After gender stratification, the association between obesity and short sleep duration was more robust in women.	There were significant associations of sleep duration with either obesity or sarcopenia in community-dwelling older adults. Gender differences in these associations were also observed.	

25720055	Abstract Prevalence studies suggest that Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common dementing illnesses in the elderly. The aim of this narrative review was to provide data on sleep-related behaviors in AD and DLB. This paper contains arguments, with a clinical approach, on both circadian rhythm changes and dissociated states of wakefulness and sleep in these two conditions. 
25717159	Understanding the dynamics of brain activity manifested in the EEG, local field potentials (LFP), and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence, and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here, we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical LFP and neuronal activity with LZC approach. We found that activated brain states-waking and rapid eye movement (REM) sleep are characterized by higher LZC compared with non-rapid eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation and toward the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiological mechanisms of brain activity in health and disease.
25715718	To assess the occurrence of bruxism in deciduous dentition and a potential association between the habit and the presence or absence of posterior crossbite.A total of 940 patient files were assessed. They were gathered from the archives of University of São Paulo City--UNICID; however, 67 patient files were dismissed for not meeting the inclusion criteria. Therefore, 873 children, males and females, comprised the study sample. They were aged between 2-6 years old and came from six different public primary schools from the east of the city of São Paulo. Data were collected through questionnaires answered by parents/guardians and by clinical examinations carried out in the school environment in order to obtain the occlusal characteristics in the transverse direction. First, a descriptive statistical analysis of all variables was performed (age, sex, race, posterior crossbite, bruxism, headache and restless sleep); then, the samples were tested by means of chi-square test with significance level set at 0.05%. A logistic regression model was applied to identify the presence of bruxism.	The prevalence of this parafunctional habit was of 28.8%, with 84.5% of patients showing no posterior crossbite. Regarding the association of bruxism with crossbite, significant results were not found. Children with restless sleep have 2.1 times more chances of developing bruxism, whereas children with headache have 1.5 more chances.	Transverse plane of occlusion was not associated with the habit of bruxism.	
25715641	Depression has been associated with sleep disturbances in pregnancy; however, no previous research has controlled the possible confounding effect of anxiety on this association. This study aims to analyze the effect of depression on sleep during the third trimester of pregnancy controlling for anxiety. The sample was composed by 143 depressed (n = 77) and non-depressed (n = 66) pregnant women who completed measures of depression, anxiety, and sleep. Differences between groups in sleep controlling for anxiety were found. Depressed pregnant women present higher number of nocturnal awakenings and spent more hours trying falling asleep during the night and the entire 24 h period. Present findings point out the effect of depression on sleep in late pregnancy, after controlling for anxiety.
25715354	To identify the amount of sleep disruption that occurs in the postoperative inpatient hospital setting, determine the relationship between sleep disruption and the quantity of narcotics taken for postoperative pain, and determine if hospital length of stay is related to sleep disruption.Prospective cohort study.	Single tertiary care academic institution.	Fifty patients undergoing total hip or knee arthroplasty at Henry Ford Hospital in Detroit, Michigan, between January 2013 and November 2013 were asked to wear an actigraph during their postoperative hospital stay. Total sleep time, sleep efficiency, awake index, total narcotic use, visual analog pain scores, and postoperative complications were analyzed.	Overall sleep efficiency was 61.2% and 66.5% with an awake index of 5.5 and 5.4 for each of the postoperative nights measured. A significant correlation was found between increased self-reported pain scores and decreased total sleep time (r = -0.31; P = .03). Spearman correlations between total sleep time, sleep efficiency, and awake index were made with narcotic use on postoperative day (POD) 0 and 1. Longer hospital length of stay was significantly correlated with decreased sleep efficiency (r = -0.35, P = .01). Complication rates were not statistically different compared with sleep parameters.	Better control of a patient's pain is associated with greater sleep efficiency and total sleep time. Improvements in sleep efficiency in hospitalized patients may be associated with a decrease in length of stay.	
25714703	Short sleep and poor sleep quality are associated with risk of cardiovascular disease, diabetes, cancer, and mortality. This study examines the contribution of sleep duration and sleep quality on a multisystem biological risk index that is known to be associated with morbidity and mortality.Analyses include a population-based sample from the Midlife Development in the United States survey recruited to the Biomarker substudy. A total of 1,023 participants aged 54.5 years (SD = 11.8), 56% female and 77.6% white, were included in the analyses. A multisystem biological risk index was derived from 22 biomarkers capturing cardiovascular, immune, lipid-metabolic, glucose-metabolic, sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems. Self-reported average sleep duration was categorized as short (<5 hrs), below normal (5 to <6.5 hrs), normal (6.5 to <8.5 hrs), and long sleepers (8.5+ hrs). Sleep quality was determined using the Pittsburgh Sleep Quality Index categorized as normal (≤5) and poor quality (>5) sleep.	Linear mixed effect models adjusting for age, gender, race, education, income, BMI, and health status were performed. As compared to normal sleepers, multisystem biological risk in both short (B(SE) = .38(.15), p<.01) and long sleepers (B(SE) = .28(.11), p<.01) were elevated. Poor quality sleep alone was associated with elevated multisystem biological risk (B(SE) = .15(.06), p = .01), but was not significant after adjustment for health status. All short sleepers reported poor sleep quality. However in the long sleepers, only those who reported poor sleep quality exhibited elevated multisystem biological risk (B(SE) = .93(.3), p = .002).	Self-reported poor sleep quality with either short or long sleep duration is associated with dysregulation in physiological set points across regulatory systems, leading to elevated multisystem biological risk. Physicians should inquire about sleep health in the assessment of lifestyle factors related to disease risk, with evidence that healthy sleep is associated with lower multisystem biological risk.	
25710788	Noise has been found to be associated with endocrine changes and cardiovascular disease. Increased cortisol levels and chronic sleep problems due to noise may increase the risk of obesity.We investigated the relationship between road traffic noise and obesity markers. Furthermore, we explored the modifying role of noise sensitivity, noise annoyance, and sleep disturbances.	We used data from a population-based study, HUBRO (N=15,085), and its follow-up study HELMILO (N=8410) conducted in Oslo, Norway. Measurements were used to define body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and these binary outcomes: BMI≥30kg/m(2), WC≥102cm (men)/88cm (women), and WHR≥0.90 (men)/0.85 (women). Modelled levels of road traffic noise (Lden) were assigned to each participant's home address. Linear and logistic regression models were used to examine the associations.	The results indicated no significant associations between road traffic noise and obesity markers in the total populations. However, in highly noise sensitive women (n=1106) a 10dB increase in noise level was associated with a slope (=beta) of 1.02 (95% confidence interval (CI): 1.01, 1.03) for BMI, 1.01 (CI: 1.00, 1.02) for WC, and an odds ratio (OR) of 1.24 (CI: 1.01, 1.53) for WHR ≥0.85. The associations appeared weaker in highly noise sensitive men. We found no effect modification of noise annoyance or sleep disturbances. In a sub-population with bedroom facing a road, the associations increased in men (e.g. an OR of 1.25 (CI: 0.88, 1.78) for BMI ≥30kg/m(2)), but not in women. Among long-term residents the associations increased for BMI ≥30kg/m(2) (OR of 1.07 (CI: 0.93, 1.24) in men and 1.10 (CI: 0.97, 1.26) in women), but not for the other outcomes.	In an adult urban Scandinavian population, road traffic noise was positively associated with obesity markers among highly noise sensitive women. The associations appeared stronger among men with bedroom facing a street, representing a population with more accurately assigned exposure.	
25710522	Disruptive sleeping patterns have been linked to serious medical conditions. Regular physical activity (PA) has a positive impact on health; however, few research have investigated the relationships between PA, body mass index (BMI), sedentary behaviors (SB), and sleep disorders (SD).Data from the 2005-2006 NHANES were analyzed for this study. Participants (N = 2989; mean age = 50.44 years) were grouped based upon responses to SD questions. Accelerometers were used to measure the average time spent in moderate or vigorous physical activity (MVPA) and SB. Multinomial logistic regression analyses were used to examine the associations between PA, SB, and SD after controlling for covariates and to explore potential moderation effects among common risk factors and the main study variables.	Among middle-aged adults, PA was significantly associated with SD [Wald χ2 (8) = 22.21; P < .001]. Furthermore, among adults in the highest tertile of SB, PA was significantly associated with SD [Wald χ2 (8) = 32.29; P < .001].	These results indicate that middle-aged adults who are less active may have increased likelihoods of SD. It is important for health care professionals to continue developing methods for increasing PA to decrease the risk of SD.	
25710495	To develop and validate a novel non-contact system for whole-night sleep evaluation using breathing sounds analysis (BSA).Whole-night breathing sounds (using ambient microphone) and polysomnography (PSG) were simultaneously collected at a sleep laboratory (mean recording time 7.1 hours). A set of acoustic features quantifying breathing pattern were developed to distinguish between sleep and wake epochs (30 sec segments). Epochs (n = 59,108 design study and n = 68,560 validation study) were classified using AdaBoost classifier and validated epoch-by-epoch for sensitivity, specificity, positive and negative predictive values, accuracy, and Cohen's kappa. Sleep quality parameters were calculated based on the sleep/wake classifications and compared with PSG for validity.	University affiliated sleep-wake disorder center and biomedical signal processing laboratory.	One hundred and fifty patients (age 54.0±14.8 years, BMI 31.6±5.5 kg/m2, m/f 97/53) referred for PSG were prospectively and consecutively recruited. The system was trained (design study) on 80 subjects; validation study was blindly performed on the additional 70 subjects.	Epoch-by-epoch accuracy rate for the validation study was 83.3% with sensitivity of 92.2% (sleep as sleep), specificity of 56.6% (awake as awake), and Cohen's kappa of 0.508. Comparing sleep quality parameters of BSA and PSG demonstrate average error of sleep latency, total sleep time, wake after sleep onset, and sleep efficiency of 16.6 min, 35.8 min, and 29.6 min, and 8%, respectively.	This study provides evidence that sleep-wake activity and sleep quality parameters can be reliably estimated solely using breathing sound analysis. This study highlights the potential of this innovative approach to measure sleep in research and clinical circumstances.	
25709424	Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies.The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified.	One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD.	The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD.	
25708515	Distress and reduced quality of life (QOL) are common among people with cancer. No study has compared these variables after breast cancer diagnosis to pre-cancer diagnosis levels.Data on women with breast cancer 50 years of age or older (n = 6949) were analyzed from the Women's Health Initiative (1993-2013). Health-related QOL (physical function, mental health) was measured using Rand-36. Depressive symptoms were measured with the six-item Center for Epidemiologic Studies Depression scale. Assessments occurred before and after the cancer diagnosis. Hierarchical linear modeling compared pre-cancer QOL and depressive symptoms to levels post-diagnosis and tested whether pre-cancer physical activity, stressful life events, sleep disturbance, and pain predicted post-diagnosis outcomes.	Compared with pre-cancer levels, depressive symptoms increased (20.0% increase at 0-6 months, 12.9% increase at 6-12 months), while physical function (-3.882 points at 0-6 months, -3.545 at 6-12 months) and mental health decreased (-2.899 points at 0-6 months, -1.672 at 6-12 months) in the first year after diagnosis (all p < .01). Depressive symptoms returned to pre-cancer levels after 10 years, but QOL remained significantly lower. At more than 10 years post-diagnosis, physical function was 2.379 points lower than pre-cancer levels (p < 0.01) while mental health was 1.922 points lower (p < 0.01). All pre-cancer predictors were associated with all outcomes. Pain predicted uniquely greater decreases in physical function post-diagnosis.	Depressive symptoms increased and QOL decreased following breast cancer diagnosis compared with pre-cancer levels, particularly in the first year.	QOL may remain lower for years after breast cancer diagnosis, although decreases are small.	
25708176	Few studies have investigated the relationship between sleep disorders (SD) and erectile dysfunction (ED). Therefore, this study explored whether patients with SD in an Asian population are at an increased risk of developing ED.This longitudinal nationwide population-based cohort study investigated the incidence and risk of developing ED in 34,548 men newly diagnosed with SD between 2002 and 2008 from the National Health Insurance Research Database. A total of 138,192 controls without SD were randomly recruited from the general population and frequency matched according to age and sex. The follow-up period began from the date of entering the study cohort until the date of an ED event, censoring, or 31 December 2010. We conducted Cox proportional hazard regression analyses to estimate the effects of SD on the risk of ED.	The SD cohort had a 2.11-fold adjusted hazard ratio (HR) of subsequent ED development compared with the non-SD cohort [95% confidence interval (CI) = 1.89-2.37]. The incidence of ED increased with age for both cohorts and was higher for the patients in the SD cohort. Compared with the participants without SD or comorbidities, the patients without SD with any comorbidity exhibited a 1.79-fold risk of developing ED (95% CI = 1.54-2.09); the highest risk was for those with both SD and any comorbidity (HR = 3.34, 95% CI = 2.82-3.95). Furthermore, SD patients who had a particular number of comorbidities showed the dose-response effect of developing ED.	This nationwide cohort study determined that ED risk evidently increased in SD patients compared with the general population.	
25707446	There is increased recognition that sleep problems may develop in children and adolescents after mild traumatic brain injury (mTBI). However, few studies have utilized both subjective and objective measures to comprehensively assess sleep problems in the pediatric population following the acute post-TBI period. The aims of this study were to compare sleep in adolescents with mTBI to healthy adolescents using subjective and objective measures, and to identify the clinical correlates associated with sleep problems. One hundred adolescents (50 adolescents with mTBI recruited from three to twelve months post-injury and 50 healthy adolescents) completed questionnaires assessing sleep quality, depression, and pain symptoms, and underwent 10 day actigraphic assessment of sleep patterns. Adolescents with mTBI reported poorer sleep quality and demonstrated significantly shorter actigraphic-measured sleep duration, poorer sleep efficiency, and more wake time after onset of sleep, compared with healthy adolescents (all, p<0.05). For both groups of adolescents, poorer self-reported sleep quality was predicted by greater depressive symptoms. Poorer actigraphic sleep efficiency was predicted by membership in the mTBI group after controlling for age, sex, depressive symptoms, and presence of pain. Our findings suggest that adolescents may experience subjective and objective sleep disturbances up to one year following mTBI. These findings require further replication in larger samples. Additionally, research is needed to identify possible mechanisms for poor sleep in youth with mTBI. 
25707283	Quality sleep is critical for daily functions of human beings and thus the timing and duration of sleep are tightly controlled. However, rare genetic variants affecting sleep regulatory mechanisms can result in sleep phenotypes of extremely deviated sleep/wake onset time or duration. Using genetic analyses in families with multiple members expressing particular sleep phenotypes, these sleep-associated genetic variants can be identified. Deciphering the nature of these genetic variants using animal models or biochemical methods helps further our understanding of sleep processes. In this chapter, we describe the methods for studying genetics of human sleep behavioral phenotypes. 
25707282	The two-process model of sleep-wake regulation posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep) and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Notably, there is a high degree of stability in neurobehavioral responses to sleep loss, suggesting that these individual differences are trait-like and phenotypic and are not explained by subjects' baseline functioning or a number of other potential predictors. The Psychomotor Vigilance Test is an important tool for phenotyping as it is sensitive to acute total sleep deprivation and chronic sleep restriction, is affected by the circadian and sleep homeostatic drives, shows large intersubject variability in the response to sleep loss, and tracks recovery from sleep restriction. Careful phenotyping is critical to accurately predict human performance (and individual differences) in situations in which the circadian and sleep homeostatic systems are perturbed such as acute total sleep loss, chronic sleep restriction, intermittent sleep loss, shift work, and jet lag. 
25706182	We examined whether women reporting nighttime pain would have more actigraphy-measured evidence for disturbed sleep and would report feeling less rested compared with women without nighttime pain.Up to 27 consecutive nights of actigraphy and sleep diary data from each participant were analyzed in this community-based study of 314 African-American (n = 118), white (n = 141), and Chinese (n = 55) women, aged 48 to 58 years, who were premenopausal, perimenopausal, or postmenopausal and were participating in the Study of Women's Health Across the Nation Sleep Study. Dependent variables were actigraphy-measured movement and fragmentation index, total sleep time, sleep efficiency, and diary self-report of "feeling rested" after waking up. All outcomes were fitted using linear mixed-effects models to examine covariate-adjusted associations between the independent variable (nighttime pain severity) and sleep outcomes.	Higher pain severity scores were associated with longer sleep duration but reduced sleep efficiency and less restful sleep. Women reporting nocturnal vasomotor symptoms had more sleep-related movement and sleep fragmentation, had reduced sleep efficiency, and were less likely to feel rested after wakening whether or not they reported pain.	Midlife women who report higher nighttime pain levels have more objective evidence for less efficient sleep, consistent with self-reported less restful sleep. Nocturnal vasomotor symptoms also can contribute to restlessness and wakefulness in midlife women.	
25705911	The association between the psychosocial work environment, including job demands, job control, and organizational justice, and employee wellbeing has been well established. However, the exposure to adverse work environments is typically measured only using self-reported measures that are vulnerable to reporting bias, and thus any associations found may be explained by reverse causality. Using linear regression models and cross-lagged structural equation modeling (SEM), we tested the direction of the association between established job stress models (job demand control and organizational justice models) and 3 wellbeing indicators (psychological distress, sleeping problems, and job satisfaction) among 1524 physicians in a 4-year follow-up. Results from the longitudinal cross-lagged analyses showed that the direction of the association was from low justice to decreasing wellbeing rather than the reverse. Although the pattern was similar in job demands and job control, a reciprocal association was found between job control and psychological distress.
25704740	The ability to transition from wakefulness to sleep is one of the most important tasks in the development of sleep during early childhood. Although establishing regular bedtime routines for children with sleep problems can be clinically effective in reducing the number of signaled night awakenings and increasing amount of sleep, it is unclear whether a regular bedtime routine would be associated with either the frequency of signaled night awakenings or nightly sleep minutes in a nonclinical sample of children. This study examined the role of a regular bedtime routine on the development of sleep regulation and consolidation in a community sample of young children. Adherence to a bedtime routine was concurrently associated with a greater amount of nightly sleep at 36 and 42 months. In addition, adherence to a bedtime routine predicted an increase in nightly sleep minutes over a 6-month period. Finally, this study demonstrated that adherence to a bedtime routine was particularly supportive of developmental gains for children of mothers who used consistent parenting practices during the day. 
25704739	Many scholars have proposed that parent-child attachment security should favor child sleep. Research has yet, however, to provide convincing support for this hypothesis. The current study used objective measures of sleep and attachment to assess the longitudinal links between mother-child attachment security and subsequent sleep, controlling for child dependency. Sixty-two middle-class families (30 girls) were met twice, when children were 15 months (Wave 1; W1) and 2 years of age (Wave 2; W2). At W1, mother-child attachment was assessed with the observer version of the Attachment Q-Sort. At W2, children wore an actigraph monitor for 72 hr. Results indicated that children more securely attached to their mothers subsequently slept more at night and had higher sleep efficiency, and these predictions were not confounded by child dependency. These findings suggest a unique role for secure attachment relationships in the development of young children's sleep regulation, while addressing methodological issues that have long precluded consensus in this literature. 
25704738	The aims of this longitudinal study were to examine (a) development of infant sleep and maternal sleep from 3 to 6 months postpartum; (b) concomitant and prospective links between maternal sleep and infant sleep; and (c) triadic links between paternal involvement in infant caregiving and maternal and infant sleep. The study included 57 families that were recruited during pregnancy. Maternal and infant sleep was assessed using actigraphy and sleep diaries for 5 nights. Both fathers and mothers completed a questionnaire assessing the involvement of fathers relative to mothers in infant caregiving. The results demonstrated moderate improvement in infant and maternal sleep percent between 3 and 6 months. Maternal sleep percent at 3 months significantly predicted infant sleep percent at 6 months. Greater paternal involvement in infant daytime and nighttime caregiving at 3 months significantly predicted more consolidated maternal and infant sleep at 6 months. These findings suggest that maternal sleep is an important predictor of infant sleep and that increased involvement of fathers in infant caregiving responsibilities may contribute to improvements in both maternal and infant sleep during the first 6 months postpartum. 
25704737	We examined longitudinal relations between adult interpartner conflict (referred to as marital conflict) and children's subsequent sleep minutes and quality assessed objectively via actigraphy, and tested parasympathetic nervous system (PNS) activity indexed through respiratory sinus arrhythmia reactivity (RSA-R) and initial sleep as moderators of predictive associations. At Wave 1 (W1), children (85 boys, 75 girls) with a mean age of 9.43 years (SD=.69) reported on marital conflict, and their sleep was assessed with actigraphs for seven nights. Sleep minutes, sleep efficiency, sleep activity, and number of long wake episodes were derived. RSA-R was measured in response to a lab challenge. Sleep parameters were assessed again 1 year later at Wave 2 (W2; mean age=10.39; SD=.64). Analyses consistently revealed 3-way interactions among W1 marital conflict, sleep, and RSA-R as predictors of W2 sleep parameters. Sleep was stable among children with more sleep minutes and better sleep quality at W1 or low exposure to marital conflict at W1. Illustrating conditional risk, marital conflict predicted increased sleep problems (reduced sleep minutes, worse sleep quality) at W2 among children with poorer sleep at W1 in conjunction with less apt physiological regulation (i.e., lower levels of RSA-R or less vagal withdrawal) at W1. Findings build on the scant literature and underscore the importance of simultaneous consideration of bioregulatory systems (PNS and initial sleep in this study) in conjunction with family processes in the prediction of children's later sleep parameters.
25704735	Sleep patterns and temperament in the first year of life are closely related. However, research utilizing objective, rather than subjective measurements of sleep and temperament is scarce and results are inconsistent. In addition, a relative lack of longitudinal data prevents inference of causality between the two constructs. In this study, infant sleep was objectively assessed among 95 infants at 3, 6, and 12 months-of-age with an actigraph in the home setting. Reactivity to sound, light, and touch, a specific aspect of temperament, was behaviorally assessed at 3 and 6 months, both during sleep (at home) and during waking (at the laboratory). Expected maturational trends were recorded in sleep, with a temporal increase in sleep efficiency and percent of motionless sleep. Quadratic (i.e., inverse U shape) relations were found, especially among girls, when predicting change in sleep by reactivity thresholds, suggesting that both hyposensitive and hypersensitive infants are at risk for poor sleep quality. These are the first research findings suggesting that low reactivity in infancy might be associated with compromised sleep quality. The observed nonlinear effects may account for null or inconsistent results in previous studies that explored only linear associations between temperament and sleep. Future studies should address both extremes of the temperament continuum when exploring relations with sleep patterns. 
25704734	Sleep is a complex phenomenon that could be understood and assessed at many levels. Sleep could be described at the behavioral level (relative lack of movements and awareness and responsiveness) and at the brain level (based on EEG activity). Sleep could be characterized by its duration, by its distribution during the 24-hr day period, and by its quality (e.g., consolidated versus fragmented). Different methods have been developed to assess various aspects of sleep. This chapter covers the most established and common methods used to assess sleep in infants and children. These methods include polysomnography, videosomnography, actigraphy, direct observations, sleep diaries, and questionnaires. The advantages and disadvantages of each method are highlighted. 
25704733	Prevalent in typically developing children, insufficient or poor-quality sleep are matters of public health concern. Programmatic studies of the predictors and sequelae of sleep are increasing rapidly and yielding novel research paradigms that explicate connections between sleep, family processes, and child development within the sociocultural milieu. In an SRCD-sponsored Forum, established researchers and junior scholars from disparate areas of inquiry (e.g., Pediatrics; Public Health; Psychology; Anthropology) convened. An overarching goal of the Forum was to promote dialogue and collaborations, identify pivotal areas in the study of typically developing children's sleep, and integrate knowledge of sleep and child development across disciplines toward making conceptual advances about the ways that sleep and waking behaviors are intertwined. In addition to conceptual advances, a second goal focused on the need for methodological advances, including contemporary approaches and tools in the measures and analyses of sleep to help accelerate the pace and enhance the quality of research in this interdisciplinary field. 
25704732	Literature on sleep and child development is growing rapidly in exciting new directions across several disciplines and with this comes a need for guiding conceptual principles and methodological tools. In this introductory chapter, the importance of sleep for child development across multiple domains is highlighted. The aims of this monograph are presented and pertain to the need to consider and integrate theory and research across multiple disciplines and use state-of-the-art methodologies. A developmental ecological systems perspective adapted to sleep illustrates the multiple levels of influence and their importance in the study of child sleep and development. A focal aim is to provide examples of longitudinal studies linking sleep with child development, which are presented in seven chapters of this volume. 
25703936	Understanding the factors that influence veterans' functional outcome after deployment is critical to provide appropriately targeted care. Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) have been related to disability, but other psychiatric and behavioral conditions are not as well examined. We investigated the impact of deployment-related psychiatric and behavioral conditions on disability among 255 OEF/OIF/OND service members and veterans. Structured clinical interviews assessed TBI and the psychiatric conditions of depression, PTSD, anxiety, and substance use. Self-report questionnaires assessed disability and the behavioral conditions of sleep disturbance and pain. Over 90% of participants had a psychiatric and/or behavioral condition, with approximately half presenting with ≥ 3 conditions. Exploratory factor analysis revealed 4 clinically relevant psychiatric and behavioral factors which accounted for 76.9% of the variance: (a) depression, PTSD, and military mTBI (deployment trauma factor); (b) pain and sleep (somatic factor); (c) anxiety disorders, other than PTSD (anxiety factor); and (d) substance abuse or dependence (substance use factor). Individuals with the conditions comprising the deployment trauma factor were more likely to be substantially disabled than individuals with depression and PTSD, but no military mTBI, OR = 3.52; 95% CI [1.09, 11.37]. Depression, PTSD, and a history of military mTBI may comprise an especially harmful combination associated with high risk for substantial disability. 
25703174	To examine clinical and psychological indicators associated with sleeplessness and insomnia in adult patients with sickle cell.PubMed, Scopus, Cochrane Library. Data were collected from adult sickle cell participants (N = 72) in outpatient clinics at a Midwest National Cancer Institute designated comprehensive cancer center. A retrospective chart review observed for clinical and psychological indicators associated with sleeplessness and insomnia.	Findings included that adults with sickle cell experienced insomnia (47%) and sleep impairment (15%). Significant associations existed between pain and sleep impairment (p = .00), insomnia and pain (p = .00), morning hours of sleep (p = .00), and evening hours (p = .00). Pain may contribute to insomnia or interrupt sleep; daytime sleeping was not conducive to nighttime sleep. Anxiolytics, antidepressants, and long-acting opioids were not associated with insomnia (p = .00, p = .43, and p = .10), respectively; reduction in anxiety may reduce insomnia. Long-acting opioids may provide for improved pain control sleep.	Healthcare providers play a pivotal role in the assessment of sleep impairment or disorders. Effective management is necessary for improved quality of life. Further investigation is warranted to understand the meaning of sleep impairment in adult patients with sickle cell with prospective controlled studies to examine the efficacy of interventions.	
25702602	Postpartum mental disorders (e.g., anxiety, depression, psychosis) are serious conditions that affect approximately 10-15% of women after childbirth, and up to 40% of women at risk for these disorders. Research reveals an association between poor sleep quality/quantity and symptoms of anxiety, depression and psychosis. The aim of this systematic review was to evaluate the available evidence for the relationship between sleep and postpartum mental disorders.Searches included MEDLINE, EMBASE, and EBM Reviews - Cochrane Central Register of Controlled Trials, PsycINFO and EBSCOHost CINAHL through June 30, 2014. Manual searching was performed on reference lists of included articles. Published primary research in any language was included.	There were 3187 unique titles/abstracts and 44 full-text articles reviewed. Thirty-one studies were included. Evidence was found for the impact of self-reported poor sleep during pregnancy and the postpartum on the development of postpartum depression, with not enough evidence for either postpartum anxiety or psychosis. The evidence for objectively assessed sleep and the development of postpartum disorders was mixed. Among the 31 studies included, 1 was strong, 13 were moderate and 17 were weak.	Research design, method of assessment, timing of assessment, recruitment strategies, representative adequacy of the samples and inclusion/exclusion criteria all varied widely. Many studies did not use tools validated for the perinatal population and had small sample sizes without power analysis.	Sleep interventions represent a potential low-cost, non-pharmacological prevention and treatment strategy for postpartum mental illness. Further high-quality research is needed on this topic area.	
25701907	Sleep disturbances affect more than half of survivors of traumatic brain injury (TBI) and have the potential to undermine rehabilitation, recovery, and outcomes. Normal sleep architecture has been well-described and the neurophysiology of sleep is becoming better understood in recent years, though this complex process continues to be dissected for better appreciation. There are numerous types of sleep disorder, most of which fall under two categories: dyssomnias and parasomnias. In more challenging scenarios patients may be plagued with more than one dyssomnia and/or parasomnia simultaneously, complicating the diagnostic and therapeutic approach. Objective and subjective methods are used to evaluate sleep disorders and help distinguish them from psychiatric and environmental contributors to poor sleep. There are several pharmacologic and nonpharmacologic treatments options for sleep disturbances after TBI, many of which have been particularly helpful in restoring adequate quantity and quality of sleep for survivors. However, to date no consensus has been established regarding how to treat this entity, and it may be that a multimodal approach is ultimately best. 
25701537	Children in families of low socioeconomic status (SES) have been found to have poor sleep, yet the reasons for this finding are unclear. Two possible mediators, presleep worries and home environment conditions, were investigated as indirect pathways between SES and children's sleep.The participants consisted of 271 children (M (age) = 11.33 years; standard deviation (SD) = 7.74 months) from families varying in SES as indexed by the income-to-needs ratio. Sleep was assessed with actigraphy (sleep minutes, night waking duration, and variability in sleep schedule) and child self-reported sleep/wake problems (e.g., oversleeping and trouble falling asleep) and sleepiness (e.g., sleeping in class and falling asleep while doing homework). Presleep worries and home environment conditions were assessed with questionnaires.	Lower SES was associated with more subjective sleep/wake problems and daytime sleepiness, and increased exposure to disruptive sleep conditions and greater presleep worries were mediators of these associations. In addition, environmental conditions served as an intervening variable linking SES to variability in an actigraphy-derived sleep schedule, and, similarly, presleep worry was an intervening variable linking SES to actigraphy-based night waking duration. Across sleep parameters, the model explained 5-29% of variance.	Sleep environment and psychological factors are associated with socioeconomic disparities, which affect children's sleep.	
25701536	The objective of this study was to investigate the effect of baseline sleep on baseline weight status and weight-loss responsiveness in obese adolescents.Twenty-five obese adolescents who participated in a 19-day summer camp-based immersion treatment (IT) program completed pre-intervention measures of sleep duration and quality, and pre- and post-intervention body mass index z-scores (zBMI) and waist circumference (WC) assessments. Objective measures of sleep were obtained by actigraphy for a random subset of six participants for 1 week pre- and post-intervention.	Shorter weekday sleep durations and more sleep debt were related to higher pre-intervention WCs (r = -0.54, p = 0.01 and r = -0.56, p = 0.01), and lower subjective sleep quality was related to higher pre-intervention zBMIs (r = -0.49, p = 0.02). Longer weekend sleep durations and more sleep debt were related to smaller reductions in pre- to post-intervention zBMIs (r = -0.47, p = 0.04 and r = -0.51, p = 0.03). For the subgroup of adolescents who wore actigraphs pre- and post-intervention, an increase in their sleep durations (d = -0.25) and a reduction in their sleep latencies (d = 0.52), zBMIs (d = 0.31), and WCs (d = 0.20) were observed.	These results provide further evidence linking poor sleep patterns and obesity in adolescence, and suggest that sleep patterns may impact the effectiveness of pediatric obesity interventions and that IT programs may improve sleep in obese adolescents. Overall, they provide support for addressing sleep problems as part of obesity interventions.	
25701321	Sleep disruption is common in inflammatory bowel diseases (IBD). However, studies demonstrating a similar prevalence in irritable bowel syndrome suggest that nighttime disruption due to diarrhea and abdominal pain may be key drivers of poor sleep quality. Whether inflammation is associated with poor sleep independently has not been examined previously.This single-center study included subjects with IBD recruited to an ongoing prospective registry who completed a questionnaire assessing sleep quality and mood. Inflammatory marker levels [C-reactive protein (CRP), erythrocyte sedimentation rate] and clinical disease activity including nighttime disruption on the day of enrollment were obtained from the medical record. Logistic regression models were used to identify predictors of sleep quality.	The study included 131 subjects (72 women) with a median age of IBD diagnosis of 25 years. Twenty-three subjects (19 %) had a high C-reactive protein level (≥8 mg/dL). Poor sleep was more common in those with high CRP levels than with normal values (70 vs. 39 %, p = 0.009). This association remained significant on multivariate analysis [Odds ratio (OR) 4.12, 95 % confidence interval (CI) 1.38-12.29]. Adjusting for the presence of nighttime disruption did not significant alter this association (OR 3.16, 95 % CI 1.01-9.90). High CRP correlated with poor sleep even in patients not experiencing nocturnal symptoms (n = 101, OR 4.89, 95 % CI 1.24-19.36).	High CRP is associated with poor sleep quality in IBD independent of the presence of nighttime disruptions, suggesting that a relationship exists between circulating inflammatory markers and sleep.	
25700883	The Board of Directors of the American Academy of Sleep Medicine (AASM) commissioned a Task Force to develop quality measures as part of its strategic plan to promote high quality patient-centered care. Among many potential dimensions of quality, the AASM requested Workgroups to develop outcome and process measures to aid in evaluating the quality of care of five common sleep disorders: restless legs syndrome, insomnia, narcolepsy, obstructive sleep apnea in adults, and obstructive sleep apnea in children. This paper describes the rationale, background, general methods development, and considerations in implementation for these sleep disorder quality measures. The Workgroup papers are published in this issue under the following titles: Quality Measures for the Care of Adult Patients with Restless Legs Syndrome, Quality Measures for the Care of Patients with Insomnia, Quality Measures for the Care of Patients with Narcolepsy, Quality Measures for the Care of Adult Patients with Obstructive Sleep Apnea, and Quality Measures for the Care of Pediatric Patients with Obstructive Sleep Apnea.
25700875	Sleep problems are a common non-motor complication of Parkinson disease (PD), and patients with essential tremor (ET) share a number of motor and non-motor features of PD. To clarify the relationship between these disorders, we evaluated the sleep problems in patients with ET and PD using assessment scales and objective polysomnographic (PSG) testing.Twenty-one consecutive patients with PD, 16 with ET, and 14 healthy subjects participated in this study and were compared in terms of sleep related complaints, final sleep related diagnosis, and polysomnographic features.	The results of our study have shown that patients with PD were more likely than were those with ET to have a history of REM sleep behavior disorders (RBD) (p = 0.001) and excessive daytime sleepiness (p ≤ 0.05). Additionally, PSG data revealed that ET patients had lower mean SpO2 values (p ≤ 0.05) and REM without atonia (RWA) (p = 0.032) than did patients with PD.	This is the first study to use PSG to evaluate sleep problems both in ET and PD patients. The results point out different sleep problems in these two common movement disorders which should be investigated in further studies.	
25700872	Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality and may frequently be complicated by sleep disorders. Insomnia and obstructive sleep apnea are commonly encountered in patients with COPD. Nocturnal hypoxemia is also prevalent in COPD may occur despite adequate awake oxygenation and can be especially severe in rapid eye movement sleep. Additionally, several factors--some of them unique to COPD--can contribute to sleep-related hypoventilation. Recognition of hypoventilation can be vital as supplemental oxygen therapy itself can acutely worsen hypoventilation and lead to disastrous consequences. Finally, accruing data establish an association between restless leg syndrome and COPD--an association that may be driven by hypoxemia and/or hypercapnia. Comorbid sleep disorders portend worse sleep quality, diminished quality of life, and multifarious other adverse consequences. The awareness and knowledge regarding sleep comorbidities in COPD has continued to evolve over past many years. There are still several lacunae, however, in our understanding of the etiologies, impact, and therapies of sleep disorders, specifically in patients with COPD. This review summarizes the latest concepts in prevalence, pathogenesis, diagnosis, and management of diverse sleep disorders in COPD.
25700869	Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). The objective of the study was to assess the relationship between nocturnal polysomnographic (PSG) findings and quality of sleep, fatigue, and increased daytime sleepiness among patients with MS.Clinical characteristics were collected. Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and International Restless Legs Syndrome Rating Scale were used to assess quality of sleep, fatigue, excessive daytime sleepiness, and the presence of restless legs syndrome (RLS). All patients underwent nocturnal diagnostic PSG examination.	Fifty patients with MS were enrolled into the study. Age was the only independent variable significantly determining apnea-hypopnea index and desaturation index (DI) (beta = 0.369, p = 0.010, beta 0.301, p = 0.040). PSQI and ESS score were significantly higher in a population with RLS (p = 0.004, p = 0.011). FSS significantly correlated with DI (r = 0.400, p = 0.048). Presence of RLS was the only independent variable significantly determining PSQI and ESS (p = 0.005, p = 0.025). DI and presence of RLS were independent variables determining FSS (p = 0.015, p = 0.024).	Presence of RLS seems to be the main factor determining poor sleep, fatigue, and daytime somnolence. Sleep disordered breathing and its severity influences only fatigue in patients with MS.	
25700196	Sleep disturbance in an intensive care unit is a common problem. One of the main factors causing sleep disturbances in an intensive care unit is nocturnal patient care interventions.This study aims to determine the impact of patient care interventions performed at night in a neurosurgical intensive care unit on patients' sleep and their nursing care satisfaction.	The descriptive study was conducted on 82 patients in a neurosurgical intensive care unit between January 2009 and March 2010. The data were collected by data collection instruments and Newcastle Satisfaction with Nursing Scales. The data were statistically analyzed by frequency, mean, standard deviation, chi-square, and Mann-Whitney U test.	The study showed that 53.7% of the patients experienced sleep disturbances in the neurosurgical intensive care unit. Because of nursing interventions at night, 39.1% of these patients had their sleep affected, but this problem did not cause any negative impact on the patients' satisfaction (Newcastle Satisfaction with Nursing Scales score = 88.21 ± 9.83). The patients received, on average, 42.21 ± 7.45 times patient care interventions at night; however, the frequency of patient care interventions at night showed no effect on sleep disturbances in this study (p > .05). The most frequently given patient care interventions were, respectively, vital signs monitoring, neurological assessment, and repositioning in bed. These interventions were performed commonly at 6 a.m., 12 a.m., and 7 p.m.	In this study, despite the patients reporting sleep disturbances in the neurosurgical intensive care unit because of nocturnal patient care interventions that prevented them from sleeping, the patients' satisfaction on the given nursing care was not negatively impacted. To reduce sleep disturbances because of nursing care initiatives and promote uninterrupted sleep in the intensive care unit, it can be useful to develop new protocols regulating night care activities.	
25698339	Increasing research indicates that sleep disturbances may confer increased risk for suicidal behaviors, including suicidal ideation, suicide attempts, and death by suicide. Despite increased investigation, a number of methodological problems present important limitations to the validity and generalizability of findings in this area, which warrant additional focus. To evaluate and delineate sleep disturbances as an evidence-based suicide risk factor, a systematic review of the extant literature was conducted with methodological considerations as a central focus. The following methodologic criteria were required for inclusion: the report (1) evaluated an index of sleep disturbance; (2) examined an outcome measure for suicidal behavior; (3) adjusted for presence of a depression diagnosis or depression severity, as a covariate; and (4) represented an original investigation as opposed to a chart review. Reports meeting inclusion criteria were further classified and reviewed according to: study design and timeframe; sample type and size; sleep disturbance, suicide risk, and depression covariate assessment measure(s); and presence of positive versus negative findings. Based on keyword search, the following search engines were used: PubMed and PsycINFO. Search criteria generated N = 82 articles representing original investigations focused on sleep disturbances and suicide outcomes. Of these, N = 18 met inclusion criteria for review based on systematic analysis. Of the reports identified, N = 18 evaluated insomnia or poor sleep quality symptoms, whereas N = 8 assessed nightmares in association with suicide risk. Despite considerable differences in study designs, samples, and assessment techniques, the comparison of such reports indicates preliminary, converging evidence for sleep disturbances as an empirical risk factor for suicidal behaviors, while highlighting important, future directions for increased investigation.
25697832	Sleep and emotion are closely linked, however the effects of sleep on socio-emotional task performance have only recently been investigated. Sleep loss and insomnia have been found to affect emotional reactivity and social functioning, although results, taken together, are somewhat contradictory. Here we review this advancing literature, aiming to 1) systematically review the relevant literature on sleep and socio-emotional functioning, with reference to the extant literature on emotion and social interactions, 2) summarize results and outline ways in which emotion, social interactions, and sleep may interact, and 3) suggest key limitations and future directions for this field. From the reviewed literature, sleep deprivation is associated with diminished emotional expressivity and impaired emotion recognition, and this has particular relevance for social interactions. Sleep deprivation also increases emotional reactivity; results which are most apparent with neuro-imaging studies investigating amygdala activity and its prefrontal regulation. Evidence of emotional dysregulation in insomnia and poor sleep has also been reported. In general, limitations of this literature include how performance measures are linked to self-reports, and how results are linked to socio-emotional functioning. We conclude by suggesting some possible future directions for this field. 

25695111	Short sleep duration is a contributing factor for decreased insulin sensitivity and hyperglycemia. Sleep architecture represents a cyclical pattern of sleep that shifts between sleep Stages N1, N2, N3 (slow wave sleep) and Stage R (rapid eye movement sleep). The aim of the present study was to examine the association between sleep architecture and glucose and insulin metabolism in both normal weight and overweight/obese children and adolescents.A total of 118 subjects participated in the study. Subjects under-went overnight polysomnography (PSG) when the percentage of total sleep time (% TST) spent at each sleep stage was recorded and an oral glucose tolerance test together was performed the next morning. We assessed glucose tolerance, insulin sensitivity and pancreatic β-cell function using 2-h glucose levels, the Matsuda index (IS(OGTT)), and insulin secretion-sensitivity index-2 (ISSI-2), respectively.	After adjustment for age, gender, body mass index z-score, pubertal status, and obstructive apnea hypopnea index, Stage N3 (% TST) was positively associated with IS(OGTT), whereas Stage N1 (%TST) exerted an opposite effect on IS(OGTT). Higher sleep efficiency and longer TST were independently associated with lower 2-h glucose levels, higher ISSI-2 and/or higher IS(OGTT).	Stage N3, sleep efficiency and TST were protective factors in maintaining glucose and insulin homeostasis; however, Stage N1 functioned in the opposite direction.	
25693818	There is a complex inter-relationship between sleep disorders and epilepsy, and there are few studies in Nigeria on sleep disorders in epilepsy. This study was carried out to determine the prevalence, pattern and predictors of sleep disturbances among persons with epilepsy (PWE).This was a multi-center, cross-sectional study of 124 PWE in Nigeria. A questionnaire was used to collect data on social and demographic variables, epilepsy- related variables and sleep disturbances in PWE. Exclusion criteria were mental retardation, and use of sedative drugs. The data was analyzed using Statistical Package for Social Sciences version 11.0 and P < 0.05 was considered as significant.	There were 77 males and 47 females with a mean age of 33.4 ± 13.1 years. The mean age of seizure onset was 23.7 ± 14.6 years, while the mean duration of epilepsy was 9.5 ± 9.4 years. The commonest type of epilepsy was secondarily generalized tonic-clonic seizures (62%). The prevalence of sleep disorders in PWE was 82%. Parasomnias occurred in 46%, followed by obstructive sleep apnea in 23%, insomnia (19%) excessive daytime sleepiness (EDS) (17%), and restless leg syndrome (11%). None of the socio-demographic or epilepsy- related variables was predictive of EDS or parasomnias in PWE (P > 0.05).	There is a high frequency of sleep disorders among PWE. Clinicians should screen PWE for sleep disturbances.	
25693785	Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials. 
25693731	Disturbed circadian rhythms have been associated with depression and anxiety, but it is unclear if disturbances in the 24-hr activity rhythm and sleep are independently and specifically related to these disorders.In 1,714 middle-aged and elderly participants of the Rotterdam Study, we collected actigraphy recordings of at least 96 hr (138 ± 14 hr, mean ± standard deviation). Activity rhythms were quantified calculating the fragmentation of the rhythm, stability of the rhythm over days, and timing of the rhythm. Total sleep time, sleep onset latency, and wake after sleep onset were also estimated with actigraphy. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale, persons with clinically relevant depressive symptoms were interviewed to diagnose DSM-IV-depressive disorder. Anxiety disorders were determined with the Munich version of the Composite International Diagnostic Interview.	More fragmented rhythms were associated with clinically relevant depressive symptoms (odds ratio (OR): 1.27, 95% confidence interval (CI): 1.04;1.54) and anxiety disorders (OR: 1.39, 95% CI: 1.14;1.70) after covariate adjustment. Less stable rhythms, longer sleep onset latency, and more wake after sleep onset were related to clinically relevant depressive symptoms or anxiety disorders only if not adjusted for covariates and other activity rhythm and sleep indicators.	Our study in middle-aged and elderly persons suggests that fragmentation of the 24-hr activity rhythm is associated with depression and anxiety. Moreover, this association also largely accounts for the effect of disturbed sleep on these psychiatric disorders.	
25692615	A growing body of literature has begun to underscore the importance of integrating family-based comprehensive psychological screening into standard medical care for children with oncology and hematology conditions. There are no known family-based measures designed to screen for clinically significant emotional and behavioral concerns in pediatric oncology and hematology patients. The aim of this study was to develop and evaluate the Family Symptom Inventory (FSI), a brief screener of patient and family member psychological symptoms. The FSI also screens for common comorbid physical symptoms (pain and sleep disturbance) and is designed for use at any point during treatment and follow-up. A total of 488 caregivers completed the FSI during regular hematology/oncology visits for 193 cancer, 219 sickle cell disease, and 76 hematology pediatric patients. Exploratory factor analysis, confirmatory factor analysis, and tests of reliability and preliminary validity were conducted. Exploratory factor analysis suggested a 34-item, 4-factor solution, which was confirmed in an independent sample using confirmatory factor analysis (factor loadings=0.49 to 0.88). The FSI demonstrated good internal reliability (α's=0.86 to 0.92) and good preliminary validity. Regular psychosocial screening throughout the course of treatment and follow-up may lead to improved quality of care for children with oncology and hematology conditions. 
25692015	Compounds modulating metabotropic glutamate type 2 (mGlu2) receptor activity may have therapeutic benefits in treating psychiatric disorders like schizophrenia and anxiety. The pharmacological and pharmacokinetic properties of a novel mGlu2 receptor-positive allosteric modulator (PAM), 1-butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-2(1H)-pyridinone (JNJ-40411813/ADX71149) are described here. JNJ-40411813 acts as a PAM at the cloned mGlu2 receptor: EC50 = 147 ± 42 nmol/L in a [(35)S]GTPγS binding assay with human metabotropic glutamate type 2 (hmGlu2) CHO cells and EC50 = 64 ± 29 nmol/L in a Ca(2+) mobilization assay with hmGlu2 G α16 cotransfected HEK293 cells. [(35)S]GTPγS autoradiography on rat brain slices confirmed PAM activity of JNJ-40411813 on native mGlu2 receptor. JNJ-40411813 displaced [(3)H]JNJ-40068782 and [(3)H]JNJ-46281222 (mGlu2 receptor PAMs), while it failed to displace [(3)H]LY341495 (a competitive mGlu2/3 receptor antagonist). In rats, JNJ-40411813 showed ex vivo mGlu2 receptor occupancy using [(3)H]JNJ-46281222 with ED50 of 16 mg/kg (p.o.). PK-PD modeling using the same radioligand resulted in an EC50 of 1032 ng/mL. While JNJ-40411813 demonstrated moderate affinity for human 5HT2A receptor in vitro (K b = 1.1 μmol/L), higher than expected 5HT2A occupancy was observed in vivo (in rats, ED50 = 17 mg/kg p.o.) due to a metabolite. JNJ-40411813 dose dependently suppressed REM sleep (LAD, 3 mg/kg p.o.), and promoted and consolidated deep sleep. In fed rats, JNJ-40411813 (10 mg/kg p.o.) was rapidly absorbed (C max 938 ng/mL at 0.5 h) with an absolute oral bioavailability of 31%. Collectively, our data show that JNJ-40411813 is an interesting candidate to explore the therapeutic potential of mGlu2 PAMs, in in vivo rodents experiments as well as in clinical studies. 
25689874	To explore associations between children's sleep problems, and behavioural difficulties and parenting approaches.Children commonly have problematic night waking; however, relationships between parenting cognitions and behaviours and children's sleep problems are rarely examined.	Longitudinal children's cohort study from 5-29 months post birth.	Data were taken from the Quebec Longitudinal Study of Child Development (1998-2007) at three phases: 5, 17 and 29 months of age. Thousand four hundred and eighty-seven families were included in our study based on: participation from phase 1 (5-months old), both parents' reports on parenting cognitions/behaviours and child behavioural difficulties at 29 months, and mothers' reports of children's sleep at 29 months. In 2013, we conducted repeated measures anovas and manovas including children's gender.	Extended night-time waking patterns (wakes of ≥20 minutes) were associated with mothers' and fathers' lower sense of parenting impact and higher overprotectiveness and mothers' lower self-efficacy and higher coerciveness for 29-month-old children. In the extended waking group, mothers consistently reported lower self-efficacy, higher overprotectiveness and lower parenting impact at 5, 17 and 29 months. For those children, fathers were only more overprotective at 5 and 29 months. Regarding 29-month-old children's behaviour, children in the extended night waking group had highest scores on externalizing and internalizing behaviours. Girls had higher scores on shyness/inhibition and boys had higher scores on aggression/hyperactivity.	Mothers' and fathers' parenting cognitions and behaviours are affected by 29-month-old children's night waking patterns and night waking patterns are associated with children's behavioural problems.	
25689653	Although sleep problems are common among adult cancer survivors, little is known about sleep problems in adolescent survivors of childhood cancer (ASCC).This study sought to describe (a) the prevalence of self-reported sleep problems among ASCC before treatment, during treatment, following treatment, and in survivorship follow-up; (b) the relationship between sleep problems and self-reported adverse psychosocial outcomes; and (c) the relationship between sleep problems, treatment, and disease.	Baseline surveys were received from 173 ASCC aged 13-19 years. Chi-square analyses and odds ratios were used to determine associations between sleep problems and adverse psychosocial outcomes and treatment-related variables.	Sleep problems were reported before treatment (6%), during treatment (18%), after treatment (15%), and at present (11%). ASCC reporting sleep problems reported more adverse psychosocial outcomes than those without. Significant associations (p ≤ 0.05) between sleep problems and difficulty in school were identified at all time points. Sleep problems were associated with depressive symptoms, memory problems, and anxiety during and after treatment and at present.	
25687697	Sleep disturbances are a common non-motor feature in patients with Parkinson's disease (PD). Early diagnosis and appropriate management are imperative for enhancing patient quality of life. Sleep disturbances can be caused by multiple factors in addition to age-related changes in sleep, such as nocturnal motor symptoms (rigidity, resting tremor, akinesia, tardive dyskinesia, and the "wearing off" phenomenon), non-motor symptoms (pain, hallucination, and psychosis), nocturia, and medication. Disease-related pathology involving the brainstem and changes in the neurotransmitter systems (norepinephrine, serotonin, and acetylcholine) responsible for regulating sleep structure and the sleep/wake cycle play a role in emerging excessive daytime sleepiness and sleep disturbances. Additionally, screening for sleep apnea syndrome, rapid eye movement sleep behavior disorder, and restless legs syndrome is clinically important. Questionnaire-based assessment utilizing the PD Sleep Scale-2 is useful for screening PD-related nocturnal symptoms. In this review, we focus on the current understanding and management of sleep disturbances in PD. 
25687438	While actigraphy has gained popularity in pediatric sleep research, questions remain about the validity of actigraphy as an estimate of sleep-wake patterns. In particular, there is little consistency in the field in terms of scoring rules used to determine sleep onset latency. The purpose of this study was to evaluate different criteria of immobility as a measure of sleep onset latency in children and adolescents.Ninety-five youth (ages 3-17 years, 46 % male) wore both the Ambulatory Monitoring Inc. Motionlogger Sleep Watch (AMI) and the Philips Respironics Mini-Mitter Actiwatch-2 (PRMM) during overnight polysomnography in a pediatric sleep lab. We examined different sleep onset latency scoring rules (3, 5, 10, 15, and 20 min of immobility) using different algorithms (Sadeh and Cole-Kripke) and sensitivity settings (low, medium, high) for the devices. Comparisons were also made across age groups (preschoolers, school-aged, adolescents) and sleep disordered breathing status (no obstructive sleep apnea [OSA], mild OSA, clinically significant OSA).	For the AMI device, shorter scoring rules performed best for children and longer scoring rules were better for adolescents, with shorter scoring rules best across sleep disordered breathing groups. For the PRMM device, medium to longer scoring rules performed best across age and sleep disordered breathing groups.	Researchers are encouraged to determine the scoring rule that best fits their population of interest. Future studies are needed with larger samples of children and adolescents to further validate actigraphic immobility as a proxy for sleep onset latency.	
25687142	Average nightly sleep times precipitously decline from childhood through adolescence. There is increasing concern that historical shifts also occur in overall adolescent sleep time.Data were drawn from Monitoring the Future, a yearly, nationally representative cross-sectional survey of adolescents in the United States from 1991 to 2012 (N = 272 077) representing birth cohorts from 1973 to 2000. Adolescents were asked how often they get ≥7 hours of sleep and how often they get less sleep than they should. Age-period-cohort models were estimated.	Adolescent sleep generally declined over 20 years; the largest change occurred between 1991-1995 and 1996-2000. Age-period-cohort analyses indicate adolescent sleep is best described across demographic subgroups by an age effect, with sleep decreasing across adolescence, and a period effect, indicating that sleep is consistently decreasing, especially in the late 1990s and early 2000s. There was also a cohort effect among some subgroups, including male subjects, white subjects, and those in urban areas, with the earliest cohorts obtaining more sleep. Girls were less likely to report getting ≥7 hours of sleep compared with boys, as were racial/ethnic minorities, students living in urban areas, and those of low socioeconomic status (SES). However, racial/ethnic minorities and adolescents of low SES were more likely to self-report adequate sleep, compared with white subjects and those of higher SES.	Declines in self-reported adolescent sleep across the last 20 years are concerning. Mismatch between perceptions of adequate sleep and actual reported sleep times for racial/ethnic minorities and adolescents of low SES are additionally concerning and suggest that health education and literacy approaches may be warranted.	
25685859	Tasimelteon (Hetlioz®), a melatonin receptor agonist, is the first, and, at the time of the publication, the only drug to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-24-hour sleep-wake disorder (non-24). This circadian rhythm disorder occurs most commonly in blind individuals without light perception, and it results from their inability to entrain to the 24-hour photoperiod, although the indication does not specify a particular patient population. Non-24 is characterized by a persistent cycle of nighttime insomnia and daytime sleepiness, alternating with asymptomatic periods depending on an individual's degree of circadian rhythm synchronization with the photoperiod at any particular time. Phase II clinical trials in healthy individuals confirmed the circadian phase-shifting potential of tasimelteon. Phase III trials in totally blind subjects diagnosed with non-24 demonstrated the efficacy of tasimelteon in reducing both nighttime wakefulness and daytime napping. Physiologic monitoring revealed that tasimelteon resulted in a higher proportion of individuals becoming entrained to the 24-hour cycle compared with placebo. Safety assessments indicated that tasimelteon is well tolerated, with the most common adverse events being headache, alanine aminotransferase elevation, nightmares or unusual dreams, and upper respiratory or urinary tract infections. Tasimelteon is available as a capsule in a single 20-mg dose and it must be obtained through Vanda Pharmaceutical's HetliozSolutions program with dispensing through a specialty pharmacy. Safety studies in blind individuals diagnosed with non-24 are ongoing and a future clinical trial with Smith-Magenis syndrome patients is planned. 
25684962	To explore the incidence and psychological and behavioral characteristics of refractory functional dyspepsia (RFD) in China.The subjects of this study were 1341 new outpatients with functional dyspepsia (FD) who were diagnosed according to the Rome III criteria at four hospitals in Guangdong Province between June and September 2012, and 100 healthy volunteers. All subjects completed questionnaires and scales administered.	Three-hundred and twenty-seven of the 1341 patients with FD had RFD (24.4%). Patients with RFD had a longer disease duration and a more severe form of the disease than patients with non-refractory FD (NRFD). The prevalence of depression and anxiety symptoms was higher in patients with RFD than in patients with NRFD. The prevalence of unhealthy eating behaviors, lack of physical activity, and sleeping disorders was higher in patients with RFD than in patients with NRFD. Patients with RFD sought medical advice on more occasions and spent more money on treatment than patients with NRFD. Finally, patients with RFD had poorer quality of life than patients with NRFD.	RFD is not rare in clinical practice and should get attention by patients and doctors because of its long duration, severe symptoms, and associations with abnormal psychology and poor quality of life.	
25683659	The purpose of this study was to assess the impact of quality of sleep on functional capacity, peripheral muscle strength and quality of life in patients with chronic obstructive pulmonary disease (COPD).Forty patients with COPD (61.6 ± 8.28 years) were included in this study. Subjective sleep quality (Pittsburgh sleep quality index), quality of life (Nottingham health profile), quadriceps muscle strength (QMS) and functional capacity (6-min walk test) were assessed.	Poor sleep quality (Pittsburgh sleep quality index total >5) was present in 57% of the patients. Patients with a poor sleep quality had significantly lower QMS and higher exercise heart rate (p < 0.05). The Pittsburgh sleep quality index total score was associated with QMS, Nottingham health profile physical mobility and sleep scores, exercise fatigue and dyspnea (p < 0.05).	Sleep quality is affected in a majority of patients with COPD. It is related with symptoms, functional capacity, peripheral muscle strength and general quality of life.	
25682254	It has been recognized that an increase in outdoor ambient temperatures has a negative impact on health, particularly fatigue and sleep quality; however, the relationship among fatigue, sleep quality, and air temperature has yet to be sufficiently elucidated.To examine whether fatigue and sleep quality in a healthy Japanese population were affected by rising air temperature at three time points in summer and to investigate the confounding factors for fatigue.	A total of 602 healthy volunteers in Osaka, Japan, participated in a survey that was conducted at the end of July, August, and September in 2010. The questionnaire consisted of four sections; demographic variables, accommodation status, fatigue, and sleep quality. We used the Chalder fatigue scale for assessment of fatigue, and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI) for assessment of sleep quality.	The fatigue score was positively correlated with the sleep quality score in the total cohort. All the questionnaires at the three time points were completed by 162 participants. There were significant differences in fatigue scores among the surveys. We stratified the subjects into two groups of good and poor sleepers using a cutoff value of the PSQI. The good sleepers did not show differences in fatigue score regardless of the change in air temperature. However, the fatigue score of poor sleepers was greater at higher air temperatures. The use of air conditioners, accommodation type, and subject's age were confounding factors for fatigue.	High air temperatures in summer increased fatigue in healthy volunteers, especially those with poor sleep patterns, depending on the use of air conditioners, accommodation status, and subject's age.	
25681211	Evidence of a relationship between non-breathing-related sleep symptoms and silent markers of cerebral small vessel disease (SVD) is scarce. The present study aimed to evaluate this association in older people living in rural Ecuador, where the burden of stroke is on the rise.A group of Atahualpa residents, aged ≥60 years, were interviewed with a validated Spanish version of the Pittsburgh Sleep Quality Index, and underwent magnetic resonance imaging (MRI) for identification of silent markers of SVD. Using multinomial logistic regression analysis, after adjusting for demographics and cardiovascular health status, it was evaluated whether sleep quality is associated with the severity of white matter hyperintensity (WMH), lacunar infarcts, and deep microbleeds.	Out of 311 people aged ≥60 years, 237 (76%) were enrolled into the study. Mean age was 70 ± 8 years, 59% were women, 83% had primary school education only, and 73% had a poor cardiovascular health status. Seventy-eight (33%) had poor sleep quality. The MRI showed: WMH in 154 (65%) participants (moderate-to-severe in 52); silent lacunar infarcts in 28 (12%); and deep microbleeds in 17 (7%). Poor sleep quality was associated with WMH presence (OR 2.44, 95% CI 1.26 to 4.71, p = 0.008) and severity (β coefficient 0.77, SE 0.37, p = 0.037), but not with silent lacunar infarcts or deep microbleeds.	The present study showed an association between poor sleep quality and WMH severity. Further longitudinal studies would help to elucidate the cause and effect of this relationship.	
25680672	During adulthood, electroencephalogram (EEG) recordings are used to distinguish wake, non-rapid eye movement sleep, and rapid eye movement sleep states. The close association between behavioral states and EEG rhythms is reached late during development, after birth in humans and by the end of the second postnatal week in rats and mice. This critical time is also when cortical activity switches from a discontinuous to a continuous pattern. We review the major cellular and network changes that can account for this transition. After this close link is established, new evidence suggests that the slow waves of non-rapid eye movement sleep may function as markers to track cortical development. However, before the EEG can be used to identify behavioral states, two distinct sleep phases--quiet sleep and active sleep--are identified based on behavioral criteria and muscle activity. During this early phase of development, cortical activity is far from being disorganized, despite the presence of long periods of neuronal silence and the poor modulation by behavioral states. Specific EEG patterns, such as spindle bursts and gamma oscillations, have been identified very early on and are believed to play a significant role in the refinement of brain circuits. Because most early EEG patterns do not map to a specific behavioral state, their contribution to the presumptive role of sleep in brain maturation remains to be established and should be a major focus for future research.
25679472	Fibromyalgia (FM) is a chronic pain condition often resulting in functional impairments. Nonrestorative sleep is a prominent symptom of FM that is related to disability, but the day-to-day mechanisms relating the prior night's sleep quality to next-day reports of disability have not been examined. This study examined the within-day relations among early-morning reports of sleep quality last night, late-morning reports of pain and positive and negative affect, and end-of-day reports of activity interference. Specifically, we tested whether pain, positive affect, and negative affect mediated the association between sleep quality and subsequent activity interference. Data were drawn from electronic diary reports collected from 220 patients with FM for 21 consecutive days. The direct and mediated effects at the within-person level were estimated with multilevel structural equation modeling. Results showed that pain and positive affect mediated the relation between sleep quality and activity interference. Early-morning reports of poor sleep quality last night predicted elevated levels of pain and lower levels of positive affect at late-morning, which, in turn, predicted elevated end-of-day activity interference. Of note, positive affect was a stronger mediator than pain and negative affect was not a significant mediator. In summary, the findings identify 2 parallel mechanisms, pain and positive affect, through which the prior night's sleep quality predicts disability the next day in patients with FM. Furthermore, results highlight the potential utility of boosting positive affect after a poor night's sleep as one means of preserving daily function in FM.
25679070	Cancer in children has detrimental effects on sleep patterns and sleep quality, which in turn impacts on the perception of, and the ability to cope with, the emotional and physical challenges associated with both the disease and its treatment. This places an added burden on their quality of life that can last many years beyond diagnosis and treatment. In addition to the effect of the cancer itself, surgery, chemotherapy and radiotherapy can all contribute both short and long term to sleep disruption. Sleep disorders have also been associated with pain, fatigue, medication and hospitalisation in children suffering from cancer. This review will explore the relationship between childhood cancer and associated sleep disorders, in the acute stage of diagnosis, during treatment and in the years following. We will discuss the possible causes and the current treatment modalities used to treat sleep disorders in children with cancer, and in childhood cancer survivors. It has been estimated that the recent advances in treatment have improved the overall five year survival rate for all childhood cancers to over 80%, with some cancers achieving a near 100% cure rate such as early stage Wilms' tumour. Thus, recognition and appropriate treatment of associated sleep disorders is essential to optimise long term quality of life. 
25679069	Sickle cell disease and thalassemia are common hereditary blood disorders associated with increased systemic inflammation, tissue hypoxia, endothelial dysfunction and end-organ damage, the latter accounting for the substantial morbidity and abbreviated lifespan associated with these conditions. Sleep perturbations in general, and sleep-disordered breathing in particular are also highly prevalent conditions and the mechanisms underlying their widespread end-organ morbidities markedly and intriguingly overlap with the very same pathways implicated in the hemoglobinopathies. However, little attention has been given to date to the potential contributing role of sleep disorders to sickle cell disease manifestations. Here, we comprehensively review the pathophysiological mechanisms and clinical manifestations linking disturbed sleep and hemoglobinopathies, with special emphasis on sickle cell disease. In addition to a broad summary of the available evidence, we identify many of the research gaps that require attention and future investigation, and provide the scientific contextual setting that should enable opportunities to investigate the intertwined pathophysiological mechanisms and clinical outcomes of sleep disorders and hemoglobinopathies. 
25678831	Melatonin, secreted by the pineal gland during the night phase, is a regulator of the biological clock and sleep tendency. Totally blind subjects frequently report severe, periodic sleep problems, with 50%-75% of cases displaying non-24-hour sleep-wake disorder (N24HSWD) due to inability to synchronize with the environmental day-night cycle. Melatonin immediate-release preparations are reportedly effective in N24HSWD. Here, we studied the efficacy and safety of prolonged-release melatonin (PRM), a registered drug for insomnia, for sleep disorders in totally blind subjects living in normal social environments. The primary endpoint was demonstration of clinically meaningful effects on sleep duration (upper confidence interval [CI] limit >20 minutes whether significant or not) to allow early decision-making on further drug development in this indication.In a randomized, double-blind, placebo-controlled proof-of-principle study, 13 totally blind subjects had 2 weeks' placebo run-in, 6 weeks' randomized (1:1) PRM (Circadin(®)) or placebo nightly, and 2 weeks' placebo run-out. Outcome measures included daily voice recorded sleep diary, Clinical Global Impression of Change (CGIC), WHO-Five Well-being Index (WHO-5), and safety.	Mean nightly sleep duration improved by 43 minutes in the PRM and 16 minutes in the placebo group (mean difference: 27 minutes, 95% CI: -14.4 to 69 minutes; P=0.18; effect size: 0.82) meeting the primary endpoint. Mean sleep latency decreased by 29 minutes with PRM over placebo (P=0.13; effect size: 0.92) and nap duration decreased in the PRM but not placebo group. The variability in sleep onset/offset and latency tended to decrease during PRM but not placebo treatment. The potentially beneficial effects of PRM persisted during the 2 weeks of discontinuation period, consistent with clock stabilizing effects. PRM was well-tolerated, adverse events were of mild or moderate severity and similar between PRM and placebo.	Nightly use of PRM may potentially improve patient-reported sleep difficulties in totally blind individuals trying to adhere to normal social lifestyle. A larger study powered to demonstrate a statistically significant effect is warranted.	
25678472	Chronic sleep deprivation combined with work during the night is known to affect performance and compromise residents' own safety. The aim of this study was to examine markers of circadian rhythm and the sleep-wake cycle in surgeons working night shifts.Surgeons were monitored prospectively for 4 days: pre call, on call, post call day 1 (PC1), and post call day 2 (PC2). The urinary metabolite of melatonin and cortisol in saliva were measured to assess the circadian rhythm. Sleep and activity were measured by actigraphy. Subjective measures were assessed by the Karolinska Sleepiness Scale and Visual Analog Scale of fatigue, general well-being, and sleep quality.	For both metabolite of melatonin and cortisol, a significant difference (P < .05) was found in the measurement period between on call and pre call values. There was increased sleep time during the day on call and on PC1. For all subjective measures, a marked deterioration was seen on PC1.	Surgeons' circadian rhythm was affected by working night shifts.	
25678361	Sleep disorders are prevalent in patients with advanced cancer. Their impact on clinical outcomes is not well understood.A post-hoc analysis was conducted in 361 chemo-naïve patients with metastatic colorectal cancer completing twice the EORTC QLQ-C30 questionnaire within a randomized international phase III trial. The study assessed the effect on overall survival (OS) of subjective sleep complaint, used as a normal or a time-dependent covariate (TDC), using a multivariate Cox proportional hazard model. Prognostic analysis was conducted on the whole study population and separately in each treatment arm (conventional FOLFOX2, or chronomodulated chronoFLO4).	Sleep problems were reported by 202 patients (56%) at baseline and by 188 (52%) on treatment. Sleep problems at baseline were independently associated with a higher risk of earlier death (HR: 1.36; p = 0.011), progression (HR: 1.43; p = 0.002) and poor treatment response (RR: 0.58; p = 0.016). TDC analysis confirmed the independent prognostic effect of sleep problems on OS (HR: 1.37; p = 0.008), while on treatment this effect was only observed using univariate analysis. The negative prognostic value of sleep problems on OS at baseline, on treatment, and as a TDC was greatest on chronoFLO4 compared to FOLFOX2.	Subjective sleep problems are associated with poor clinical outcomes in metastatic colorectal cancer patients and affect chronotherapy effectiveness. There is a need for a well-tuned circadian timing system in order to increase chronotherapy activity. Prospective studies are needed for determining the impact of therapeutic approaches on sleep disorders upon quality of life and survival of cancer patients.	
25678032	Since many of the children with BCECTSs display electrical status epilepticus during sleep and many present with different comorbidities, mainly ADHD and behavioral disturbances, clinicians are often confronted with the dilemma of how aggressive they should be with their efforts of normalizing the EEG. We conducted a retrospective study by screening medical records of all consecutive patients with BCECTSs, spike-wave index (SWI) >30%, and ADHD/ADD that were evaluated in our pediatric epilepsy service and were followed up for at least two years. Patients with neurocognitive deterioration detected by formal testing were excluded. A total of 17 patients with mean age of 6.9years at BCECTS diagnosis were identified. The patients' mean SWI was 60% and that dense electrical activity lasted 1.5years on average (range: 1-4.5years). Six children were formally diagnosed with learning disabilities in addition to ADD/ADHD. All of them were treated with an average of three antiepileptic medications, mainly for the purpose of normalizing the EEG, but none of them was treated with steroids or high-dose diazepam. The mean duration of follow-up was 5.5years. A cognitive or behavioral deterioration was not detected in any of them. Our data suggest that when treating a child with BCECTSs, high SWI, and school difficulties, the most critical parameter that determines the necessity of using second-line antiepileptic agents such as steroids or high-dose diazepam is a formal psychological evaluation that proves cognitive (I.Q.) decline. Otherwise, these agents may be avoided. 
25677777	The neuropeptide nociceptin/orphanin FQ (N/OFQ), acting on its receptors (NOP), modulates a variety of biological functions and neurobehavior including nociception, stress responses, water and food-intake, locomotor activity, and spatial attention. N/OFQ is conventionally regarded as an "antiopiate" peptide in the brain because central administration of N/OFQ attenuates stress-induced analgesia (SIA) and produces anxiolytic effects. However, naloxone-irreversible SIA and anxiolytic action are unlikely to be mediated by the opiate system. Both N/OFQ and NOP receptors are expressed most abundantly in the hypothalamus, where two other neuropeptides, the hypocretins/orexins (Hcrts), are exclusively synthesized in the lateral hypothalamic area. N/OFQ and Hcrt regulate most cellular physiological responses in opposite directions (e.g., ion channel modulation and second messenger coupling), and produce differential modulations for almost all neurobehavior assessed, including sleep/wake, locomotion, and rewarding behaviors. This chapter focuses on recent studies that provide evidence at a neuroanatomical level showing that a local neuronal circuit linking N/OFQ to Hcrt neurons exists. Functionally, N/OFQ depresses Hcrt neuronal activity at the cellular level, and modulates stress responses, especially SIA and anxiety-related behavior in the whole organism. N/OFQ exerts its attenuation of SIA and anxiolytic action on fear-induced anxiety through direct modulation of Hcrt neuronal activity. The information obtained from these studies has provided insights into how interaction between the Hcrt and N/OFQ systems positively and negatively modulates the complex and integrated stress responses. 
25677595	The pathogenesis of poststroke fatigue is unclear. In this prospective study, we explored whether reduced physical activity might contribute to poststroke fatigue or be a consequence of it.Patients with a recent acute stroke were assessed at 1, 6, and 12 months with, Fatigue Assessment Scale (FAS), a fatigue case definition, Hospital Anxiety and Depression Score, sleepiness, quality of life, and accelerometry (ActivPAL). Bivariate analyses determined associations between fatigue and step count at each time point. Multiple linear regression tested whether 1-month step count independently predicted 6- and 12-month FAS.	A total of 136 participants (mean age, 72 years; 64% men) attended ≥1 assessment. ActivPAL data were available for 84 (64%), 69 (66%), and 58 (64%) participants at 1, 6, and 12 months, respectively. At 6 and 12 months, a positive fatigue case definition was associated with lower daily step counts (P=0.014 and 0.013, respectively). At 1, 6, and 12 months, higher FAS (more fatigue) was associated with lower step count (P<0.001, 0.01, and 0.007), higher depression (P<0.001), anxiety scores (P<0.001) and sleepiness (P<0.001), and poorer quality of life (P<0.001). Lower daily step count (P<0.002 and 0.006) and greater anxiety (P<0.001 for both) at 1 month independently predicted higher FAS at 6 and 12 months.	Lower step counts at 1 month independently predicted greater FAS for ≤12 months. Physical activity might be a therapeutic target for poststroke fatigue.	
25677576	The limitations of the current systems of automatic sleep stage classification (ASSC) are essentially related to the similarities between epochs from different sleep stages and the subjects' variability. Several studies have already identified the situations with the highest likelihood of misclassification in sleep scoring. Here, we took advantage of such information to develop an ASSC system based on knowledge of subjects' variability of some indicators that characterize sleep stages and on the American Academy of Sleep Medicine (AASM) rules.An ASSC system consisting of a two-step classifier is proposed. In the first step, epochs are classified using support vector machines (SVMs) spread into different nodes of a decision tree. In the post-processing step, the epochs suspected of misclassification (dubious classification) are tagged, and a new classification is suggested. Identification and correction are based on the AASM rules, and on misclassifications most commonly found/reported in automatic sleep staging. Six electroencephalographic and two electrooculographic channels were used to classify wake, non-rapid eye movement (NREM) sleep--N1, N2 and N3, and rapid eye movement (REM) sleep.	The proposed system was tested in a dataset of 14 clinical polysomnographic records of subjects suspected of apnea disorders. Wake and REM epochs not falling in the dubious range, are classified with accuracy levels compatible with the requirements for clinical applications. The suggested correction assigned to the epochs that are tagged as dubious enhances the global results of all sleep stages.	This approach provides reliable sleep staging results for non-dubious epochs.	
25677558	In this study, we aimed at assessing Inflammatory Bowel Disease patients' needs and current nursing practice to investigate to what extent consensus statements (European Crohn's and Colitis Organization) on the nursing roles in caring for patients with IBD concur with local practice.We used a mixed-method convergent design to combine quantitative data prospectively collected in the Swiss IBD cohort study and qualitative data from structured interviews with IBD healthcare experts. Symptoms, quality of life, and anxiety and depression scores were retrieved from physician charts and patient self-reported questionnaires. Descriptive analyses were performed based on quantitative and qualitative data.	230 patients of a single center were included, 60% of patients were males, and median age was 40 (range 18-85). The prevalence of abdominal pain was 42%. Self-reported data were obtained from 75 out of 230 patients. General health was perceived significantly lower compared with the general population (p < 0.001). Prevalence of tiredness was 73%; sleep problems, 78%; issues related to work, 20%; sexual constraints, 35%; diarrhea, 67%; being afraid of not finding a bathroom, 42%; depression, 11%; and anxiety symptoms, 23%. According to experts' interviews, the consensus statements are found mostly relevant with many recommendations that are not yet realized in clinical practice.	Identified prevalence may help clinicians in detecting patients at risk and improve patient management.	
25674924	Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).	We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies	Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.	Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.	We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.	Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.	

25672690	Sleep disturbance is common in patients with dementia. Circadian rhythm sleep disorders are caused by the disturbance of sleep-wake regulation in the central nervous system, disturbed input into the sensory organs, and decreased social activities. Diurnal change of serum melatonin level in Alzheimer's disease showed decreased amplitude and shifted peak secretion. Age related sleep disturbances and sleep disorders due to the neurodegeneration including REM sleep behavior disorder also increase in dementia. Identifying and treating underlying sleep disorders along with therapeutic approach to circadian mechanism is effective. Treatment of circadian abnormality in dementia require light therapy and increased daytime activity. Use of oral melatonin is also effective for the improvement of nocturnal sleep. Treatment of sleep problems in dementia also contribute to the better management of dementia. 
25672689	Headache and sleep problems are both some of the most commonly reported symptoms in clinical practice. There is a clear association between chronic headache and sleep disorders, especially headaches occurring during the night or early morning. Identification of sleep problems in chronic headache patients is worthwhile because treatment of sleep disorders among chronic headache patients may be followed by improve of the headache. Morning headache has been recognised as an obstructive sleep apnoea related symptom. Treatment with continuous positive airway pressure usually reduced headache, however, we often encounter obstructive sleep apnoea patients who present various characteristics of morning headache that often do not fulfil the criteria for "sleep apnoea headache" according to the International Classification of Headache Disorders: 2nd edition (ICHD-2) criteria. The pathophysiologic background for a relation between obstructive sleep apnoea and morning headache is multifactorial. We should also be noted that tension-type headache and migraine might be coexisted in obstructive sleep apnoea patients. In addition, we review the relationship between migraine and sleep disorders such as restless legs syndrome, narcolepsy and parasomnia (dream enacting behaviour) including our studies. 
25672687	In neuromuscular diseases, respiratory disorder is related to sleep disorder. In Duchenne muscular dystrophy, respiratory muscle disorder progresses and induces alveolar hypoventilation. Hypoxemia and hypercapnia develop, requiring appropriate management. Hypoxemia first appears during sleep, initially occurring during the REM period, and it progresses and becomes persistent. Not only a decrease in the respiratory muscle strength but also upper respiratory tract obstruction due to soft palatal hypertrophy or a decrease in the muscle tension during sleep causes noctural ventilatory impairment. Hypoxemia is severe at dawn, and reduces the quality of life, inducing poor arousal in the morning, headache, and decreased appetite. Sleep fragmentation causes hypersomnia during the day. When ventilation is maintained using a respirator, almost all problems are overcome. In myotonic dystrophy type 1, there are respiratory control and sleep disorders due to central nerve abnormalities in addition to respiratory muscle lesions. Even in the stage of mild respiratory muscle lesions, hypoxemia during sleep sometimes appears. Hypersomnia during the day is also an important symptom. Hypersomnia does not disappear even after the correction of hypoxemia using a respirator.
25670162	Successful adaptation to modern civilization requires the internal circadian clock to make large phase shifts in response to circumstances (e.g., jet travel and shift work) that were not encountered during most of our evolution. We found that the magnitude and direction of the circadian clock's phase shift after the light/dark and sleep/wake/meal schedule was phase-advanced (made earlier) by 9 hours differed in European-Americans compared to African-Americans. European-Americans had larger phase shifts, but were more likely to phase-delay after the 9-hour advance (to phase shift in the wrong direction). The magnitude and direction of the phase shift was related to the free-running circadian period, and European-Americans had a longer circadian period than African-Americans. Circadian period was related to the percent Sub-Saharan African and European ancestry from DNA samples. We speculate that a short circadian period was advantageous during our evolution in Africa and lengthened with northern migrations out of Africa. The differences in circadian rhythms remaining today are relevant for understanding and treating the modern circadian-rhythm-based disorders which are due to a misalignment between the internal circadian rhythms and the times for sleep, work, school and meals.
25669189	To explore the association between the non-apnea sleep disorder (NSD) and autoimmune diseases.Cohort study.	Nationwide database research.	84,996 adult patients with NSD diagnoses recorded in the Taiwan National Health Insurance Research Database between 2000 and 2003, after excluding those with antecedent autoimmune diseases. A comparison cohort of 84,996 participants was formed by age-, gender-, income-, and urbanization-matched controls.	None.	The two cohorts were followed up for occurrence of autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and systemic sclerosis (SSc). A Cox proportional hazards regression model was used for muti-variate adjustment. In patients with NSD, the overall risk for incident autoimmune diseases was significantly higher than in controls (adjusted hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 1.41-1.53). With regard to individual diseases, the risks for SLE, RA, AS and SS among NSD patients were also significantly higher than in controls (HR [95% CI] for SLE, RA, AS, and SS were 1.81 [1.50-2.18], 1.45 [1.36-1.54], 1.53 [1.38-1.70], and 1.51 [1.43-1.60], respectively), whereas the increased risk for SSc did not reach statistical significance (HR: 1.36 [0.82-2.26]).	Patients with non-apnea sleep disorder were associated with a higher risk for developing autoimmune diseases.	
25669184	Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR.A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function.	Animal laboratory, rodent walking-wheel apparatus.	Male Sprague-Dawley rats.	Acute total sleep deprivation (TSD, 1 day × 18 or 24 h, N = 12), CSR (10 days × 18 h TSD, N = 5, or 5 days × 20 h TSD, N = 6).	Behavioral rebounds were consistent with model predictions for proportional control of cumulative times in wake, nonrapid eye movement (NREM) and rapid eye movement (REM). Delta (D) energy homeostasis was secondary to behavioral homeostasis; a biphasic NREM D power rebound contributed to the dynamics (rapid response) but not to the magnitude of the rebound in D energy. REM behavioral homeostasis was little affected by CSR. NREM behavioral homeostasis was attenuated in proportion to cumulative NREM deficit, whereas the biphasic NREM D power rebound was only slightly suppressed, indicating decoupled regulatory mechanisms following CSR.	We conclude that sleep homeostasis is achieved through behavioral regulation, that the NREM behavioral homeostat is susceptible to attenuation during CSR and that the concept of sleep intensity is not essential in a model of sleep-wake regulation.	Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR.	A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function.	Animal laboratory, rodent walking-wheel apparatus.	Male Sprague-Dawley rats.	Acute total sleep deprivation (TSD, 1 day × 18 or 24 h, N = 12), CSR (10 days × 18 h TSD, N = 5, or 5 days × 20 h TSD, N = 6).	Behavioral rebounds were consistent with model predictions for proportional control of cumulative times in wake, nonrapid eye movement (NREM) and rapid eye movement (REM). Delta (D) energy homeostasis was secondary to behavioral homeostasis; a biphasic NREM D power rebound contributed to the dynamics (rapid response) but not to the magnitude of the rebound in D energy. REM behavioral homeostasis was little affected by CSR. NREM behavioral homeostasis was attenuated in proportion to cumulative NREM deficit, whereas the biphasic NREM D power rebound was only slightly suppressed, indicating decoupled regulatory mechanisms following CSR.	We conclude that sleep homeostasis is achieved through behavioral regulation, that the NREM behavioral homeostat is susceptible to attenuation during CSR and that the concept of sleep intensity is not essential in a model of sleep-wake regulation.	
25669182	The trend in sleep duration in the United States population remains uncertain. Our objective was to examine changes in sleep duration from 1985 to 2012 among US adults.Trend analysis.	Civilian noninstitutional population of the United States.	324,242 US adults aged ≥ 18 y of the National Health Interview Survey (1985, 1990, and 2004-2012).	Sleep duration was defined on the basis of the question "On average, how many hours of sleep do you get in a 24-h period?" The age-adjusted mean sleep duration was 7.40 h (standard error [SE] 0.01) in 1985, 7.29 h (SE 0.01) in 1990, 7.18 h (SE 0.01) in 2004, and 7.18 h (SE 0.01) in 2012 (P 2012 versus 1985 < 0.001; P trend 2004-2012 = 0.982). The age-adjusted percentage of adults sleeping ≤ 6 h was 22.3% (SE 0.3) in 1985, 24.4% (SE 0.3) in 1990, 28.6% (SE 0.3) in 2004, and 29.2% (SE 0.3) in 2012 (P 2012 versus 1985 < 0.001; P trend 2004-2012 = 0.050). In 2012, approximately 70.1 million US adults reported sleeping ≤ 6 h.	Since 1985, age-adjusted mean sleep duration has decreased slightly and the percentage of adults sleeping ≤ 6 h increased by 31%. Since 2004, however, mean sleep duration and the percentage of adults sleeping ≤ 6 h have changed little.	
25669179	To determine the associations of 25-hydroxyvitamin D (25(OH)D) concentration with sleep continuity, quality, and symptoms, and to explore race/ethnic variation.Cross-sectional study.	Multi-Ethnic Study of Atherosclerosis (MESA).	There were 1,721 adults.	Sleep outcomes were measured by polysomnography, actigraphy, and questionnaires. Serum 25(OH)D concentration was expressed by clinical thresholds (< 20, 20-29, ≥ 30 ng/mL) and continuously. Using linear regression, we determined the associations between 25(OH)D concentration and sleep duration, efficiency, and symptoms, and assessed race/ethnic variation. Mean age was 68.2 ± 9.1 y, and 37.2% were white, 27.7% African American, 11.9% Chinese Americans, and 23.2% Hispanic. Mean 25(OH)D concentration was 25.4 ± 10.5 ng/mL. 25(OH)D deficient participants had the shortest sleep duration, lowest sleep efficiency, and highest sleepiness scores. After adjusting for demographics, obesity, and health habits, deficient individuals slept an average of 13.0 min (95% confidence interval, -22.8, -3.2) shorter than sufficient individuals. Race/ethnic-stratified analyses indicated that the strongest associations were in African Americans, in whom adjusted sleep duration was 25.6 ± 11.7 min shorter in deficient versus sufficient individuals (P = 0.04), and in Chinese Americans, adjusted apnea-hypopnea index (AHI) was 7.5 ± 3.3 events/h higher in deficient versus sufficient individuals.	Overall, there were modest associations between 25-hydroxyvitamin D (25(OH)D) concentration and sleep traits. However, race-stratified analyses suggested the association between 25(OH)D concentration and sleep traits varied by race/ethnicity. Vitamin D deficiency was most strongly associated with short sleep duration in African Americans and with elevated apnea-hypopnea index in Chinese Americans, suggesting that race/ethnicity may modify these associations.	
25668196	Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep.Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown.	This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects.	The study was conducted in a laboratory-based study.	The subjects were 11 healthy young men.	We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00.	Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods.	The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition.	Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.	
25668054	Obesity has become a major health risk in industrialized countries, with disturbed sleep identified as a correlate. This study used data drawn from Taiwan's 2005 Social Development Trend Survey on Health and Safety and the propensity-score-matching method to shed light on gender-specific associations between sleep problems and obesity among 24,113 adults aged 20-64 years. The average increase in obesity prevalence among respondents with disrupted sleep was 1.85%, as compared to those who did not report disrupted sleep, with similar psycho-social attributes. Similarly, the prevalence of obesity among those who reported restless sleep was increased by an average of 1.40% compared to those who did not report restless sleep with similar psycho-social attributes. We also found gender-specific vulnerability to different types of sleep problems. Among men who reported disrupted sleep, we found a 3.12% increase in the prevalence of obesity. Among women exposed to restless sleep, the increase in obesity prevalence was 1.84%. The observed gender difference in the prevalence of increases in obesity may be attributed to gender-specific behavioral responses to poor sleep. With poor sleep, men may respond to hunger by overeating; women may respond by physical inactivity. Both can contribute to an elevated risk of obesity. 

25666847	This study sought to characterize sleep patterns and sleep problems in a large sample of women across all months of pregnancy.A total of 2427 women completed an Internet-based survey that included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, vitality scale of the Short Form 36 Health Survey (SF-36), Insomnia Severity Index (ISI), Berlin questionnaire, International Restless Legs Syndrome (IRLS) question set, and a short version of the Pregnancy Symptoms Inventory (PSI).	Across all months of pregnancy, women experienced poor sleep quality (76%), insufficient nighttime sleep (38%), and significant daytime sleepiness (49%). All women reported frequent nighttime awakenings (100%), and most women took daytime naps (78%). Symptoms of insomnia (57%), sleep-disordered breathing (19%), and restless legs syndrome (24%) were commonly endorsed, with no difference across the month of pregnancy for insomnia, sleep-disorder breathing, daytime sleepiness, or fatigue. In addition, high rates of pregnancy-related symptoms were found to disturb sleep, especially frequent urination (83%) and difficulty finding a comfortable sleep position (79%).	Women experience significant sleep disruption, inadequate sleep, and high rates of symptoms of sleep disorder throughout pregnancy. These results suggest that all women should be screened and treated for sleep disturbances throughout pregnancy, especially given the impact of inadequate sleep and sleep disorders on fetal, pregnancy, and postpartum outcomes.	

25662277	Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms. 

25660813	The diagnostic boundaries of sleep disorders are under considerable debate. The main sleep disorders are partly heritable; therefore, defining heritable pathophysiologic mechanisms could delineate diagnoses and suggest treatment. We collected clinical data and DNA from consenting patients scheduled to undergo clinical polysomnograms, to expand our understanding of the polymorphisms associated with the phenotypes of particular sleep disorders.Patients at least 21 years of age were recruited to contribute research questionnaires, and to provide access to their medical records, saliva for deoxyribonucleic acid (DNA), and polysomnographic data. From these complex data, 38 partly overlapping phenotypes were derived indicating complaints, subjective and objective sleep timing, and polysomnographic disturbances. A custom chip was used to genotype 768 single-nucleotide polymorphisms (SNPs). Additional assays derived ancestry-informative markers (eg, 751 participants of European ancestry). Linear regressions controlling for age, gender, and ancestry were used to assess the associations of each phenotype with each of the SNPs, highlighting those with Bonferroni-corrected significance.	In peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), rs6888451 was associated with several markers of obstructive sleep apnea. In aryl hydrocarbon receptor nuclear translocator-like (ARNTL), rs10766071 was associated with decreased polysomnographic sleep duration. The association of rs3923809 in BTBD9 with periodic limb movements in sleep was confirmed. SNPs in casein kinase 1 delta (CSNK1D rs11552085), cryptochrome 1 (CRY1 rs4964515), and retinoic acid receptor-related orphan receptor A (RORA rs11071547) were less persuasively associated with sleep latency and time of falling asleep.	SNPs associated with several sleep phenotypes were suggested, but due to risks of false discovery, independent replications are needed before the importance of these associations can be assessed, followed by investigation of molecular mechanisms.	
25660546	The paternal allele of Ube3a is silenced by imprinting in neurons, and Angelman syndrome (AS) is a disorder arising from a deletion or mutation of the maternal Ube3a allele, which thereby eliminates Ube3a neuronal expression. Sleep disorders such as short sleep duration and increased sleep onset latency are very common in AS.We found a unique link between neuronal imprinting of Ube3a and circadian rhythms in two mouse models of AS, including enfeebled circadian activity behavior and slowed molecular rhythms in ex vivo brain tissues. As a consequence of compromised circadian behavior, metabolic homeostasis is also disrupted in AS mice. Unsilencing the paternal Ube3a allele restores functional circadian periodicity in neurons deficient in maternal Ube3a but does not affect periodicity in peripheral tissues that are not imprinted for uniparental Ube3a expression. The ubiquitin ligase encoded by Ube3a interacts with the central clock components BMAL1 and BMAL2. Moreover, inactivation of Ube3a expression elevates BMAL1 levels in brain regions that control circadian behavior of AS-model mice, indicating an important role for Ube3a in modulating BMAL1 turnover.	Ube3a expression constitutes a direct mechanistic connection between symptoms of a human neurological disorder and the central circadian clock mechanism. The lengthened circadian period leads to delayed phase, which could explain the short sleep duration and increased sleep onset latency of AS subjects. Moreover, we report the pharmacological rescue of an AS phenotype, in this case, altered circadian period. These findings reveal potential treatments for sleep disorders in AS patients.	
25660440	Psychiatric disorders can be described and treated from both a Western (allopathic) and an Eastern perspective, which should be taken into account when conducting research. Patients with schizophrenia or depression are likely to be undergoing Western treatment when they are referred to an acupuncturist for (add-on) treatment, and knowledge of both types of treatments is necessary to integrate them successfully. In this study, the different Traditional Oriental Medicine (TOM) diagnostic patterns in patients with a Western diagnosis of schizophrenia, depression, or sleep disorders are described from a literature and a clinical perspective. The data on 30 depression and 30 schizophrenia patients from a German study are presented. Our results show that if a psychiatric group, sorted in accordance to Western diagnostic principles, is diagnosed on the basis of TOM diagnostic patterns, it can be categorized into different groups of patients with psychiatric disorders; this finding has far-reaching consequences in scientific research on acupuncture. Moreover, we found a high prevalence of sleep disorders in patients with both schizophrenia and depression, which could be explained from the perspective of a TOM diagnostic pattern. Finally, we discuss sleep quality as a treatment objective that may play a crucial role in mediating acupuncture-induced treatment effects in patients with schizophrenia and depression. 
25660429	The climacteric syndrome is characterized by several symptoms: hot flashes are the most common and reported by about 70% of peri- post-menopausal women. Sleep disorders, particularly decreased sleep quality, and irritability are also commonly reported. There is a clinical and epidemiological relationship between these symptoms. Common biological mechanisms may explain in part the relationship between hot flushes, sleep disorders and irritability. For example, withdrawal of hormones causes change in the serotonin levels. Tryptophan is an essential amino acid. it is the precursor for the serotonin synthesis and is naturally found in food such as turkey, cheese, and nuts. The serotonergic system is implicated in sleep, mood, and hot flashes. Glycine is an amino acid found mainly in protein-rich food such as meat, fish, dairy products, cheese and vegetables. It is an inhibitory neurotransmitter in the central nervous system. Studies have shown that glycine can promote a deeper level of sleep. Resveratrol has a similar chemical structure to the diethylstilbestrol and 17-beta estradiol and acts as a phytoestrogen. Resveratrol at doses of 3-10 micromoles inhibited the estradiol-estrogen receptor binding and showed an estrogen-like activity. Vitamin E is found naturally in some food and available as a dietary supplement. It has an antioxidant activity. It has been suggested that the oxidative stress may also play a role in sleep disorders. Some studies have shown protective effect of vitamins E on sleep quality. In conclusion, hot flashes, sleep disturbances and mood disorders may represent a continuum in the climacteric syndrome, which recognize in the hormonal changes and the neurotrasmettitors level alteration a potential common pathway. The nutraceutical approach may be useful in a preventive perspective. Among the large choice of functional food available, the combination of resveratrol, tryptophanum, glycine and vitamin E may represent an interesting opportunity in the routine clinical practice. 

25659923	The aim of the present study was to investigate changes in the prevalence of short and long sleepers in Denmark, and to explore the associations between socioeconomic status, body mass index and sleep duration.Sleeping behavior is considered to be a risk factor for morbidity and mortality, but there is little information on population sleep in Denmark; however, it is suspected that sleep durations have declined over time.	Data were used from five Danish population-representative time-use studies spanning 1964-2008/09.	The proportion of short sleepers increased significantly until the end of the 1980s, whereafter it decreased significantly. The proportion of long sleepers reached a maximum in 1975. It was also found that the increase in women's employment rates was associated with half the decrease in their sleep duration over the last 45 years. In accordance with previous literature, it can be shown that both short and long sleep are associated with being overweight/obesity.	In Denmark, the same number of hours is slept today as in the mid-1960s, with nearly the same prevalence of short and long sleepers.	
25658956	Tasimelteon is a novel dual melatonin receptor agonist and is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. This study was conducted to assess the absolute bioavailability of tasimelteon and to further assess the single-dose pharmacokinetics, safety, and tolerability of oral and intravenous (IV) routes of administration of the drug. This study was an open-label, single-dose, randomized, 2-period, 2-treatment, 2-sequence, crossover study in which 14 healthy volunteers were randomly administered tasimelteon as either a 20-mg capsule or IV administration of 2 mg infused over 30 minutes. Each subject received both treatments in a random order, separated by a washout period of 5 ± 2 days. The total clearance and volume of distribution of tasimelteon, from the IV treatment, were 505 mL per minute and 42.7 L, respectively. Based on the statistical comparison of dose-corrected area under the curve to infinity, the absolute bioavailability was 38%, with a 90% confidence interval of 27%-54%. The mean elimination half-life was the same for the oral and IV routes. The exposure ratios, oral-to-IV, for metabolites M9, M11, M12, and M13, were 133.27%, 118.28%, 138.76%, and 112.36%, respectively, suggesting presystemic or first-pass metabolism. Three (21.4%) subjects experienced a treatment-emergent adverse event (TEAE) during the study. All TEAEs were mild, considered related to study medication, and consistent with what has been seen in other studies. There were no deaths, serious adverse events, or discontinuations due to TEAEs. Both tasimelteon treatments were well tolerated during the study. 
25658214	There are a wide variety of paroxysmal nonepileptic events (PNEEs) in children that can mimic seizures. The type of PNEEs that need to be considered in the differential diagnosis depends on the age of symptom onset and the clinical features. In infants and toddlers, conditions that are relatively common in clinical practice such as apnea, jitteriness, shuddering attacks, and breath-holding spells may not present much of a diagnostic conundrum, whereas unusual conditions such as hyperekplexia may cause concern. Similarly, although most types of migraine are easily distinguished from seizures in school-aged children, certain variants such as the "Alice in Wonderland" syndrome or basilar migraine can create diagnostic confusion. Most types of PNEE are exclusive to childhood; therefore, the pediatrician must be familiar with a variety of physiological processes and pathological entities that can raise concern in parents. The pediatrician is in the unique position of being able to reassure families and/or guide further work-up. Many of the PNEEs in young children require no treatment and resolve spontaneously. It is important to distinguish these episodes from true seizures as to avoid unnecessary testing and pharmacological treatment. This review highlights common PNEEs in children, beginning with the neonatal age group and moving upward to adolescence.


25651010	To analyze the occurrence of sleep-related disorders among adults from Presidente Prudente, Brazil, as well as to identify associations with behavioral, socio-demographic and nutritional status variables.After random selection of the sample, interviews were performed with 743 adults of both genders, living in Presidente Prudente, Brazil. Sleep-related disorders, demographic variables (sex, age, ethnicity and schooling), behavioral variables (leisure physical activity, alcohol consumption, and smoking) and nutritional status were analyzed by questionnaires.	The prevalence of sleep-related disorders was 46.7%, with 95% confidence interval (95%CI) 43.1 - 50.2. In the multivariate analysis, female sex, with odds ratio (OR) 1.74 (95%CI 1.26 - 2.40), schooling (OR = 0.49; 95%CI 0.28 - 0.82), overweight (OR = 1.99; 95%CI 1.39 - 2.85) and obesity (OR = 2.90; 95%CI 1.94 - 4.35) were associated with sleep-related disorders.	There is high occurrence of sleep-related disorders in this sample, which was associated with female sex, lower schooling, overweight and obesity.	
25649866	Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression.A postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group < 2500 g and ≥ 2500 g.	In the co-twin analyses restricted growth (birth weight < 2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p < 0.0001), respectively). The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR = 2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR = 2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR = 3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR = 4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g.	Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.	
25649738	Although poor sleep is common in numerous gastrointestinal diseases, data are scarce on the risk of poor sleep in celiac disease. The objective of this study was to estimate the risk of repeated use of hypnotics among individuals with celiac disease as a proxy measure for poor sleep.This is a nationwide case-control study including 2933 individuals with celiac disease and 14,571 matched controls from the general Swedish population. Poor sleep was defined as ≥2 prescriptions of hypnotics using prospective data from the National Prescribed Drug Register (data capture: July 2005-January 2008). We estimated odds ratios and hazard ratios for poor sleep before and after celiac disease diagnosis respectively.	In this study, poor sleep was seen in 129/2933 individuals (4.4%) with celiac disease, as compared with 487/14,571 controls (3.3%) (odds ratio = 1.33; 95% CI = 1.08-1.62). Data restricted to sleep complaints starting ≥1 year before celiac disease diagnosis revealed largely unchanged risk estimates (odds ratio = 1.23; 95% CI = 0.88-1.71) as compared with the overall risk (odds ratio 1.33). The risk of poor sleep in celiac disease was essentially not influenced by adjustment for concomitant psychiatric comorbidity (n = 1744, adjusted odds ratio =1.26; 95% CI = 1.02-1.54) or restless legs syndrome (n = 108, adjusted odds ratio = 1.33; 95% CI = 1.08-1.63). Poor sleep was also more common after celiac disease diagnosis as compared with matched controls (hazard ratio = 1.36; 95% CI = 1.30-1.41).	In conclusion, individuals with celiac disease suffer an increased risk of poor sleep, both before and after diagnosis. Although we cannot rule out that surveillance bias has contributed to our findings, our results are consistent with previous data suggesting that sleep complaints may be a manifestation of celiac disease.	
25649251	The Pittsburgh Sleep Quality Index (PSQI) is a widely used measure for assessing sleep impairment. Although it was developed as a unidimensional instrument, there is much debate that it contains multidimensional latent constructs. We examined the dimensionality of the underlying factor structure of PSQI in Singapore, a rapidly industrialising Asian country with multi-ethnicities representing the Chinese, Malays and Indians.The PSQI was administered through an interviewer-based questionnaire in two separate population-based cross-sectional surveys. An explanatory factor analysis (EFA) was first used to explore the underlying construct of the PSQI in both studies. Then, a confirmatory factor analysis (CFA) was conducted to evaluate an optimal factor model by comparing against other possible models identified in EFA.	There are three correlated yet distinguishable factors that account for an individual's sleep experience from the same best-fit model obtained in both studies: perceived sleep quality, daily disturbances and sleep efficiency. Our three-factor structure of PSQI is superior to the originally intended unidimensional model. Our model also shows the best-fit indices when compared to the previously reported single-factor, two-factor and three-factor (by Cole et al.) models in a multi-ethnic Asian population.	There is strong evidence that the PSQI contains a three-factor rather than a unidimensional structure in a multi-ethnic Asian population. Scoring the PSQI along their multidimensional perspectives may provide a more accurate understanding of the relationship between sleep impairment and health conditions rather than using a single global score.	
25649087	Researchers have reported that sleep duration is positively related to baseline neurocognitive performance. However, researchers have yet to examine the effect of preinjury sleep difficulties on postconcussion impairments.To compare neurocognitive impairment and symptoms of athletes with preinjury sleep difficulties to those without after a sport-related concussion (SRC).	Cohort study; Level of evidence, 3.	The sample included 348 adolescent and adult athletes (age, mean ± SD, 17.43 ± 2.34 years) with a diagnosed SRC. The sample was divided into 2 groups: (1) 34 (10%) participants with preinjury sleep difficulties (sleeping less as well as having trouble falling asleep; SLEEP SX) and (2) 231 (66%) participants without preinjury sleep difficulties (CONTROL). The remaining 84 (24%) participants with minimal sleep difficulties (1 symptom) were excluded. Participants completed the Immediate Postconcussion Assessment and Cognitive Test (ImPACT) and Postconcussion Symptom Scale (PCSS) at baseline and 3 postinjury intervals (2, 5-7, and 10-14 days after injury). A series of repeated-measures analyses of covariance with Bonferroni correction, controlling for baseline non-sleep-related symptoms, were conducted to compare postinjury neurocognitive performance between groups. Follow-up exploratory t tests examined between-group differences at each time interval. A series of analyses of variance were used to examine total PCSS score, sleep-related, and non-sleep-related symptoms across time intervals between groups.	Groups differed significantly in PCSS scores across postinjury intervals for reaction time (P < .001), with the preinjury SLEEP SX group performing worse than controls at 5-7 days (mean ± SD, 0.70 ± 0.32 [SLEEP SX], 0.60 ± 0.14 [CONTROL]) and 10-14 days (0.61 ± 0.17 [SLEEP SX]; 0.57 ± 0.10 [CONTROL]) after injury. Groups also differed significantly on verbal memory performance (P = .04), with the SLEEP SX (68.21 ± 18.64) group performing worse than the CONTROL group (76.76 ± 14.50) 2 days after injury. The SLEEP SX group reported higher total symptom (P = .02) and sleep-related symptom (P = .02) scores across postinjury time intervals.	Preinjury sleep difficulties may exacerbate neurocognitive impairment and symptoms after concussion. The findings may help clinicians identify athletes who are at risk for worse impairments after a concussion due to preinjury sleep difficulties.	



25647293	Hypertension is a common complication of pregnancy, and studies show that pregnant women are more likely to suffer from restless legs syndrome (RLS). Pregnant women with hypertension and RLS often experience disrupted sleep patterns because of activation of the nervous system. The present study aimed to clarify the relationship between hypertension and RLS in pregnant women, and their impact on sleep. We enrolled 3,781 pregnant women who were admitted at our hospital for delivery between May 2011 and May 2014. The face-to-face questionnaire used to gather data included the International RLS Study Group criteria for diagnosis, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and hypertension diagnosis. Depending on the time of occurrence of hypertension, it was divided into two different types: pregnancy-induced hypertension and chronic hypertension in pregnancy. Out of 3,781 patients, 453 fulfilled the diagnostic criteria for RLS and 486 met the diagnostic criteria for hypertension. Among patients with RLS, prophylactic iron supplementation was less frequently taken during pregnancy. Pregnancy-induced hypertension, rather than chronic hypertension in pregnancy, was found to be more frequent in patients with RLS; pregnant women with RLS had higher PSQI and ESS scores than pregnant controls. In our study, RLS was frequent in pregnant women, especially in those without prophylactic iron supplementation. Patients with RLS described more serious sleep disruption and excessive daytime sleepiness (EDS). In addition, pregnancy-induced hypertension was more common in patients with RLS. 
25646809	To examine whether behavioural strategies designed to improve children's sleep problems could also improve the symptoms, behaviour, daily functioning, and working memory of children with attention deficit hyperactivity disorder (ADHD) and the mental health of their parents.Randomised controlled trial.	21 general paediatric practices in Victoria, Australia.	244 children aged 5-12 years with ADHD attending the practices between 2010 and 2012.	Sleep hygiene practices and standardised behavioural strategies delivered by trained psychologists or trainee paediatricians during two fortnightly consultations and a follow-up telephone call. Children in the control group received usual clinical care.	At three and six months after randomisation: severity of ADHD symptoms (parent and teacher ADHD rating scale IV-primary outcome), sleep problems (parent reported severity, children's sleep habits questionnaire, actigraphy), behaviour (strengths and difficulties questionnaire), quality of life (pediatric quality of life inventory 4.0), daily functioning (daily parent rating of evening and morning behavior), working memory (working memory test battery for children, six months only), and parent mental health (depression anxiety stress scales).	Intervention compared with control families reported a greater decrease in ADHD symptoms at three and six months (adjusted mean difference for change in symptom severity -2.9, 95% confidence interval -5.5 to -0.3, P=0.03, effect size -0.3, and -3.7, -6.1 to -1.2, P=0.004, effect size -0.4, respectively). Compared with control children, intervention children had fewer moderate-severe sleep problems at three months (56% v 30%; adjusted odds ratio 0.30, 95% confidence interval 0.16 to 0.59; P<0.001) and six months (46% v 34%; 0.58, 0.32 to 1.0; P=0.07). At three months this equated to a reduction in absolute risk of 25.7% (95% confidence interval 14.1% to 37.3%) and an estimated number needed to treat of 3.9. At six months the number needed to treat was 7.8. Approximately a half to one third of the beneficial effect of the intervention on ADHD symptoms was mediated through improved sleep, at three and six months, respectively. Intervention families reported greater improvements in all other child and family outcomes except parental mental health. Teachers reported improved behaviour of the children at three and six months. Working memory (backwards digit recall) was higher in the intervention children compared with control children at six months. Daily sleep duration measured by actigraphy tended to be higher in the intervention children at three months (mean difference 10.9 minutes, 95% confidence interval -19.0 to 40.8 minutes, effect size 0.2) and six months (9.9 minutes, -16.3 to 36.1 minutes, effect size 0.3); however, this measure was only completed by a subset of children (n=54 at three months and n=37 at six months).	A brief behavioural sleep intervention modestly improves the severity of ADHD symptoms in a community sample of children with ADHD, most of whom were taking stimulant medications. The intervention also improved the children's sleep, behaviour, quality of life, and functioning, with most benefits sustained to six months post-intervention. The intervention may be suitable for use in primary and secondary care.Trial registration Current Controlled Trials ISRCTN68819261.	
25646723	Sleep problems are a common complaint in the majority of people suffering from depression. While sleep complaints were traditionally seen as a symptom of mood disorders, accumulating evidence suggests that in many cases the relationship may be reverse as well. A long list of longitudinal studies shows that sleep complaints often precede the onset of depression and constitute an independent risk factor for the development of the disorder. Additionally, experimental studies in animals show that chronically restricted or disrupted sleep may gradually induce neurobiological changes that are very similar to what has been reported for depressed patients. The mechanisms through which insufficient sleep increases the risk for depression are poorly understood but may include effects of sleep disturbance on neuroendocrine stress systems, serotonergic neurotransmission, and various interacting signaling pathways involved in the regulation of neuronal plasticity and neurogenesis. Because sleep is considered to play a crucial role in regulating neuronal plasticity and synaptic strength, chronically insufficient sleep may contribute to depression through an impairment of these plasticity processes leading to altered connectivity and communication within and between brain regions involved in the regulation of mood. 
25646103	As hard as it may be for clinicians to adopt new practices, it is often harder for them to "de-innovate," or give up old practices, even when new evidence reveals that those practices offer little value. In this article we explore recent controversies over screening for breast and prostate cancer and testing for sleep disorders. We show that these controversies are not caused solely by a lack of clinical data on the harms and benefits of these tests but are also influenced by several psychological biases that make it difficult for clinicians to de-innovate. De-innovation could be fostered by making sure that advisory panels and guideline committees include experts who have competing biases; emphasizing evidence over clinical judgment; resisting "indication creep," or the premature extension of innovations into unproven areas; and encouraging clinicians to explicitly consider how their experiences bias their interpretations of clinical evidence. 

25645131	We conducted a meta-analysis to summarise and quantify the effects of non-pharmacological interventions on sleep quality improvement in uraemic patients on dialysis. We defined the primary outcome as the change of sleep quality before and after interventions (evaluated by polysomonography or subjective questionnaires such as Pittsburgh sleep quality index, PSQI). The change of fatigue scales, inflammatory cytokines and adverse events were analysed as secondary outcomes. Twelve eligible randomised controlled trials and one prospective cohort study were identified. All three identified non-pharmacological interventions could result in a greater PSQI score reduction compared to controls: 1) cognitive-behavioural therapy (CBT) versus sleep hygiene education (standardised mean difference (SMD) 0.85, 95% CI 0.37-1.34); 2) physical training versus no training (SMD 3.36, 95% CI 2.16-4.57) and 3) Acupressure (including other acupoints massages) versus control (SMD 1.77, 95% CI 0.80-2.73). In terms of subscores, we found that CBT may shorten sleep latency, alleviate sleep disturbance and reduce the use of sleep medications. The finding of the cohort study suggested that intradialytic aerobic exercise training improved sleep quality in haemodialysis patients with restless leg syndrome. In conclusion, in dialysis-dependent patients, CBT could shorten sleep latency, alleviate sleep disturbance and reduce the use of sleep medications. Acupressure (including other acupoints massages) and exercise training are promising interventions but the results in these subgroups should be interpreted cautiously due to the concern of methodological quality and potential confounding factors. 
25645127	Cognitive-behavioral treatment for insomnia and continuous positive airway pressure therapy for obstructive sleep apnea are among the most efficacious sleep interventions. Unfortunately, adherence levels are disappointingly low for these interventions. Behavioral economics offers a promising framework for promoting adherence, often through relatively brief and straightforward strategies. The assumptions, goals, and key strategies of behavioral economics will be introduced. These strategies include providing social norms information, changing defaults, using the compromise effect, utilizing commitment devices, and establishing lottery-based systems. Then, this review will highlight specific behavioral economic approaches to promote patient adherence for three major sleep interventions: 1) behavioral treatment for pediatric insomnia, 2) cognitive-behavioral treatment for adult insomnia, and 3) continuous positive airway pressure for obstructive sleep apnea. Next, behavioral economic strategies will be discussed as ways to improve health care provider adherence to clinical practice guidelines regarding appropriate prescribing of hypnotics and ordering sleep-promoting practices for hospitalized inpatients. Finally, possible concerns that readers may have about behavioral economics strategies, including their efficacy, feasibility, and sustainability, will be addressed. 
25645126	Workers often attribute poor sleep to factors at work. Despite the large number of workers with sleep disturbances, there is a lack of consensus on the relationship between the work environment and sleep. The purpose of this systematic review therefore was to conduct a comprehensive evaluation. To this end, we employed standardized methods to systematically locate, review, and tabulate the results of prospective or randomized studies of the impact of work factors on sleep disturbances. From the 7981 articles located in five databases, 24 fulfilled our inclusion criteria and formed the base of the review including meta-analyses of the effect sizes. Results showed that the psychosocial work variables of social support at work, control, and organizational justice were related to fewer sleep disturbances, while high work demands, job strain, bullying, and effort-reward imbalance were related to more future sleep disturbances. Moreover, working a steady shift was associated with disturbances while exiting shift work was associated with less disturbed sleep. We conclude that psychosocial work factors and the scheduling of work have an impact on sleep disturbances and this might be utilized in the clinic as well as for planning work environments. Future research needs to employ better methodology and focus on underlying mechanisms. 



25644221	Abundant evidence suggests that allelic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) influences susceptibility to stress and its affective consequences due to brain serotonergic vulnerability. Based on recent assumptions, the present study examined whether the 5-HTTLPR genotype may also interact with a vulnerability to chronic stress experience (conceptualized by trait neuroticism) in order to influence sleep quality and, additionally, whether this is influenced by brain serotonergic manipulations.In a well-balanced experimental design, homozygous S-allele (n = 57) and L-allele (n = 54) genotypes with high and low chronic stress vulnerability (neuroticism) were first assessed for general past sleep quality during a month before onset of the experiment. Then subjects were assessed for sleep quality following 7 days of tryptophan (3.0g/day) or placebo intake.	Although high neuroticism was significantly related to a higher frequency of stressful life events and daily hassles, it did not interact with the 5-HTTLPR genotype on general past sleep quality. However, as expected, a 7 day period of tryptophan administration was exclusively associated with better sleep quality scores in the S'/S' genotype with high trait neuroticism.	Current findings suggest that 5-HTTLPR does not directly interact with stress vulnerability in order to influence sleep quality. Instead, based on current and previous findings, it is suggested that the S'/S' 5-HTTLPR genotype promotes the risk for stress-related sleep disturbances because of an increased susceptibility to the depressogenic consequences of stress. Accordingly, by way of reducing depressive symptomatology, tryptophan augmentation may particularly improve sleep quality in stress-vulnerable individuals carrying the 5-HTTLPR S-allele.	
25643981	Melatonin is a hormone produced by the pineal gland during the night in response to light/dark information received by the retina and its integration by the suprachiasmatic nucleus. When administered to selected populations of adults, in particular those displaying delayed sleep phase disorder, melatonin may advance the time of sleep onset. It is, however, being increasingly prescribed for children with sleep disorders despite the fact that (i) it is not registered for use in children anywhere in the world; (ii) it has not undergone the formal safety testing expected for a new drug, especially long-term safety in children; (iii) it is known to have profound effects on the reproductive systems of rodents, sheep and primates, as well as effects on the cardiovascular, immune and metabolic systems; and (iv) there is the potential for important interactions with drugs sometimes prescribed for children. In this review, I discuss properties of melatonin outside its ability to alter sleep timing that have been widely ignored but which raise questions about the safety of its use in infants and adolescents. 
25643973	Survivors of childhood cancer may experience persistent symptoms, including fatigue, sleep disturbance, and balance impairment. Yoga is a complementary therapy that improves fatigue, sleep, and quality of life in adult cancer survivors. Using a one group, repeated measures design, we evaluated the feasibility of a yoga program and assessed if cancer survivor participants ages 10 to 17 years (n = 13) had significantly less fatigue and anxiety, and better balance and sleep, after a 6-week yoga intervention compared with a 6-week pre-intervention wait period. Study recruitment was challenging with a 32% enrollment rate; yoga attendance was 90%. None of the scores for anxiety, fatigue, sleep, and balance had significant changes during the wait period. After the 6-week yoga program, children (n = 7) had a significant decrease in anxiety score (P = .04) while adolescent scores (n = 7) showed a decreasing trend (P = .10). Scores for fatigue, sleep, and balance remained stable post-intervention. Fatigue and balance scores were below norms for health children/adolescents while sleep and anxiety scores were similar to healthy peers. 
25643316	This issue provides a clinical overview of Perimenopause focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic. 
25642948	The relationship between recent episodes of poor sleep and cognitive testing performance in healthy cognitively intact older adults is not well understood. In this exploratory study we examined the impact of recent sleep disturbance, sleep duration, and sleep variability on cognitive performance in 63 cognitively intact older adults using a novel unobtrusive in-home sensor-based sleep assessment methodology. Specifically, we examined the impact of sleep the night prior, the week prior, and the month prior to a neuropsychological evaluation on cognitive performance. Results showed that mildly disturbed sleep the week prior and month prior to cognitive testing was associated with reduced working memory on cognitive evaluation. One night of mild sleep disturbance was not associated with decreased cognitive performance the next day. Sleep duration was unrelated to cognition. In-home, unobtrusive, sensor monitoring technologies provide a novel method for objective, long-term, and continuous assessment of sleep behavior and other everyday activities that might contribute to decreased or variable cognitive performance in healthy older adults. 
25642589	The changing hormonal milieu around menopause is implicated in the development of sleep disturbances. No studies have assessed the association between concurrent physiological measures of sleep and serum hormone concentrations in perimenopausal women.This study aimed to assess the interaction between physiological sleep and reproductive hormone measures in perimenopausal women.	This was a cross-sectional laboratory study of 33 perimenopausal women age 43-52 years (17 with no sleep complaints and 16 with a clinical diagnosis of insomnia). Eleven premenopausal women without sleep complaints (18-27 y), were included to determine whether hormone-sleep relationships differed depending on reproductive stage.	Concurrent polysomnographic sleep indices and serum hormone levels (estradiol and follicle stimulating hormone [FSH]) were measured.	FSH was positively associated with polysomnographic-defined wakefulness after sleep onset, and number of awakenings and arousals in perimenopausal women (P < .05) without sleep complaints independent of age, body mass index, and hot flashes. Similarly, FSH correlated with wakefulness after sleep onset and light N1 sleep in premenopausal women (P < .05). In contrast, in perimenopausal insomniacs amount of sleep correlated with anxiety and depression (P < .05) but not with FSH. Estradiol did not correlate with sleep in perimenopausal groups but correlated negatively with arousals in premenopausal women (P < .01).	Our results suggest an interaction between the hypothalamic-pituitary-ovarian (HPO) axis and sleep-wake regulatory systems in pre- and peri-menopausal women without sleep complaints. There was no relationship between hormones and sleep in perimenopausal insomniacs, whose sleep may be influenced by other factors intrinsic to insomnia, such as hyperactivity, poor mood, and night-to-night variability.	
25642184	Cerebral metabolism varies dramatically as a function of sleep state. Brain concentration of lactate, the end product of glucose utilization via glycolysis, varies as a function of sleep state, and like slow wave activity (SWA) in the electroencephalogram (EEG), increases as a function of time spent awake or in rapid eye movement sleep and declines as a function of time spent in slow wave sleep (SWS). We sought to determine whether lactate concentration exhibits homeostatic dynamics akin to those of SWA in SWS. Lactate concentration in the cerebral cortex was measured by indwelling enzymatic biosensors. A set of equations based conceptually on Process S (previously used to quantify the homeostatic dynamics of SWA) was used to predict the sleep/wake state-dependent dynamics of lactate concentration in the cerebral cortex. Additionally, we applied an iterative parameter space-restricting algorithm (the Nelder-Mead method) to reduce computational time to find the optimal values of the free parameters. Compared to an exhaustive search, this algorithm reduced the computation time required by orders of magnitude. We show that state-dependent lactate concentration dynamics can be described by a homeostatic model, but that the optimal time constants for describing lactate dynamics are much smaller than those of SWA. This disconnect between lactate dynamics and SWA dynamics does not support the concept that lactate concentration is a biochemical mediator of sleep homeostasis. However, lactate synthesis in the cerebral cortex may nonetheless be informative with regard to sleep function, since the impact of glycolysis on sleep slow wave regulation is only just now being investigated. 
25641899	Resilience Training has the potential to mitigate mental health symptoms when provided during initial military training.The present study examined the impact of Resilience Training on US soldier well-being and attitudes during Basic Combat Training. Platoons were randomly assigned to Resilience Training or Military History provided during the first few days of Basic Combat Training. Surveys were conducted at baseline, post-intervention, and 3, 6, and 9 weeks.	The sample resulted in a total of 1,939 soldiers who completed at least the baseline and one follow-up survey. There were no significant differences between conditions in terms of depression symptoms, anxiety symptoms, or sleep problems. However, while anxiety decreased in both conditions, the rate of decrease was faster in the Resilience Training condition. In contrast, Resilience Training had a slower rate of increase in group cohesion over time than the Military History condition. In addition, Resilience Training was associated with greater confidence in helping others and received more positive ratings than Military History.	Findings demonstrate that the brief Resilience Training studied here may have some utility in supporting mental health and peer support but may not benefit unit climate.	
25641765	Addiction is a widespread public health issue with social and economic ramifications. Substance abuse disorders are often accompanied by disruptions in circadian rhythms including sleep/wake cycles, which can exacerbate symptoms of addiction and dependence. Additionally, genetic disturbance of circadian molecular mechanisms can predispose some individuals to substance abuse disorders. In this review, we will discuss how circadian genes can regulate midbrain dopaminergic activity and subsequently, drug intake and reward. We will also suggest future directions for research on circadian genes and drugs of abuse.
25640603	Cortisol and inflammatory proteins are released into the blood in response to stressors and chronic elevations of blood cortisol and inflammatory proteins may contribute to ongoing disease processes and could be useful biomarkers of disease. How chronic circadian misalignment influences cortisol and inflammatory proteins, however, is largely unknown and this was the focus of the current study. Specifically, we examined the influence of weeks of chronic circadian misalignment on cortisol, stress ratings, and pro- and anti-inflammatory proteins in humans. We also compared the effects of acute total sleep deprivation and chronic circadian misalignment on cortisol levels. Healthy, drug free females and males (N=17) aged 20-41 participated. After 3weeks of maintaining consistent sleep-wake schedules at home, six laboratory baseline days and nights, a 40-h constant routine (CR, total sleep deprivation) to examine circadian rhythms for melatonin and cortisol, participants were scheduled to a 25-day laboratory entrainment protocol that resulted in sleep and circadian disruption for eight of the participants. A second constant routine was conducted to reassess melatonin and cortisol rhythms on days 34-35. Plasma cortisol levels were also measured during sampling windows every week and trapezoidal area under the curve (AUC) was used to estimate 24-h cortisol levels. Inflammatory proteins were assessed at baseline and near the end of the entrainment protocol. Acute total sleep deprivation significantly increased cortisol levels (p<0.0001), whereas chronic circadian misalignment significantly reduced cortisol levels (p<0.05). Participants who exhibited normal circadian phase relationships with the wakefulness-sleep schedule showed little change in cortisol levels. Stress ratings increased during acute sleep deprivation (p<0.0001), whereas stress ratings remained low across weeks of study for both the misaligned and synchronized control group. Circadian misalignment significantly increased plasma tumor necrosis factor-alpha (TNF-α), interleukin 10 (IL-10) and C-reactive protein (CRP) (p<0.05). Little change was observed for the TNF-α/IL-10 ratio during circadian misalignment, whereas the TNF-α/IL-10 ratio and CRP levels decreased in the synchronized control group across weeks of circadian entrainment. The current findings demonstrate that total sleep deprivation and chronic circadian misalignment modulate cortisol levels and that chronic circadian misalignment increases plasma concentrations of pro- and anti-inflammatory proteins. 

25639732	The aim of the present exploratory clinical study was to evaluate LD as an add-on therapy for treating nightmares.Thirty-two subjects having nightmares (ICD-10: F51.5) at least twice a week participated. Subjects were randomly assigned to group: A) Gestalt therapy group (= GTG), or B) Gestalt and lucid dreaming group therapy (= LDG). Each group lasted ten weeks. Participants kept a sleep/dream diary over the treatment. Examinations with respect to nightmare frequency and sleep quality (Pittsburgh Sleep Quality Index) were carried out at the beginning, after five and ten weeks and at a follow-up three months later.	Concerning nightmare frequency, a significant reduction was found in both groups after the ten-week-study and at the follow-up (Wilcoxon test: P ≤ 0.05). Significant reduction in dream recall frequency could only be observed in the GTG (Wilcoxon test: P ≤ 0.05). For subjects having succeeded in learning lucid dreaming, reduction was sooner and higher. Sleep quality improved for both groups at the follow-up (P ≤ 0.05, Wilcoxon test). Only the LDG showed significant improvement at the end of therapy (P ≤ 0.05).	Lucid dreaming, in combination with Gestalt therapy, is a potent technique to reduce nightmare frequency and improve the subjective quality of sleep.	
25639725	Chronic use of benzodiazepines and Z-drugs (BZD/Zs) has been linked to cognitive decline. In this one-year prospective cohort study, we explored the impact of chronic BZD/Z use on cognitive decline compared to nonusers.In cognitively capable BZD/Z users and nonusers in 10 Belgian nursing homes, we investigated cognition with the MiniMentalStateExamination(MMSE) at baseline and one year. A decrease of ≥ 4 points on the MMSE (clinically relevant decrease) was used in multiple logistic regression. We collected baseline demographics, functional, psychometric and social characteristics potentially influencing cognition.	In both the 131 BZD/Z users and 95 nonusers, the cognition decreased significantly over time, but without significant difference between the groups. Clinically relevant decrease was present in 34% BZD/Z users and 27% nonusers (NS). Controlled for age, gender, education and BZD/Z use, the significant risk factors for clinically relevant cognitive decline were depression, hearing and functional impairment. Frequent reading was associated with less MMSE decrease. Our findings could not demonstrate with statistical significance that BZD/Z use was associated with fast cognitive decline. The risk factors for fast decline were depression, hearing and functional impairment, and the absence of a reading attitude. In addition, BZD/Z use and depression were associated, indicating a complex relationship.	
25639339	Sleep disturbances are particularly troublesome in patients with painful rheumatic disease. This article reviews the literature specifically published on sleep disturbances in osteoarthritis, a prevalent pathology and leading cause of disability. Several aspects of the relationship between sleep and osteoarthritis are discussed, including epidemiology, pathophysiological hypotheses, and treatment outcomes. Sleep is of central importance in the well-being of patients and should systematically be assessed in patients with osteoarthritis. When needed, a specific treatment of sleep disorders should be associated with an optimal management of pain to achieve synergistic improvements in quality of life. More large-scale studies are needed to identify predictive factors of sleep impairment in osteoarthritis. 
25639241	Circadian rhythms, among other factors, have been shown to regulate key physiological processes involved in athletic performance. Personal best performance of athletes in the evening was confirmed across different sports. Contrary to this view, we identified peak performance times in athletes to be different between human "larks" and "owls" (also called "morningness/eveningness types" or "chronotypes" and referred to as circadian phenotypes in this paper), i.e., individuals with well-documented genetic and physiological differences that result in disparities between their biological clocks and how they entrain to exogenous cues, such as the environmental light/dark cycle and social factors. We found time since entrained awakening to be the major predictor of peak performance times, rather than time of day, as well as significant individual performance variations as large as 26% in the course of a day. Our novel approach combining the use of an athlete-specific chronometric test, longitudinal circadian analysis, and physical performance tests to characterize relevant sleep/wake and performance parameters in athletes allows a comprehensive analysis of the link between the circadian system and diurnal performance variation. We establish that the evaluation of an athlete's personal best performance requires consideration of circadian phenotype, performance evaluation at different times of day, and analysis of performance as a function of time since entrained awakening.
25638516	Parents and youth often report discrepant target problems upon seeking treatment for youth psychopathology, which can have important impact on therapy processes (e.g., dropout) and treatment outcomes, as entry-level attitudes have been found to be influential in ultimate use and benefit of treatment. The current study examined parent-youth agreement within an anxiety disordered sample by assessing demographic and diagnostic factors that may predict matching, as well as the impact of matching on attrition, treatment outcome, and parental satisfaction. Ninety-five youth with principal anxiety disorders received cognitive-behavioral treatment for anxiety at a university outpatient clinic. Youth and parents independently identified target problems during the pretreatment assessment. Target problems were coded into 25 qualitative categories representing diagnostic, symptom, and functional impairment domains, including diffuse anxiety, social anxiety, academic achievement, oppositional/behavior problems, sleep problems, suicidal ideation, and family functioning. The majority of parent-youth dyads (67.4%) agreed on at least one target problem. Although problems related to diffuse anxiety and social anxiety were reported most frequently, relatively low rates of agreement were found in these domains. Kappa values demonstrated higher levels of agreement for problems with specific fears, school attendance, and panic and lower levels of agreement for difficulties with worry, shame, and self-esteem. Further, youth diagnosed with comorbid externalizing disorders were less likely to agree with their parents on at least one target problem. No effects were found for gender, age, or number of diagnoses in predicting agreement. Target problem agreement did not significantly impact rates of attrition or diagnostic remission, but did predict some measures of parental satisfaction. Results suggest that disagreement on treatment goals exists even within a narrow treatment population and may predict important consumer variables such as satisfaction. Findings emphasize that initial goals disagreement warrants careful assessment and monitoring. 
25638417	Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders with a great impact on the patient lives. While many studies have been carried out in order to assess daytime sleepiness, the automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on non-linear dynamical analysis of EEG signal was proposed. Multichannel EEG signals were recorded during five maintenance of wakefulness (MWT) and multiple sleep latency (MSLT) tests alternated throughout the day from patients suffering from sleep disordered breathing. A group of 20 patients with excessive daytime sleepiness (EDS) was compared with a group of 20 patients without daytime sleepiness (WDS), by analyzing 60-s EEG windows in waking state. Measures obtained from cross-mutual information function (CMIF) and auto-mutual-information function (AMIF) were calculated in the EEG. These functions permitted a quantification of the complexity properties of the EEG signal and the non-linear couplings between different zones of the scalp. Statistical differences between EDS and WDS groups were found in β band during MSLT events (p-value < 0.0001). WDS group presented more complexity than EDS in the occipital zone, while a stronger nonlinear coupling between occipital and frontal zones was detected in EDS patients than in WDS. The AMIF and CMIF measures yielded sensitivity and specificity above 80% and AUC of ROC above 0.85 in classifying EDS and WDS patients.
25637807	Sleep perturbations including fragmented sleep with frequent night-time awakenings and daytime naps are common in patients with Alzheimer's disease (AD), and these daily disruptions are a major factor for institutionalization. The objective of this study was to investigate if sleep-wake patterns are altered in 5XFAD mice, a well-characterized double transgenic mouse model of AD which exhibits an early onset of robust AD pathology and memory deficits. These mice have five distinct human mutations in two genes, the amyloid precursor protein (APP) and Presenilin1 (PS1) engineered into two transgenes driven by a neuron-specific promoter (Thy1), and thus develop severe amyloid deposition by 4 months of age. Age-matched (4-6.5 months old) male and female 5XFAD mice were monitored and compared to wild-type littermate controls for multiple sleep traits using a non-invasive, high throughput, automated piezoelectric system which detects breathing and gross body movements to characterize sleep and wake. Sleep-wake patterns were recorded continuously under baseline conditions (undisturbed) for 3 days and after sleep deprivation of 4h, which in mice produces a significant sleep debt and challenge to sleep homeostasis. Under baseline conditions, 5XFAD mice exhibited shorter bout lengths (14% lower values for males and 26% for females) as compared to controls (p<0.001). In females, the 5XFAD mice also showed 12% less total sleep than WT (p<0.01). Bout length reductions were greater during the night (the active phase for mice) than during the day, which does not model the human condition of disrupted sleep at night (the inactive period). However, the overall decrease in bout length suggests increased fragmentation and disruption in sleep consolidation that may be relevant to human sleep. The 5XFAD mice may serve as a useful model for testing therapeutic strategies to improve sleep consolidation in AD patients.
25637698	Rapid eye movement sleep (REMS) serves house-keeping function of the brain and its loss affects several pathophysiological processes. Relative levels of neurotransmitters including orexin A (Orx-A) in various parts of the brain in health and diseases are among the key factors for modulation of behaviors, including REMS. The level of neurotransmitter in an area in the brain directly depends on number of projecting neurons and their firing rates. The locus coeruleus (LC), the site of REM-OFF neurons, receives densest, while the pedunculo-pontine area (PPT), the site of REM-ON neurons receives lesser projections from the Orx-ergic neurons. Further, the Orx-ergic neurons are active during waking and silent during REMS and NREMS. Therefore, the level of Orx-A in discrete regions of the brain is likely to be different during normal and altered states, which in turn is likely to be responsible for altered behaviors in health and diseases, including in relation to REMS. Therefore, in the present study, we estimated Orx-A level in LC, cortex, posterior hypothalamus (PH), hippocampus, and PPT after 96 h REMSD, in post-deprivation recovered rats and in control rats. This is the first report of estimation of Orx-A in different brain regions after prolonged REMSD. It was observed that after REMSD the Orx-A level increased significantly in LC, cortex and PH which returned to normal level after recovery; however, the level did not change in the hippocampus and PPT. The Orx-A induced modulation of REMS could be secondary to increased waking.
25637104	Sleep disturbance is reported to be frequent in epilepsy. The role of comorbidity, which is frequently accompanied by sleep disturbance, has not been investigated. The present study assessed sleep disorders and circadian rhythm in patients with epilepsy, in whom relevant comorbidity was carefully excluded.Two hundred patients with epilepsy (100 generalized, 100 partial), without relevant psychiatric, neurological or internal comorbidity, were compared with 100 matched controls. The questionnaire contained specifically tailored questions to address the association between epilepsy and sleep disturbance, and validated questionnaires aimed at sleep quality, excessive daytime sleepiness (EDS), circadian rhythm, sleep disorders, and quality of life.	Forty-one percent of the participants reported on the acute effects of present or past seizures on sleep-wake rhythm, whereas chronic effects were not evident. Participants and controls did not differ in the rates of chronic sleep disturbance, EDS, and presence of sleep disorders (all p-values non-significant or n.s.). Apart from earlier sleep times on workdays (p = 0.001) in those with epilepsy, circadian variables were similarly distributed. Epilepsy was well controlled, with 75.9% being seizure free for ≥ 1 year. Longer durations of epilepsy showed a negative correlation with sleep quality (rho = -0.256, p < 0.001). Participants with generalized and partial epilepsies did not differ in rates of sleep disturbance, EDS, sleep disorders, and variables of circadian rhythm (all p-values n.s.).	The present study demonstrated that chronic sleep disturbance is not increased in patients with well-controlled epilepsy without relevant comorbidity. This supports comorbidity and insufficient seizure control as major contributors of sleep disturbance in epilepsy.	
25635957	To investigate the prevalence of sleep disturbance and psychologic distress in a population of Chinese patients with temporomandibular disorders (TMD) and whether sleep disturbance and psychologic distress are risk indicators for TMD.Validated Chinese versions of the Self-Rating Scale of Sleep (SRSS) and Depression, Anxiety and Stress Scales-21 (DASS-21) were used to measure sleep disturbance and psychologic distress of 510 TMD patients with a mean (± SD) age of 31.06 ± 14.40 years. TMD signs/symptoms and sociodemographic data were also collected. The patients were divided into seven diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). For statistical analysis, the patients were subsequently grouped into those with (n = 128) and without (n = 382) myofascial pain. The data were analyzed using chi-square tests, independent-samples t test, as well as stepwise logistic regression at a significance level of P < .05.	The prevalence of moderate to severe sleep disturbance and psychologic distress was significantly higher in the myofascial pain group than in the non-myofascial pain group (P < .05). Stepwise logistic regression analysis demonstrated that sleep disturbance and anxiety were possible risk indicators for myofascial pain, with odds ratios of 2.41 and 4.10, respectively (P < .05).	The Chinese population of TMD patients frequently reported a disturbed sleep condition and psychologic distress symptoms. Sleep disturbance and psychologic distress symptoms are possible risk indicators for myofascial pain in this population.	
25635956	To evaluate the impact of cigarette smoking on the sleep quality of patients with masticatory myofascial pain and to determine whether the association between smoking and impaired sleep is influenced by other factors such as demographic, psychological, and behavioral variables.Data from a retrospective case series of 529 patients diagnosed with masticatory myofascial pain according to group I of the Research Diagnostic Criteria for Temporomandibular Disorders were obtained. Patients completed a standardized pain questionnaire and psychometric tests. Differences between smokers and nonsmokers were evaluated using independent samples t tests and chi-square tests. Hierarchical linear multiple regression models were used to examine predictors of sleep disturbances.	Of the entire sample, 170 (32%) reported that they were smokers. Smokers reported higher pain severity and more sleep disturbances and psychological distress than nonsmokers. Cigarette smoking significantly predicted sleep disturbance (β = 0.229, P < .001), but this relationship was attenuated after controlling for pain severity and psychological distress (β = 0.122, P < .001).	Cigarette smoking is associated with numerous adverse health outcomes, including pain severity, alterations in mood, and disrupted sleep, and seems to be a significant predictor of sleep quality in patients with masticatory myofascial pain.	
25635245	Sleep/wake disturbance is a feature of almost all common age-related neurodegenerative diseases. Although the reason for this is unknown, it is likely that this inability to maintain sleep and wake states is in large part due to declines in the number and function of wake-active neurons, populations of cells that fire only during waking and are silent during sleep. Consistent with this, many of the brain regions that are most susceptible to neurodegeneration are those that are necessary for wake maintenance and alertness. In the present review, these wake-active populations are systematically assessed in terms of their observed pathology across aging and several neurodegenerative diseases, with implications for future research relating sleep and wake disturbances to aging and age-related neurodegeneration. 
25635236	To detect and quantify eye blinks during 24-hour intraocular pressure (IOP) monitoring with a contact lens sensor (CLS).A total of 249 recordings of 24-hour IOP patterns from 202 participants using a CLS were included. Software was developed to automatically detect eye blinks, and wake and sleep periods. The blink detection method was based on detection of CLS signal peaks greater than a threshold proportional to the signal amplitude. Three methods for automated detection of the sleep and wake periods were evaluated. These relied on blink detection and subsequent comparison of the local signal amplitude with a threshold proportional to the mean signal amplitude. These methods were compared to manual sleep/wake verification. In a pilot, simultaneous video recording of 10 subjects was performed to compare the software to observer-measured blink rates.	Mean (SD) age of participants was 57.4 ± 16.5 years (males, 49.5%). There was excellent agreement between software-detected number of blinks and visually measured blinks for both observers (intraclass correlation coefficient [ICC], 0.97 for observer 1; ICC, 0.98 for observer 2). The CLS measured a mean blink frequency of 29.8 ± 15.4 blinks/min, a blink duration of 0.26 ± 0.21 seconds and an interblink interval of 1.91 ± 2.03 seconds. The best method for identifying sleep periods had an accuracy of 95.2 ± 0.5%.	Automated analysis of CLS 24-hour IOP recordings can accurately quantify eye blinks, and identify sleep and wake periods.	This study sheds new light on the potential importance of eye blinks in glaucoma and may contribute to improved understanding of circadian IOP characteristics.	
25634873	Depression has become a severe global health problem, and sleeping difficulties are typically associated with depression. The purpose of this study was to investigate the relationships among subjective sleep quality, objective sleep quality, and the sleep hygiene practices of hospitalized patients with major depressive disorder.Daily sleep logs and actigraphy were used to obtain subjective and objective sleep data. Thirty patients were recruited from a regional teaching hospital in Taipei and completed the Hamilton Rating Scale for Depression and the Sleep Hygiene Practice Scale.	Significant differences were found between subjective and objective sleep data in patients with major depressive disorder (MDD). For patients with more severe depression, subjective measurements obtained using sleep logs, such as total sleep time and sleep efficiency, were significantly lower than those obtained using actigraphy by controlling for demographics.	The results regarding the differences between subjective and objective sleep data can be a reference for care providers when comforting depression patients who complain of sleep disturbance.	
25634385	Previous studies have shown that lack of sleep exerts deleterious effects on a variety of systems with detectable changes in metabolic, endocrine and immune pathways. Both short and long sleep durations are related to increased likelihood of diabetes and hypertension. However, the relation between sleep duration, sleep quality and Coronary Artery Disease (CAD) is not clear in the Indian population. We examined the hypothesis that sleep duration (compared with <6 h) and quality of sleep (PSQI > 5) are risk factors for CAD.A retrospective & controlled study was conducted on 352 adult (>18 yrs) subjects (176 controls and 176 cases, 60% men, age M = 51 ± 9.38). Sleep quality and duration was measured with Pittsburg Sleep Quality Index (PSQI). Poor sleep quality and short sleep duration was defined as PSQI >5 and total sleep time <6.0 h, respectively. OSA patients were excluded from the study. The main outcome of interest was the presence of any CAD (n = 176), including MI, angina, and stroke. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using Multivariate Logistic Regression analysis.	We found both poor quality of sleep and short sleep duration to be independently associated with CAD. Compared with a total sleep time of 6.0 h, the multivariate odds ratio (95% confidence interval) of CAD was 3.81 (1.69-8.58) whereas for poor sleep quality (PSQI > 5) it came out to be 16.62 (9.13-30.28).	There was a positive association between both short sleep duration and poor sleep quality with CAD in a selected sample of Indian adults. These results suggest that poor sleep quality and short sleep duration may be important modifiable CAD risk factors in the Indian population.	
25634175	Nonapnea sleep disorders (NASDs) are associated with an increased risk of stroke, diabetes, and hypertension. No longitudinal study has yet examined the association between NASD and chronic kidney disease (CKD) by using epidemiologic study methods. To test this hypothesis, we examined the effect of NASD on the incidence of CKD in a large population-based retrospective cohort study. Based on a retrospective cohort study of a general population sample of 128 to 436 patients in the Taiwan National Health Insurance Research Database from January 1, 1998 to December 31, 2001, 42 to 812 NASD patients were followed up for 10.2 ± 3.12 years, and additional 85 to 624 individuals had no NASD at baseline. The International Classification of Diseases, Ninth Revision, Clinical Modification was used to identify the diagnosis of disease. Cox proportional hazard regression models were used to assess the association between NASD and subsequent CKD risk. The incidence rate of CKD was significantly higher in the NASD cohort than in the comparison cohort (2.68 vs 1.88 per 1000 person-years, respectively). After we adjusted for age, sex, and comorbidities, the risk of developing CKD was significant for patients with NASD (adjusted hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 1.05-1.22; P < 0.01). Among different types of NASDs, patients with sleep disturbance associated disorders had a 14% increased risk of developing CKD (95% CI = 1.03-1.26; P < 0.01), whereas patients with insomnia had a 13% increased risk of subsequent CKD (95% CI = 1.02-1.25; P < 0.05) compared with the non-NASD cohort. Kaplan-Meier survival analysis indicated that the CKD-free rate was 1% lower in the NASD cohort than in the comparison cohort (log-rank test, P < 0.0001). Our study provides evidence that patients with NASD have an increased risk of developing subsequent CKD compared with patients without NASD; men, elderly people, and patients with concomitant comorbidities are at the greatest risk.
25634045	Circadian clock generates a variety of biological rhythms such as sleep/wake cycles and blood hormone rhythms. The circadian clock also bolsters daily mental activities. In fact, abnormalities of the circadian rhythms are found in several neurological disorders. The circadian clock has two important functions: (i) a cell-autonomous oscillatory function and (ii) a phase-adjusting function that synchronizes the clock oscillation with environmental cycling conditions such as light/dark cycle. Behavioral rhythms are controlled by the central clock in hypothalamic suprachiasmatic nucleus (SCN). The central clock orchestrates peripheral clocks in the other tissues via neuronal connection and/or actions of humoral factors. The molecular mechanism of the cell-autonomous clock is based on transcriptional feedback regulation of clock genes by their encoded products. Ca2+ is essential for not only the light response of the clock but also the cell autonomous oscillation mechanism. This article provides an overview of recent progress in studies of Ca2+-dependent regulatory mechanism of the molecular clockwork.
25633375	Migraine is associated with sleep disturbances in men and non-pregnant women. However, relatively little is known about sleep disturbances among pregnant migraineurs. We investigated sleep disturbances among pregnant women with and without history of migraine.This cross-sectional study was conducted among 1324 women who were recruited during early pregnancy. Migraine diagnoses were based on the International Classification of Headache Disorders-II criteria. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to evaluate sleep-related characteristics including sleep duration, sleep quality, excessive daytime sleepiness, and other sleep traits. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs).	Migraineurs were more likely than non-migraineurs to report short sleep duration (<6.5 hours) (AOR = 1.47, 95% CI 1.07-2.02), poor sleep quality (PSQI>5) (AOR = 1.73, 95% CI 1.35-2.23), and daytime dysfunction due to sleepiness (AOR = 1.51, 95% CI 1.12-2.02). Migraineurs were also more likely than non-migraineurs to report taking sleep medication during pregnancy (AOR = 1.71, 95% CI 1.20-2.42). Associations were generally similar for migraine with or without aura. The odds of sleep disturbances were particularly elevated among pre-pregnancy overweight migraineurs.	Migraine headache and sleep disturbances are common comorbid conditions among pregnant women.	
25633255	Excess sitting is emerging as a novel risk factor for cardiovascular disease, diabetes, mental illness, and all-cause mortality. Physical activity, distinct from sitting, is associated with better sleep and lower risk for OSA, yet relationships among sitting behaviors and sleep/OSA remain unknown. We examined whether total sitting time and sitting while viewing television were associated with sleep duration and quality, OSA risk, and sleepiness.The 2013 National Sleep Foundation Sleep in America Poll was a cross-sectional study of 1,000 adults aged 23 to 60 years. Total sitting time, time watching television while sitting, sleep duration and quality, OSA risk, and daytime sleepiness were assessed.	After adjusting for confounding factors (including BMI and physical activity), each additional hour per day of total sitting was associated with greater odds of poor sleep quality (OR [95% CI] = 1.06 [1.01, 1.11]) but not with other sleep metrics (including sleep duration), OSA risk, or daytime sleepiness. For television viewing while sitting, each additional hour per day was associated with greater odds of long sleep onset latency (≥ 30 min) (OR = 1.15 [1.04, 1.27]), waking up too early in the morning (OR = 1.12 [1.03, 1.23]), poor sleep quality (OR = 1.12 [1.02, 1.24]), and "high risk" for OSA (OR = 1.15 [1.04, 1.28]). Based upon an interaction analysis, regular physical activity was protective against OSA risk associated with television viewing (P = .04).	Excess sitting was associated with relatively poor sleep quality. Sitting while watching television was associated with relatively poor sleep quality and OSA risk and may be an important risk factor for sleep disturbance and apnea risk.	
25632834	Epilepsy with electrical status epilepticus in sleep (ESES) is a devastating disease, and we sought to evaluate the efficacy of levetiracetam (LEV) for the treatment of patients with this epileptic encephalopathy in China.Clinical data from all patients with ESES who received LEV therapy at our pediatric neurology outpatient clinic between 2007 and 2014 (n=71) were retrospectively analyzed. The LEV dosage was 30-50mg/kg/day. Electroencephalography recordings and neuropsychological evaluations were performed repeatedly for 3-75months after the start of LEV therapy.	Thirty-five (70%) of 50 patients who had seizures at the start of LEV therapy had a >50% reduction in seizure frequency. Positive response on EEG was found during the first 3-4months of LEV therapy in 32 (45%) of 71 patients, with normalization of EEG in 5 patients. Relapse occurred in 8 (25%) of the initial electrical responders. Hence, 47 patients (66%) still suffered from ESES and only 13 patients regained their baseline level of function at the last follow-up. The response to LEV was significantly associated with ESES duration, age at onset of ESES, and etiology of epilepsy. Although fatigue and anorexia were the primary adverse events, LEV was well-tolerated by all patients.	Levetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.	
25632791	We presented a case of 54-year old man, with dyslipidemia who, during his work, was exposed to prolonged electromagnetic radiation. Because of his concerns about the development of atherosclerosis, higher doses of simvastatin than recommended by the doctor, were used by him. After five weeks of such therapy the central nervous system symptoms such as: memory loss, cognitive disorders, sleeplessness, nervousness were presented. It is probable that the mentioned above symptoms were caused by high doses of drug took by the patient, and increased in blood-brain barrier permeability caused by electromagnetic radiation which lasted for about eight years.
25632617	To study the prevalence ofexcessive daytime sleepiness (EDS) and nighttime sleep quality (NSQ) in Thai patients with Parkinson's disease (PD) and compare their sleep characteristics with controls.The Epworth Sleep Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and questions about sudden onset of sleep (SOS) were applied in a study of 73 PD patients without dementia to that of healthy controls.	There were 36 females and 37 males with a mean (SD) age of 65.9 (9.1) years. All patients had a mean Hoehn and Yahr stage of 2.0 (range 0 to 4). EDS and poor NSQ were found in 15.1% and 37% of patients, respectively. There was a significant difference in the mean PSQI total scores (p = 0.003) between patients and controls. The subset analysis of the components of PSQI revealed that sleep disturbance and the need of medication to sleep had significantly higher scores than those of controls. Twenty point five percent of patients had experienced SOS occurring during driving, meals, and working. Four point one percent ofpatient with SOS had had an accident.	This study demonstrated a prevalence of EDS and poor NSQ in Thai patients with PD. Screening for these two problems among PD patients should be considered in routine practice evaluations.	
25632516	Dental professionals can intervene in head, neck and facial pain found in female patients who suffer from post-traumatic stress disorder (PTSD). There are three theories for why women are predisposed to pain: hormonal differences, nervous system rewiring and sympathetic issues. This article includes case studies of three patients who are representative of these theories. A rapid, nonintrusive intervention will also be described.
25631640	Advanced medical technology has resulted in an increased survival rate of children suffering from congenital central hypoventilation syndrome. After hospitalization, these technology-dependent patients require special home care for assuring ventilator support and the monitoring of vital parameters mainly during sleep. The daily challenges associated with caring for these children can place primary caregivers under significant stress, especially at night. Our study aimed at investigating how this condition affects mothers and fathers by producing poor sleep quality, high-level diurnal sleepiness, anxiety, and depression.The study included parents of 23 subjects with congenital central hypoventilation syndrome and 23 healthy subjects. All parents filled out the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI-II), and Beck Anxiety Inventory (BAI).	A comparison between the two groups showed that parents of patients had poorer sleep quality, greater sleepiness, and higher BDI-II scores compared to that of parents of healthy subjects (respectively, PSQI score 6.5 vs 3.8, ESS score 6.2 vs 4.3, BDI-II score 8.4 vs 5.7). Specifically, mothers of patients showed poorer sleep quality and higher BDI-II scores compared to that of mothers of controls (respectively, PSQI score 7.5 vs 3.8, BDI-II score 9.3 vs 5.9), whereas fathers of patients showed greater levels of sleepiness with respect to fathers of healthy children (respectively, ESS score 6.8 vs 4.0). These differences emerged in parents of younger children.	Congenital central hypoventilation syndrome impacts the family with different consequences for mothers and fathers. Indeed, while the patients' sleep is safeguarded, sleeping problems may occur in primary caregivers often associated with other psychological disorders. Specifically, this disease affects sleep quality and mood in the mothers and sleepiness levels in the fathers.	
25630812	The purpose of this study was to assess acceptability of study design and utility of assessment tools for determining causes of sleep disturbance in children with cerebral palsy (CP) and their caregivers.This pilot study explored parental report (n = 8) of the child's sleep using a validated sleep questionnaire, a survey, and a time use diary.	The selected tools were appropriate. Study design provided challenges for recruitment. Future research should include qualitative data.	Although further research is required to confirm results, sleep problems for children with CP and resulting sleep disturbances for caregivers may be an important part of clinical assessment.	

25626854	Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality.To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst of work, or both, in workers undertaking shift work.		We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews.	We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while of work, alertness and sleepiness, or fatigue at work.	Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate.	We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined caffeine plus naps to decrease sleepiness or to increase alertness.	
25623650	It has been anecdotally reported that nocturnal leg cramps in pregnant women are worse in summer. We analyzed population-level data to determine whether the symptom burden of nocturnal leg cramps is seasonal in the general population.We examined time-series data for 2 independent measures of the symptom burden of leg cramps: (a) new quinine prescriptions (reflecting new or escalating treatment of leg cramps) from December 2001 to October 2007 among adults aged 50 years and older, which were obtained from linked health care databases that contain the prescribing information for the 4.2 million residents of British Columbia, Canada; and (b) the Internet search volume from February 2004 to March 2012 for the term "leg cramps" (reflecting public interest), which we obtained from Google Trends data and geographically limited to the United States and Australia. We assessed seasonality by determining how well a least-squares sinusoidal model predicted variability in the outcomes.	New quinine prescriptions and Internet searches related to leg cramps were both seasonal, with highs in mid-summer and lows in mid-winter, and a peak-to-peak variability that was about two-thirds of the mean. Seasonality accounted for 88% of the observed monthly variability in new quinine prescriptions (p < 0.001) and 70% of the observed variability in Internet searches related to leg cramps (p < 0.001).	New quinine prescriptions and Internet searches related to leg cramps were seasonal and roughly doubled between the winter lows and summer highs. Why a disorder of peripheral motor neurons displays such strong seasonality warrants exploration.	


25621768	Women report many nonvasomotor symptoms across the menopausal transition, including sleep disturbances, depressed mood, and sexual problems. The co-occurrence of these three symptoms may represent a specific menopausal symptom triad. We sought to evaluate the interrelatedness of disturbed sleep, depressed mood, and sexual problems in the Study of Women's Health Across the Nation (SWAN) and determine the characteristics of women exhibiting this symptom triad.SWAN is a multisite, multiethnic observational cohort study of the menopausal transition in the United States. Sleep disturbance, sexual problems, and depressed mood were determined based on self-report. Women who reported all three symptoms simultaneously were compared to those who did not. Logistic regression models estimated the association of demographic, psychosocial, and clinical characteristics with the symptom triad.	Study participants (n=1716) were 49.8 years old on average and primarily in very good or excellent health. Sixteen and a half percent had depressed mood, 36.6% had a sleep problem, and 42.2% had any sexual problem. Five percent of women (n=90) experienced all three symptoms. Women with the symptom triad compared with those without had lower household incomes, less education, were surgically postmenopausal or late perimenopausal, rated their general health as fair or poor, and had more stressful life events and lower social support.	The symptom triad of sleep disturbance, depressed mood, and sexual problems occurred in only 5% of women, and occurred most often among women with lower socioeconomic status, greater psychosocial distress, and who were surgically menopausal or in the late perimenopause.	
25620673	The objective of this study is to examine sleep quality and correlates of poor sleep in patients with rheumatoid arthritis (RA). Five hundred patients with RA were recruited from a rheumatology outpatient clinic and included in this cross-sectional study. Sleep quality and disturbances were assessed using the Pittsburgh Sleep Quality Index (PSQI). Other instruments included the Multidimensional Fatigue Inventory, the Epworth Sleepiness Scale, and the Health Assessment Questionnaire. Disease activity was assessed according to disease activity score DAS28-CRP-based. Complete scores on PSQI were obtained from 384 patients (77 %). In those, the prevalence of poor sleep (PSQI >5) was 61 %, and the mean global PSQI score was 7.54 (SD 4.17). A linear association was found between poor sleep and mental fatigue, reduced activity related to fatigue, physical fatigue, and general fatigue. Mental fatigue and general fatigue were independently associated with sleep quality, sleep latency, sleep duration, sleep efficiency, and daytime dysfunction. However, in the linear multivariate analysis, only general fatigue 1.06 (95 % CI 1.03-1.09) and mental fatigue 1.03 (95 % CI 1.01-1.05) were found to be significant correlates for reporting poor sleep. This study shows that a majority of patients with RA experience poor sleep and that general fatigue and mental fatigue are associated with poor sleep.


25617878	Sleep disturbances are found in a majority of individuals diagnosed with posttraumatic stress disorder (PTSD). The purpose of this literature review is to provide information about PTSD, in addition to assessing sleep quality. Current research observes that the lifetime prevalence of PTSD diagnosis in women is increasing. Although there are several studies that have been conducted to assess PTSD and sleep, there is a gap in the research that pertains to women, PTSD, and sleep quality. The current study will compile information on the subject to aid in decreasing the gender disparity in PTSD research, which is important for treating the entire PTSD population. Using the PubMed and PsycINFO databases, a comprehensive search was conducted to find relevant research about sleep difficulties and PTSD. Sleep disturbances such as insomnia, re-current nightmares, REM sleep dysfunction, and obstructive sleep apnea (OSA) affect sleep quality in PTSD patients. The implications of this study suggest that more research should be conducted pertaining to women and PTSD with sleep difficulties. This research is needed to decrease both PTSD symptoms and sleep-related disorders. 
25616465	Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients.Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography.	We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T > C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T > C; p.C286R) in a sporadic patient with auditory seizures.	We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1, the second so far identified, suggests that LGI1 microrearrangements may not be exceptional.	
25616389	Studies involving genetic engineering on animal models and mathematical analysis of cardiovascular signals on humans are shedding new light on the interactions between the arterial baroreceptor reflex (baroreflex) and arousal. Baroreceptor stimulation, if very mild or performed under anaesthesia, may inhibit cortical arousal. However, substantial increases or decreases in baroreflex activation cause arousal in animal models and human subjects in physiological conditions. On the other hand, cardiovascular changes during autonomic arousals and between the states of wakefulness and sleep involve changes in the baroreflex set point and balance with central autonomic commands. Neural connectivity and functional data suggest that the nucleus of the solitary tract, adrenergic C1 neurons of the medulla, and the parabrachial nucleus of the pons mediate the bidirectional interactions between the baroreflex and arousal. These interactions may constitute a positive feedback loop that facilitates sharp and coordinated brain state and autonomic transitions upon arousal: upon arousal, central autonomic commands may increase blood pressure, thereby loading baroreceptors and further increasing arousal. Anomalies of this feedback loop may play a role in the pathophysiology of disease conditions associated with cardiovascular and sleep-wake cycle alterations. These conditions include: obstructive sleep apnoea syndrome, with its association with excessive daytime sleepiness and baroreflex impairment; and insomnia, with its association with autonomic hyperarousal and hypertension. When faced with disorders associated with cardiovascular and sleep-wake cycle alterations, clinical reasoning should entertain the possibility that both conditions are strongly influenced by anomalies of baroreflex function. 
25614750	This research was designed to identify whether Gastrodiae Rhizoma ethanol extract (GREE) enhances pentobarbital-induced sleep via  γ-aminobutyric acid- (GABA-) ergic systems and modulated sleep architectures in animals. GREE (25, 50, and 100 mg/kg, p.o.) inhibited locomotor activity in mice, in a dose-dependent manner. GREE not only prolonged total sleep time, but also reduced sleep latency time in pentobarbital (42 mg/kg)-treated mice. Subhypnotic pentobarbital (28 mg/kg, i.p.) also increased the number of total sleeping animals in concomitant administration of GREE. GREE (100 mg/kg) alone reduced the count of sleep-wake cycles in electroencephalogram. Furthermore, GREE increased total sleep time and rapid eye movement (REM) sleep. From the in vitro experiments, GREE increased intracellular chloride level in primary cultured cerebellar granule cells. Protein expressions of glutamine acid decarboxylase (GAD) and GABAA receptors subtypes by western blot were increased. Therefore, our study suggested that GREE enhances pentobarbital-induced sleeping behaviors and increased REM via the activation of GABAA-ergic transmission in rodents. 
25614508	The current review aims to examine melatonin therapy for both sleep disturbances and cognitive function in dementia. We searched all randomized controlled trials published in Medline, Embase, the Cochrane Library, China National Knowledge Infrastructure, the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register, and Clinical Trials.gov. The grading of recommendations assessment, development and evaluation framework was used to assess the quality of evidence. Seven studies were included (n = 520). Treated participants showed prolonged total sleep time (TST) by 24.36 minutes (P = .02). Sleep efficacy (SE) was marginally improved (P = .07). This effect was stronger under a longer intervention period lasting more than 4 weeks (P = .02). Conversely, cognitive function did not change significantly. Additionally, there was no report of severe adverse events. Given the current studies, we conclude that melatonin therapy may be effective in improving SE and prolonging TST in patients with dementia; however, there is no evidence that this improvement impacts cognitive function.

25613401	The study investigates if the circadian rhythm of heart rate is apparent during the working periods of day and night shifts in Swiss and Japanese nurses and if it is influenced by work organization. For a better interpretation of the heart rate, the activity profile over these working periods was monitored.Heart rate and activity profile of 18 Swiss and 24 Japanese nurses were measured during one day and one night shift. The day and the night shift data of each subject were combined, resulting in an approximately 18-h working period.	A significant time effect of the mean hourly value of the heart rate was found in Swiss nurses (change in amplitude 7.1 bpm) as well as in Japanese nurses (11.8 bpm). These effects could be modeled with cosine curves for the Swiss and Japanese subjects. For the activity level significant time effects, similar to the ones in heart rate, were found in Swiss nurses (87 % of SD) but not in Japanese nurses (26 % of SD).	We found a significant time effect in heart rate similar to the known circadian rhythm under normal sleep-wake conditions while working in the studied shift work schedules. In the Japanese nurses, studied heart rate followed a circadian rhythm independently of the level of physical activity. Therefore, an activity profile following the circadian rhythm, especially a reduced workload from 2 to 4 a.m., is proposed. The proposed activity profile could be reached with an adapted work organization.	

25608723	Schizophrenia is a devastating mental illness with a worldwide prevalence of approximately 1%. Although the clinical features of the disorder were described over one hundred years ago, its neurobiology is still largely elusive despite several decades of research. Schizophrenia is associated with marked sleep disturbances and memory impairment. Above and beyond altered sleep architecture, sleep rhythms including slow waves and spindles are disrupted in schizophrenia. In the healthy brain, these rhythms reflect and participate in plastic processes during sleep. This chapter discusses evidence that schizophrenia patients exhibit dysfunction of sleep-mediated plasticity on a behavioral, cellular, and molecular level and offers suggestions on how the study of sleeping brain activity can shed light on the pathophysiological mechanisms of the disorder.
25608119	This study intended to compare the circadian rhythm and circadian profile between patients with juvenile myoclonic epilepsy (JME) and patients with temporal lobe epilepsy (TLE).We enrolled 16 patients with JME and 37 patients with TLE from the Outpatient Clinic of UNICAMP. We applied a questionnaire about sleep-wake cycle and circadian profile.	Fourteen (87%) out of 16 patients with JME, and 22 out of 37 (59%) patients with TLE reported that they would sleep after seizure (p < 0.05). Three (19%) patients with JME, and 17 (46%) reported to be in better state before 10:00 AM (p < 0.05).	There is no clear distinct profile and circadian pattern in patients with JME in comparison to TLE patients. However, our data suggest that most JME patients do not feel in better shape early in the day.	


25604848	Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although the mechanisms of this association have not been fully elucidated, nighttime reflux plays a central role. However, the detailed characteristics of nighttime reflux occurring during sleep are unknown. The aim of the present study was to examine the characteristics and prevalence of nighttime reflux in the natural sleep environment of GERD patients. Seventeen patients experiencing daily moderate-to-severe heartburn and/or regurgitation were studied using multichannel intraluminal impedance pH monitoring and electroencephalography off-proton pump inhibitor treatment. Nighttime reflux was divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or alkaline) and extent (distal only or proximal migration) according to the standard criteria. Nighttime phases were divided as follows: recumbent-awake before falling asleep, nonrapid eye movement, rapid eye movement, awakening from sleep, and post-awakening in the morning. Among 184 nighttime refluxes, 43 (23%) occurred during recumbent-awake before falling asleep, 28 (15%) during nonrapid eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from sleep, and 13 (7%) during post-awakening in the morning. Liquid reflux was more common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid eye movement (100%) compared with awakening before falling asleep (68%). The prevalence of proximal migration was significantly lower in nonrapid eye movement and rapid eye movement than in the other phases. There were no differences in acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of 425 awakening episodes during sleep. Different reflux patterns at each phase during nighttime might explain the pathogenesis of GERD and its related sleep disturbances. 
25603383	Sleep complaints are highly prevalent in adolescents suffering from major depressive disorder (MDD). The aims of this study were to describe the longitudinal course of sleep complaints, and to assess the association between sleep complaints and clinical outcome in a sample of adolescents with MDD during naturalistic follow-up.A sample of adolescent outpatients (n = 166; age 13-19 years, 17.5% boys) diagnosed with MDD was followed-up during one year in naturalistic settings. Sleep symptoms and psychiatric symptoms were assessed with interviews and self-report questionnaires.	All sleep complaints were less frequent at one-year follow-up compared to baseline. Baseline sleep complaints did not adversely affect clinical outcome at one-year follow-up: severity of the sleep complaints at baseline was associated with a steeper improvement of depressive and anxiety symptoms, suicidality/self-harm symptoms, and overall psychosocial functioning over time.	Our results suggest that sleep disturbances at baseline do not necessarily lead to poorer clinical outcome during follow-up. Larger longitudinal studies combining both subjective and objective measures of sleep in depressed adolescents are needed to clarify the link between sleep and depression further.	
25602361	Over a quarter million individuals in the United States have multiple sclerosis (MS). Chronic pain and depression are disproportionately high in this population. The purpose of this study was to examine the relationship between chronic pain and depression in MS and to examine potentially meditational effects of anxiety, fatigue, and sleep.We used cross-sectional data from self-reported instruments measuring multiple symptoms and quality of life indicators in this study. We used structural equation modeling to model direct and indirect effects of pain on depression in a sample of 1,245 community-dwelling individuals with MS. Pain interference, depression, fatigue, and sleep disturbance were modeled as latent variables with 2 to 3 indicators each. The model controlled for age, sex, disability status (Expanded Disability Status Scale), and social support.	A model with indirect effects of pain on depression had adequate fit and accounted for nearly 80% of the variance in depression. The effects of chronic pain on depression were almost completely mediated by fatigue, anxiety, and sleep disturbance. Higher pain was associated with greater fatigue, anxiety, and sleep disturbance, which in turn were associated with higher levels of depression. The largest mediating effect was through fatigue. Additional analyses excluded items with common content and suggested that the meditational effects observed were not attributable to content overlap across scales.	Individuals living with MS who report high levels of chronic pain and depressive symptoms may benefit from treatment approaches that can address sleep, fatigue, and anxiety.	
25601739	Exposure to mould or dampness at home has been associated with adverse respiratory effects in all age groups. This exposure has also been related to insomnia in adults. We aimed to investigate the association between exposure to visible mould or dampness at home and sleep problems in children.The study population consisted of 1719 10-year-old children from the German population-based birth cohort LISAplus with available data on current mould or dampness at home and sleep problems. The presence of visible mould or dampness at home was assessed by questionnaire. Parent-reported sleep problems of their child were analysed by four binary variables: presence of any sleep problems, problems to fall asleep, problems sleeping through the night and a 24h sleep time of less than 9h. Logistic regression models adjusted for study centre, sex, age and level of parental education were applied to examine the association between visible mould or dampness at home and sleep problems. Sensitivity analyses included a further adjustment for bedroom sharing and subgroup analyses in children without current allergic diseases.	Thirteen percent of parents reported visible mould or dampness at home. We observed increased risks for all four sleep problem variables for children exposed to visible mould or dampness at home. Results were significant for any sleep problems (odds ratio (OR)=1.77 (95%-confidence interval (CI): 1.21-2.60), problems sleeping through the night (OR=2.52(1.27-5.00) and a short sleep time (OR=1.68(1.09-2.61)). While a further adjustment for bedroom sharing and the exclusion of children with asthma or eczema led to similar results, only the association with a short sleep time was still present in children without allergic rhinoconjunctivitis.	Our data suggests that visible mould or dampness at home might negatively influence sleep in children. The influence of allergic rhinoconjunctivitis on this association needs to be investigated in future studies.	
25601624	The incubus phenomenon is a paroxysmal condition characterised by sleep paralysis coinciding with a sensed presence and the frightening sensation that something or somebody is exerting pressure on the thorax.To present an overview of the literature on the incubus phenomenon and to provide practical advice regarding diagnosis and treatment.	To obtain information for our paper we carried out a search in PubMed and the historical literature.	The incubus phenomenon is a relatively unknown condition, even though, world-wide, it has a lifetime prevalence rate of 30% in the general population. The prevalence is even higher among students, psychiatric patients and patients with narcolepsy. It is attributed to a dissociation of the rem sleep phase and the subsequent intrusion of endogenously mediated percepts. The condition rarely requires treatment because it is self-limiting, and generally occurs only once in a lifetime. Repeated attacks, however, may warrant additional diagnostic testing with the aid of polysomnography and may require treatment with anxiolytics, antidepressants, anticholinergics or anti-epileptics.	The incubus phenomenon is an intrusive condition, but, as far as we currently know, it is benign. Nevertheless, it is important that the condition is recognised and not confused with a psychotic disorder or any other type of severe mental illness. When necessary, it should be treated lege artis.	
25600783	Most cases of sudden unexpected death in epilepsy (SUDEP) follow a seizure, and most deaths occur while people are in bed, presumably sleeping. Nocturnal seizures are reported to be a risk factor for SUDEP. People with nocturnal frontal lobe epilepsy (NFLE) have seizures predominantly or exclusively during sleep, often many times per night. The present study aimed to assess whether NFLE represents a high-risk condition for SUDEP.The present study retrospectively assessed the incidence of SUDEP in a cohort reconstructed from a dedicated database of consecutive patients referred to the Epilepsy and Sleep Centres of the Institute of Neurological Sciences of Bologna from 1980 to 2012 with: (1) a diagnosis of NFLE, (2) at least 90% of seizures during sleep, and (3) at least one-year of follow-up.	One hundred and three people were included. The median time from seizure onset to last observation was 26 years, equal to a follow-up of 2789 person-years. One person died of SUDEP during the follow-up period. The incidence rate of SUDEP was 0.36 per 1000 person-years (95% CI 0.01 to 2.0).	The incidence of SUDEP in the participant population was not higher than the rates previously reported in prevalent epilepsy populations (0.4 to 2.3 per 1000 person-years). The low prevalence of SUDEP might reflect the low occurrence of generalised tonic-clonic seizures in people with NFLE.	
25600781	Children with autism spectrum disorder (ASD) are at high risk for sleep problems. Previous research suggests that sensory problems and anxiety may be related to the development and maintenance of sleep problems in children with ASD. However, the relationships among these co-occurring conditions have not been previously studied. The current study examined the interrelations of these symptoms in a large well-characterized sample of children and adolescents with ASD.The current study examined the relationships among sleep problems, sensory over-responsivity, and anxiety in 1347 children enrolled in the Autism Speaks Autism Treatment Network. The primary measures included the Children's Sleep Habits Questionnaire, the Child Behavior Checklist, and the Short Sensory Profile.	In bivariate correlations and multivariate path analyses, anxiety was associated with all types of sleep problems (ie, bedtime resistance, sleep-onset delay, sleep duration, sleep anxiety, and night wakings; p < 0.01 to p < 0.001; small to medium effect sizes). Sensory over-responsivity (SOR) was correlated with all sleep problems in bivariate analyses (p < 0.01 to p < 0.001; small effect sizes). In multivariate path models, SOR remained significantly associated with all sleep problems except night awakenings for older children, while SOR was no longer significantly associated with bedtime resistance or sleep anxiety for younger children.	Children with ASD who have anxiety and SOR may be particularly predisposed to sleep problems. These findings suggest that some children with ASD and sleep disturbance may have difficulties with hyperarousal. Future research using physiological measures of arousal and objective measures of sleep are needed.	
25599986	Comorbidities are common in epilepsy, and their role in quality of life (QOL) is receiving increasing scrutiny. Considerable attention has been focused on the role of depression, the most common comorbidity, with rather less attention paid to its frequent concomitant, anxiety, and other conditions known to be at increased prevalence among people with epilepsy (PWE) when compared to the general population. In this paper, we report findings from a UK-based survey in which we examined self-reporting of two common comorbidities, anxiety and sleep problems, factors associated with them, and their role in QOL in people with and without epilepsy. Data were obtained via mailed questionnaires, supplemented by an internet survey, from PWE and age- and gender-matched controls. Based on self-reported symptoms, PWE were at higher risk of anxiety and sleep problems. Contributory factors for anxiety included poorer general health, worry about seizures, and self-reported antiepileptic drug (AED) side effects. Good social support emerged as protective for anxiety in PWE. Nighttime sleep problems were very common even in controls but were further elevated in PWE. Antiepileptic drug adverse events emerged as an important contributory factor for sleep problems. Trait anxiety emerged as significant for defining overall QOL, and its importance over state anxiety supports the notion of anxiety in PWE as a primarily premorbid condition. In contrast, sleep quality was not consistently predictive of QOL. Our study has important implications for clinical management, emphasizing the need for a holistic approach to address wider patient-reported problems as well as any epilepsy-specific ones. 
25599968	To evaluate the impact of buprenorphine (Butrans®) transdermal System (BTDS) treatment on sleep outcomes for patients with moderate-to-severe chronic low back pain (CLBP).Two enriched-enrollment, randomized-withdrawal, double-blind, controlled trials examined BTDS treatment for patients with moderate-to-severe CLBP. Trial I evaluated BTDS 10 and 20 mcg/hour against a placebo control among opioid-naïve patients. Trial II compared BTDS 20 mcg/hour against a lower-dose control (BTDS 5 mcg/hour) among opioid-experienced patients. The patient-reported Medical Outcomes Study Sleep Scale (MOS-SS) assessed overall sleep quality (Sleep Problems Index [SPI]), Disturbance, and other sleep outcomes. In each trial, MOS-SS scores were compared between target treatment and control arms during the 12-week double-blind phase. Correspondence of changes in sleep outcomes and pain severity and the degree to which pain reduction mediates treatment impact on sleep outcomes were examined.	Medical Outcomes Study Sleep Scale scores were collected from 541 (Trial I) and 441 (Trial II) patients prior to randomization and from 369 (Trial I) and 274 (Trial II) patients at week 12. Patients receiving target treatment showed statistically significantly more improvement in SPI and Disturbance scores at 12 weeks than their respective controls (Ps < 0.05). Improvements in SPI and Disturbance for target treatment arms were statistically larger those of the controls by week 4 of the double-blind phase. The clinical significance of these differences was not determined. Pain reduction predicted improvements in sleep outcomes.	Buprenorphine Transdermal System improved sleep quality and disturbance for opioid-naïve and opioid-experienced patients with moderate-to-severe CLBP. Benefits of BTDS for these sleep outcomes emerged within 4 weeks and were maintained over the entire 12-week treatment period.	
25597026	Depression, sleep disturbance, and vasomotor symptoms are common in breast cancer survivors (BCS), especially in younger women diagnosed before menopause. Risk factors and mechanisms for depression in this population are relatively unexplored. In 163 young BCS, vasomotor symptoms were significantly associated with higher depressive symptoms (β = 0.26, p = 0.001) and 64 % of the total effect was mediated through sleep disturbance (beta for specific indirect effect = 1.296, 95 % CI 0.591-2.212). Treatments reducing vasomotor symptoms might alleviate sleep disturbance and depression in this population. 
25595977	Human African trypanosomiasis or sleeping sickness is a severe, neglected tropical disease caused by the extracellular parasite Trypanosoma brucei. The disease, which leads to chronic neuroinflammation, is characterized by sleep and wake disturbances, documented also in rodent models. In rats and mice infected with Trypanosoma brucei brucei, we here tested the hypothesis that the disease could target neurons of the lateral hypothalamus (LH) containing orexin (OX)-A or melanin-concentrating hormone (MCH), implicated in sleep/wake regulation. In the cerebrospinal fluid of infected rats, the OX-A level was significantly decreased early after parasite neuroinvasion, and returned to the control level at an advanced disease stage. The number of immunohistochemically characterized OX-A and MCH neurons decreased significantly in infected rats during disease progression and in infected mice at an advanced disease stage. A marked reduction of the complexity of dendritic arborizations of OX-A neurons was documented in infected mice. The evaluation of NeuN-immunoreactive neurons did not reveal significant neuronal loss in the LH of infected mice, thus suggesting a potential selective vulnerability of OX-A and MCH neurons. Immunophenotyping and quantitative analysis showed in infected mice marked activation of microglial cells surrounding OX-A neurons. Day/night oscillation of c-Fos baseline expression was used as marker of OX-A neuron activity in mice. In control animals Fos was expressed in a higher proportion of OX-A neurons in the night (activity) phase than in the day (rest) phase. Interestingly, in infected mice the diurnal spontaneous Fos oscillation was reversed, with a proportion of OX-A/Fos neurons significantly higher at daytime than at nighttime. Altogether the findings reveal a progressive decrease of OX-A and MCH neurons and dysregulation of OX-A neuron diurnal activity in rodent models of sleeping sickness. The data point to the involvement of these peptidergic neurons in the pathogenesis of sleep/wake alterations in the disease and to their vulnerability to inflammatory signaling. 
25595299	Untreated caries in young children can result in a referral for extraction in hospital under general anaesthetic (GA). This study aims to explore the impact of caries during the ensuing wait for GA on children resident in the North West of England.The study involved 456 respondents referred to six hospitals in the Northwest of England. Over a two-month period each of these children/ families completed a questionnaire and gave permission to access their referral and consultation notes.	Children (6.78 years old: 1.50 to 16.42) had on average five teeth extracted (ranging from one to a full clearance, with all teeth removed). Sixty seven per cent of parents reported their child had been in pain, 26% reported schools days being missed and 38% having sleepless nights. The average time from referral to operation was 137 days. Results indicated that children could be in discomfort during their wait, as pain was experienced, on average, 14 days before the operation. Wait time significantly predicated the number of sleepless nights b = .004, t(340) = 2.276, p = .023.	It is clear that pain, sleepless nights and missed school are a feature during a wait for dental GA and can be exacerbated by an extended wait. These data support the need for not only effective prevention of caries within primary care to reduce wait times and experience of GA but also effective management of pain and infection during a prolonged wait for treatment.	
25595147	Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increased in patients as compared to controls (8.3 ± 1.1 h versus 7.1 ± 0.8 h, P < 0.0001). Objective daytime sleepiness was found in 57% of trauma patients and 19% of healthy subjects, and the average sleep latency in patients was reduced to 8.7 ± 4.6 min (12.1 ± 4.7 min in controls, P = 0.0009). Patients, but not controls, markedly underestimated both excessive sleep need and excessive daytime sleepiness when assessed only by subjective means, emphasizing the unreliability of self-assessment of increased sleep propensity in traumatic brain injury patients. At polysomnography, slow wave sleep after traumatic brain injury was more consolidated. The most important risk factor for developing increased sleep need after traumatic brain injury was the presence of an intracranial haemorrhage. In conclusion, we provide controlled and objective evidence for a direct relation between sleep-wake disturbances and traumatic brain injury, and for clinically significant underestimation of post-traumatic sleep-wake disturbances by trauma patients. 
25594527	Recurrent apnea is common in preterm infants with consequent episodes of loss of effective breathing and the bronchodilator theophylline prevents apnea and reduces the number of apneic attacks. This drug also reduces hypoxaemic episodes. Theophylline acts on the lungs, kidneys and brain. Theophylline inhibits solute reabsorption in various segments of the nephron and a marked diuresis which occurs immediately after the administration of theophylline. This drug ameliorates kidney dysfunction and prophylaxis given early after birth, preventing vasomotor nephropathy. Theophylline reduces brain activity and reduces the spontaneous activity transients and alters the sleep-wake state in pre-term infants. Theophylline is extensively metabolized in premature infants and its major metabolic product is caffeine. The demethylation pathway occurring predominantly in adults is substituted by N-methylation to caffeine in premature infants. The halflife of theophylline is 5-fold longer in neonates than in adults and reaches the adult value at the age of 55 weeks. Theophylline may be administered trans-cutaneously by applying this drug to the back or abdomen of the infants and the mean fractional absorbance at 30 hours is 0.25. Theophylline is present in saliva and the concentration of this drug in saliva is similar to that in plasma, saliva may be used to monitor theophylline concentration. In conclusion, theophylline is a useful drug to treat apnea and ameliorate kidney dysfunction. 
25592161	Recent research with small non-clinical and clinical samples suggests a positive association between attachment insecurity and sleep disturbances. The present study extends this line of research by exploring this relationship in a large sample of the U.S. population and by statistically adjusting for health conditions and psychiatric disorders as potential confounds.The data used were from the National Comorbidity Survey Replication (N=5692). The main interview consisted of the Composite International Diagnostic Interview used to assess psychiatric diagnoses. Ratings of three adult attachment styles (viz., secure, avoidant, and anxious) were obtained along with self-reports of health conditions and four sleep disturbances (viz., difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, and daytime sleepiness).	Bivariate logistic regression analyses indicated that ratings of secure attachment were negatively associated with each sleep disturbance and ratings of insecure attachment were positively associated with each sleep disturbance. Multivariate logistic regression analyses were used to examine associations between the attachment ratings and sleep disturbances while statistically controlling for sociodemographic variables, the presence of a health condition, and psychiatric disorders (viz., depressive disorders, bipolar disorders, anxiety disorders, alcohol/substance disorders, and attention deficit disorder). With one exception, the insecure attachment ratings continued to be positively associated with sleep disturbances.	The findings demonstrate that attachment insecurity is related to sleep disturbances independent of health conditions and concurrent psychiatric disorders. Research aimed at delineating the mechanisms responsible for these associations is warranted.	
25591633	To study chronobiological characteristics of ischemic stroke (II) and post stroke cognitive impairment (CI).We examined 80 patients with acute ischemic stroke. The cognitive status, sleep quality, chronobiological parameters and night urinary level of 6-sulfatoxymelatonin were assessed. The clinical observation of the efficacy of melaxen treatment in intensive care unit was performed.	The results of the study indicate the significance of social and environmental factors which determine the sleep-wake behavior in the development of pineal dysfunction. The pineal dysfunction probably underlies the development of stroke and accompanied neurodegenerative process.	The use of melaxen in hyperacute stroke was associated with better recovery of circadian rhythms and rehabilitation results.	
25591569	Sleep/wake disturbances in patients with amyotrophic lateral sclerosis (ALS) are well-documented, however, no animal or mechanistic studies on these disturbances exist. Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation, and may play an important role in sleep disturbances in ALS. In this study, we used SOD1-G93A transgenic mice as an ALS mouse model to investigate the sleep/wake disturbances and their possible mechanisms in ALS.Electroencephalogram/electromyogram recordings were performed in SOD1-G93A transgenic mice and their littermate control mice at the ages of 90 and 120 days, and the samples obtained from these groups were subjected to quantitative reverse transcriptase-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay.	For the first time in SOD1-G93A transgenic mice, we observed significantly increased wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin A and B) at both 90 and 120 days. Correlation analysis confirmed moderate to high correlations between sleep/wake time (total sleep time, wakefulness time, rapid eye movement [REM] sleep time, non-REM sleep time, and deep sleep time) and increase in orexins (prepro-orexin, orexin A and B).	Sleep/wake disturbances occur before disease onset in this ALS mouse model. Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS. Further studies are required to elucidate the underlying mechanisms in the future.	
25591476	Sleep is a homeostatically regulated behavior and sleep loss evokes a proportional increase in sleep time and delta slow wave activity. Glutamate and pharmacological modulation of the metabotropic glutamate receptors (mGluR) signaling have been implicated in the organization of vigilance states. Here, the role of the mGluR5 on homeostatic regulation of sleep-wake cycle and electroencephalographic (EEG) activity was examined in mGluR5 (-/-) mice. We first characterized the sleep-wake EEG phenotype in mGluR5 (-/-) and wild-type (WT) littermates mice by continuous recording for 72h of EEG, body temperature (BT) and locomotor activity (LMA). Next, we investigated the influence of sleep deprivation on the recovery sleep and EEG slow wave activity (1-4Hz) during NREM sleep to assess whether mGluR5 deletion affects the sleep homeostasis process. Like the control animals, mGluR5 (-/-) mice exhibited a clear-cut circadian sleep-wake architecture, however they showed reduced REM sleep time during the light phase with shorter REM sleep bouts and reduced state transitions in the NREM sleep-REM sleep cycle during the first and last 24h of the spontaneous 72h recording period. In addition, mGluR5 (-/-) mice had decreased slow EEG delta power during NREM sleep and enhanced LMA associated with elevated BT during the dark phase. Moreover, mGluR5 (-/-) mice exhibited reduced slow wave activity and sleep drive after sleep deprivation, indicating altered sleep homeostatic processes. The findings strongly indicate that mGluR5 is involved in shaping the stability of NREM sleep-REM sleep state transitions, NREM slow wave activity and homeostatic response to sleep loss. 
25591116	This study aimed to identify predictors of changes in diurnal cortisol patterns during the 8-month follow up period for young breast cancer survivors. Among the potential predictors were tumor size, lymph node metastasis, changes in sleep problems, habitual time of awakening and bedtime, physical activity levels, body mass index (BMI), and depressive levels across 8 months.The participants were 62 breast cancer women who were aged 40 years and below, and had completed active breast cancer treatment. The longitudinal data were collected at four points: baseline assessment (T0) and three follow-ups after baseline: T1 (in the 2nd month), T2 (in the 5th month), and T3 (in the 8th month). The participants collected their salivary cortisol at home at six time points: upon waking, 30 and 45min after waking, and at 1200h, 1700h, and 2100h. They also completed several questionnaires: the Medical Outcomes Study Sleep scale; the Beck Depression Inventory-II, physical activity levels on a 10-point scale, time of going to bed, time of awakening, and total sleep hours.	This study found that the main predictors of changes toward flatter diurnal cortisol patterns during the 8-month follow ups were greater tumor sizes, increases of BMI scores, and habitually later times of awakening.	While greater tumor sizes represent biological vulnerability of disruption of cortisol circadian rhythm, maintaining an appropriate BMI and good sleep habits could be a protective factor for normal cortisol regulation, which likely helps to reduce early mortality in young breast cancer survivors.	
25591044	To investigate the presence of sleep problems and their reaction to CBT in pediatric obsessive compulsive disorder (OCD). Moreover, we investigated whether sleep problems predict the outcome of CBT on OCD-symptoms.269 children and adolescents, age 7-17 years, with DSM-IV primary OCD that took part in the first step of a stepwise treatment trial, were assessed with regard to both individual sleep problems and a sleep composite score (SCS) using the Child Behavior Checklist (CBCL). Their OCD symptoms were rated using the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS).	We found elevated symptoms of sleep deprivation and nightmares before treatment. However most sleep problems (e.g. nightmares (p=.03), too little sleep (p<.001), trouble sleeping (p<.001) and parasomnias p=.03)) as well as being over-tired (p<.001) reduced during CBT treatment. Co-morbidities had no effect on the reduction of SCS. Moreover, elevated levels of sleep problems using the SCS (p<.001), as well as any sleep problem at baseline (p<.001) predicted less effect of CBT on the OCD symptoms.	Sleep problems in paediatric OCD are frequent and interfere with treatment outcome. They need to be assessed using better methods in future trials. Moreover, lack of resolution of sleep problems need to be recognized and treated as it seems probable that continued sleep problems may have a negative impact on CBT efficacy.	
25590906	To investigate and correlate the sleep pattern and quality of life in individuals with cerebral palsy (CP) compared to healthy controls.Seventy-eight subjects (aged 4-18 years, both genders) comprised two groups: CP, composed of 43 individuals with CP, and control, composed of 35 individuals without neurodevelopmental disorders. General Sleep Habits Questionnaire, Sleep Disturbance Scale for Children, sleep diary, Child Health Questionnaire, and Children's Quality of Life Scale were used.	This study identified that 60.5% individuals with CP had sleep disorders. The respiratory disorders (25.6%) and the sleep hyperhidrosis (34.9%) were the most common disturbances in the group with CP. Moreover, 23.2% individuals of the group with CP reported awaking in the middle of the night and 37.2% of them snore, both percentages were higher than those in the control group. The sleep diary showed that individuals in the group with CP spend more time to initiate sleep (around 21 minutes). The group with CP also showed deficits in all parameters analyzed by the Child Health Questionnaire, except in family activity and the sleep-wake pattern, and quality of life showed negative correlation in several respects.	The altered pattern of sleep in individuals with CP directly affects their physical and emotional well-being.	
25590417	Although eye movements are a highly valuable variable in attempts to precisely identify different periods of the sleep-wake cycle, their indirect measurement by electrooculography is not good enough. The present article describes an accurate and portable scleral search coil that allows the detection of tonic and phasic characteristics of eye movements in free-moving animals. Six adult Wistar rats were prepared for chronic recording of electroencephalography, electromyography and eye movements using the scleral search coil technique. We developed a miniature magnetic field generator made with two coils, consisting of 35 turns and 15 mm diameter of insulated 0.2 mm cooper wire, mounted in a frame of carbon fibre. This portable scleral search coil was fixed on the head of the animal, with each magnetic coil parallel to the eye coil and at 5 mm from each eye. Eye movements detected by the portable scleral search coil were compared with those measured by a commercial scleral search coil requiring immobilizing the head of the animal. No qualitative differences were found between the two scleral search coil systems in their capabilities to detect eye movements. This innovative portable scleral search coil system is an essential tool to detect slow changes in eye position and miniature rapid eye movements during sleep. The portable scleral search coil is much more suitable for detecting eye movements than any previously available system because of its precision and simplicity, and because it does not require immobilization of the animal's head. 

25588355	Sleep disturbance and cognitive impairment are correlated in non-diseased populations, but their association in Parkinson's disease (PD) is uncertain. Prior studies examining measures of cognition in relation to sleep have used either self-report or actigraphically measured sleep and have produced conflicting findings.In this descriptive study, we correlated measurements of sleep in PD patients derived from the gold-standard measurement, in-lab polysomnography, with an extensive battery of cognitive measures. We hypothesized that poorer sleep would be related to relatively more impaired cognition.	Idiopathic PD patients (n = 34) completed a cognitive battery encompassing three broad domains (executive function, immediate memory and delayed memory), and underwent PSG for two nights. Scores for each domain from individual cognitive measures were converted to z-scores and then averaged to produce a composite score. We used second night PSG data and quantified measures of sleep architecture, sleep continuity, sleep apnea and nocturnal movement (periodic leg movements, PLMS).	Lower executive function was associated with higher PLMS after controlling for chronological age, mini-mental state examination scores, and UPDRS motor subscale scores. These results were independent from psychomotor speed. There was a marginally significant positive correlation between the proportion of time spent in REM and immediate recall ability. Measures of sleep continuity and sleep apnea were unrelated to cognition in these patients.	PLMS, known to be a frequent feature of PSG-measured sleep in PD, may be an important correlate of impaired executive function in PD. Whether treating this disorder of sleep results in improvement in cognition remains to be determined.	
25587746	Sleep disturbances are a common symptom following concussions to include athletic concussion.This review applies literature on sleep following traumatic brain injury and concussion to sport concussions and places these considerations in the context of sleep and athletic performance. It also includes a description of sleep abnormalities in sleep duration, quality and timing as well as recommended treatment approaches. Finally, it includes a brief discussion of emerging paradigms of sleep and concussion recovery.	
25586916	A marital status of divorced or separated, as opposed to married, predicts increased risk of health problems, but not for all persons. Focusing on one established health risk that has been linked with divorce--poor subjective sleep quality--the present cross-sectional study examined whether a history of physical intimate partner victimization (IPV) helps identify divorced women at potentially greater risk of health problems. Community midlife women with divorce histories, all of whom were free of current IPV, reported on their past month sleep quality and lifetime IPV. The predicted odds of poor sleep quality were significantly greater for women with, versus without, IPV histories. This held after adjusting for socioemotional, medical, or sociodemographic risks. A dose-response relationship between IPV chronicity and poor quality sleep was observed. IPV history may help identify divorced women at increased risk of poor quality sleep and, more broadly, poor health.
25585730	Yoga has been introduced at a care home to help residents sleep better and improve their posture and mobility. 
25585138	Sleep is considered to be a recovery process of prior wakefulness. Not only duration of the waking period affects sleep architecture and sleep EEG, the quality of wakefulness is also highly important. Studies in rats have shown that social defeat stress, in which experimental animals are attacked and defeated by a dominant conspecific, is followed by an acute increase in NREM sleep EEG slow wave activity (SWA). However, it is not known whether this effect is specific for the stress of social defeat or a result of the conflict per se. In the present experiment, we examined how sleep is affected in both the winners and losers of a social conflict. Sleep-wake patterns and sleep EEG were recorded in male wild-type Groningen rats that were subjected to 1h of social conflict in the middle of the light phase. All animals were confronted with a conspecific of similar aggression level and the conflict took place in a neutral arena where both individuals had an equal chance to either win or lose the conflict. NREM sleep SWA was significantly increased after the social conflict compared to baseline values and a gentle stimulation control condition. REM sleep was significantly suppressed in the first hours after the conflict. Winners and losers did not differ significantly in NREM sleep time, NREM sleep SWA and REM sleep time immediately after the conflict. Losers tended to have slightly more NREM sleep later in the recovery period. This study shows that in rats a social conflict with an unpredictable outcome has quantitatively and qualitatively largely similar acute effects on subsequent sleep in winners and losers. 
25584524	The case definitions for Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), ME, and CFS each include a disability criterion requiring substantial reductions in activity in order to meet diagnostic criteria. Difficulties have been encountered in defining and operationalizing the substantial reduction disability criterion within these various illness definitions. The present study sought to relate measures of past and current activities in several domains including the SF-36, an objective measure of activity (e.g., actigraphy), a self-reported quality of life scale, and measures of symptom severity. Results of the study revealed that current work activities had the highest number of significant associations with domains such as the SF-36 subscales, actigraphy, and symptom scores. As an example, higher self-reported levels of current work activity were associated with better health. This suggests that current work related activities may provide a useful domain for helping operationalize the construct of substantial reductions in activity. 
25581929	Maintaining adequate serum levels of vitamin D may be important for sleep duration and quality; however, these associations are not well understood. We examined whether levels of serum 25(OH)D are associated with objective measures of sleep in older men.Cross-sectional study within a large cohort of community-dwelling older men, the MrOS study.	Among 3,048 men age 68 years or older, we measured total serum vitamin D. Objective estimates of nightly total sleep time, sleep efficiency, and wake time after sleep onset (WASO) were obtained using wrist actigraphy worn for an average of 5 consecutive 24-h periods.	16.4% of this study population had low levels of vitamin D (< 20.3 ng/mL 25(OH)D). Lower serum vitamin D levels were associated with a higher odds of short (< 5 h) sleep duration, (odds ratio [OR] for the highest (≥ 40.06 ng/mL) versus lowest (< 20.3 ng/mL) quartile of 25(OH)D, 2.15; 95 % confidence interval (CI), 1.21-3.79; Ptrend = 0.004) as well as increased odds of actigraphy-measured sleep efficiency of less than 70% (OR, 1.45; 95% CI, 0.97-2.18; Ptrend = 0.004), after controlling for age, clinic, season, comorbidities, body mass index, and physical and cognitive function. Lower vitamin D levels were also associated with increased WASO in age-adjusted, but not multivariable adjusted models.	Among older men, low levels of total serum 25(OH)D are associated with poorer sleep including short sleep duration and lower sleep efficiency. These findings, if confirmed by others, suggest a potential role for vitamin D in maintaining healthy sleep.	

25581923	That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice.In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery.	Mouse sleep-recording facility.	Per2::Luciferase knock-in mice.	N/A.	Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls.	Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health.	
25581920	Coregulation of biological systems is a defining feature of normative attachment in close adult relationships. Sleep is a shared, intimate biological process between couples; however, sleep is usually examined at the individual level. We examined minute-by-minute concordance in couples' actigraphy-defined sleep-wake patterns, and how attachment style and marital satisfaction relate to concordance.Couples completed measures of avoidant and anxious attachment styles and relationship functioning and wore wrist actigraphs for 10 days. Minute-by-minute concordance of sleep and wake (i.e., the percentage of epochs in which both partners were asleep, or both were awake) was calculated for each sleep period. Mixed modeling was used to account for measurement occasions across time.	Percent concordance ranged from 53-88% and was not associated with couples' sleep quality or circadian preference. For wives, neither anxious nor avoidant attachment was associated with sleep-wake concordance. For husbands, anxious attachment style was associated with higher concordance, but was moderated by wives' marital satisfaction. High marital satisfaction in wives was associated with higher concordance, regardless of husbands' attachment style. In couples in which wives reported low satisfaction, concordance was higher when husbands had an anxious attachment style. Avoidant attachment style in husbands was not related to concordance.	Sleep concordance provides a unique measure of couples' cosleep and varies depending on attachment style and relationship satisfaction.	
25581916	To investigate the correlates of sleep disturbance and to assess escitalopram treatment effects of depression on sleep disturbance in patients with acute coronary syndrome (ACS).A cross-sectional study in patients with ACS within 2 w post-ACS, and a 24-w double-blind controlled trial of escitalopram against placebo for patients with ACS who have comorbid depressive disorders.	A university hospital in South Korea.	There were 1,152 patients with ACS who were consecutively recruited. Of 446 patients with comorbid depressive disorders, 300 were randomized to the trial.	Sleep disturbance was evaluated by the Leeds Sleep Evaluation Questionnaire. Demographic and clinical characteristics were assessed, including cardiovascular risk factors, current cardiac status, and depressive symptoms. Depressive symptoms were most strongly and consistently associated with sleep disturbance. In addition, older age, female sex, hypertension, and more severe ACS status were associated with certain aspects of sleep disturbance. Escitalopram was significantly superior to placebo for improving sleep disturbance over the 24-w treatment period. These effects were substantially explained by improvement in depressive symptoms.	Depression screening is indicated in patients with acute coronary syndrome with sleep disturbance. Successful treatment of depression has beneficial effects on sleep outcomes in these patients.	
25581914	Periodic breathing is sleep disordered breathing characterized by instability in the respiratory pattern that exhibits an oscillatory behavior. Periodic breathing is associated with increased mortality, and it is observed in a variety of situations, such as acute hypoxia, chronic heart failure, and damage to respiratory centers. The standard quantification for the diagnosis of sleep related breathing disorders is the apnea-hypopnea index (AHI), which measures the proportion of apneic/ hypopneic events during polysomnography. Determining the AHI is labor-intensive and requires the simultaneous recording of airflow and oxygen saturation. In this paper, we propose an automated, simple, and novel methodology for the detection and qualification of periodic breathing: the estimated amplitude modulation index (eAMI).Antarctic Cohort (3800 meters): 13 normal individuals. Sleep Clinic Cohort: 39 different patients suffering from diverse sleep-related pathologies.	When tested in a population with high levels of periodic breathing (Antarctic Cohort), eAMI was closely correlated with AHI (r = 0.95, P < 0.001). When tested in the clinical setting, the proposed method was able to detect portions of the signal in which subclinical periodic breathing was validated by an expert (n = 93; accuracy = 0.85). Average eAMI was also correlated with the loop gain for the combined clinical and Antarctica cohorts (r = 0.58, P < 0.001).	In terms of quantification and temporal resolution, the eAMI is able to estimate the strength of periodic breathing and the underlying loop gain at any given time within a record. The impaired prognosis associated with periodic breathing makes its automated detection and early diagnosis of clinical relevance.	
25581551	Hyperarousal and sleep disturbances are common, debilitating symptoms of post-traumatic stress disorder (PTSD). PTSD patients also exhibit abnormalities in quantitative electroencephalography (qEEG) power spectra during wake as well as rapid eye movement (REM) and non-REM (NREM) sleep. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for PTSD, provide modest remediation of the hyperarousal symptoms in PTSD patients, but have little to no effect on the sleep-wake architecture deficits. Development of novel therapeutics for these sleep-wake architecture deficits is limited by a lack of relevant animal models. Thus, the present study investigated whether single prolonged stress (SPS), a rodent model of traumatic stress, induces PTSD-like sleep-wake and qEEG spectral power abnormalities that correlate with changes in central serotonin (5-HT) and neuropeptide Y (NPY) signaling in rats. Rats were implanted with telemetric recording devices to continuously measure EEG before and after SPS treatment. A second cohort of rats was used to measure SPS-induced changes in plasma corticosterone, 5-HT utilization, and NPY expression in brain regions that comprise the neural fear circuitry. SPS caused sustained dysregulation of NREM and REM sleep, accompanied by state-dependent alterations in qEEG power spectra indicative of cortical hyperarousal. These changes corresponded with acute induction of the corticosterone receptor co-chaperone FK506-binding protein 51 and delayed reductions in 5-HT utilization and NPY expression in the amygdala. SPS represents a preclinical model of PTSD-related sleep-wake and qEEG disturbances with underlying alterations in neurotransmitter systems known to modulate both sleep-wake architecture and the neural fear circuitry. 
25581296	Sleep disturbances are common among older women; however, little is known about sleep experiences among chronic benzodiazepine users. The experience of sleep, sleep troubles, and management of sleep problems were explored through semistructured interviews with 12 women aged 65-92 who had used a benzodiazepine for three months or longer to treat a sleep disturbance. Themes that emerged from an interpretive phenomenological analysis included multiple reasons for sleep disruptions (health problems, mental disturbances, and sleeping arrangements), opposing effects of benzodiazepines on sleep (helps or does not work), and several supplemental sleep strategies (modification of the environment, distraction, and consumption). 
25580603	Several strategies have been found to be effective for the treatment of childhood behavioral sleep disorders. One which has yet to be evaluated is the Zurich 3-step concept, which combines basic notions of the two-process model of sleep regulation (introducing a regular rhythm and adjusting bedtime to sleep need) with behavioral strategies. This uncontrolled before-and-after study describes our concept and its step-wise approach, assesses changes in sleep-wake variables and behavior problems, and also examines associations between changes in sleep-wake variables and behavior problems.A total of 79 children with sleep problems (age range 6-47 months, 42% females) were included. Sleep problems were assessed by the Infant Sleep Questionnaire, sleep-wake variables by diary and actigraphy, and behavior problems of children ≥ 18 months by the Child Behavior Checklist.	A significant decrease in nocturnal wake duration (Cohen's d = -0.34) and a significant increase in the duration of the longest continuous nocturnal sleep period (Cohen's d = 0.19) were found from before to after intervention (on average 2.7 months, SD 1.5). The variability for sleep onset and end time decreased, and actigraphically measured circadian rest-activity cycle measures improved. Parent-reported internalizing and total behavior problems also decreased (Cohen's d = 0.66).	The findings of both objective and subjective assessment techniques suggest that the Zurich 3-step concept is effective. Thus, the intervention concept may be useful in clinical practice with sleep-disordered children.	
25580602	Heart attacks and motor vehicle crashes are the leading causes of death in US firefighters. Given that sleep disorders are an independent risk factor for both of these, we examined the prevalence of common sleep disorders in a national sample of firefighters and their association with adverse health and safety outcomes.Firefighters (n = 6,933) from 66 US fire departments were assessed for common sleep disorders using validated screening tools, as available. Firefighters were also surveyed about health and safety, and documentation was collected for reported motor vehicle crashes.	A total of 37.2% of firefighters screened positive for any sleep disorder including obstructive sleep apnea (OSA), 28.4%; insomnia, 6.0%; shift work disorder, 9.1%; and restless legs syndrome, 3.4%. Compared with those who did not screen positive, firefighters who screened positive for a sleep disorder were more likely to report a motor vehicle crash (adjusted odds ratio 2.00, 95% CI 1.29-3.12, p = 0.0021) and were more likely to self-report falling asleep while driving (2.41, 2.06-2.82, p < 0.0001). Firefighters who screened positive for a sleep disorder were more likely to report having cardiovascular disease (2.37, 1.54-3.66, p < 0.0001), diabetes (1.91, 1.31-2.81, p = 0.0009), depression (3.10, 2.49-3.85, p < 0.0001), and anxiety (3.81, 2.87-5.05, p < 0.0001), and to report poorer health status (p < 0.0001) than those who did not screen positive. Adverse health and safety associations persisted when OSA and non-OSA sleep disorders were examined separately.	Sleep disorders are prevalent in firefighters and are associated with increased risk of adverse health and safety outcomes. Future research is needed to assess the efficacy of occupational sleep disorders prevention, screening, and treatment programs in fire departments to reduce these safety and health risks.	

25576803	Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly associated with vigilance and sleep complaints. Because sleep is required for learning, plasticity and recovery, we here evaluated the bidirectional relationship between mTBI and sleep with two specific objectives: (1) Test that mTBI rapidly impairs sleep-wake architecture and the dynamics of the electrophysiological marker of sleep homeostasis (i.e., non-rapid eye movement sleep delta (1-4Hz) activity); (2) evaluate the impact of sleep loss following mTBI on the expression of plasticity markers that have been linked to sleep homeostasis and on genome-wide gene expression. A closed-head injury model was used to perform a 48h electrocorticographic (ECoG) recording in mice submitted to mTBI or Sham surgery. mTBI was found to immediately decrease the capacity to sustain long bouts of wakefulness as well as the amplitude of the time course of ECoG delta activity during wakefulness. Significant changes in ECoG spectral activity during wakefulness, non-rapid eye movement and rapid eye movement sleep were observed mainly on the second recorded day. A second experiment was performed to measure gene expression in the cerebral cortex and hippocampus after a mTBI followed either by two consecutive days of 6h sleep deprivation (SD) or of undisturbed behavior (quantitative PCR and next-generation sequencing). mTBI modified the expression of genes involved in immunity, inflammation and glial function (e.g., chemokines, glial markers) and SD changed that of genes linked to circadian rhythms, synaptic activity/neuronal plasticity, neuroprotection and cell death and survival. SD appeared to affect gene expression in the cerebral cortex more importantly after mTBI than Sham surgery including that of the astrocytic marker Gfap, which was proposed as a marker of clinical outcome after TBI. Interestingly, SD impacted the hippocampal expression of the plasticity elements Arc and EfnA3 only after mTBI. Overall, our findings reveal alterations in spectral signature across all vigilance states in the first days after mTBI, and show that sleep loss post-mTBI reprograms the transcriptome in a brain area-specific manner and in a way that could be deleterious to brain recovery. 
25575625	Histaminergic neurons are exclusively located in the hypothalamic tuberomamillary nucleus, from where they project to many brain areas. The histaminergic system is involved in basic physiological functions, such as the sleep-wake cycle, energy and endocrine homeostasis, sensory and motor functions, cognition, and attention, which are all severely affected in neuropsychiatric disorders. Here, we present recent postmortem findings on the alterations in this system in neuropsychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), depression, and narcolepsy. In addition, we highlight the need to validate animal models for these diseases and also for Tourette's syndrome (TS) in relation to alterations in the histaminergic system. Moreover, we discuss the potential for, and concerns over, the use of novel histamine 3 receptor (H3R) antagonists/inverse agonists as treatment for such disorders. 
25575370	Assessment of sleep only by sleep duration is not sufficient. This cross-sectional study aimed to investigate the potential association of self-reported global sleep status, which contained both qualitative and quantitative aspects, with hypertension prevalence in Chinese adults.A total of 5461 subjects (4076 of them were male) were enrolled in the current study and were divided into two groups with the age of 45 years as the cut-off value. Sleep status of all subjects was assessed using the standard Pittsburgh Sleep Quality Index (PSQI). Hypertension was defined as blood pressure ≥140/90 mmHg in the current study.	After adjusting for basic cardiovascular characteristics, the results of multivariate logistic regression indicated that sleep status, which was defined as the additive measurement of sleep duration and sleep quality, was associated with hypertension prevalence in males of both age groups (odds ratio (OR) = 1.11, 95% confidence interval (CI), 1.07-1.15, p < 0.05; OR = 1.12, 95% CI, 1.08-1.15, p < 0.05) and in females aged ≤45years (OR = 1.10, 95% CI, 1.02-1.18, p < 0.05). As one component of PSQI, short sleep duration was associated with hypertension prevalence only in Chinese male subjects, but this association disappeared after the further adjustment of the other components of PSQI that measured the qualitative aspect of sleep.	Association between sleep status and hypertension prevalence in Chinese adults varied by age and sex. Sleep should be measured qualitatively and quantitatively when investigating its association with hypertension.	
25574827	Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza. 
25572670	Sleep disorder and poor sleep quality are common in chronic hemodialysis (HD) patients. They have been claimed as a cause of morbidity and mortality. The relationship between the degree of sleepiness and survival has not been studied. We studied the degree of sleepiness in 1,252 adult HD patients (age ≥20 years) recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS III), using the Japanese version of the Epworth Sleepiness Scale (JESS) questionnaire. Demographic data were presented for three subgroups: low, intermediate, and high JESS score. Cox proportional hazard regression analysis was performed to estimate the independent effect of several variables on survival. The hazard ratio for mortality was 2.312 (95% CI 1.267-4.220; p = 0.006) for those with a high JESS score (vs. those with a low JESS score) after adjusting for age, vintage (length of time on HD), sex, diabetes, body mass index, cardiovascular disease, HD treatment regimen (time, frequency, and single-pool Kt/V), laboratory data (serum albumin, creatinine, and total cholesterol), and medication (antihypertensive drugs, erythropoietin, vitamin D, and phosphate binders). Patients ≥70 years of age with comorbid conditions (congestive heart failure, stroke, and diabetes) showed a significantly higher JESS score (≥16). The JESS score did not show interaction by age. Results showed that the degree of sleepiness is related to survival in Japanese HD patients, particularly in elderly patients.
25572038	Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.
25571126	A number of automatic sleep scoring algorithms have been published in the last few years. These can potentially help save time and reduce costs in sleep monitoring. However, the use of both R&K and AASM classification, different databases and varying performance metrics makes it extremely difficult to compare these algorithms. In this paper, we describe some readily available polysomnography databases and propose a set of recommendations and performance metrics to promote uniform testing and direct comparison of different algorithms. We use two different polysomnography databases with a simple sleep staging algorithm to demonstrate the usage of all recommendations and presentation of performance results. We also illustrate how seemingly similar results using two different databases can have contrasting accuracies in different sleep stages. Finally, we show how selection of different training and test subjects from the same database can alter the final performance results. 
25570112	This paper presents the comparison of sleep-wake classification using electroencephalogram (EEG) and multi-modal data from a wrist wearable sensor. We collected physiological data while participants were in bed: EEG, skin conductance (SC), skin temperature (ST), and acceleration (ACC) data, from 15 college students, computed the features and compared the intra-/inter-subject classification results. As results, EEG features showed 83% while features from a wrist wearable sensor showed 74% and the combination of ACC and ST played more important roles in sleep/wake classification. 
25570080	Little is understood about the sleep quality of children with autism and other developmental disabilities. Conventional sensors and instrumentation for objective sleep quality assessment, such as those used in polysomnography, are highly obtrusive and not well-suited to this patient population. This paper presents a set of sensors and instrumentation for unobtrusive measurement of physiological and behavioral parameters indicative of sleep quality. Specifically, load cells, an electromechanical film, and thermocouples are used to measure respiratory rate, pulse rate, and physical activity of a subject lying on a bed. The sensor suite is being developed to monitor sleep quality of children at Heartspring, a residential and educational facility in Wichita, KS that serves children with severe developmental disabilities. These technologies have the potential to provide objective sleep quality assessment for children in their home environment. 
25569089	Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine's antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression. 
25568076	Sleep disorders are highly prevalent during late pregnancy and can impose adverse effects, such as preeclampsia and diabetes. However, the consequences of sleep fragmentation (SF) on offspring metabolism and epigenomic signatures are unclear. We report that physical activity during early life, but not later, reversed the increased body weight, altered glucose and lipid homeostasis, and increased visceral adipose tissue in offspring of mice subjected to gestational SF (SFo). The reversibility of this phenotype may reflect epigenetic mechanisms induced by SF during gestation. Accordingly, we found that the metabolic master switch Foxo1 was epigenetically misregulated in SFo livers in a temporally regulated fashion. Temporal Foxo1 analysis and its gluconeogenetic targets revealed that the epigenetic abnormalities of Foxo1 precede the metabolic syndrome phenotype. Importantly, regular physical activity early, but not later in life, reversed Foxo1 epigenetic misregulation and altered the metabolic phenotype in gestationally SF-exposed offspring. Thus, we have identified a restricted postnatal period during which lifestyle interventions may reverse the Foxo1 epigenetically mediated risk for metabolic dysfunction later in the life, as induced by gestational sleep disorders.
25567819	The purpose of this study was to elucidate the effects of injection at trigger points on pain and sleep disturbance in patients with nocturnal calf cramps (NCCs).Patients with NCCs that occurred at least once per week and who had myofascial trigger points (MTrPs) on the gastrocnemius muscles were enrolled in the study for 9 months. At the first visit (T0), we measured the intensity of NCC pain on an 11-point numeric rating scale, recorded the frequency of NCCs, and calculated the Insomnia Severity Index (ISI). We then checked for MTrPs on the gastrocnemius muscles and injected 1-2 mL of 0.25% lidocaine into each of the trigger points. At 1 (T1), 2 (T2), and 4 (T3) weeks after the first visit, we repeated the process performed at T0.	Twelve patients completed the treatment schedule and attended the follow-up visits. Mean values of the numeric rating scale pain score, frequency of cramps, and ISI declined significantly at T1, T2, and T3 compared with baseline (all P < .01). Of 12 patients, 10 had clinical insomnia before treatment, and this number decreased significantly to 3 patients at T2 and 1 patient at T3 (P = .012 and P = .001, respectively).	These preliminary data show that injection at MTrPs in patients with NCCs not only alleviated pain and reduced the frequency of cramps but also lessened the severity of insomnia as measured by the ISI. A larger randomized controlled trial is needed to confirm these findings and determine whether the effect lasts over the long term.	
25567147	To compare the risk factors on the functional dependence between the oldest-old and elderly veterans.A cross-sectional survey was conducted among veterans ( ≥ 60 years of age) lived in 44 veterans' communities in Beijing. The socio-demographic information and history of non-communicable chronic diseases were collected via face-to-face interviews, and the functional status was assessed by the 20-item version of the Activities of Daily Living Scale.	The risk factors associated with increased hazard of the functional dependence in the oldest-old ( ≥ 80 years old) were cognitive impairment, extrapyramidal diseases, cerebral infarction, transient ischemic attack, sleep disorders, hypnotics, osteoarthrosis, hypertension and fall with the odds ratio (OR) of 1.241-2.962 (all P < 0.05). Stroke, depression, cognitive impairment, extrapyramidal diseases, sleep disorders, hypnotics, fall, cardiovascular diseases, osteoarthrosis and hearing loss were the risk factors for that in the elderly subjects (aged 60-79 years). The OR was 1.232-5.790 (all P < 0.05). However, avocational activities such as social activity, physical exercise, photography, reading and games, decreased the risk of functional dependence in both the oldest-old and elderly people.	Neuropsychiatric disorders are the leading causes contributed to the functional dependence among oldest-old and elderly population. Neurodegenerative diseases in the oldest-old, stroke and depression in elderly people should be the priorities in ameliorating disability. Healthy lifestyle and avocational activities could improve the functional status of the oldest-old and elderly population.	
25566182	To determine the off-shift sleep strategies of bi-ethnic night-shift nurses, the relationship between these sleep strategies and adaptation to shift work, and identify the participant-level characteristics associated with a given sleep strategy.African-American and non-Hispanic White female, night-shift nurses from an academic hospital were recruited to complete a survey on sleep-wake patterns (n = 213). Participants completed the standard shiftwork index and the biological clocks questionnaire to determine sleep strategies and adaptation to night-shift work. In addition, chronotype was determined quantitatively with a modified version of the Munich ChronoType Questionnaire. Most participants worked ~3 consecutive 12-h night-shifts followed by several days off.	Five sleep strategies used on days off were identified: (a) night stay, (b) nap proxy, (c) switch sleeper, (d) no sleep, and (e) incomplete switcher. Nap proxy and no sleep types were associated with poorer adaptation to night-shift work. The switch sleeper and incomplete switcher types were identified as more adaptive strategies that were associated with less sleep disturbance, a later chronotype, and less cardiovascular problems.	Behavioral sleep strategies are related to adaptation to a typical night-shift schedule among hospital nurses. Nurses are crucial to the safety and well-being of their patients. Therefore, adoption of more adaptive sleep strategies may reduce sleep/wake dysregulation in this population, and improve cardiovascular outcomes.	
25566173	Sleep-wake disturbances are common in hospitalized patients but few studies have assessed them systematically. The aim of the present study was to assess sleep quality in a group of medical inpatients, in relation to environmental factors, and the switch to daylight-saving time.Between March and April 2013, 118 consecutive inpatients were screened and 99 (76 ± 11 years; hospitalization: 8 ± 7 days) enrolled. They slept in double or quadruple rooms, facing South/South-East, and were qualified as sleeping near/far from the window. They underwent daily sleep assessment by standard questionnaires/diaries. Illuminance was measured by a luxmeter at each patient's eye-level, four times per day. Noise was measured at the same times by a phonometer. Information was recorded on room lighting, position of the rolling shutters and number/type of extra people in the room.	Compliance with sleep-wake assessment was poor, with a range of completion of 2-59%, depending on the questionnaires. Reported sleep quality was sufficient and sleep timing dictated by hospital routine; 33% of the patients reported one/more sleepless nights. Illuminance was generally low, and rolling shutters half-way down for most of the 24 h. Patients who slept near the window were exposed to more light in the morning (i.e., 222 ± 72 vs. 174 ± 85 lux, p < 0.05 before the switch; 198 ± 72 vs. 141 ± 137 lux, p < 0.01 after the switch) and tended to sleep better (7.3 ± 1.8 vs. 5.8 ± 2.4 on a 1-10 scale, before the switch, p < 0.05; 7.7 ± 2.3 vs. 6.6 ± 1.8, n.s. after the switch). Noise levels were higher than recommended for care units but substantially comparable across times/room types. No significant differences were observed in sleep parameters before/after the switch.	Medical wards appear to be noisy environments, in which limited attention is paid to light/dark hygiene. An association was observed between sleep quality and bed position/light exposure, which is worthy of further study.	


25564830	To explore the relationships of perceived stress and depressive symptoms to sleep problems, testing for mediation by adaptive and maladaptive coping strategies.Alternative high school students (N = 1676) completed self-report surveys. Cross-sectional data were analyzed via Preacher and Hayes' procedures for multiple mediation.	The positive relationship between depressive symptoms and sleep problems was mediated partially by anger coping (positively related to sleep problems). The positive relationship between perceived stress and sleep problems was not mediated by coping strategies.	Findings provide information on psychological factors that may lead to poor sleep outcomes, and are useful for developing health promotion interventions to impact lifelong health behaviors.	

25561130	Introducción: Existe escasa información sobre la evaluación de la constipación en los sujetos de edad avanzada. Dentro de la variedad de factores causantes, usualmente no es tomado en cuenta un factor que también podría incidir sobre la presencia de constipación: las horas de sueño. Objetivos: Determinar la asociación entre horas de sueño durante la semana y fin de semana con el estreñimiento en adultos mayores (AM). Materiales y métodos: Se evaluó mediante diversas encuestas validadas la calidad de sueño, consistencia de las heces, actividad física (AF) e ingesta de fibra dietaria en 424 AM sanos de ambos sexos, autónomos de la ciudad de Santiago. Resultados: La mitad de los participantes refirieron tener deposiciones anormales (estreñimiento y diarrea). Los sujetos que presentaron estreñimiento tenían menor AF y mayor dificultad para conciliar el sueño que los sujetos con deposiciones normales. Los AM constipados presentaron una mayor cantidad de sueño durante la semana y fin de semana, que los sujetos con una evacuación normal (9,4 ± 1,6 vs 8,8 ± 1,8 horas; p=0,013). Los AM constipados duermen significativamente más que los AM con evacuación normal (9,7 ± 1,5 vs 9,2 ± 1,8; p=0,024). No se encontraron diferencias en el EN y el consumo de fibra entre pacientes con distintas consistencias. Conclusiones: Existe una asociación entre las horas de sueño que duermen los AM y la consistencia de sus deposiciones. Resultaría de interés evaluar a largo plazo si el mejoramiento de uno de estos factores podría incidir positivamente sobre el otro.There is scarce information about constipation in elderly subjects. Among the variety of factors causing constipation, the sleeping hours are a factor usually not taken into account.	To determine the association between hours of sleep during the week and weekend, with constipation in older adults.	Sleep quality, stool consistency, physical activity (PA) and dietary fiber intake was assessed using various validated surveys in 424 healthy autonomous elderly men and women, living in Santiago, Chile.	Half of the participants reported having abnormal stools (constipation and diarrhea). Subjects who had constipation had lower PA and greater difficulty falling asleep than subjects with normal bowel movements. The elderly participants with constipation had a higher amount of sleep during the week and weekend, that subjects with normal bowel movements (9.4 ± 1.6 vs 8.8 ± 1.8 hours, p = 0.013). The constipated subjects slept significantly more than those with normal evacuation (9.7 ± 1.5 vs 9.2 ± 1.8, p = 0.024). No differences in the nutritional status and fiber intake among patients with different consistencies were found.	There is an association between sleep and the consistency of the stools in elderly patients. It would be interesting to evaluate whether long-term improvement of these factors could have a positive impact on the other.	
25560052	Antidepressant drug use increases worldwide. It is pivotal to closely monitor the use of antidepressants and to determine in what subpopulations the rise is most substantial. In a Dutch primary care database, we aimed to investigate the (sex- and age-specific) prevalence and incidence of antidepressant prescription and to monitor the indication of incident prescriptions over a 17-year period (1996-2012).This study, embedded in the Integrated Primary Care Information database, included all patients aged 10 years or older. Per calendar year, prevalence and incidence of antidepressant drug prescription were calculated by drug class (tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and others), sex, and age. The indication of incident prescriptions (e.g., depression, anxiety, sleep disorders, and neuropathic pain) was determined based on the International Classification of Primary Care codes.	In total, 1.49 million patients were included. For all antidepressants together, the prevalence increased over time. However, incident prescription of specific SSRIs decreased from 2000 onward. During the study period, incidence and prevalence were higher in older and female patients. The increase in prevalence and the decrease in incidence were more pronounced in females than that in males. Furthermore, antidepressants were increasingly prescribed for indications such as neuropathic pain and sleep disorders.	In Dutch primary care, prevalent prescription of antidepressants continued to increase, but incident prescription of particular SSRIs decreased from 2000 onward. In later years, antidepressants were less frequently prescribed for depression-related indications in incident users.	
25558741	Disruption in police officers. In recent years there has been a widespread growth in services, available regardless of time or day organization (24/7 service) and a diffuse increase in their use, both in work and private lives, generally ignoring the importance of a regular sleep organization. Police officers - often need to work extended shifts and long hours under highly stressful conditions, which results in reduced levels of safety and operational effectiveness. In numerous studies, perceived stress has been found to correlate with both subjective and objective disturbances in sleep. Consequently, excessive daytime sleepiness is one of the most frequent health and safety hazards that police officers have to deal with. Sleep deprivation affects performance outcomes through a wide range of cognitive domains. Sleepiness and fatigue, caused by sleep loss, extended work and wakefulness, circadian misalignment and sleep disorders are major causes of workplace human errors, incidents, and accidents. Therefore, prevention of sleep loss, high levels of stress and fatigue is a key factor to consider when assessing emergency intervention. In order to combat fatigue and sleepiness, a 30-90 minutes nap before night shift could be a viable option.
25558590	Sleep disorders are common in pregnancy. Several hormonal and physiological changes have been shown to affect the quality of sleep. Sleep disorders have been related to various pregnancy complications, e.g. pre-eclampsia. In particular, sleep apnea is more common among women who develop hypertension in pregnancy or pre-eclampsia. Compared with control patients, snoring is similarly more often apparent in women who will have pre-eclampsia manifested. Hence, the relationship between sleep disorders and pre-eclampsia warrants investigation. CPAP treatment has been proven to be effective in sleep apnea, but also in lowering blood pressure. CPAP may be useful also in the prevention and treatment of pre-eclampsia.
25558587	We report a 21-year-old male patient with dentatorubral-pallidoluysian atrophy (DRPLA) showing progressive myoclonus epilepsy (PME), who responded to levetiracetam (LEV) at an initial dose of 1,000 mg/day. The patient developed epilepsy at the age of 10 years, and also showed intellectual regression. Various antiepileptic drugs showed no effects on generalized tonic seizures, tonic-clonic seizures, and myoclonus. Addition of LEV (1,000 mg/day) led to the reduction of myoclonus and tonic-clonic seizures, and improved the EEG and sleep-wake rhythm. He had a better appetite and gain weight. It is suggested that LEV may improve quality of life in patients with DRPLA, in addition to reducing the frequency of epileptic seizures.
25557603	This study was the first to explore whether individuals with fibromyalgia (FM) have different cognitive alterations (i.e., in alertness, orienting, and executive control) depending on their sex. We also analysed possible gender differences in the relationships between cognitive functioning and some of the main symptoms of FM.Cross-sectional study.	Two clinical groups with FM (n = 58 women and n = 20 men) and two healthy control groups (n = 21 women and n = 27 men) aged between 30 and 60 years old participated in this study. Pain intensity, sleep disturbance, depression, anxiety, pain catastrophizing, and daily functioning were evaluated with self-report measures. Attentional function was assessed with the ANT-I task (Attentional Network Test-Interactions).	Mixed ANOVAs showed impairment in vigilance and executive control in both male and female patients with FM compared with controls. Control men were faster than control women, but FM eliminated sex differences. In addition, attention deficit was associated with worse daily functioning in women but not in men with FM. Emotional distress and sleep disruption seemed to contribute differently to these cognitive alterations in both sexes.	Therapy strategies aimed at reducing emotional distress and sleep disruption are likely to improve cognitive function by enhancing vigilance. Therapies aimed at reducing emotional distress seem to improve attentional function more in women than in men; those aimed at improving sleep quality are likely to reduce a vigilance/alertness deficit in women and executive problems in men.	
25557272	Cluster headache (CH) is a primary headache disorder characterized by severe attacks of unilateral pain following a chronobiological pattern. There is a close connection with sleep as most attacks occur during sleep. Hypothalamic involvement and a particular association with rapid eye movement (REM) sleep have been suggested. Sleep in a large, well-characterized population of CH patients was investigated.Polysomnography (PSG) was performed on two nights in 40 CH patients during active bout and one night in 25 age, sex and body mass index matched controls in hospital. Macrostructure and other features of sleep were analyzed and related to phenotype. Clinical headache characterization was obtained by semi-structured interview.	Ninety-nine nights of PSG were analyzed. Findings included a reduced percentage of REM sleep (17.3% vs. 23.0%, P = 0.0037), longer REM latency (2.0 vs. 1.2 h, P = 0.0012) and fewer arousals (7.34 vs. 14.1, P = 0.003) in CH patients. There was no difference in prevalence of sleep apnea between patients (38%) and matched controls (32%, P = 0.64) although the apnea index in patients was numerically higher (mean apnea-hypopnea index 10.75 vs. 4.93). No temporal association between nocturnal attacks (n = 45) and particular sleep stages was observed.	To date, this is the largest study of sleep in CH. It is demonstrated that REM sleep is affected which is in line with our current understanding of CH and hypothalamic involvement in the regulation of this sleep stage. Further, fewer arousals were found in CH patients but no association between apnea events or specific sleep stages. The findings support a central role of the hypothalamus and arousal systems in CH.	
25557165	Fatigue is a prevalent and substantial phenomenon in many patients with chronic inflammatory diseases, often rated by patients as the most troublesome symptom and aspect of their disease. It frequently interferes with physical and social functions and may lead to social withdrawal, long-standing sick leave and disability. Although psychological and somatic factors such as depression, sleep disorders, pain and anaemia influence fatigue, the underlying pathophysiological mechanisms by which fatigue is generated and regulated are largely unknown. Increasing evidence points towards a genetic and molecular basis for fatigue as part of the innate immune system and cellular stress responses. Few studies have focused on fatigue in dermatological diseases. Most of these studies describe fatigue as a phenomenon related to psoriatic arthritis and describe the beneficial effects of biological agents on fatigue observed in clinical studies. It is therefore possible that this problem has been underestimated and deserves more attention in the dermatological community. In this review, we provide a definition and explanation for chronic fatigue, describe some commonly used instruments for measuring fatigue, and present hypothetical biological mechanisms with an emphasis on activation of the innate immune system and oxidative stress. An overview of relevant clinical studies covering the theme 'psoriasis and fatigue' is given. 
25556401	Interictal high frequency oscillations (HFOs) are a promising candidate as a biomarker in epilepsy as well as for defining the seizure-onset zone as for the prediction of the surgical outcome after epilepsy surgery. The purpose of the study is to investigate properties of HFOs in long-term recordings with respect to the sleep-wake cycle and anatomic regions to verify previous results based on observations from short intervals and patients mainly with temporal lobe epilepsy to the analysis of hours of recordings and focal epilepsies with extratemporal origin.Automatic HFO detection using a radial basis function neural network detector was performed in long-term recordings of 15 presurgical patients investigated with subdural strip, grid, and depth contacts. Periods with visual marked sleep stages based on parallel scalp recordings from two consecutive nights were compared to awake intervals. Statistical analysis was based on the Kruskal-Wallis test, Mann-Whitney U-test and Spearman's rank correlations.	HFO rates in seizure-onset contacts differed from other brain regions independent of the sleep-wake cycle. For temporal contacts, the HFO rate increased significantly with sleep stage. In addition, contacts covering the parietal lobe, including rolandic cortex, showed a significant increase of HFO rates during sleep. However, no significant HFO rate changes depending on the sleep-wake cycle were found for frontal contacts.	The rate of interictal HFOs predicted the SOZ with statistical significance at the group level, but properties other than the HFO rate may need to be considered to improve the diagnostic utility of HFOs. This study gives evidence that the modulation of HFO rates by states of the sleep-wake cycle has particular characteristics within different neocortical regions and in mesiotemporal structures, and contributes to the establishment of HFOs as a biomarker in epilepsy.	
25554349	After the pandemic H1N1 influenza ASO3-adjuvanted vaccine, Pandemrix©, was used in late 2009 and early 2010, the incidence of narcolepsy increased in many European countries. This incidence mainly increased in children and adolescents and, to a lesser degree, in adults.125 unmedicated patients, aged 4 to 61 years, were included in this case-series study. Of these, 69 were diagnosed to have an H1N1-vaccine-related narcolepsy and 57 had sporadic narcolepsy. Most of these patients had: an actigraphy recording of 1-2 weeks, polysomnography, a Multiple Sleep Latency Test (MSLT), and cerebrospinal fluid hypocretin-1 concentration analysis.	Patients with H1N1-vaccine-related narcolepsy had shorter diagnostic delays, lower periodic leg movement index during sleep, earlier sleep-wake rhythm, and were younger in age at diagnosis, compared with sporadic cases. They also had shorter sleep latency and more sleep onset REM periods in MSLT, but these results were strongly age-dependent. Actigraphy showed quantitatively less sleep and more sleep fragmentation than polysomnography.	Regarding polysomnographic and actigraphic characteristics, there were no dramatic deviations between H1N1-vaccine-related and sporadic narcolepsy. Circadian rhythms indicated some interesting new findings with respect to the H1N1-vaccine-related disease. An actigraphy recording of 1-2 weeks is useful when studying the nocturnal aspects of narcolepsy and sleep-wake rhythms of narcoleptic patients.	
25553845	Melatonin, an indoleamine secreted by the pineal gland, plays a key role in regulating circadian rhythm. It has chronobiotic, antioxidant, anti-inflammatory and free radical scavenging properties.A conference in Rome in 2014 aimed to establish consensus on the roles of melatonin in children and on treatment guidelines.	The best evidence for efficacy is in sleep onset insomnia and delayed sleep phase syndrome. It is most effective when administered 3-5 h before physiological dim light melatonin onset. There is no evidence that extended-release melatonin confers advantage over immediate release. Many children with developmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder and intellectual disability have sleep disturbance and can benefit from melatonin treatment. Melatonin decreases sleep onset latency and increases total sleep time but does not decrease night awakenings. Decreased CYP 1A2 activity, genetically determined or from concomitant medication, can slow metabolism, with loss of variation in melatonin level and loss of effect. Decreasing the dose can remedy this. Animal work and limited human data suggest that melatonin does not exacerbate seizures and might decrease them. Melatonin has been used successfully in treating headache. Animal work has confirmed a neuroprotective effect of melatonin, suggesting a role in minimising neuronal damage from birth asphyxia; results from human studies are awaited. Melatonin can also be of value in the performance of sleep EEGs and as sedation for brainstem auditory evoked potential assessments. No serious adverse effects of melatonin in humans have been identified.	
25553718	Pain and sleep disturbance have been shown to have a profound influence on the outcomes of cancer treatment. This study sought to determine whether administering opioid analgesics or sleeping medication to cancer patients during their first admission to a hospital is associated with poor prognoses.We conducted a population-based retrospective cohort study by analyzing data obtained from the National Health Insurance Research Database in Taiwan. The study population comprised cancer patients whose first admission to a hospital for initial cancer treatment was in 2004.	We collected data on 2302 cancer patients. To analyze the effect of opioid analgesic and sleeping medication usage on cancer patient survival, we compared the 3-year survival rates among 4 groups of patients (no use, sleeping medications-only, opioid analgesics-only, both used). The 3-year Kaplan-Meier plots for these 4 groups show that the difference was statistically significant (log rank 48.244, p < 0.001). The longevity of cancer patients was the greatest among the no-use group, followed by the sleeping medications-only group, then the opioid analgesics-only group, and finally, the group in which both sleeping medications and opioid analgesics were used.	The use of opioid analgesics or sleeping medication was shown to be negatively correlated with the survival rate of cancer patients.	
25552436	Sleep problems in adolescence have been identified as an international public health issue. Over the past few decades, notable advances have been made in our understanding of the patterns and consequences of sleep in adolescence. Despite these important gains, there is much about the role of sleep in adolescence that remains to be understood. This Special Issue brings together studies that examine sleep as it specifically pertains to adolescent development and adjustment. In this introductory article, we argue for the importance of grounding the study of sleep and adolescence in developmental science and a developmental psychopathology framework. First, a review of the literature is used to outline a biopsychosocial and contextual model of sleep in adolescence. Second, attention-deficit/hyperactivity disorder (ADHD) is used as an exemplar of the proposed model given the pervasiveness of sleep problems among youth with ADHD and the likelihood that sleep problems and ADHD symptoms are interconnected in complex ways. Finally, a brief introduction to the empirical articles included in the Special Issue is provided, with particular attention given to how these articles fit within the proposed biopsychosocial and contextual model. Along with the framework proposed in this article, the studies included in this Special Issue advance the current literature and point to critical directions for future research. 
25551586	The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) are questionnaires used to assess sleep quality and excessive daytime sleepiness in clinical and population-based studies. The present study aimed to evaluate the construct validity and factor structure of the PSQI and ESS questionnaires among young adults in four countries (Chile, Ethiopia, Peru and Thailand).A cross-sectional study was conducted among 8,481 undergraduate students. Students were invited to complete a self-administered questionnaire that collected information about lifestyle, demographic, and sleep characteristics. In each country, the construct validity and factorial structures of PSQI and ESS questionnaires were tested through exploratory and confirmatory factor analyses (EFA and CFA).	The largest component-total correlation coefficient for sleep quality as assessed using PSQI was noted in Chile (r = 0.71) while the smallest component-total correlation coefficient was noted for sleep medication use in Peru (r = 0.28). The largest component-total correlation coefficient for excessive daytime sleepiness as assessed using ESS was found for item 1 (sitting/reading) in Chile (r = 0.65) while the lowest item-total correlation was observed for item 6 (sitting and talking to someone) in Thailand (r = 0.35). Using both EFA and CFA a two-factor model was found for PSQI questionnaire in Chile, Ethiopia and Thailand while a three-factor model was found for Peru. For the ESS questionnaire, we noted two factors for all four countries.	Overall, we documented cross-cultural comparability of sleep quality and excessive daytime sleepiness measures using the PSQI and ESS questionnaires among Asian, South American and African young adults. Although both the PSQI and ESS were originally developed as single-factor questionnaires, the results of our EFA and CFA revealed the multi- dimensionality of the scales suggesting limited usefulness of the global PSQI and ESS scores to assess sleep quality and excessive daytime sleepiness.	
25550239	The aim of this review is to summarize the state of knowledge concerning the relationship between cardiovascular risk, sleep abnormalities, and emotional reactivity in patients with bipolar disorder (BD).A scientific literature search of international articles was performed during August and September 2014 using the PubMed electronic database. We used the following MeSH terms : "Bipolar Disorders", "Cardiovascular risk", "Emotional reactivity", "Sleep apnea", and "Sleep disorder".	Obstructive sleep apnea (OSA) is a sleep disorder strongly associated with BD, which tends to fragment sleep. OSA is associated with an increased cardiovascular risk. Furthermore, emotional hyper-reactivity is favored by "hostility" temperaments, BD and sleep deprivation. The combination of these factors interacts and also results in an increased cardiovascular risk. Taken as a whole, both sleep disorders and emotional hyper-reactivity seem to increase the risk of cardiovascular diseases in BD.	These data emphasize the central role of sleep abnormalities and emotional reactivity in the vulnerability of BD to express cardiovascular diseases. From a clinical point of view, these data also emphasize the importance of identifying and care for sleep abnormalities in BD in order to improve BD outcome.	
25549368	The incidence of chronic heart failure (CHF) increases with the aging of the population and with the improvement in survival of patients with hypertension, coronary heart disease and diabetes, diseases which constitute the most common causes for the development of CHF. Despite the significant improvement in the treatment of patients with CHF, mortality in recent years has improved slightly. The primary treatment method for chronic heart failure is pharmacotherapy, but it has limitations. The existing data encourages to look for new treatment methods for CHF, replacing or enhancing traditional ones while constituting a low nuisance for patients. New non-pharmacological methods, including therapies based on the use of stem cells, molecular therapy, modern devices supporting the heart such as cardiac contractility modulation, spinal cord stimulation, carotid sinus nerve stimulation, cervical and intracardiac atrioventricular nodal vagal stimulation, implantable monitoring devices and wearable cardioverter-defibrillator or the treatment of comorbid diseases such as hypertension and sleep dis- orders could be of particular importance.
27103930	Circadian rhythms play an integral role in human behavior, physiology and health. Individual differences in daily rhythms (chronotypes) can affect individual sleep-wake cycles, activity patterns and behavioral choices. Diurnal preference, the tendency towards morningness or eveningness among individuals, has been associated with interpersonal variation in circadian clock-related output measures, including body temperature, melatonin levels and clock gene mRNA in blood, oral mucosa, and dermal fibroblast cell cultures.Here we report gene expression data from two principal clock genes sampled from hair follicle cells, a peripheral circadian clock. Hair follicle cells from fourteen individuals of extreme morning or evening chronotype were sampled at three time points. RNA was extracted and quantitative PCR assays were used to measure mRNA expression patterns of two clock genes, Per3 and Nr1d2.	We found significant differences in clock gene expression over time between chronotype groups, independent of gender or age of participants. Extreme evening chronotypes have a delay in phase of circadian clock gene oscillation relative to extreme morning types. Variation in the molecular clockwork of chronotype groups represents nearly three-hour phase differences (Per3: 2.61 hours; Nr1d2: 3.08 hours, both: 2.86) in circadian oscillations of these clock genes.	The measurement of gene expression from hair follicles at three time points allows for a direct, efficient method of estimating phase shifts of a peripheral circadian clock in real-life conditions. The robust phase differences in temporal expression of clock genes associated with diurnal preferences provide the framework for further studies of the molecular mechanisms and gene-by-environment interactions underlying chronotype-specific behavioral phenomena, including social jetlag.	
27103928	The mammalian circadian clock is composed of single-cell oscillators. Neurochemical and electrical signaling among these oscillators is important for the normal expression of circadian rhythms. Prokineticin 2 (PK2), encoding a cysteine-rich secreted protein, has been shown to be a critical signaling molecule for the regulation of circadian rhythms. PK2 expression in the suprachiasmatic nucleus (SCN) is highly rhythmic, peaking during the day and being essentially absent during the night. Mice with disrupted PK2 gene or its receptor PKR2 display greatly reduced rhythmicity of broad circadian parameters such as locomotor activity, body temperature and sleep/wake patterns. PK2 has been shown to increase the firing rate of SCN neurons, with unknown molecular mechanisms. Here we report that TRPV2, an ion channel belonging to the family of TRP, is co-expressed with PKR2 in the SCN neurons. Further, TRPV2 protein, but not TRPV2 mRNA, was shown to oscillate in the SCN in a PK2-dependent manner. Functional studies revealed that TRPV2 enhanced signaling of PKR2 in calcium mobilization or ion current conductance, likely via the increased trafficking of TRPV2 to the cell surface. Taken together, these results indicate that TRPV2 is likely part of the downstream signaling of PK2 in the regulation of the circadian rhythms. 
25548885	The aim of the study was to explore which variables predict poor sleep among clinically depressed Chinese adults.In total, 100 participants were recruited from Shanghai Mental Health Centre. The dependent variables were number of hours spent sleeping as well as the quality of sleep and number of times the participants woke during the night. The independent variables were gender, age, length of depression and severity of depression. The use of antipsychotic medication was controlled for in all analyses.	The results demonstrated that depression severity was the most important predictor of sleep quality and night waking. Gender and age were also found to be predictors of sleep problems.	The findings demonstrated that depressed Chinese patients experienced similar relationships between sleep disturbance and depression to Westerners. Future studies should include other measures of sleep quality as well as variables consistently found to be associated with both depression and sleep difficulty, such as the use of addictive substances and psychosocial factors.	
25548191	Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep. 

25547038	Patients with temporomandibular disorders (TMD) and/or orofacial pain (OFP) frequently experience poor sleep quality or suffer from comorbid sleep disorders. Study results suggest that in chronic pain patients, an improvement in sleep quality critically influences the outcomes of interventions on mood and pain. Yet, only a few studies have systematically sought to evaluate the sleep quality of TMD/OFP patients. Standardized and validated self-reported instruments designed for screening sleep disturbances or for the evaluation of treatment outcomes in this population would therefore enhance evidence and improve treatment options. The objectives of the present study were: (1) to review the self-reported instruments that measure sleep dysfunction in studies on TMD/OFP patients, by conducting a systematic literature search; (2) to evaluate their clinimetric evidence; and (3) to provide guidance for future research using such instruments. A total of 26 papers, using eight different instruments, were identified. The most frequently used questionnaires and the only ones with good clinimetric properties were the Insomnia Severity Index followed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. They were most reliable, valid and time-effective for measuring sleep dysfunctions in patients with TMD/OFP, with only a few practical constraints. Yet, in future studies, an assessment of the relationship between sleep disturbances and chronic pain will have to include instruments measuring the effect of mediator variables such as cognitive or emotional arousal. Research is required to clarify if existing self-reported questionnaires measuring these aspects will promote further insights or if there is a need for new instruments. This future research direction would blend into the overall biopsychosocial concept of TMD/OFP diagnoses and treatment. 
25547035	To evaluate the reliability of actigraphy to distinguish the features of estimated daytime and nighttime sleep between patients with central disorders of hypersomnolence and healthy controls.Thirty-nine drug-naïve patients with Narcolepsy Type 1, twenty-four drug-naïve patients with Idiopathic Hypersomnia, and thirty age- and sex- matched healthy controls underwent seven days of actigraphic and self-report monitoring of sleep/wake behavior. The following variables were examined: estimated time in bed (eTIB), estimated total sleep time, estimated sleep latency (eSOL), estimated sleep efficiency, estimated wake after sleep onset, number of estimated awakenings (eAwk), number of estimated awakenings longer than 5 minutes, estimated sleep motor activity (eSMA), number of estimated naps, mean duration of the longest estimated nap (eNapD), and daytime motor activity.	All actigraphic parameters significantly differentiated the three groups, except eTIB and eSOL. A discriminant score computed combining actigraphic parameters from nighttime (eSMA, eAwk) and daytime (eNapD) periods showed a wide area under the curve (0.935) and a good balance between positive (95%) and negative predictive (87%) values in Narcolepsy Type 1 cases.	Actigraphy provided a reliable objective measurement of sleep quality and daytime napping behavior able to distinguish central disorders of hypersomnolence and in particular Narcolepsy Type 1. The nycthemeral profile, combined with a careful clinical evaluation, may be an ecological information, useful to track disease course.	
25547034	Studies investigating the relationship between sleep disorders (SDs) and the risk of venous thromboembolism (VTE) are scarce. The present study from Taiwan evaluated whether the risk of VTE was associated with SDs other than sleep apnea.The present study investigated the incidence and risk of VTE in 46,371 people with SDs, compared with 92,742 controls without SDs. The follow-up period began from the date of entering the study cohort to the date of a VTE event, censoring, or December 31, 2011. A Cox proportional hazards regression analysis was conducted to estimate the effects of SDs on the risk of VTE.	The SD cohort had a 1.79-fold adjusted hazard ratio (HR) of subsequent VTE, compared with the non-SD cohort (95% CI 1.49-2.16). The incidence of VTE increased with age for both cohorts but was higher for those in the SD cohort. However, the adjusted HRs for VTE were significantly higher for the people with SDs aged ≦49 years (HR 3.29, 95% CI 2.12-5.12) and 50-64 years (HR 2.43, 95% CI 1.76-3.35), but were not significant for the oldest group (HR 1.11, 95% CI 0.84-1.47), compared with the controls. The multiplicative increased risk of VTE was significant for the people with SDs with any comorbidity.	This nationwide cohort study determined that the VTE risk significantly increased in people with SDs compared with those of the general population.	
25546732	Declarative memory is consolidated during sleep in healthy children. We tested the hypothesis that consolidation processes are impaired in idiopathic focal epilepsies (IFE) of childhood in association with frequent interictal epileptiform discharges (IEDs) during sleep.A verbal (word-pair association) and a nonverbal (2D object location) declarative memory task were administrated to 15 children with IFEs and 8 control children 6-12 years of age. Patients had either centrotemporal (11 patients) or occipital (4 patients) IEDs. All but 3 patients had a history of unprovoked seizures, and 6 of them were treated with valproate (VPA). The learning procedure (location of object pairs presented on a grid; association of word pairs) was executed in the evening. Retrieval was tested immediately after learning and on the next morning after a night of sleep. Participants were tested twice, once in natural home conditions and one month later in the unfamiliar conditions of the sleep unit under EEG monitoring.	Overnight recall performance was lower in children with IFE than in control children on both tasks (ps<0.05). Performance in home conditions was similar to that in hospital conditions. Higher spike-wave index (SWI) during nonrapid eye movement (NREM) sleep was associated with poorer performance in the nonverbal task (p<0.05). Valproate treatment was not associated with overnight recall performance for both tasks (ps>0.05).	Memory consolidation is impaired in IFE of childhood. The association between higher SWI during NREM sleep and poorer nonverbal declarative memory consolidation supports the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation.	
25546305	Ultradian (~4 hr) rhythms in locomotor activity that do not depend on the master circadian pacemaker in the suprachiasmatic nucleus have been observed across mammalian species, however, the underlying mechanisms driving these rhythms are unknown. We show that disruption of the dopamine transporter gene lengthens the period of ultradian locomotor rhythms in mice. Period lengthening also results from chemogenetic activation of midbrain dopamine neurons and psychostimulant treatment, while the antipsychotic haloperidol has the opposite effect. We further reveal that striatal dopamine levels fluctuate in synchrony with ultradian activity cycles and that dopaminergic tone strongly predicts ultradian period. Our data indicate that an arousal regulating, dopaminergic ultradian oscillator (DUO) operates in the mammalian brain, which normally cycles in harmony with the circadian clock, but can desynchronize when dopamine tone is elevated, thereby producing aberrant patterns of arousal which are strikingly similar to perturbed sleep-wake cycles comorbid with psychopathology.
25545545	Circadian clocks play a significant role in the correct timing of physiological metabolism, and clock disruption might lead to pathological changes of metabolism. One interesting method to assess the current state of metabolism is metabolomics. Metabolomics tries to capture the entirety of small molecules, i.e. the building blocks of metabolism, in a given matrix, such as blood, saliva or urine. Using mass spectrometric approaches we and others have shown that a significant portion of the human metabolome in saliva and blood exhibits circadian modulation; independent of food intake or sleep/wake rhythms. Recent advances in mass spectrometry techniques have introduced completely non-invasive breathprinting; a method to instantaneously assess small metabolites in human breath. In this proof-of-principle study, we extend these findings about the impact of circadian clocks on metabolomics to exhaled breath. As previously established, our method allows for real-time analysis of a rich matrix during frequent non-invasive sampling. We sampled the breath of three healthy, non-smoking human volunteers in hourly intervals for 24 hours during total sleep deprivation, and found 111 features in the breath of all individuals, 36-49% of which showed significant circadian variation in at least one individual. Our data suggest that real-time mass spectrometric "breathprinting" has high potential to become a useful tool to understand circadian metabolism, and develop new biomarkers to easily and in real-time assess circadian clock phase and function in experimental and clinical settings. 
25545189	Poststroke apathy affects 19-55% of patients following stroke and has a negative impact on functional recovery, general health, and quality of life, as well as being a source of significant burden for caregivers.A major clinical issue is the delayed diagnosis of poststroke apathy, and so the aim of our study is to evaluate the relationship between early poststroke alterations of circadian rhythms of sleep/wake cycles and the occurrence of poststroke apathy.	Forty-six patients with a recent magnetic resonance imaging confirmed stroke were included. Main exclusion criteria were a mild to severe disability impeding home discharge from the hospital and the presence of apathy or dementia before stroke. Cerebrovascular lesions were evaluated by magnetic resonance imaging. At hospital discharge, an actigraph was used to measure patient's global activity as well as parameters of circadian rhythmicity (relative amplitude, interdaily stability, intradaily variability) and sleep (sleep duration, sleep efficiency, fragmentation index) over seven-days. Apathy was assessed at hospital discharge as well as at three-months using the Apathy Inventory and the Lille Apathy Rating Scale.	Of the 46 patients evaluated, 10 (22%) showed apathy three-months after stroke (median Apathy Inventory = 4·5). Before inclusion, these 10 subjects did not differ significantly from other patients concerning their sleep and, at inclusion, they did not differ concerning apathy, anxiety, depression, or cognitive and functional abilities. However, actigraphy measured at discharged identified significant alterations of sleep (P < 0·005). Future poststroke apathy patients exhibited a decrease in sleep efficiency (actual sleep time expressed as a percentage of time in bed) and an increase in the fragmentation index (degree of fragmentation during the sleep period) at three-months. No association was observed between poststroke apathy and the characteristics of cerebrovascular lesions (stroke location, extent of leucoencephalopathy, number of lacunes and microbleeds).	These results indicate that early poststroke alterations of sleep/wake circadian rhythms--easily evaluated by actigraphy--are associated with a higher risk of poststroke apathy at three-months. In terms of clinical outcomes, our results provide targets for very early identification of patients at risk to develop apathy after stroke and for assessing when to start specific therapy to optimize rehabilitation efficiency.	

25542735	Cytokines such as TNFα play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFα gene (TNFα G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFα 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFα G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFα in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFα G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation. 
25542734	In mammals, one of the most salient outputs of the circadian (daily) clock is the timing of the sleep-wake cycle. Modern industrialized society has led to a fundamental breakdown in the relationship between our endogenous timekeeping systems and the solar day, disrupting normal circadian rhythms. We have argued that disrupted circadian rhythms could lead to changes in allostatic load, and the capacity of organisms to respond to other environmental challenges. In this set of studies, we apply a model of circadian disruption characterized in our lab in which mice are housed in a 20h long day, with 10h of light and 10h of darkness. We explored the effects of this environmental disruption on sleep patterns, to establish if this model results in marked sleep deprivation. Given the interaction between circadian, sleep, and immune systems, we further probed if our model of circadian disruption also alters the innate immune response to peripheral bacterial endotoxin challenge. Our results demonstrate that this model of circadian disruption does not lead to marked sleep deprivation, but instead affects the timing and quality of sleep. We also show that while circadian disruption does not lead to basal changes in the immune markers we explored, the immune response is affected, both in the brain and the periphery. Together, our findings further strengthen the important role of the circadian timing system in sleep regulation and immune responses, and provide evidence that disrupting the circadian clock increases vulnerability to further environmental stressors, including immunological challenges. 
25542636	Despite evidence of autonomic disturbances in chronic multisymptom illnesses such as temporomandibular disorder (TMD) and fibromyalgia, additional work is needed to characterize the role of parasympathetic reactivity in these disorders. Given the high levels of comorbidity with psychiatric disorders characterized by stronger parasympathetic decline than controls in safe contexts (leading to higher arousal), it was hypothesized that individuals with TMD and fibromyalgia would respond similarly. In this preliminary investigation, 43 women with TMD (n = 17), TMD + fibromyalgia (n = 11), or neither (controls; n = 15) completed a baseline assessment of respiratory sinus arrhythmia (a measure of parasympathetic activity) followed by ongoing parasympathetic assessment during a questionnaire period. As predicted, patients showed greater parasympathetic decline during psychosocial assessment, suggesting an autonomic stance that supports defensive rather than engagement behaviors. Individual differences in parasympathetic reduction during the questionnaire period were related to a variety of physical and psychosocial variables. Although this study has a number of key limitations, including a convenience sampling approach and small group sizes, if replicated in larger samples, the findings would have important implications for the treatment of patients with these disorders.Compared to controls, individuals with TMD or TMD and fibromyalgia demonstrated greater parasympathetic decline during psychosocial assessment, and individual differences in parasympathetic decline predicted negative patient outcomes. Such parasympathetic decline may demonstrate a tendency to readily perceive danger in safe environments.	
25542533	It is now accepted that hippocampal- and striatal-dependent memory systems do not act independently, but rather interact during both memory acquisition and consolidation. However, the respective functional roles of the hippocampus and the striatum in these processes remain unknown. Here, functional magnetic resonance imaging (fMRI) was used in a daytime sleep/wake protocol to investigate this knowledge gap. Using a protocol developed earlier in our lab (Albouy et al., 2013a), the manipulation of an explicit sequential finger-tapping task, allowed us to isolate allocentric (spatial) and egocentric (motor) representations of the sequence, which were supported by distinct hippocampo- and striato-cortical networks, respectively. Importantly, a sleep-dependent performance enhancement emerged for the hippocampal-dependent memory trace, whereas performance was maintained for the striatal-dependent memory trace, irrespective of the sleep condition. Regression analyses indicated that the interaction between these two systems influenced subsequent performance improvements. While striatal activity was negatively correlated with performance enhancement after both sleep and wakefulness in the allocentric representation, hippocampal activity was positively related to performance improvement for the egocentric representation, but only if sleep was allowed after training. Our results provide the first direct evidence of a functional dissociation in consolidation processes whereby memory stabilization seems supported by the striatum in a time-dependent manner whereas memory enhancement seems linked to hippocampal activity and sleep-dependent processes. 
25541361	In developing countries, youngsters start to work during the high school years. Several studies have shown the difficulties associated with double shift, i.e. to work and study concomitantly, and its negative health consequences. Work and study time, as social synchronizers, have significant effects on the sleep-wake cycle (SWC). The purpose of this study was to evaluate sleep patterns and sleepiness in young students before and after entering the workforce as apprentices or trainees. Participants were 40 adolescents (26 males), 15-18 years old (mean = 15.8 years old) engaged in a first-job program at a non-governmental organization (NGO) while attending evening high school in the outskirts of the city of São Paulo, Brazil. The participants wore actigraphs (Ambulatory Monitoring, Inc.) and registered subjective sleepiness on KSS (Karolinska Sleepiness Scale) along 7 consecutive days, before and after admission to the job. Descriptive analyses were performed, and the variables were tested by means of the t-test and repeated measures ANOVA taking factors day of the week and time of the day into consideration. The participants' sleep duration on weekdays exhibited significant difference before and after starting work (F = 4.55; p = 0.04); the mean sleep duration was 492 min (SD = 44 min) before admission to the job to decrease to 405 min (SD = 58 min) after starting work. The mid-sleep time exhibited significant difference on weekdays before and after starting work (04:57 h; SD = 45 min versus 03:30 h; SD = 54 min; F = 4.91; p = 0.03). Finally, also sleepiness on weekdays (F = 6.41; p = 0.04) and at the waking time (F = 10.75; p < 0.01) exhibited significant difference before and after admission to the job. This article emphasizes the fact that social synchronizers like working during the day and studying in the evening changed the participants' SWC and were associated with sleep restriction. Brazilian governmental incentives notwithstanding, simultaneous performance of several activities by young workers should be considered as an occupational health hazard. Employment policies targeting young workers should take the dual shift - study and work - and its effects on the sleep-wake cycle into account. 
25536536	Fatigue is a multidimensional construct that has significant implications for physical function in chronic noncancer pain populations but remains relatively understudied. The current study characterized the independent contributions of self-reported ratings of pain intensity, sleep disturbance, depression, and fatigue to ratings of physical function and pain-related interference in a diverse sample of treatment-seeking individuals with chronic pain. These relationships were examined as a path modeling analysis of self-report scores obtained from 2,487 individuals with chronic pain from a tertiary care outpatient pain clinic. Our analyses revealed unique relationships of pain intensity, sleep disturbance, and depression with self-reported fatigue. Further, fatigue scores accounted for significant proportions of the relationships of both pain intensity and depression with physical function and pain-related interference and accounted for the entirety of the unique statistical relationship between sleep disturbance and both physical function and pain-related interference. Fatigue is a complex construct with relationships to both physical and psychological factors that has significant implications for physical functioning in chronic noncancer pain. The current results identify potential targets for future treatment of fatigue in chronic pain and may provide directions for future clinical and theoretical research in the area of chronic noncancer pain.Fatigue is an important physical and psychological variable that factors prominently in the deleterious consequences of pain intensity, sleep disturbance, and depression for physical function in chronic noncancer pain.	
25535358	In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength-enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety. 
25534582	We aimed to determine the association between psychomotor vigilance task (PVT) performance and sleep-related factors including sleep duration, daytime sleepiness, poor sleep quality, insomnia, and habitual snoring in a population-based sample.This was a cross-sectional analysis from the ongoing prospective cohort study, the Korean Genome and Epidemiology Study. We measured PVT performance and documented demographics, sleep-related factors, life style, and medical conditions in community dwelling adults (N = 2499; mean age 57.1 ± 7.3; male 1259). Associations between PVT parameters and sleep-related factors were tested, adjusting for age, gender, smoking, alcohol use, education, body mass index, hypertension, diabetes, depression, and the interval between mid-sleep time and PVT test.	High Epworth Sleepiness Scale (ESS, ≥8) was associated with slower mean reciprocal response speed (mean RRT) (3.69 ± 0.02 vs. 3.77 ± 0.01, p < 0.001), higher probability for increased lapses (≥4) (OR 1.48, CI 1.12-1.88, p = 0.001), and more negative RRT slope (-0.036 ± 0.002 vs. -0.030 ± 0.001, p = 0.02). Older age, female gender, low education level, depressive mood, and the interval between mid-sleep and PVT test were also associated with poor performance. Sleep duration, habitual snoring, insomnia, or poor sleep quality (the Pittsburgh Sleep Quality Index score > 5) was not related to PVT parameters.	At the population level, our results revealed important modifiers of PVT performance, which included subjective reports of daytime sleepiness.	
25534555	Hetlioz(®) (tasimelteon) is the first approved treatment in the United States for Non-24-Hour Sleep-Wake Disorder (Non-24). We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). Tasimelteon was also shown to have no appreciable affinity for more than 160 other pharmacologically relevant receptors and several enzymes.
25534169	Psychogenic nonepileptic seizures (PNES), a form of functional neurological symptom disorder (FNSD), are very rarely seen in genuine, electroencephalography (EEG)-confirmed sleep. However, they are more commonly reported as a nocturnal occurrence, likely from a state that is misidentified as sleep (termed by some as "pseudosleep"). Sleep state can be helpful to distinguish FNSD from other neurological disorders. Pseudo-cataplexy, a form of "psychogenic" narcolepsy, "pseudo-parasomnia" and PNES can have a similar presentation. PNES and posttraumatic stress disorder (PTSD) frequently share previously experienced psychological trauma, and therefore the sleep abnormalities found in PTSD may be similarly present in PNES. Future research should use EEG monitoring to evaluate the sleep physiology of patients with FNSD such as PNES, as insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES. 

25533542	This article aims to reconstruct the elements of continuity and/or discontinuity in Sante De Sanctis' (1862-1935) contributions in the scientific understanding of sleep and dreaming as compared to the scientific research of his time. An Italian psychologist and psychiatrist, De Sanctis, in his work conducted between the 19th and 20th centuries, has framed the study of dreams using multi-methodology. In addition, De Sanctis experimentally established the correspondence between the deep and desynchronization phases of sleep with respect to dreaming. In this context, De Sanctis' subjects described the periodicity of sleep and consciousness, influencing the explanations of the themes that modern sleep research has, after decades, systematically studied. We demonstrate that De Sanctis' work has been underestimated, and in our opinion, deserves to be reconsidered as a source of the psychophysiological explanation of dreams and sleep. Finally, we present a graphical representation of De Sanctis' psycho- and neurophysiological model of dreaming. 

25533539	This study aimed to evaluate safety and efficacy of sodium oxybate (SXB) titrated to effect.SXB-naive patients who had participated in a randomized SXB clinical trial and had not been titrated to adequate clinical effect were initiated on open-label SXB at 4.5 g/night and titrated in 1.5-g increments to 6, 7.5, or 9 g/night or down to 3 g/night, based on individual clinical response. Treatment was 12 weeks; safety was the primary outcome. Efficacy was evaluated using the Narcolepsy Symptom Assessment Questionnaire (NSAQ), a five-point scale ("much improved" to "much worse") that assessed changes from baseline in specific symptoms. Response was defined as "much improved" or "somewhat improved" overall at weeks 6 and 12.	Of 202 patients, 171 (85%) completed treatment; final doses were 3 g (n = 5), 4.5 g (n = 29), 6 g (n = 80), 7.5 g (n = 66), and 9 g (n = 22). Adverse events (AEs) were reported in 114 patients (56%), serious AEs in five (2%). The most common AEs were nausea (10%), headache (7%), and dizziness (5%). Response rate was 92% at week 6 and 90% at week 12; most patients reported improvements in all individual symptoms. Overall, 60% of patients rated their symptoms at 12 weeks as "much improved," and this improvement was dose dependent.	The SXB safety profile was consistent with parent trials. Ninety percent of patients reported improvements as measured by the NSAQ.	
25533301	Several studies have suggested that comorbid neurologic disorders are more common than expected in multiple sclerosis (MS).To estimate the incidence and prevalence of comorbid seizure disorders and sleep disorders in persons with MS and to evaluate the quality of studies included.	The PUBMED, EMBASE, Web of Knowledge, and SCOPUS databases, conference proceedings, and reference lists of retrieved articles were searched. Two reviewers independently screened abstracts to identify relevant articles, followed by full-text review of selected articles. We assessed included studies qualitatively and quantitatively (I² statistic), and conducted meta-analyses among population-based studies.	We reviewed 32 studies regarding seizure disorders. Among population-based studies the incidence of seizure disorders was 2.28% (95% CI: 1.11-3.44%), while the prevalence was 3.09% (95% CI: 2.01-4.16%). For sleep disorders we evaluated 18 studies; none were population-based. The prevalence ranged from 0-1.6% for narcolepsy, 14.4-57.5% for restless legs syndrome, 2.22-3.2% for REM behavior disorder, and 7.14-58.1% for obstructive sleep apnea.	This review suggests that seizure disorders and sleep disorders are common in MS, but highlights gaps in the epidemiological knowledge of these conditions in MS worldwide. Other than central-western Europe and North America, most regions are understudied.	
25532787	All living organisms depend on homeostasis, the complex set of interacting metabolic chemical reactions for maintaining life and well-being. This is no less true for psychiatric well-being than for physical well-being. Indeed, a focus on homeostasis forces us to see how inextricably linked mental and physical well-being are. This paper focuses on these linkages. In particular, it addresses the ways in which understanding of disturbed homeostasis may aid in creating classes of patients with mood and anxiety disorders based on such phenotypes. At the cellular level, we may be able to compensate for the inability to study living brain tissue through the study of homeostatic mechanisms in fibroblasts, pluripotent human cells, and mitochondria and determine how homeostasis is disturbed at the level of these peripheral tissues through exogenous stress. We also emphasize the remarkable opportunities for enhancing knowledge in this area that are offered by advances in technology. The study of human behavior, especially when combined with our greatly improved capacity to study unique but isolated populations, offers particularly clear windows into the relationships among genetic, environmental, and behavioral contributions to homeostasis.
25532785	When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE2 is the principal mediator of fever, and both PGE2 and PGD2 regulate sleep-wake behavior. The extent to which PGE2 and PGD2 are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE2 receptors type EP3 or EP4, in mice with total body KO of microsomal PGE synthase-1 or the PGD2 receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP4 receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP3 receptors or in the presence of a COX inhibitor. 
25532691	It is not unusual for patients with head and neck cancer (HNC) to suffer from both tumor- and treatment-related pain that is difficult to alleviate despite individualized pain management. The aim of this qualitative study was to describe how HNC patients experience pain and how pain influences those who are treated with radiotherapy (RT). Qualitative semistructured interviews were performed 1 and 6 months after patients completed RT. The interviews addressed symptoms, moods, and suffering. The study included 26 patients with HNC who had recently completed RT. The interviews were analyzed using manifest content analysis. The main category was: HNC patients did not report that their severe physical pain influenced their psychological suffering, but it did influence their social lives. Furthermore, four categories were revealed: pain in the head and neck region, overwhelming fatigue, altered mood and preoccupied mind, and decreased participation and changed relationships. Physical pain, psychological distress, and social withdrawal were prominent at both interviews and consequently their situation can be considered as chronic. Remarkably, patients did not express a clear relationship between pain and psychological load. This may imply a biomedical view of pain or may reflect the difficult situation patients were in (i.e., facing a possibly life-threatening cancer). Thus, their situation might require a prioritization and might negatively affect the possibility of identifying the interaction between the different pain dimensions. The biopsychosocial model of chronic pain aims to understand the interaction between pain and psychosocial factors. Interventions aiming to teach patients with HNC how to internalize the biopsychosocial model framework to manage pain could be useful and should be evaluated in future research. 
25531866	Human sleep is a natural part of every individual's life. Clear relationship between sleep and endocrine system has been already established. In particular, melatonin and cortisol are known to affect and regulate sleep/wake patterns. Here we report the development of an ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous measurement of 6-sulfatoxymelatonin (MT6s), cortisol and cortisone in urine. A separate method was developed for measurement of creatinine in urine. These levels were used to normalise the levels of analytes. First void morning urine samples were collected from 24 healthy volunteers. Samples were diluted 1:1 in water prior to injection onto reversed-phase C18 column and analysed using UHPLC-MS/MS method. Linear calibrations were obtained for all analytes with correlation coefficient in the range 0.998-0.999. The observed concentration was found to be in the range 92-105% for cortisol, 92-107% for cortisone and between 93 and 120% for MT6s of the reference levels. The total run time of 6 min with all peaks of interest eluting within 3 min was obtained. This demonstrates the feasibility of utilising the method for large multi-scale studies, where high throughput is required for studying the circadian rhythm of melatonin and cortisol secretion. These hormones play significant role in circadian rhythm and sleep/wake cycle; therefore it is important to monitor the levels of these endocrine markers in individuals suffering from sleep disorders. It is also beneficial with clinical applications to analyse melatonin and cortisol simultaneously in order to assess their interrelationships of these substances, such as their effect on diurnal rhythm and sleep.
25530872	In children diagnosed with pediatric bipolar disorder (PBD), disturbances in the quality of sleep and wakefulness are prominent. A novel phenotype of PBD called Fear of Harm (FOH) associated with separation anxiety and aggressive obsessions is associated with sleep onset insomnia, parasomnias (nightmares, night-terrors, enuresis), REM sleep-related problems, and morning sleep inertia. Children with FOH often experience thermal discomfort (e.g. feeling hot, excessive sweating) in neutral ambient temperature conditions, as well as no discomfort during exposure to the extreme cold, and alternate noticeably between being excessively hot in the evening and cold in the morning. We hypothesized that these sleep- and temperature-related symptoms were overt symptoms of an impaired ability to dissipate heat, particularly in the evening hours near the time of sleep onset. We measured sleep/wake variables using actigraphy, and nocturnal skin temperature variables using thermal patches and a wireless device, and compared these data between children with PBD/FOH and a control sample of healthy children. The results are suggestive of a thermoregulatory dysfunction that is associated with sleep onset difficulties. Further, they are consistent with our hypothesis that alterations in neural circuitry common to thermoregulation and emotion regulation underlie affective and behavioral symptoms of the FOH phenotype. 
25529939	The objective of this study was to examine levels of awareness and knowledge regarding male climacteric or andropause in Japanese women. We also examined whether there are differences in these levels between nurses as a health profession group and office workers as a general population group.Two thousand and eight hundred female registered nurses and women with office-related general occupations aged 20-65 years in Japan completed health questionnaires regarding awareness and knowledge of male climacteric, including male menopausal symptoms and treatments.	The proportion in women who had heard of the term male climacteric in nurses was significantly higher than that in office workers. Nurses with past or current experience of menopausal symptoms were likely to recognize male climacteric. Nurses also had a higher level of knowledge than did office workers regarding male menopausal symptoms. High proportions of both nurses and office workers acknowledged depressed mood, irritability, nervousness and sleep problems as male menopausal symptoms. The proportions of women with sympathy for men with male climacteric were high in women with experience of past or current menopausal symptoms and in women who were close to men who suffered from menopausal symptoms.	Nurses with past or current experience of menopausal symptoms had high levels of awareness and knowledge of male climacteric. To spread more information and knowledge regarding male climacteric, provision of education for these nurses may be needed.	
25529787	Psychological distress is associated with sleep disturbances; however there is little research on sleep quality in dental anxiety (DA) patients.To measure the sleep quality in patients with DA compared to patients with an exacerbated gag reflex (GAG) and controls and to analyze its association with various demographic and behavioral parameters.	67 DA patients, 54 GAG patients and 100 controls with no history of DA or GAG participated in the study. Data regarding: demographic details, smoking habits, the Pittsburgh Sleep Quality Index (PSQI), Numeric Rating Scale (NRS) for pain assessment, Corah's dental anxiety scale (DAS) and Oral Health Impact Profile-14 (OHIP-14), plaque index (PI) and Decay, Missing and Filled Teeth (DMFT) scores were collected.	49.3% of the DA group and 38.9% of the GAG group were poor sleepers (mean PSQI score > 5), compared to 29.0% of the controls (PSQI mean scores: 5.8 ± 3.4, DA group; 5.2 ± 3.6 GAG group vs. 4.5 ± 2.7, control group; p = 0.029). Compared to controls, DA and GAG patients exhibited poorer scores in the sleep disturbances PSQI component (p = 0.001). DA patients exhibited poorer scores in the sleep duration PSQI component compared to the control (p = 0.002) and GAG groups (p = 0.033). Female gender (p = 0.039), higher current (p = 0.046) and maximal NRS (p = 0.019), higher DAS (p < 0.001) and OHIP-14 (p < 0.001) scores and more missing teeth (p = 0.003) were positively associated with higher PSQI scores.	DA patients suffered more from impaired sleep than controls and GAGs. Impaired sleep in DA patients is multidimensional phenomenon influenced by the specific diagnosis, gender, pain, dental anxiety levels, dental experience and oral health related quality of life.	
25528321	Bevezetés: Az egészségügy veszélyes üzem, a benne dolgozók számára is. A rosszabb egészségi állapotot számos részvizsgálat állapította meg anélkül, hogy feltárták volna a hátterét. Célkitűzés: A szerzők helyzetképet kívánnak adni az egészségügyben dolgozók egészségi állapotáról és megpróbálják az ide vezető okokat kideríteni. Módszer: 2004-ben 276, ágy mellett dolgozó nővér, majd 2009-ben 1250 kórházi dolgozó adatait dolgozták fel. A székesfehérvári Szent György Egyetemi Oktató Kórházban 1979–2010 között osztályvezető főorvosi feladatokat ellátó kollégák sorsát is követték és hasonlították össze egy negyedakkora budapesti kórház osztályvezető főorvosainak sorsával. Eredmények: A betegágy mellett dolgozó nővérek többsége 30–35 éves korára elérte a testtömegindex tartományának felső határát (7 évvel korábban, mint az átlaglakosság), ami a kor előrehaladtával tovább emelkedett, az országos átlag fölé. A kórházi dolgozók körében a testtömegindex-érték emelkedésével a krónikus betegségek száma is jelentősen növekedett; vezető helyen a magas vérnyomás, allergia, pajzsmirigy- és mozgásszervi betegségek mellett a cukorbetegség, fekélybetegség, daganatok és depresszió álltak. Az osztályvezető főorvosoknál az elhalálozást és annak okát követték. A halálokok között Magyarországon a rákhalálozás 2011-ben 25,4% volt, míg a vizsgált időszak alatt a székesfehérvári kórházban a főorvosok 77%-a, a budapesti kórházban pedig a főorvosok 82%-a hunyt el rákbetegségben. Következtetések: A rosszabb egészségi állapot hátterében a pszicho-neuro-immunológiai kutatások eredményei alapján a feldolgozatlan sorozatos stresszhelyzetek, az éjszakai műszak, az állandó készenlét okozta immunelnyomás tehetők felelőssé. A megoldás a prevenció lenne, ennek része a stresszkontroll oktatása lehet. Orv. Hetil., 2014, 155(52), 2082–2092.Several studies have shown that healthcare service is a dangerous workplace, but the reasons have been remained unexplained.	The aim of the authors was to obtain data on the health condition of health care professionals and identify the underlying risk factors for the increased morbidity.	Health care data obtained from 276 bedside nurses in 2004 and 1250 hospital employees in 2009 were analysed. In addition, the fate of department directors of Szent György University Hospital in Székesfehérvár between 1979 and 2010 was recorded and the data were compared to those obtained from a smaller hospital in Budapest during the same time period.	The body mass index of bedside nurses between the age of 30-35 years reached the upper limit of normal (which occurred 5-10 years earlier as compared to the average population) and then it increased continuously above the average value. In hospital employees the increase of body mass index was accompanied by an increase in the frequency of chronic diseases such as hypertension, allergy, thyroid dysfunction, rheumatologic diseases, diabetes, peptic ulcer, cancer and depression. When the cause of death of the department directors who died between 1979 and 2010 was analyzed the authors found that cancer death occurred in 77% and 82% of department directors in Székesfehérvár and Budapest hospitals, respectively, while cancer death rate in 2011 was 25.4% in Hungary.	The authors propose that continuous psychological stress, night shifts, nonstop standby and surcharge may all suppress the activity of the immune system. This proposal seems to be supported by novel psycho-neuro-immunological research data. The solution could be early prevention using stress control.	
25528319	A különböző alvászavarok prevalenciája és klinikai-tüneti megnyilvánulása eltérő lehet a férfiak és a nők körében. Az utóbbi évek kutatásai hívták fel a figyelmet az obstruktív alvási apnoe gyakori előfordulására nők körében is, mivel a férfiakkal ellentétben, főként az atípusos tünetek miatt (mint a reggeli fejfájás, depresszióra jellemző tünetek, nappali fáradtság) az esetek nagy részében nem diagnosztizálják ezt a betegséget. Mindkét nemnél nagy jelentősége van az alvászavarok korai felismerésének és kezelésének, az életminőség, társbetegségek és a mortalitás szempontjából. Orv. Hetil., 2014, 155(52), 2067–2073.The prevalence of sleep disturbances and their symptomatic manifestations may be different in men and women. Women with obstructive sleep apnea are less likely to be diagnosed with sleep apnea compared to men, probably due to atypical symptoms such as morning headaches, symptoms of depression and daytime fatigue. There is a great importance of diagnosis and treatment of sleep disorders regarding quality of life, co-morbidity and mortality in both genders.	
25527963	Self-rated health (SRH) is a well-established measure within social epidemiology. However, most studies on SRH tend to be amongst the general population, where SRH has been found to be lower in women than in men. Few studies have specifically investigated patterns of SRH just within an employed population. The purpose of this study was to (1) investigate whether there are gender differences in reporting suboptimal SRH in an employed Swedish population and (2) study whether these differences could be explained by socio-economic, work-, health- and/or lifestyle-related factors.This study is cross-sectional analysis of data from the 2008 wave of Swedish Longitudinal Occupational Survey of Health, a nationally representative cohort of the Swedish working population. This study includes the responses of 9,756 employed individuals. Logistic regression analyses were performed.	After adjusting for age, income and working hours (full vs. part time), men had significantly higher odds of suboptimal SRH than women OR 1.38 (95 % CI 1.22-1.55). With stepwise inclusion of health factors such as long-standing disease, sleep quality and fatigue, the OR for men increased to 1.65 (95 % CI 1.44-1.89). Gender differences in reporting suboptimal SRH were attenuated to 1.29 (95 % CI 1.11-1.51) with the inclusion of lifestyle factors. However, they remained significant after inclusion of all explanatory variables.	In contrast to findings in general population studies, our results show that men in employment have higher odds of suboptimal SRH than their female counterparts. As SRH is an important indicator of health with a strong association with mortality, an excess risk of suboptimal SRH amongst employed men shows that more attention should be paid to men's health in the workplace.	
25527511	A significant number of children with a range of complex conditions and health care needs are being cared for by parents in the home environment. This mixed methods systematic review aimed to determine the amount of sleep obtained by these parents and the extent to which the child-related overnight health or care needs affected parental sleep experience and daily functioning. Summary statistics were not able to be determined due to the heterogeneity of included studies, but the common themes that emerged are that parents of children with complex needs experience sleep deprivation that can be both relentless and draining and affects the parents themselves and their relationships. The degree of sleep deprivation varies by diagnosis, but a key contributing factor is the need for parents to be vigilant at night. Of particular importance to health care professionals is the inadequate overnight support provided to parents of children with complex needs, potentially placing these parents at risk of poorer health outcomes associated with sleep deprivation and disturbance. This needs to be addressed to enable parents to remain well and continue to provide the care that their child and family require. 
25526429	This study compared post-operative quality of life and sleep according to the type of cataract opacity and color of the implanted intra-ocular lens (IOL).This is a cohort study and participants were 206 patients (average age 74.1 years) undergoing cataract surgery with the implantation of a clear ultra-violet (UV)-blocking IOL (C) or a yellow blue-light-blocking IOL (Y). Participants were evaluated using the National Eye Institute Visual Function Questionnaire (VFQ-25) and Pittsburgh Sleep Quality Index (PSQI) before surgery and 2 and 7 months after surgery. Changes in sub-scale scores of VFQ-25 and PSQI were compared.	Sub-scale analyses for improvement after surgery revealed significant differences in ocular pain scores on the VFQ-25 (Y>C; the higher the score, the better the outcome). Furthermore, there were significant differences between the two IOLs in terms of the sleep latency score (C>Y) and sleep disturbances score (C>Y). A posterior sub-capsular cataract was significantly correlated with improvements in ocular pain and sleep latency scores. These effects were successfully represented by the change in scores rather than absolute post-operative scores because individual standard of response may often change after intervention, recognized as a response shift phenomenon in patient-reported outcome study. Regarding seasonal differences, patients who had surgery in summer exhibited relatively better sleep quality than those who had surgery in winter.	Analysis of sub-scales of health indices demonstrated characteristic prognoses for each IOL and cataract type. Cataract surgery may potentially contribute to systemic health in older adults.	
25525678	Based on risk coefficients for cardiovascular and psychiatric disease derived from a case-control study in the vicinity of a major German airport, statistics on persons exposed to night-time railroad noise in the vicinity of the Rotterdam-Genova Transversal, and on health expenditure calculations by the Federal Statistical Office of Germany a prognosis on effects of railroad noise was performed. It resulted for 1 10-year period in nearly 75 000 excess cases of diseases, nearly 30 000 excess deaths and health expenditures of 3.8 billion euros. 
25525361	Sleep-wake disturbances have frequently been reported in bipolar disorder and schizophrenia, and are considered to be caused by an underlying circadian rhythm disorder. The study presented here was designed to investigate the existence of Per3 polymorphism in bipolar disorder type I (BD-I) and schizophrenic patients in South India.Blood samples were collected from 311 BD-I patients, 293 schizophrenia patients, and 346 age- and sex-matched normal controls. Per3 genotyping was performed on DNA by polymerase chain reaction using specific primers.	An increased prevalence of five repeat homozygotes was seen in BD-I patients as compared with healthy controls (odds ratio =1.72 [95% confidence interval: 1.08-2.76, P=0.02]). In BD-I patients, the frequency of the five repeat allele was higher (allele frequency =0.41), and that of the four repeat allele lower (allele frequency =0.36) (χ (2)=4.634; P<0.03) than in the control group. No significant association was observed in the allele frequencies of four and five repeat alleles in schizophrenia patients when compared with controls.	The occurrence of the five repeat allele of Per3 may be a risk factor for BD-I onset in this ethnic group.	
25524851	Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy.
25523890	The Edmonton Symptom Assessment System (ESAS) measures the severity of nine symptoms. Constipation and sleep disturbance are common in patients with cancer, but are not currently included in the ESAS.To validate the numerical rating scale (NRS) versions of ESAS and its revised version (ESAS-r), with the additional symptoms of constipation and sleep (CS), and to assess patient preference for either version.	Outpatients with advanced cancer (N = 202) completed three assessments during a single clinic visit: ESAS-CS, and an added time window of "past 24 hours"; ESAS-r-CS, with a time window of "now" and symptom definitions; and the Memorial Symptom Assessment Scale (MSAS). Internal consistency was calculated using Cronbach's alpha. Paired t-tests compared ESAS-CS and ESAS-r-CS scores; these were correlated with MSAS using Spearman correlation coefficients. Test-retest reliability at 24 hours was assessed in 26 patients.	ESAS-CS and ESAS-r-CS total scores correlated well with total MSAS (Spearman's rho 0.62 and 0.64, respectively). Correlation of individual symptoms with MSAS symptoms ranged from 0.54-0.80 for ESAS-CS and 0.52-0.74 for ESAS-r-CS. Although participants preferred the ESAS-r-CS format (42.8% vs. 18.6%) because of greater clarity and understandability, the "past 24 hours" time window (52.8%) was favored over "now" (21.3%). Shortness of breath and nausea correlated better for the "past 24 hours" time window (0.8 and 0.72 vs. 0.74 and 0.64 in ESAS-r-CS, respectively). The 24-hour test-retest of the ESAS-CS demonstrated acceptable reliability (intraclass correlation coefficient = 0.69).	The ESAS-CS and ESAS-r-CS NRS versions are valid and reliable for measuring symptoms in this population of outpatients with advanced cancer. Although the ESAS-r-CS was preferred, patients favored the 24-hour time window of the ESAS-CS, which also may best characterize fluctuating symptoms.	

25520301	Sleep disturbances are a hallmark sign after a sport-related concussion (SRC). Poor sleep has been shown to adversely affect baseline neurocognitive test scores, but it is not comprehensively understood how neurocognitive function is affected by disrupted sleep during recovery from a concussion.To identify the correlation between adolescent athletes' neurocognitive function and their self-reported sleep quantity and sleep disturbance symptoms during recovery from SRC.	Cross-sectional study; Level of evidence, 3.	Immediate Post-Concussion Assessment and Cognition Testing (ImPACT) data were retrospectively collected for 545 adolescent athletes treated for SRC at a sports medicine concussion clinic. Patients were stratified into groups based on 2 criteria: self-reported sleep duration and self-reported sleep disturbance symptoms during postinjury ImPACT testing. Sleep duration was classified as short (<7 hours), intermediate (7-9 hours), and long (>9 hours). Sleep disturbance symptoms were self-reported as part of the Post-Concussion Symptom Scale (PCSS) as either sleeping less than normal, sleeping more than normal, or having trouble falling asleep. One-way analyses of variance were conducted to examine the effects that sleep duration as well as self-reported sleep disturbance symptoms had on composite scores. A total of 1067 ImPACT tests were analyzed: test 1, 545; test 2, 380; and test 3, 142.	Sleeping fewer than 7 hours the night before testing correlated with higher PCSS scores (P < .001), whereas sleeping longer than 9 hours correlated with worse visual memory (P = .01), visual motor speed (P <.001), and reaction time (P = .04) composite scores. With regard to self-reported sleep disturbance symptoms, patients demonstrated worse composite scores during ImPACT testing when they self-reported sleeping more than normal (ImPACT test 1: verbal memory, P < .001; visual motor speed, P = .05; reaction time, P = .01; ImPACT test 2: verbal memory, P < .001; visual memory, P < .001; visual motor speed, P < .001; reaction time, P = .01). Adolescent patients recovering from SRC demonstrated higher (worse) PCSS scores (P < .001) when they sensed that their sleep had been disrupted.	Adolescent patients who perceive that their sleep is somehow disrupted after SRC may report a greater number of concussion symptoms during their recovery. In addition, the study results suggest that sleeping more than normal may identify an individual who continues to be actively recovering from concussion, given the correlation between lower neurocognitive function and this self-reported symptom.	
25518508	To evaluate the efficacy of cytoflavin in the treatment of patients with hypertensive encephalopathy (HE).One hundred and forty patients aged 39 to 73 years, diagnosed with HE, were examined and randomized to 2 groups. A study group (n = 74) received cytoflavin in a dose of 2 tablets b.i.d. on days 1 to 25 days inclusive during standard basic therapy. A comparison group (n = 66 persons) had standard basic therapy only. A control group consisted of 30 apparently healthy individuals. The investigators studied the frequency of headache, dizziness, and other complaints and the intensity of cephalalgic syndrome, by using a visual analog scale, the quality of life by the Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) questionnaire, that of sleep by the subjective sleep characteristics questionnaire elaborated at the Moscow City Somnological Center, the level of asthenia by a subjective asthenia rating scale (Multidimensional Fatigue Inventory (MFI-20), and autonomic status, by applying objective and subjective scales on days 1 and 25 of therapy.	The study has shown that cytoflavin used in the above dose for 25 days reduces the frequency and magnitude of complaints of headache, dizziness, "venous" complaints, the degree of autonomic and asthenic disorders, and impairments in the quality of sleep and life in the patients with HE at all disease stages. A stepwise discriminant analysis has indicated that the degree of cephalgic syndrome, and autonomic disorders, and worse sleep quality are the most effective points for using the energy-modifier cytoflavin.	HE treatment based on the current pathogenetic principles may have a preventive impact on the development of HE or slow down the rate of its progression.	
25517910	We aimed to investigate the effect of sleep problems, depression, and cognitive processes on suicidal risk among 460 young adults. They completed self-report questionnaires assessing suicidal behavior, sleep quality, depressive symptoms, emotion regulation, rumination, and impulsivity. Suicidal participants exhibited higher rates of depressive symptoms, sleep problems, expressive suppression, rumination, and impulsivity. A confirmatory factor analysis model revealed pathways to suicidal risk that showed no direct pathways between sleep problems and suicidal risk. Instead, sleep was related to suicidal risk via depression and rumination, which in turn increased suicidal risk. These results suggest that addressing sleep problems will be useful in either the treatment or prevention of depressive and rumination symptoms and reduction in suicidal risk. 
25517022	To highlight the recent findings on sleep-obesity associations in children. We focus on sleep duration, sleep timing and chronotype, and describe the potential mechanisms underlying sleep-obesity associations.Poor sleep is increasingly common in children and associations between short sleep duration in early childhood and obesity are consistently found. Less is known about the infancy period, and the findings in adolescents are inconsistent. Sleep timing patterns may also contribute to obesity risk. Variable and shifted sleep schedules and evening chronotypes have recently been linked to adiposity in adults; less is known about children. Further, there is little understanding regarding the mechanisms of association. The timing of eating, dietary intake, obesogenic eating behaviors, and changes in appetite-regulating hormones have been identified as possible mechanisms for sleep-obesity associations and may be promising avenues for future research. Longitudinal and experimental work with children is needed to determine the nature of associations.	Beyond sleep duration, sleep timing patterns may contribute to obesity risk. Biological and behavioral processes have been proposed as mechanisms that may explain the association. Understanding the pathways through which poor sleep patterns could increase obesity risk in children may provide novel avenues for intervention.	
25516029	To investigate the association between self-reported sleep duration and serum vitamin D level in elderly Korean adults.Cross-sectional data analysis.	Korean National Health and Nutrition Examination Survey 2010.	Noninstitutionalized adults aged 60 to 80 (N = 1,614).	The confounding variables were serum 25-hydroxy vitamin D level, age, sex, body mass index, smoking history, alcohol consumption, and self-reported daily sun exposure and sleep duration. Self-reported daily sleep duration was divided into four groups: Q1 (≤4 hours), Q2 (5-6 hours), Q3 (7-8 hours), and Q4 (≥9 hours).	Mean serum vitamin D levels of subjects in the Q1, Q2, Q3, and Q4 groups were 44.18, 48.08, 48.83, and 51.78 nmol/L, respectively. On multivariate linear regression analysis, subjects in the Q2 (B = 3.80, 95% confidence interval (CI) = 0.42-7.19), Q3 (B = 4.89, 95% CI = 1.54-8.24), and Q4 (B = 5.18, 95% CI = 0.78-9.58) groups had significantly higher serum vitamin D levels than subjects in the Q1 group.	Serum vitamin D level is positively associated with self-reported daily sleep duration in elderly Korean individuals. These results suggest that inadequate sleep duration may be associated with lower vitamin D levels in elderly adults.	
25516028	To compare the effects of different types of physical and mental activity on self-reported sleep quality over 12 weeks in older adults with cognitive and sleep complaints.Randomized controlled trial.	General community.	Seventy-two inactive community-dwelling older adults with self-reported sleep and cognitive problems (mean age 73.3 ± 6.1; 60% women).	Random allocation to four arms using a two-by-two factorial design: aerobic+cognitive training, aerobic+educational DVD, stretching+cognitive training, and stretching+educational DVD arms (60 min/d, 3 d/wk for physical and mental activity for 12 weeks).	Change in sleep quality using seven questions from the Sleep Disorders Questionnaire on the 2005 to 2006 National Health and Nutrition Examination Survey (range 0-28, with higher scores reflecting worse sleep quality). Analyses used intention-to-treat methods.	Sleep quality scores did not differ at baseline, but there was a significant difference between the study arms in change in sleep quality over time (P < .005). Mean sleep quality scores improved significantly more in the stretching+educational DVD arm (5.1 points) than in the stretching+cognitive training (1.2 points), aerobic+educational DVD (1.1 points), or aerobic+cognitive training (0.25 points) arms (all P < .05, corrected for multiple comparisons). Differences between arms were strongest for waking at night (P = .02) and taking sleep medications (P = .004).	Self-reported sleep quality improved significantly more with low-intensity physical and mental activities than with moderate- or high-intensity activities in older adults with self-reported cognitive and sleep difficulties. Future longer-term studies with objective sleep measures are needed to corroborate these results.	
25515951	The aims of this study were to examine differences between partners of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) and partners of men from the population regarding sleep and two aspects of quality of life, partner-specific quality of life and health-related quality of life (HRQoL), and to identify factors related to the partner-specific quality of life and the parameter sleep efficiency.The design was descriptive and comparative. The subjects were partners of men with LUTS suggestive of BPO (n = 126) and partners of randomly selected men from the general population (n = 131). Self-administered questionnaires about demography, comorbidity, sleep, sexuality, partner-specific quality of life and HRQoL were used.	Partners of men with LUTS suggestive of BPO were significantly more affected in all variables measuring partner-specific quality of life compared with partners from the population. The most impaired aspects were compassion and worry about an operation or cancer. In logistic regression, the only explanatory factors were having a partner belonging to the LUTS group for impaired partner-specific quality of life and having a bed partner for high sleep efficiency. There were no significant differences between the two groups regarding the quantity and quality of sleep or the HRQoL.	The partner-specific quality of life was impaired in partners of men with LUTS suggestive of BPO. Sleep and HRQoL did not differ between partners of men with LUTS and partners from the population.	
25515766	Several studies have reported that depression and anxiety are very common in atrial fibrillation due to impaired quality of life. Dabigatran is an anti-aggregation agent used for the treatment of atrial fibrillation. In terms of drug interactions during treatment with dabigatran, patients suffering from minor depression are reported to be a population at risk. This report is about a 68-year-old man whose depressive symptoms were aggravated after taking dabigatran for atrial fibrillation. The case is discussed in terms of his aggravated depressive symptoms and the interaction between his prescription medications. 
25515647	Poor sleep is often associated with a series of health problems in patients with chronic obstructive pulmonary disease (COPD), but the relationship between sleep quality and functional exercise capacity has not been previously investigated.To evaluate the relationship between quality of sleep and functional exercise capacity in clinically stable COPD.	One hundred three consecutive subjects with stable COPD were recruited. The subjects were assessed with the Pittsburgh Sleep Quality Index (PSQI) and divided into poor sleep group (PSQI >5) and good sleep group (PSQI ≤5). Subjects were also assessed with spirometry, 6-min walk distance (6MWD), oxygen saturation (SP O2 ), the Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, COPD Assessment Test (CAT), Modified Medical Research Council dyspnea scale and quadriceps muscle function.	Poor sleep was present in 43.69% of the patients with COPD. Subjects with poor sleep had shorter 6MWD (t = -3.588, P < 0.001), greater age (t = 2.519, P = 0.013), worse quality of life (t = 5.487, P < 0.001) and more depression (t = 6.576, P < 0.001) or anxiety (t = 4.245, P < 0.001) symptoms. 6MWD showed significant negative correlations with the PSQI global score (r = -0.373, P < 0.001). Multiple stepwise regresion analysis showed that PSQI global score was an independent psychological predictor of 6MWD, and 6MWD was the only physical predictor of PSQI total score in patients with COPD.	There is a close relationship between sleep quality and functional exercise capacity in patients with COPD.	
25515641	Sleep is a complex behavioural state, the ultimate functions of which remain poorly understood. It becomes more fragmented as we age, with more night-time awakenings and greater tendency for daytime sleep. The magnitude of disordered sleep among individuals affected by dementia has been clearly demonstrated, and disturbed sleep is a major clinical problem in dementia. Comorbid insomnia and other sleep disturbances are common in patients with neurodegenerative disorders, such Alzheimer's disease and other dementing disorders. How and when sleep problems manifest themselves can depend on the type of dementia involved as well as the stage of the dementia. However, differences in sleep pattern presentation show more variation during the initial stages of dementias than they do during the later stages. Effective, pragmatic interventions are largely anecdotal and untested.



25515275	We aimed to evaluate the association between sleep quality and physical disability in community-dwelling older adults.There were 213 community-dwelling adults (76 men and 137 women) aged 65 years and above participated into this investigation. The Groningen Activity Restriction Scale and the Pittsburgh Sleep Quality Index were utilized to evaluate physical disability and subjective sleep quality, respectively. Global functional capacity was measured by the 6-minute walk test (6MWT). The Mini Mental State Examination and the Chinese Geriatric Depression Screening Scale were used to evaluate cognitive function and depression.	Univariate analysis revealed a correlation between physical disability and poor sleep quality, older age, 2 or more comorbidities, depression, functional capacity, and poor cognitive function. However, in the multivariate analyses, depression failed to show significant association with physical disability. In contrast, an independent association was observed between poor sleep quality and physical disability (OR = 2.03; 95% CI: 1.02-4.05).	In community-dwelling older adults, subjective poor sleep was significantly associated with physical disability, even after controlling for the effects of other established risk factors.	
25515274	Medical students carry a large academic load which could potentially contribute to poor sleep quality above and beyond that already experienced by modern society. In this global literature review of the medical students' sleep experience, we find that poor sleep is not only common among medical students, but its prevalence is also higher than in non-medical students and the general population. Several factors including medical students' attitudes, knowledge of sleep, and academic demands have been identified as causative factors, but other potential mechanisms are incompletely understood. A better understanding about the etiology of sleep problems in medical trainees is essential if we hope to improve the overall quality of medical students' lives, including their academic performance. Sleep self-awareness and general knowledge appear insufficient in many studied cohorts, so increasing education for students might be one beneficial intervention. We conclude that there is ample evidence for a high prevalence of the problem, and research in this area should now expand towards initiatives to improve general sleep education for medical students, identify students at risk, and target them with programs to improve sleep.
25515273	In this study, we examine the association of asthma (asthma symptoms, asthma control, lung function) and sleep problems in a group of urban children. The role of allergic rhinitis (AR), a comorbid condition of asthma, on children's sleep problems is also examined. Finally, we investigate whether sleep hygiene moderates the association between asthma and sleep problems, and whether there are differences in these associations based on ethnic background.Non-Latino White, Latino, and African American urban children with asthma (n = 195) ages 7-9 (47% female) and their primary caregivers participated in a baseline visit involving interview-based questionnaires on demographics, asthma and rhinitis control, and caregiver report of children's sleep problems and sleep hygiene. Children and their caregivers participated in a clinical evaluation of asthma and AR, followed by a month monitoring period of children's asthma using objective and subjective methods.	Total sleep problem scores were higher in children of the sample who were from African American and Latino backgrounds, compared to non-Latino white children. Poor asthma control was predictive of higher levels of sleep problems in the entire sample. Poorer AR control also was related to more sleep problems, over and above children's asthma in the sample. This association was more robust in non-Latino white children. Poor sleep hygiene heightened the association between poor asthma control and sleep problems in the entire sample and in African American children.	Multidisciplinary interventions integrating the co-management of asthma, AR, and the effects of both illnesses on children's sleep, need to be developed and tailored to children and their families' ethnic background.	
25512763	Excessive daytime sleepiness is a commonly reported problem in dementia with Lewy bodies (DLB). We examined the relationship between nighttime sleep continuity and the propensity to fall asleep during the day in clinically probable DLB compared to Alzheimer's disease (AD) dementia.A full-night polysomnography was carried out in 61 participants with DLB and 26 with AD dementia. Among this group, 32 participants with DLB and 18 with AD dementia underwent a daytime Multiple Sleep Latency Test (MSLT). Neuropathologic examinations of 20 participants with DLB were carried out.	Although nighttime sleep efficiency did not differentiate diagnostic groups, the mean MSLT initial sleep latency was significantly shorter in participants with DLB than in those with AD dementia (mean 6.4 ± 5 minutes vs 11 ± 5 minutes, P <0.01). In the DLB group, 81% fell asleep within 10 minutes compared to 39% of the AD dementia group (P <0.01), and 56% in the DLB group fell asleep within 5 minutes compared to 17% in the AD dementia group (P <0.01). Daytime sleepiness in AD dementia was associated with greater dementia severity, but mean MSLT latency in DLB was not related to dementia severity, sleep efficiency the night before, or to visual hallucinations, fluctuations, parkinsonism or rapid eye movement sleep behavior disorder. These data suggest that abnormal daytime sleepiness is a unique feature of DLB that does not depend on nighttime sleep fragmentation or the presence of the four cardinal DLB features. Of the 20 DLB participants who underwent autopsy, those with transitional Lewy body disease (brainstem and limbic) did not differ from those with added cortical pathology (diffuse Lewy body disease) in dementia severity, DLB core features or sleep variables.	Daytime sleepiness is more likely to occur in persons with DLB than in those with AD dementia. Daytime sleepiness in DLB may be attributed to disrupted brainstem and limbic sleep-wake physiology, and further work is needed to better understand the underlying mechanisms.	
25512240	Unrefreshing sleep and lowered physical activity are commonly observed in chronic fatigue syndrome (CFS) patients, but how they might influence each other remains unexplored. Therefore, this study simultaneously examined the exercise capacity, sleep characteristics and physical activity in CFS patients.Handgrip strength and cycle exercise capacity were assessed in 42 female CFS patients and 24 inactive control subjects. During four consecutive days and nights, energy expenditure, activity and sleep-wake pattern were objectively registered using a Sensewear Armband.	Exercise capacity was significantly lower in CFS patients. In both groups VO2peak correlated with the time subjects were physically active. In CFS patients only, VO2peak correlated negatively with sleeping during the day whilst physical activity level and energy expenditure correlated negatively with sleep latency and lying awake at night.	In the present study, CFS patients with higher VO2peak tend to sleep less over day. Occupation in physical activities was negatively associated with sleep latency and lying awake at night. Increased physical activity potentially has beneficial effects on sleep quality in CFS. However, a close monitoring of the effects of increasing physical activity is essential to avoid negative effects on the health status of patients.	Female patients with chronic fatigue syndrome (CFS) have normal sleep latency and sleep efficiency, but sleep more and spent more time in bed as compared to healthy inactive women. Female CFS patients have lower exercise capacity, and a lower physical activity level as compared to healthy inactive women. CFS patients appear to be more sensitive for sleep quality (sleep latency and lying awake at night), which is associated with a low physical activity level.	

25511388	The neuropeptides orexin-A and orexin-B are produced by one group of neurons located in the lateral hypothalamic/perifornical area. However, the orexins are widely released in entire brain including various central motor control structures. Especially, the loss of orexins has been demonstrated to associate with several motor deficits. Here, we first summarize the present knowledge that describes the anatomical and morphological connections between the orexin system and various central motor control structures. In the next section, the direct influence of orexins on related central motor control structures is reviewed at molecular, cellular, circuitry, and motor activity levels. After the summarization, the characteristic and functional relevance of the orexin system's direct influence on central motor control function are demonstrated and discussed. We also propose a hypothesis as to how the orexin system orchestrates central motor control in a homeostatic regulation manner. Besides, the importance of the orexin system's phasic modulation on related central motor control structures is highlighted in this regulation manner. Finally, a scheme combining the homeostatic regulation of orexin system on central motor control and its effects on other brain functions is presented to discuss the role of orexin system beyond the pure motor activity level, but at the complex behavioral level. 
25510740	Poor sleep contributes to the developmental problems seen in preterm infants. We evaluated sleep problems in preterm infants 6 months of post-gestational age using the subjective Brief Infant Sleep Questionnaire (BISQ) and objective sleep tests. We also compared the sleep of premature infants with that of full-term infants.The study included 68 6-month-old full-term healthy infants and 191 premature infants born at <37 weeks gestation. All parents completed the BISQ-Chinese version and sleep diaries. At the same time, all premature infants were submitted to one night of polysomnography (PSG) in the sleep laboratory and also were set up with an actigraph kept for 7 days. Statistical analyses were performed using correlation coefficients and the t-test with SPSS version 18 to compare questionnaire responses with other subjective and objective measures of sleep.	The sleep problems indicated in the subjective questionnaire for the premature infants, particularly: "the nocturnal sleep duration, number of night awakenings, daytime sleep duration, duration of time with mouth breathing, and loud-noisy breathing" had significant correlations with sleep diaries, actigraphy and PSG results. The BISQ showed that duration of infant's sleeping on one side, nocturnal sleep duration, being held to fall asleep, number of nighttime awakenings, daytime sleep duration, subjective consideration of sleep problems, loud-noisy breathing, and duration spent crying during the night were significantly different between the premature infants and the term infants. PSG confirmed the presence of a very high percentage (80.6%) of premature infants with AHI > 1 event/hour as indicated by the questionnaire.	Premature infants have more sleep problems than full-term infants, including the known risk of abnormal breathing during sleep, which has been well demonstrated already with the BISQ-Chinese (CBISQ).	
25510361	Sleep disturbance may influence the development of cancer and responses to treatment. It is also closely tied to recovery and quality of life in cancer patients, survivors, and caregivers, and recent studies have begun to show beneficial effects of sleep-promoting interventions. Despite the importance of sleep to cancer and its treatment and the availability of numerous tools for measuring sleep quality and quantity, sleep measurements are underutilized in cancer studies.This review, written for cancer researchers interested in incorporating sleep measures into their studies, is designed to raise awareness about the importance of sleep and suggests strategies for including sleep evaluation in cancer studies.	Inclusion of readily available sleep measures may ultimately improve cancer care by facilitating studies that lead to a greater understanding of how sleep and sleep disturbance influence all aspects of cancer care and the patient experience.	

25509176	Neocortical EEG slow wave activity (SWA) in the delta frequency band (0.5-4.0 Hz) is a hallmark of slow wave sleep (SWS) and its power is a function of prior wake duration and an indicator of a sleep need. SWS is considered the most important stage for realization of recovery functions of sleep. Possibility of impact on characteristics of a night sleep by rhythmic (0.8-1.2 Hz) subthreshold electrocutaneous stimulation of a hand during SWS is shown: 1st night--adaptation, 2nd night--control, 3d and 4th nights--with stimulation during SWA stages ofa SWS. Stimulation caused significant increase in average duration of SWS and EEG SWA power (in 11 of 16 subjects), and also well-being and mood improvement in subjects with lowered emotional tone. It is supposed that the received result is caused by functioning of a hypothetical mechanism directed on maintenance and deepening of SWS and counteracting activating, awakening influences of the afferent stimulation. The results can be of value both for understanding the physiological mechanisms of sleep homeostasis and for development of non-pharmacological therapy of sleep disorders.
25509175	The present article is an attempt to perform a conceptual clinical and physiological analysis of a large spec- trum of sleep-related phenomena called parasomnias in children, based on data from three independent in- stitutions. Parasonmias appear in the process of falling asleep, at the time of sleep stage changes, and upon awakening. They are common for both healthy children and those with neurological and psychiatric disorders. Brief descriptions of clinical pictures of several groups of parasomnias and their polysomnographic characteristics are presented. Instances of stereotyped rhythmic movements (e.g. head rocking), paroxysmal somatic and behavioral episodes (night terrors and nightmares), "static" phenomena (sleep with open eyes, strange body positions), as well as somnambulism are specifically described. Common features of parasomnias as a group have been identified (the "Parasomnia syndrome"). It was found that sleep architecture frequently normalizes after a parasomnia episode, whereas parasomnias are self-liquidated after sleep matures (self-cure). The significance of gender differences in parasomnias have been reviewed. Possible compensatory physiological functions of parasomnias acting as "switches" or "stabilizers" of sleep stages to "off-set" deviated or immature sleep-wake mechanisms were discussed.
25509172	The work examines the influence of degree ofstenosis or occlusion of the internal carotid artery (ICA) of noc- turnal sleep and discusses possible neurophysiological mechanisms of sleep disorders when blood flow in ca- rotid system. 24 patients (19 male and 5 female) were examined. The mean age of men was 49.75 ± 6.55; women--46.67 ± 5.86. Six patients with a single unilateral internal carotid stenosis (ICA) 50%; seven patients--stenosis of ICA 50-70%; eleven patients--occlusion of ICA completed the study. Polysomnography was recorded with "Neuro-Spectr-5/EP" ("NeuroSoft", Russia) and "Delta Flash" ("Deltamed", France) according to international recommendation. Stages of sleep were identified according to Re- chtschaffen A., Kales A. (1968) criteria. Patients were asked to fill in the questionnaire prior to clinical and polysomnographic evaluation. Regional cerebral blood flow (mL/100g/min) with 99mTechnetium (Gamma-camera, DST-Xli "General electric", USA) was study by single photon emission CT imaging. The result of this study showed that with stenosis of the ICA to 50% structure of nocturnal sleep is not changed: records all phases and stages of sleep, quantitative parameters that match the normative data; or decline in the representation of only the stage II sleep; at stenosis ICA of 50-70% is violation of mostly stage II sleep and slow-wave sleep, and with occlusion ICA violation slow-wave sleep and in 45% of cases--REM-sleep.
25509171	The purpose of the research was to study effect of long-term isolation on night sleep. The data were collected during international ground simulation of an interplanetary manned flight--"Mars-500". The polysomnographic recordings of six healthy men were performed before, four times during and after 520-days confinement. During the isolation sleep efficiency and delta-latency decreased, while sleep latency increased. Post-hoc analysis demonstrate significant differences between background and the last (1.5 months before the end of the experiment) measure during isolation. Frequency of nights with low sleep efficiency rose on the eve of the important for the crew events (simulation of Mars landing and the end of the confinement). Two weeks after the landing simulation, amount of the nights with a low sleep efficiency significantly decreased. Therefore, anticipation of significant event under condition of long-term isolation might result in sleep worsening in previously healthy men, predominantly difficulties getting to sleep.
25509167	The study of human vital functions during sleep could have advantage over studies during wakefulness because sleep potentially is more predictable condition. Besides the factors accompanying sleep (minimization of external stimulation and social interactions, low mental activity, antigravity posture) also increase the quality of data acquisition comparing with wake states. Properly organized clinical investigation in the framework of sleep medicine concept could reveal these advantages and increase the interest to the sleep studies from the community and authorities. This could also promote the investigations in the field of fundamental somnology.
25507136	To investigate the effects of the Sini San at different doses on each sleeping state [slow-wave sleep 1 (SWS 1), slow-wave sleep 2 (SWS2), rapid-eye-movement (REM), wakefulness (W)] in insomnia rats and to identify its mode of action for improving sleep.The insomnia rats were randomly divided into a high-, medium- or low-dose group of Sini San (equal to crude drug 8.8, 4.4, or 2.2 g/kg, respectively) for seven consecutive days.	Compared with pre-administration, SWS2 was significantly increased after administration of the low dose. Compared with pre-administration, W was significantly decreased and SWS1, SWS2, and the total sleeping time (TST) were markedly increased after administration of the medium dose. Compared with pre-administration, W was significantly decreased and SWS1, SWS2, rapid-eye-movement sleep, and TST were significantly longer after administration of the high dose. The effects of Sini San on sleep-wake cycle are dose-dependent.	The results suggest that Sini San extends SWS1 and SWS2, which increases the total sleeping time.	
25505312	Experimental advances in the study of neuroglia signaling have been greatly accelerated by the generation of transgenic mouse models. In particular, an elegant manipulation that interferes with astrocyte vesicular release of gliotransmitters via overexpression of a dominant-negative domain of vesicular SNARE (dnSNARE) has led to documented astrocytic involvement in processes that were traditionally considered strictly neuronal, including the sleep-wake cycle, LTP, cognition, cortical slow waves, depression, and pain. A key premise leading to these conclusions was that expression of the dnSNARE was specific to astrocytes. Inconsistent with this premise, we report here widespread expression of the dnSNARE transgene in cortical neurons. We further demonstrate that the activity of cortical neurons is reversibly suppressed in dnSNARE mice. These findings highlight the need for independent validation of astrocytic functions identified in dnSNARE mice and thus question critical evidence that astrocytes contribute to neurotransmission through SNARE-dependent vesicular release of gliotransmitters.
25501763	To investigate the association between various sleep problems and self-rated health (SRH), a total of 43,092 (34,164 men and 8,928 women) employees were surveyed by means of a self-administered questionnaire. The risk of suboptimal (poor, very poor) SRH associated with sleep problems was estimated using multivariable logistic regression with odds ratios (ORs) as measures of associations. Because the prevalence of suboptimal SRH differed by sex (men 29.4% and women 34.1%, P < 0.001), the analyses were done separately for men and women. Employees sleeping less than 6 hrs/day (OR = 1.39 for men, 1.40 for women), with difficulty initiating sleep (OR=4.44 for men, 3.85 for women), with difficulty maintaining sleep (OR=5.72 for men, 4.85 for women), with early morning awakening (OR=3.87 for men, 4.25 for women), with difficulty waking up in the morning (OR=3.30 for men, 3.40 for women), feeling tired when waking up in the morning (OR=4.97 for men, 4.82 for women), and excessive daytime sleepiness at work (OR=2.34 for men, 2.11 for women) had a significantly higher odds of suboptimal SRH compared to those without sleep problems. The association between sleep problems and suboptimal SRH did not differ between men and women. In conclusion, the data point to an independent relationship between sleep problems and suboptimal SRH among Japanese employees. 

25501300	The majority of studies on child sleep problems focus primarily on mothers, neglecting paternal influences. Guided by the transactional framework, we explored how child temperament, paternal and maternal stress, and the parent-child interactions differ between families having children with sleep disturbances and a selected comparison group. The role of paternal involvement in child caregiving as a moderator of these differences was assessed. The sample consisted of 51 children (1-3 years old) and their mothers and fathers. Data were collected during home visits, when mothers and fathers completed questionnaires and were interviewed. In addition, mother-child and father-child interactions were videotaped. Results indicate that compared to the comparison group, fathers rated children with sleep disturbances as fussier, both their mothers and fathers experienced higher levels of stress, and reported using more bedtime interactions that interfere with child's sleep-wake self-regulation. In addition, their fathers were less sensitive during father-child interaction and less involved in child caregiving. Finally, paternal involvement moderated the group differences seen in maternal stress, suggesting that high paternal involvement acted as a buffer to protect parents of children with sleep disturbances from experiencing parental stress. The important role of fathers in families having children with sleep disturbances is discussed. 
25500332	Propriospinal myoclonus (PSM) is a rare type of spinal myoclonus characterized by muscle jerks that usually start in the midthoracic segments and then slowly propagate up and down into the spinal cord, resulting in repetitive and irregular jerky flexion, or extension of the trunk, neck, knees and hips. PSM can be symptomatic, but up to 80% of reported cases appear idiopathic. PSM tends to occur especially while the subject is lying down. PSM at sleep onset was first described by experts in sleep medicine. The original electrophysiological features included fixed pattern of muscle activations, slow spinal cord conduction (5-15 m/s), electromyographic burst duration less than 1000 ms, synchronous activation of agonist and antagonist muscles and no involvement of facial muscles. PSM has been reported to be a functional (psychogenic) movement disorder in a number of cohorts. The differential diagnosis between idiopathic PSM and the functional forms is not always straightforward. A consistent polymyographically documented muscle activation pattern may be supportive but by no means sufficient and additional neurophysiological investigations are required. PSM should be differentiated from other movement disorders involving the abdomen and trunk, or occurring at sleep-wake transition. This article offers a comprehensive overview of the spectrum of PSM phenotypes. 
25500219	Tumor necrosis factor (TNF) is considered a key molecule in the regulation of sleep in health and disease. Conversely, sleep compared to sleep deprivation can modulate TNF release, but overall results are conflicting. In this study we focused on the influence of sleep on spontaneous, i.e., unstimulated TNF production, which might be involved in sleep regulation under normal non-infectious conditions, and on lipopolysaccharide (LPS)-stimulated TNF production, which reflects the capacity of the immune system to respond to a pathogen. To this end, we monitored 10 healthy men during a regular sleep-wake cycle and during 24h of wakefulness while blood was sampled repeatedly to analyze circulating TNF levels in serum as well as intracellular TNF production in monocytes spontaneously and after stimulation with LPS employing whole blood cell cultures. In addition we assessed numbers of monocyte subsets and levels of various hormones in blood. In comparison with nocturnal wakefulness, sleep acutely decreased serum TNF levels, with no parallel decrease in spontaneous monocytic TNF production, but was associated with a striking nighttime increase in the percentage of TNF producing monocytes after stimulation with LPS. The following day circulating TNF showed a reverse pattern with higher levels after regular sleep than after the nocturnal vigil. The mechanisms mediating the differential effects of sleep on circulating TNF (acutely decreased) vs. stimulated monocytic TNF production (acutely increased) remain unclear, although explorative correlational analyses pointed to a regulatory involvement of cortisol, norepinephrine and prolactin. The acute enhancing effect of sleep on LPS stimulated monocytic TNF production adds to the notion that nocturnal sleep favors immune defense to a microbial challenge. 
25499829	Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired sleep homeostasis. In conclusion, we suggest that alcohol may disrupt sleep homeostasis to cause sleep disruptions.
25498564	Histaminergic neurons have been reported to play an important role in the regulation of sleep-wake behavior through the histamine H1 receptor (R, H1R). First generation H1R antagonists, such as doxepin and diphenhydramine, produce drowsiness in humans, and are occasionally used to treat insomnia. However, if H1R antagonists function via physically blocking the H1R remains unclear. In the current study, we used H1R knockout (KO) mice to investigate if the sleep-promoting effects of doxepin and diphenhydramine are dependent on blockade of the H1R. When doxepin was administered, non-rapid eye movement (NREM) sleep in wild type (WT) mice increased for 4h, with an increase in the numbers of NREM sleep bouts of 256-512 s and 512-1024 s. These effects were not observed in the H1R KO mice. Furthermore, diphenhydramine increased NREM sleep for 6h in WT, and not in the H1R KO mice after the injection. These results indicate that both doxepin at 15 mg/kg and diphenhydramine at 10 mg/kg induce NREM sleep through blockade of H1R.
25498083	Following improvements in patient and graft survival after liver transplantation (LT), the recipients' quality of life has become an important focus of patient care. Sleep is closely related to physical and mental health; however, sleep disturbances in LT patients have not yet been evaluated.We assessed 59 LT patients (aged ≥18 years) between September 2011 and September 2012. The patients completed the restless legs syndrome (RLS), 36-item short-form health survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) questionnaires. In addition, laboratory data were obtained and neuropsychological tests (NPT) were performed during study entry.	Thirty-eight patients (64%) were included in the poor sleep group (PSQI ≥6 or ESS ≥10). The SF-36 scores were lower in the poor sleep group than in the good sleep group. Eleven patients (18%) had RLS. An NPT score ≥3 indicated minimal hepatic encephalopathy (MHE3). The MHE3 group consisted of 22 patients (43%). The time after LT was shorter; serum albumin, branched chain amino acid/tyrosine molar ratio (BTR), and role limitations due to poor physical health were lower; and serum ammonia levels were higher in the MHE3 group than in the MHE0-2 group. When the poor sleep group was divided into subgroups (control, MHE, RLS, and unknown), MHE patients had high model for end-stage liver disease scores, high ammonia levels, and low BTR, whereas RLS patients showed a short time after LT.	Sixty-four percent of recipients were classified as poor sleepers. SF-36 scores were lower for poor sleepers than good sleepers. RLS and MHE are major diseases that cause sleep disturbances in patients after LT.	

25496798	The purpose of this review article is to explore the links between sleep and epilepsy and the treatment of sleep problems in children with autism spectrum disorder (ASD). Epilepsy and sleep have bidirectional relationships, and problems with both are highly prevalent in children with ASD. Literature is reviewed to support the view that sleep is particularly important to address in the context of ASD. Identification and management of sleep disorders may improve seizure control and challenging behaviors. In closing, special considerations for evaluating and treating sleep disorders in children with ASD and epilepsy are reviewed. This article is part of a Special Issue entitled "Autism and Epilepsy". 
25496235	In patients who exhibit myotonic dystrophy type 1 (DM1), sleep disorders and breathing impairments are common; however, in those with DM type 2 (DM2), limited studies on polysomnography (PSG) and none on phrenic compound motor action potential (CMAP) have been performed, which is the aim of this study.Sixteen patients with DM2 were questioned about respiratory symptoms. They underwent PSG with morning arterial gas analyses (AGA). Respiratory functions and phrenic CMAPs were studied. The data were compared to those of 16 healthy controls and 25 patients with DM1.	Daytime tiredness is the most common symptom, but orthopnea was reported in 13% of patients with DM2. A detailed sleep architecture analysis revealed a significantly greater proportion of time in stage 3 and REM sleep, and a shorter time in stage 2 in the DM2 than in controls. Lower respiratory volumes and pressures, abnormalities in AGA, night oxygen desaturation and higher EtCO2 are present in DM2, but are less pronounced than in the DM1 population. Small CMAP amplitudes were presented in 12% of patients with DM2, correlating with smaller respiratory functions and poorer sleep quality. AHI was abnormal in 38% of DM2, mainly due to obstructive apneas. PSG did not reveal hypoventilation.	Diaphragm weakness and sleep apneas might be present in patients with DM2; therefore, we suggest regular questioning about symptoms of respiratory insufficiency and monitoring of phrenic CMAP. PSG should be recorded, when patients have suggestive symptoms, abnormalities in AGA or higher BMI.	
25496226	Subjective symptoms of temporomandibular disorders (TMDs) have rarely been studied by age group. We aimed to compare self-reported pain intensity, sleeping difficulty, and treatment outcomes of patients with myofascial TMDs among three age groups.The study population included 179 consecutive patients (151 women and 28 men) who underwent comprehensive clinical examinations at a university-based orofacial pain center. They were classified into myofascial pain subgroups based on the Research Diagnostic Criteria for Temporomandibular Disorders. They were stratified by age group: M1, under 20 years; M2, 20-39 years; and M3, 40 years and older. The patients scored their pretreatment symptoms (first visit) and post-treatment symptoms (last visit) on a form composed of three items that assessed pain intensity and one item that assessed sleeping difficulty. Their treatment options (i.e., pharmacotherapy, physical therapy, and orthopedic appliances) and duration were recorded. All variables were compared between sexes in each group and between the age groups by using the Kruskal-Wallis test, the Mann-Whitney U test, the chi-square test, and analysis of variance (p < 0.05).	No significant sex differences were found in any age group. Only sleeping difficulty was significantly different before treatment (p = 0.009). No significant differences were observed in the treatment options or treatment duration. After treatment, the intensity of jaw/face pain and headache and sleeping difficulty was significantly reduced in groups M2 and M3, but only the intensity of jaw/face pain was significantly decreased in group M1. The changes in the scores of pain intensity and sleeping difficulty were not different between the groups.	Pain intensity does not differ by age group, but older patients with myofascial TMDs had greater sleeping difficulties. However, there were no differences between the age groups in the treatment outcomes. Clinicians should carefully consider the age-related characteristics of patients with myofascial TMDs when developing appropriate management strategies.	
25493268	Sleep disruption in the acute phase after stroke has detrimental effects on recovery in both humans and animals. Conversely, the effect of sleep promotion remains unclear. Baclofen (Bac) is a known non-rapid eye movement (NREM) sleep-promoting drug in both humans and animals. The aim of this study was to investigate the effect of Bac on stroke recovery in a rat model of focal cerebral ischemia (isch).Rats, assigned to three experimental groups (Bac/isch, saline/isch, or Bac/sham), were injected twice daily for 10 consecutive days with Bac or saline, starting 24 h after induction of stroke. The sleep-wake cycle was assessed by EEG recordings and functional motor recovery by single pellet reaching test (SPR). In order to identify potential neuroplasticity mechanisms, axonal sprouting and neurogenesis were evaluated. Brain damage was assessed by Nissl staining.	Repeated Bac treatment after ischemia affected sleep, motor function, and neuroplasticity, but not the size of brain damage. NREM sleep amount was increased significantly during the dark phase in Bac/isch compared to the saline/isch group. SPR performance dropped to 0 immediately after stroke and was recovered slowly thereafter in both ischemic groups. However, Bac-treated ischemic rats performed significantly better than saline-treated animals. Axonal sprouting in the ipsilesional motor cortex and striatum, and neurogenesis in the peri-infarct region were significantly increased in Bac/isch group.	Delayed repeated Bac treatment after stroke increased NREM sleep and promoted both neuroplasticity and functional outcome. These data support the hypothesis of the role of sleep as a modulator of poststroke recovery.	
25492836	Humans spend a third of their lives asleep. A well-balanced synchrony between sleep and wakefulness is needed to maintain a healthy lifestyle. Optimal sleep is based on an individual's inherent sleep requirement and circadian rhythm. If either one or both of these critical elements are disrupted, daytime dysfunction, non-restorative sleep, and/or reduced sense of well-being may result. While the medical community is more familiar with sleep disorders such as sleep apnea, insomnia, and narcolepsy, circadian rhythm sleep wake disorders (CRSWDs) are less known, despite these being common within the general population. CRSWDs are comprised of the following: shiftwork disorder, delayed sleep phase disorder, advanced sleep phase disorder, jet lag disorder, non-24-hour sleep-wake disorder, and irregular sleep-wake rhythm disorder. In general, a CRSWD results when there is misalignment between the sleep pattern and the desired sleep schedule, dictated by work, family, and social schedules. Subsequently, patients have difficulty falling asleep, maintaining sleep, and/or experience poor quality sleep predisposing them to insomnia or excessive sleepiness. In this article, we review the core concepts related to sleep, and sleep deprivation in the context of CRSWDs. 
25491080	Sleep disturbance at high altitude is common in climbers. In this study, we intended to evaluate the effect of rapid ascent on sleep architecture using polysomnography (PSG) and to compare the differences between subjects with and without acute mountain sickness (AMS).The study included 40 non-acclimatized healthy subjects completing PSG at four time points, 3 days before the ascent (T0), two successive nights at 3150 m (T1 and T2), and 2 days after the descent (T3). All subjects were transported by bus from 555 to 3150 m within 3 h. AMS was diagnosed using self-reported questionnaire of Lake Louise score.	Twenty of 40 (50%) subjects developed AMS. At high altitude, awakening percentages increased in AMS group but changed insignificantly in non-AMS group. Arousal index and apnea/hypopnea index (AHI) increased irrespective of AMS. The increases of AHI were more evident in non-AMS group than in AMS group. Compared to subjects without AMS, those with AMS had significantly lower sleep efficiency, lower central apnea index, and longer latencies to sleep and rapid eye movement (REM) sleep at T1 and lower REM sleep percentages at T1 and T2. Subjects with older age and lower minimum arterial oxygen saturation during sleep at sea level were prone to develop AMS.	Higher AHI did not cause more frequent awakenings and arousals at high altitude. Central sleep apneas were observed in non-AMS but not in AMS group. Subjects unacclimatized to acute hypobaric hypoxia might have delayed and less REM sleep.	
25491077	In the 24/7 modern society, sleep disorders and the role of normal amounts and timing of sleep for health are often neglected by both doctors and their patients. Sleep has been said to be "of the brain, by the brain and for the brain" and the most immediate and obvious consequence of disrupted sleep is impaired brain function. This review will cover some of the recent papers published in both the Journal of Neurology and elsewhere in 2013/2014 that have advanced our knowledge of sleep and circadian rhythm disorders. 

25489999	The aim of this study is to investigate the relationships between road traffic noise exposure, annoyance caused by different noise sources and validated health indicators in a cohort of 1375 adults from the region of Basel, Switzerland. Road traffic noise exposure for each study participant was determined using modelling, and annoyance from various noise sources was inquired by means of a four-point Likert scale. Regression parameters from multivariable regression models for the von Zerssen score of somatic symptoms (point symptom score increase per annoyance category) showed strongest associations with annoyance from industry noise (2.36, 95% CI: 1.54, 3.17), neighbour noise (1.62, 95% CI: 1.17, 2.06) and road traffic noise (1.53, 95% CI: 1.09, 1.96). Increase in modelled noise exposure by 10 dB(A) resulted in a von Zerssen symptom score increase of 0.47 (95% CI: -0.01, 0.95) units. Subsequent structural equation modelling revealed that the association between physical noise exposure and health-related quality of life (HRQOL) is strongly mediated by annoyance and sleep disturbance. This study elucidates the complex interplay of different factors for the association between physical noise exposure and HRQOL. 
25489996	The present cohort study examined how lifestyle, household environment, and caries activity test score of Japanese children at age 1.5 years affected their dental caries incidence at age 3. Inclusion criteria were 1.5-year-old children with no dental caries. Dental examinations were performed for 33,655 children who participated in routine dental examinations at 1.5 years of age, and the exam was repeated approximately 21 months later (at age 3) at the Kobe City Public Health Center in Japan. After excluding 622 children who had caries at age 1.5 and 1831 children with missing lifestyle and household environment data in the questionnaires, the final data analysis was performed on a total of 31,202 children (16,052 boys, 15,150 girls).The multivariate logistic regression analysis indicated a strong association of the consumption of sugar-sweetened beverages/snacks, less frequent tooth brushing by the parents, lack of fluoride varnish, family history of smoking, with the risk of developing dental caries. A child's late bedtime is also one of the major risk factors for dental caries development. Further investigation is needed to examine whether the short duration or the irregularity of the sleep-wake cycle would affect early childhood oral health and whether there is a relationship between late bedtime and late night snack intake. 

25487182	For determining relationship between quality of sleep and spiritual well-being/religious activities in Muslim women with breast cancer (WBC), we conducted a cross-sectional study on 80 WBC who presented at all chemotherapy clinics in Qom, Iran, in 2012. We used Pittsburgh Sleep Quality Index (PSQI), spiritual well-being scale (SWBS), and religious activities (RA) questionnaire. Global PSQI score and its seven components score were not significantly correlated with total score of SWBS and its two subscales. Global PSQI score was not significantly correlated with total score of RA questionnaire (P = 0.278), but its "sleep latency" (r = 0.235, P = 0.044) and "use of sleep medications" (r = 0.237, P = 0.040) components were significantly correlated with total score of RA. Global PSQI was significantly correlated with "I don't get much personal strength and support from my God," "I believe there is some real purpose for my life" questions in SWBS, and "Attendance in mosque or religious places" subscale of RA.
25486204	Patients with lung cancer have the poorest sleep quality compared with other patients with cancer and noncancer control subjects. However, few studies have examined sleep longitudinally.The objective of this study was to characterize and correlate sleep quality, daytime sleepiness, sleep-wake actigraphy, and quality of life (QOL) before, during, and after chemotherapy for non-small cell lung cancer (NSCLC).	Using a prospective repeated-measures 1-group design, patients scheduled to receive chemotherapy for NSCLC were recruited. Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Functional Assessment of Cancer Treatment-Lung (FACT-L), and Motionlogger Actigraph were used for data collection.	Poor nocturnal sleep and QOL were evident among 29 patients with NSCLC before treatment. The FACT-L subscale scores worsened and then improved significantly from baseline through 2 rounds of chemotherapy. Objective sleep duration and sleep efficiency were positively associated with FACT-L scores, whereas objective sleep latency and wake after sleep onset were negatively associated with FACT-L scores. Sleepy patients had significantly worse FACT-L scores than did nonsleepy patients. The FACT-L subscale items that demonstrated significant worsening and then improvement over time were shortness of breath, weight loss, coughing, and chest tightness. Lung cancer patients experience early and middle insomnia before and during treatment.	Poor sleep quality is common in patients receiving treatment for NSCLC and is related to poorer QOL and respiratory symptoms.	Patients with NSCLC require routine screening for sleep disturbances. A positive screen for sleep disturbance warrants a thorough sleep assessment using practice guidelines and, if necessary, referral to a sleep specialist for diagnosis and treatment.	
25485908	Epilepsy is one of the most common and intractable brain disorders. Mutations in the human gene LGI1, encoding a neuronal secreted protein, cause autosomal dominant lateral temporal lobe epilepsy (ADLTE). However, the pathogenic mechanisms of LGI1 mutations remain unclear. We classified 22 reported LGI1 missense mutations as either secretion defective or secretion competent, and we generated and analyzed two mouse models of ADLTE encoding mutant proteins representative of the two groups. The secretion-defective LGI1(E383A) protein was recognized by the ER quality-control machinery and prematurely degraded, whereas the secretable LGI1(S473L) protein abnormally dimerized and was selectively defective in binding to one of its receptors, ADAM22. Both mutations caused a loss of function, compromising intracellular trafficking or ligand activity of LGI1 and converging on reduced synaptic LGI1-ADAM22 interaction. A chemical corrector, 4-phenylbutyrate (4PBA), restored LGI1(E383A) folding and binding to ADAM22 and ameliorated the increased seizure susceptibility of the LGI1(E383A) model mice. This study establishes LGI1-related epilepsy as a conformational disease and suggests new therapeutic options for human epilepsy. 
25485322	Psychotropic medications have a significant adverse drug event profile, particularly in older adults, and appropriate use is paramount. Patterns of prescribing in community-dwelling older adults in New Zealand remain unknown.This study aimed to determine the prevalence and the pattern of psychotropic use amongst community-dwelling older people in New Zealand and to identify any association between depressive symptomatology and psychotropic medication use.	Data were collected on the demographics, medication use and mood status of community-dwelling older adults from two New Zealand studies: the BRIGHT trial, which recruited potentially disabled participants (N=141) and the DeLLITE trial, which recruited potentially depressed participants (N=193). The prevalence and the pattern of psychotropic use were established and the gender, age and level of depression assessed using regression analysis.	The use of any psychotropic medication was 28.9% in the BRIGHT trial and 43.5% in the DeLLITE trial. Antidepressants were the most commonly used psychotropic medication in the two studies, followed by hypnotics and sedatives. Psychotropic use was highly correlated with the presence of depressive symptoms in the BRIGHT trial and with female gender in the DeLLITE trial. Age was not associated with psychotropic medication use. In both studies, there is possible underdiagnosed, undertreated and inappropriately treated depression.	The prevalence of psychotropic medication use is high in community-dwelling older people with disability and very high in community-dwelling older people with depressive symptoms, but varies by gender and level of depression.	
25484267	Primary lymphedema in children, especially generalized disease with facial involvement, is rare.We sought to report 3 childhood cases of lymphedema with associated neurologic findings and to provide a pathophysiologic explanation for this association.	Clinical observations, electroencephalography, and neuroimaging studies were evaluated. Microcomparative genomic hybridization was performed in 1 case.	The 3 children had primary lymphedema of all 4 limbs and the face. This was confirmed by lymphoscintigraphy, which showed hypoplasia of vessels and hypofixation of lymph nodes. They had nonspecific neurologic disorders and electroencephalography abnormalities, without intellectual deficit. Neuroimaging revealed normal findings. Microcomparative genomic hybridization in 1 patient revealed no cytogenetic anomaly. The outcome was fatal in 1 case with development of visceral lymphedema and coma.	Genetic studies were performed in only 1 case.	These observations suggest that neurologic assessment and electroencephalography are indicated for patients with lymphedema of the limbs and face to identify this syndrome.	
25482669	Tandem two-pore potassium channels (K2Ps) have widespread expression in the central nervous system and periphery where they contribute to background membrane conductance. Some general anaesthetics promote the opening of some of these channels, enhancing potassium currents and thus producing a reduction in neuronal excitability that contributes to the transition to unconsciousness. Similarly, these channels may be recruited during the normal sleep-wake cycle as downstream effectors of wake-promoting neurotransmitters such as noradrenaline, histamine and acetylcholine. These transmitters promote K2P channel closure and thus an increase in neuronal excitability. Our understanding of the roles of these channels in sleep and anaesthesia has been largely informed by the study of mouse K2P knockout lines and what is currently predicted by in vitro electrophysiology and channel structure and gating. 
25482053	Based on successive samples totaling more than 5000 higher education students, we scrutinized the reliability, structure, initial validity and normative scores of a brief self-report seven-item scale to screen for the continuum of nighttime insomnia complaints/perceived sleep quality, used by our team for more than a decade, henceforth labeled the Basic Scale on Insomnia complaints and Quality of Sleep (BaSIQS). In study/sample 1 (n = 1654), the items were developed based on part of a larger survey on higher education sleep-wake patterns. The test-retest study was conducted in an independent small group (n = 33) with a 2-8 week gap. In study/sample 2 (n = 360), focused mainly on validity, the BaSIQS was completed together with the Pittsburgh Sleep Quality Index (PSQI). In study 3, a large recent sample of students from universities all over the country (n = 2995) answered the BaSIQS items, based on which normative scores were determined, and an additional question on perceived sleep problems in order to further analyze the scale's validity. Regarding reliability, Cronbach alpha coefficients were systematically higher than 0.7, and the test-retest correlation coefficient was greater than 0.8. Structure analyses revealed consistently satisfactory two-factor and single-factor solutions. Concerning validity analyses, BaSIQS scores were significantly correlated with PSQI component scores and overall score (r = 0.652 corresponding to a large association); mean scores were significantly higher in those students classifying themselves as having sleep problems (p < 0.0001, d = 0.99 corresponding to a large effect size). In conclusion, the BaSIQS is very easy to administer, and appears to be a reliable and valid scale in higher education students. It might be a convenient short tool in research and applied settings to rapidly assess sleep quality or screen for insomnia complaints, and it may be easily used in other populations with minor adaptations. 
25482026	Brain recordings in large animal models and humans typically rely on a tethered connection, which has restricted the spectrum of accessible experimental and clinical applications. To overcome this limitation, we have engineered a compact, lightweight, high data rate wireless neurosensor capable of recording the full spectrum of electrophysiological signals from the cortex of mobile subjects. The wireless communication system exploits a spatially distributed network of synchronized receivers that is scalable to hundreds of channels and vast environments. To demonstrate the versatility of our wireless neurosensor, we monitored cortical neuron populations in freely behaving nonhuman primates during natural locomotion and sleep-wake transitions in ecologically equivalent settings. The interface is electrically safe and compatible with the majority of existing neural probes, which may support previously inaccessible experimental and clinical research. 
25481765	The locus coeruleus (LC) is a noradrenergic brainstem structure that is considered to play a role in promoting arousal. To further clarify the role of LC noradrenergic neurons, we performed an optogenetic assay by injecting AAV-channelrhodopsin-2 (ChR2) into the LC of cre-tyrosine hydrolase (TH) mice. We found here that the specific activation of LC noradrenergic neurons produced a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep during photostimulation. On the other hand, neuropathic pain is believed to significantly interfere with sleep, and inadequate sleep may contribute to the stressful negative consequences of living with pain. In the present study, sciatic nerve ligation, which produced significant thermal hyperalgesia, significantly increased the levels of noradrenaline released in the prefrontal cortex (PFC) by the weak electrical stimulation of neurons in the LC. Under these conditions, the systemic administration of adrenaline α and β inhibitor cocktail at 7 days after sciatic nerve ligation restored the increased wakefulness and decreased NREM sleep to normal levels. These results suggest that neuropathic pain may accelerate neurons in the LC, and its overactivation may be, at least in part, associated with sleep disturbance under neuropathic pain. 
25479294	To examine the relationship between health conditions and the risk for membership in longitudinal trajectories of productivity loss.Trajectories of productivity loss from the ages of 25 to 44 years, previously identified in the National Longitudinal Survey of Youth (NLSY79), were combined with information on health conditions from the age 40 years health module in the NLSY79. Multinomial logistic regression was used to examine the relative risk of being in the low-risk, early-onset increasing risk, late-onset increasing risk, or high-risk trajectories compared with the no-risk trajectory for having various health conditions.	The trajectories with the greatest probability of productivity loss longitudinally had a greater prevalence of the individual health conditions and a greater total number of health conditions experienced.	Health conditions are associated with specific longitudinal patterns of experiencing productivity loss.	
25479262	This study examined the uptake and effectiveness of fatigue mitigation guidance material including sleep recommendations for a trip with a westward ultra-long-range flight and return long-range flight.There were 52 flight crew (4-pilot crews, mean age 55 yr) who completed a sleep/duty diary and wore an actigraph prior to, during, and after the trip. Primary crew flew the takeoff and landing, while relief crew flew the aircraft during the Primary crew's breaks. At key times in flight, crewmembers rated their fatigue (Samn-Perelli fatigue scale) and sleepiness (Karolinska Sleepiness Scale) and completed a 5-min Psychomotor Vigilance Task.	Napping was common prior to the outbound flight (54%) and did not affect the quantity or quality of in-flight sleep (mean 4.3 h). Primary crew obtained a similar amount on the inbound flight (mean 4.0 h), but Secondary crew had less sleep (mean 2.9 h). Subjective fatigue and sleepiness increased and performance slowed across flights. Performance was faster on the outbound than inbound flight. On both flights, Primary crew were less fatigued and sleepy than Secondary crew, particularly at top of descent and after landing. Crewmembers slept more frequently and had more sleep in the first 24 h of the layover than the last, and had shifted their main sleep to the local night by the second night.	The suggested sleep mitigations were employed by the majority of crewmembers. Fatigue levels were no worse on the outbound ultra-long-range flight than on the return long-range flight.	
25479103	The paraventricular thalamic nucleus (PVT), the main component of the dorsal thalamic midline, receives multiple inputs from the brain stem and hypothalamus, and targets the medial prefrontal cortex, nucleus accumbens and amygdala. PVT has been implicated in several functions, especially adaptation to chronic stress, addiction behaviors and reward, mood, emotion. We here focus on the wiring and neuronal properties linking PVT with circadian timing and sleep/wake regulation, and their behavioral implications. PVT is interconnected with the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus, receives direct and indirect photic input, is densely innervated by orexinergic neurons which play a key role in arousal and state transitions. Endowed with prominent wake-related Fos expression which is suppressed by sleep, and with intrinsic neuronal properties showing a diurnal oscillation unique in the thalamus, PVT could represent a station of interaction of thalamic and hypothalamic sleep/wake-regulatory mechanisms. PVT could thus play a strategic task by funneling into limbic and limbic-related targets circadian timing and state-dependent behavior information, tailoring it for cognitive performance and motivated behaviors. 
25478944	To investigate the resolution of heartburn and gastroesophageal reflux disease (GERD)-related sleep disturbances during the first 14 days of treatment with esomeprazole 20 mg compared to placebo in subjects with frequent nighttime heartburn and GERD-related sleep disturbances.This was a post hoc analysis of 2 week data from two previously published, similarly designed randomized, placebo-controlled trials of 4 weeks' duration comparing esomeprazole 20 mg, 40 mg (one study), and placebo. Inclusion and exclusion criteria for both trials were the same.	The main outcome measures for this analysis were the resolution and/or relief of GERD-related sleep disturbances during 2 weeks of treatment with esomeprazole 20 mg or placebo. Resolution and/or relief of heartburn symptoms were also measured.	In trial 1, 455 subjects were randomized, with 225 and 229 receiving esomeprazole 20 mg and placebo, respectively. In trial 2, 276 subjects were randomized, with 142 and 132 receiving esomeprazole and placebo, respectively. After 2 weeks, significantly more subjects who received esomeprazole 20 mg (50.5% [95% confidence interval: 43.8%-57.1%] and 39.4% [31.2%-47.6%] in trials 1 and 2, respectively) had resolution of sleep disturbances compared to placebo (19.9% [14.6%-25.2%] and 16.0% [9.6%-22.4%], respectively; p < 0.0001 for both trials). The median time to resolution of sleep disturbances with esomeprazole 20 mg was 1 day in both trials. After 2 weeks, significantly more subjects receiving esomeprazole 20 mg (32.3% [26.1%-38.5%] and 26.3% [18.9%-33.6%] in trials 1 and 2, respectively) had resolution of nighttime heartburn symptoms compared to placebo (5.4% [2.4%-8.4%] and 4.8% [1.1%-8.5%], respectively; p < 0.0001 for both trials).	Esomeprazole 20 mg significantly and effectively reduced nighttime heartburn and GERD-related sleep disturbances in the first 2 weeks of treatment compared to placebo, with rapid resolution of sleep disturbances in the first days of treatment.	
25478876	Data on the association between chronic conditions or the number of chronic conditions and sleep problems in low- or middle-income countries is scarce, and global comparisons of these associations with high-income countries have not been conducted.Data on 42116 individuals 50 years and older from nationally-representative samples of the Collaborative Research on Ageing in Europe (Finland, Poland, Spain) and the World Health Organization's Study on Global Ageing and Adult Health (China, Ghana, India, Mexico, Russia, South Africa) conducted between 2011-2012 and 2007-2010 respectively were analyzed.	The association between nine chronic conditions (angina, arthritis, asthma, chronic lung disease, depression, diabetes, hypertension, obesity, and stroke) and self-reported severe/extreme sleep problems in the past 30 days was estimated by logistic regression with multiple variables. The age-adjusted prevalence of sleep problems ranged from 2.8% (China) to 17.0% (Poland). After adjustment for confounders, angina (OR 1.75-2.78), arthritis (OR 1.39-2.46), and depression (OR 1.75-5.12) were significantly associated with sleep problems in the majority or all of the countries. Sleep problems were also significantly associated with: asthma in Finland, Spain, and India; chronic lung disease in Poland, Spain, Ghana, and South Africa; diabetes in India; and stroke in China, Ghana, and India. A linear dose-dependent relationship between the number of chronic conditions and sleep problems was observed in all countries. Compared to no chronic conditions, the OR (95%CI) for 1,2,3, and ≥ 4 chronic conditions was 1.41 (1.09-1.82), 2.55 (1.99-3.27), 3.22 (2.52-4.11), and 7.62 (5.88-9.87) respectively in the overall sample.	Identifying co-existing sleep problems among patients with chronic conditions and treating them simultaneously may lead to better treatment outcome. Clinicians should be aware of the high risk for sleep problems among patients with multimorbidity. Future studies are needed to elucidate the best treatment options for comorbid sleep problems especially in developing country settings.	
25476601	Interactions of neurons with microglia may play a dominant role in sleep regulation. TNF may exert its somnogeneic effects by promoting attraction of microglia and their processes to the vicinity of dendrites and synapses. We found TNF to stimulate neurons (i) to produce CCL2, CCL7 and CXCL10, chemokines acting on mononuclear phagocytes and (ii) to stimulate the expression of the macrophage colony stimulating factor (M-CSF/Csf1), which leads to elongation of microglia processes. TNF may also act on neurons by affecting the expression of genes essential in sleep-wake behavior. The neuronal expression of Homer1a mRNA, increases during spontaneous and enforced periods of wakefulness. Mice with a deletion of Homer1a show a reduced wakefulness with increased non-rapid eye movement (NREM) sleep during the dark period. Recently the TNF-dependent increase of NREM sleep in the dark period of mice with CD40-induced immune activation was found to be associated with decreased expression of Homer1a. In the present study we investigated the effects of TNF and IL-1β on gene expression in cultures of the neuronal cell line HT22 and cortical neurons. TNF slightly increased the expression of Homer1a and IL-1β profoundly enhanced the expression of Early growth response 2 (Egr2). The data presented here indicate that the decreased expression of Homer1a, which was found in the dark period of mice with CD40-induced increase of NREM sleep is not due to inhibitory effects of TNF and IL-1β on the expression of Homer1a in neurons. 
25476055	To characterise sleep-wake patterns and their influence on academic performance for a sample of Portuguese adolescents.Cross-sectional, analytical-explanatory, correlational epidemiological research. The protocol includes the composite morningness questionnaire (Barton et al, 1985 adapted by Silva et al, 1985), the Epworth Sleepiness Scale (Murray, 1991), chronic fatigue scale (Smith et al, 1995), the Pittsburgh Sleep Quality Index (Buysse, 1988), Educational Achievement (Fermin, 2005), personal and academic data.	2094 students (55.3% girls; 16-23 years old; M=16.82±1.25) attending secondary school in central Portugal. Living in urban areas, living with their parents and about 57.1% are in a family with reasonable economic resources.	Adolescents' sleep patterns reveal that they sleep on average between 8-9 hours a night, do not use medication to sleep, with sleep latency within the normal range, with good sleep efficiency, without daytime dysfunction and with undisturbed sleep, predominantly intermediate chronotype. Minor drowsiness, increased sleep efficiency, improved subjective sleep satisfaction, less sleep disturbance, less daytime dysfunction, not consuming hypnotic medications, associated with better academic performance. Morningness/eveningness, sleep efficiency, daytime dysfunction and sleep latency emerge as predictors of academic performance. The chronotype interacts to predict the quality of sleep enhancing it as a mediator of school performance.	Sleep and associated individual characteristics should be considered in the diagnosis and intervention process in secondary education.	
25475495	This review describes empirical evidence for a bidirectional relationship between tension-type headache (TTH) and sleep. In its most severe form, chronic TTH (CTTH) affects 2-3 % of the population and can be very disabling. Sleep dysregulation triggers episodic TTH, and sleep disorders may complicate and exacerbate headache. The majority of CTTH sufferers also have insomnia, and longitudinal data suggest that insomnia is a risk factor for new-onset TTH. Similarly, observational studies suggest that sleep disturbance is a risk factor for new-onset TTH and for progression from episodic to chronic TTH (i.e., headache "chronification"). CTTH is the most common headache secondary to sleep apnea and other sleep-related breathing disorders. Psychiatric disorders are comorbid with both TTH and insomnia and may further complicate diagnosis and treatment. Developments in diagnostic classification of sleep-related headache are presented.

25474244	To assess whether problematic internet use is associated with somatic complaints and whether this association remains when checking for internet activity among a random sample of adolescents living in the canton of Vaud, Switzerland.Cross-sectional survey of 3,067 8th graders (50.3% females) divided into average (n = 2,708) and problematic (n = 359) Internet users and compared for somatic complaints (backache, overweight, headaches, musculoskeletal pain, sleep problems and sight problems) controlling for sociodemographic and internet-related variables. Logistic regressions were performed for each complaint and for all of them simultaneously controlling variables significant at the bivariate level.	At the multivariate level, when taken separately, problematic internet users were more likely to have a chronic condition (adjusted odds ratio [aOR] with 95% CI: 1.58 [1.11:2.23]) and to report back pain (aOR: 1.46 [1.04:2.05]), overweight (aOR: 1.74 [1.03:2.93]), musculoskeletal pain (aOR: 1.36 [1.00:1.84]) and sleep problems (aOR: 2.16 [1.62:2.88]). When considered in the full model, only sleep problems remained significant (aOR: 2.03 [1.50:2.74]).	Our results confirm that problematic internet users report health problems more frequently, with lack of sleep being the most strongly associated and seeming to act as mediator regarding the other ones. Clinicians should remember to screen for excessive internet use their patients complaining of sleep-related problems, back or musculoskeletal pain or overweight. Clinicians should advise parents to limit the amount of time their adolescent children can spend online for leisure activities. Furthermore, limiting the number of devices used to connect to the internet could help warrant enough sleeping time.	
25471376	There is a growing amount of evidence to suggest that besides motor features, patients with essential tremor (ET) may exhibit significant nonmotor features, such as mild cognitive deficits, fatigue, neuropsychiatric symptoms, and sleep disturbances. The goal of this study was to examine nonmotor features in young patients with ET and their impact on quality of life. 45 patients (24.55 ± 7.16 years old) with ET and 35 controls were evaluated using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Inventory, Beck Anxiety Scale, Fatigue Severity Scale, and Short Form-36. Cognitive functions were evaluated using the Turkish version of the Montreal Cognitive Assessment Battery (MoCA). We ruled out other possible causes of the tremor. The tremor rate was evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale. Poor sleep quality, fatigue, anxiety, and depressive symptoms were more common, and MoCA total scores were lower in the patient group. Fatigue, depressive symptoms, and higher anxiety levels were seen to have a negative effect on physical and mental health. Excessive daytime sleepiness had a negative effect on physical health. There is an emerging interest in nonmotor features of ET. This study showed that even young patients have nonmotor features that decrease their quality of life. This might tell us that nonmotor symptoms could be a part of the disease in the early stages.
25470858	Brain fag syndrome since the 1960s was identified as a medical problem among Nigerian students and till date there are varying opinions on its aetiology and classification. Recently it was grouped among the culture bound syndromes in the Diagnostic and Statistical Manual of Diseases (IV). This is a critical report on the clinical presentations of the brain fag syndrome in Nigerian undergraduate students.Previous literatures on brain fag syndrome were carefully reviewed and related to the syndrome presentations in the presently reported cases.	The clinical findings indicate underlying primary memory problems in the students and secondary other manifestations like depression, anxiety, and varying somatic complaints.	Brain fag syndrome might be a primarily reversible dysfunction of the working memory circuitry with multiple piedispositions and precipitants.	
25470605	Assessment of the influence of gender and increasing years at university on sleep health of students.Four hundred and eighteen students from different streams across years of undergraduate to postgraduate courses participated. Descriptive statistics, test of differences, and correlation were used. The sleep health data comprised of subjective evaluation using a questionnaire and personal interviews.	Overall, 43.1% had sleep problems, females were more affected (51.67% vs. 48.33% in males) but were early bed goers. The prevalence of circadian rhythm sleep disorder (11.6% vs. 9.5%) and delayed sleep phase syndrome (4.5% vs. 2.7%) was slightly higher in males. The daytime dysfunction and hypnotic use significantly differed in students of the same class among gender. Bedtime got significantly delayed along years [H(2)=29.769, p<0.001], and hypnotic use [H(2)=8.807, p=0.012] differed significantly among them. The moderate-very strong correlational statistics among sleep health elements was very similar across gender and years of university education. However, more pronounced influence of years of university education than gender was seen in the significant differences for correlated correlation among sleep health parameters.	Gender and years of university education influence sleep among university students both separately and concomitantly.	
25468840	We carried out a cross-sectional online survey of fellows and members of the Royal College of Physicians to establish physicians' experiences of adverse patient safety events and near misses, and the professional and personal impact of these. 1,755 physicians answered at least one question; 1,334 answered every relevant question. Of 1,463 doctors whose patients had an adverse event or near miss, 1,119 (76%) believed this had affected them personally or professionally. 1,077 (74%) reported stress, 995 (68%) anxiety, 840 (60%) sleep disturbance and 886 (63%) lower professional confidence. 1,192 (81%) became anxious about the potential for future errors. Of 1,141 who had used NHS incident reporting systems, only 315 (28%) were satisfied with this process. 201 (14%) received useful feedback, 201 (19%) saw local improvements and 277 (19%) saw system changes. 364 (25%) did not report an incident that they should have. Adverse safety events affect physicians, but few formal sources of support are available. Most doctors use incident-reporting systems, but many describe a lack of useful feedback, systems change or local improvement. 
25468656	The association between sleep duration and predicted cardiovascular risk has been poorly characterized. The objective of this study was to examine the association between self-reported sleep duration and predicted 10-year cardiovascular risk among US adults.Data from 7690 men and nonpregnant women who were aged 40 to 79 years, who were free of self-reported heart disease and stroke, and who participated in a National Health and Nutrition Examination Survey from 2005 to 2012 were analyzed. Sleep duration was self-reported. Predicted 10-year cardiovascular risk was calculated using the pooled cohort equations. Among the included participants, 13.1% reported sleeping ≤5 hours, 24.4% reported sleeping 6 hours, 31.9% reported sleeping 7 hours, 25.2% reported sleeping 8 hours, 4.0% reported sleeping 9 hours, and 1.3% reported sleeping ≥10 hours. After adjustment for covariates, geometric mean-predicted 10-year cardiovascular risk was 4.0%, 3.6%, 3.4%, 3.5%, 3.7%, and 3.7% among participants who reported sleeping ≤5, 6, 7, 8, 9, and ≥10 hours per night, respectively (PWald chi-square<0.001). The age-adjusted percentages of predicted cardiovascular risk ≥20% for the 6 intervals of sleep duration were 14.5%, 11.9%, 11.0%, 11.4%, 11.8%, and 16.3% (PWald chi-square=0.022). After maximal adjustment, however, sleep duration was not significantly associated with cardiovascular risk ≥20% (PWald chi-square=0.698).	Mean-predicted 10-year cardiovascular risk was lowest among adults who reported sleeping 7 hours per night and increased as participants reported sleeping fewer and more hours.	

25468384	Diabetic polyneuropathy (DPN) is one of the most common complications of diabetes and can exist with or without neuropathic pain. We were interested in how neuropathic pain impairs the quality of life in diabetic patients and what is the role of comorbidities in this condition.The study included 80 patients with painful DPN (group "P") and 80 patients with DPN, but without neuropathic pain (group "D"). Visual analogue scale (VAS) and Leeds assessment of neuropathic symptoms and signs (LANSS) pain scale were used for assessment of neuropathic pain, SF-36 standardized questionnaire for assessment of the quality of life and BDI questionnaire for assessment of depression.	Subjects in group P had statistically significantly lower values compared to group D in all 8 dimensions and both summary values of the SF-36 scale. We ascribe the extremely low results of all parameters of SF-36 scale in group P to painful diabetic polyneuropathy with its complications. The patients in group D showed higher average values in all dimension compared to group P, but also somewhat higher quality of life compared to general population of Croatia in 4 of 8 dimensions, namely vitality (VT), social functioning (SF), role-emotional (RE) and mental health (MH), which was unexpected result. Clinically, the most pronounced differences between two groups were noted in sleeping disorders and problems regarding micturition and defecation , which were significantly more expressed in group P. The similar situation was with walking distance and color-doppler sonography of carotid arteries, which were significantly worse in group P. Consequently, subjects in group P were more medicated than the patients in group D, particularly with tramadol, antiepileptics and antidepressants.	Painful DPN is a major factor that influences various aspects of quality of life in diabetic patients. Additionally, this study gives an overview of diabetic population in the Republic of Croatia, information that could prove useful in future studies.	
25466290	Sleep and sleep disorders are complex and highly variable phenotypes regulated by many genes and environment. The catechol-O-methyltransferase (COMT) gene is an interesting candidate, being one of the major mammalian enzymes involved in the catabolism of catecholamines. The activity of COMT enzyme is genetically polymorphic due to a guanine-to-adenine transition at codon 158, resulting in a valine (Val) to methionine (Met) substitution. Individuals homozygous for the Val allele show higher COMT activity, and lower dopaminergic signaling in prefrontal cortex (PFC) than subjects homozygous for the Met allele. Since COMT has a crucial role in metabolising dopamine, it was suggested that the common functional polymorphism in the COMT gene impacts on cognitive function related to PFC, sleep-wake regulation, and potentially on sleep pathologies. The COMT Val158Met polymorphism may predict inter-individual differences in brain electroencephalography (EEG) alpha oscillations and recovery processes resulting from partial sleep loss in healthy individuals. The Val158Met polymorphism also exerts a sexual dimorphism and has a strong effect on objective daytime sleepiness in patients with narcolepsy-cataplexy. Since the COMT enzyme inactivates catecholamines, it was hypothesized that the response to stimulant drugs differs between COMT genotypes. Modafinil maintained executive functioning performance and vigilant attention throughout sleep deprivation in subjects with Val/Val genotype, but less in those with Met/Met genotype. Also, homozygous Met/Met patients with narcolepsy responded to lower doses of modafinil compared to Val/Val carriers. We review here the critical role of the common functional COMT gene polymorphism, COMT enzyme activity, and the prefrontal dopamine levels in the regulation of sleep and wakefulness in normal subjects, in narcolepsy and other sleep-related disorders, and its impact on the response to psychostimulants. 
25465518	To identify the prevalence of sleep disturbance in women seeking treatment for pelvic organ prolapse (POP) and identify correlates of poor sleep quality in this population by using a validated sleep scale.This is a cohort study of female patients with pelvic organ prolapse.	Pittsburgh Sleep Quality Index (PSQI), Pelvic Floor Disorders Inventory (PFDI), and Pelvic Floor Impact Questionnaire (PFIQ) measures were completed. Demographic data, medical comorbidities, medications, and physical examinations were also recorded.	407 Women were enrolled. Analysis was performed on the 250 subjects who completed all PSQI components. Subjects were predominantly white, with a mean age of 61 ± 11 years and mean BMI of 28 ± 5 kg/m(2). The majority (71%) had Stage III prolapse. Half (N=127) had poor sleep quality (PSQI > 5). Women with poor sleep quality were younger, had more medical comorbidities, more pelvic floor symptoms, more nocturia, more depressive symptoms, and took more time to fall asleep. Factors associated with sleep quality were evaluated using multivariable linear regression models. Worse sleep scores were associated with each of the PFDI subscores (urinary, prolapse, bowel), depressive symptoms, severe nocturia symptoms, and number of comorbidities.	Poor sleep is prevalent in women with prolapse. Pelvic floor symptoms as measured by PFDI sub-scales, were associated with poor sleep quality. Future studies are needed to better understand how sleep disturbances may contribute to the impact of pelvic floor symptoms on quality of life.	
25462597	Because of their dreamlike character, authors have speculated about the role that the sleep-wake cycle plays in dissociative symptoms. We investigated whether sleep loss fuels dissociative symptoms and undermines cognitive efficiency, particularly memory functioning.Fifty-six healthy undergraduate students were randomly assigned to an experimental group (n = 28) and a control group (n = 28). The experimental group was deprived of sleep for 36 h in a sleep laboratory; the control group had a regular night of sleep. Sleepiness, mood, and dissociative symptoms were assessed 6 times in the experimental group (control group: 4 times). Several cognitive tasks were administered.	Sleep deprivation led to an increase in dissociative symptoms, which was mediated by levels of general distress. Feelings of sleepiness preceded an increase of dissociative symptoms and deterioration of mood. Finally, sleep loss also undermined memory of emotional material, especially in highly dissociative individuals.	Limitations included moderate reliability of the mood scale, limited generalizability due to student sample, and a relatively short period of intensive sleep deprivation rather than lengthy but intermittent sleep loss, representative of a clinical population.	We found that sleep deprivation had significant effects on dissociation, sleepiness, and mood. Specifically, sleepiness and dissociation increased during the night, while mood deteriorated. Our findings stress the importance of sleep deficiencies in the development of dissociative symptoms. They support the view that sleep disruptions fuel distress, but also degrade memory and attentional control. It is against this background that dissociative symptoms may arise.	
25462194	The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost. 
25462136	Many opioid receptors are located in the same nuclei that are active in sleep regulation. It has been suggested that opioid peptides are involved in the induction of the sleep state. Prolonged opioid use has been hypothesized to cause disturbed sleep. It also causes excessive daytime sleepiness and fatigue. This study was conducted to compare the polysomnographic sleep profile of patients with opioid dependence with normal matched controls and to see the correlation between various clinical profiles of patients with opioid dependence with their polysomnographic sleep profile.Fifteen opioid-dependent male patients were selected, and after the detoxification procedure, the patients were assessed using Objective Opioid Withdrawal Scale, Obsessive Compulsive Drug Use Scale, Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and Global Assessment of Functioning. Fifteen healthy volunteers matched for age, education, and handedness were taken as controls and were assessed using Epworth sleepiness scale and General Health Questionnaire-12. All night polysomnography recording was done on patient and control group, and staging of sleep was done.	Patients had significantly decreased total sleep time, sleep efficiency and stage N1 sleep, prolonged sleep latency, and increased limb movement index. No significant correlation was found between sleep profile and various clinical variables.	Use of opioids cause sleep disturbance, and these changes occurring in sleep can persist even after substance use has been stopped. Opioids seem to affect non-rapid eye movement stages of sleep.	
25462013	The aim of this study was to examine sleep disturbances in patients with chronic mountain sickness (CMS). The sleep of 14 patients with CMS and 11 healthy controls with or without sleep disorders (control N: without sleep disorders; control D: with sleep disorders) was studied by polysomnography. Hypopnea was the sleep disorder most commonly suffered by CMS patients and control D subjects. No major differences were observed in sleep structure between CMS and control groups, with the exception of shorter rapid eye movement latency in controls and increased deep non-rapid eye movement in the control N group. Periodic breathing was observed in only two study participants, one each in the CMS and control D groups. The level of saturated oxygen was significantly lower in the CMS group during sleep than the control groups (P<0.05). CMS scores were positively correlated with the apnea-hypopnea index, and negatively correlated with saturated oxygen levels. These results demonstrate that sleep disorders and nocturnal hypoxia are important in the development of CMS. 
25461671	Depression, fatigue, and sleep disturbances have been identified as a symptom cluster among breast cancer patients. However, few longitudinal studies have examined the temporal relations between these symptoms surrounding diagnosis and treatment.The present study investigated the co-occurrence of and interrelations between nonsomatic depressive symptoms, fatigue, and sleep disturbances in breast cancer patients at three time points: before, after, and six to eight months following adjuvant chemotherapy treatment.	Separate samples of premenopausal (n = 67) and postmenopausal (n = 67) breast cancer patients completed self-report measures of depression, fatigue, and sleep disturbances at all three time points. Path analysis was used to explore within- and cross-symptom paths across time.	Depression, fatigue, and sleep disturbances were correlated within each time point. Continuity paths, whereby prior levels of symptom severity tended to predict subsequent severity of the same symptom at the subsequent time point, were significant in both samples, except for depression in the premenopausal sample. Instead, significant cross-symptom paths emerged whereby baseline fatigue predicted postchemotherapy depression, and postchemotherapy fatigue predicted depression at follow-up in the premenopausal patients. No significant cross-symptom paths emerged for the postmenopausal sample.	Findings supported the notion that depression, fatigue, and sleep disturbances manifest as a symptom cluster. Fatigue may precede nonsomatic symptoms of depression among premenopausal breast cancer patients and represents a potential intervention target.	
25460255	Previous studies show contradictory results about the emergence of 24-h rhythms and the influence of external time cues on sleep-wake behavior in preterm compared to term infants.To examine whether very preterm infants (<32 weeks of gestational age) differ in their emergence of the 24-h sleep-wake rhythm at 5, 11 and 25 weeks corrected age compared to term infants and whether cycled light conditions during neonatal intermediate care affects postnatal 24-h sleep-wake rhythms in preterm infants.	Prospective cohort study with nested interventional trial.	34 preterm and 14 control term infants were studied. During neonatal hospitalization, preterm infants were randomly assigned to cycled light [7 am-7 pm lights on, 7 pm-7 am lights off, n=17] or dim light condition [lights off whenever the child is asleep, n=17].	Sleep and activity behavior recorded by parental diary and actigraphy at 5, 11 and 25 weeks corrected age.	Sleep at nighttime and the longest consolidated sleep period between 12 pm-6 am was longer (mixed model analysis, factor group: p=0.02, resp. p=0.01) and activity at nighttime was lower (p=0.005) at all ages in preterm compared to term infants. Cycled light exposed preterm infants showed the longest nighttime sleep duration. Dim light exposed preterm infants were the least active.	
25458772	Sleep and sleep disturbances are increasingly recognized as determinants of women's health and well-being, particularly in the context of the menstrual cycle, pregnancy, and menopause. At present, however, little is known about whether fertility is affected by sleep quantity and quality. That is, to what degree, and by what mechanisms, do sleep and/or its disturbances affect fertility? The purpose of this review is to synthesize what is known about sleep disturbances in relation to reproductive capacity. A model is provided, whereby stress, sleep dysregulation, and circadian misalignment are delineated for their potential relevance to infertility. Ultimately, if it is the case that sleep disturbance is associated with infertility, new avenues for clinical intervention may be possible. 
25458325	The aim of this study is to investigate sleep quality and quality of life, and to assess the relationship between sleep quality and quality of life in Chinese patients with type 2 diabetes mellitus (T2DM).944 patients with T2DM were enrolled in our study. General characteristics and laboratory testing such as glycosylated hemoglobin A1c (HbA1c) were measured. Each patient completed a Chinese version of the Pittsburgh sleep quality index (PSQI) and the diabetes specificity quality of life scale (DSQL) questionnaires. A PSQI global score >7 was defined as poor sleep quality. A global DSQL score <40 was defined as a good quality of life. Multiple logistic regression analysis was used to examine the relationships between PSQI and DSQL.	Poor quality of life in participants was associated with a longer duration of diabetes, a greater number of diabetes complications, no alcohol drinking, poor glycemic control and having depression and anxiety (all P<0.001). Of the participants, 33.6% of them were poor sleepers according to their PSQI. Poor sleepers had significantly lower DSQL (P<001). After adjustment for confounders, poor sleep quality was positively associated with a lower health-related quality of life (OR: 3.67, 95% CI: 1.30-10.33, P<0.001).	Our results suggest that poor sleep is prevalent in T2DM and inversely associated with quality of life. It is necessary for primary health-care workers to include sleep related knowledge in diabetes self-management programs to improve sleep quality in diabetes patients.	
25458251	Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy. 
25457619	Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes. 
25457450	To retrospectively analyze the electroclinical characteristics, etiology, treatment, and prognosis of patients with epileptic encephalopathy with status epilepticus during sleep (ESES) with unusual EEG features and to corroborate if this series of patients is part of the ESES syndrome.Charts of 17 patients with typical clinical manifestations of the ESES syndrome with focal ESES of non-REM sleep at onset and during the focal ESES phase, or bilateral synchronic and asynchronic ESES with a symmetric or asymmetric morphology, continuous or subcontinuous and sometimes multifocal paroxysms with or without slow-wave activity during slow sleep seen between 2000 and 2012 were analyzed.	Mean patient follow-up from onset was 7.5 years. An idiopathic cause was found in seven patients, a structural cause in eight, and etiology was unknown in the remaining two. The median age at onset of the unusual ESES syndrome was 7 years. During the ESES phase, 15 children developed new seizure types, negative myoclonus was observed in seven patients, positive myoclonus in five, and absences in nine. Six patients had motor impairment, two had auditory verbal agnosia, and two had motor speech impairment. Attention deficit hyperactivity disorder was observed in four, aggressiveness in six, memory deficit in two, and impaired temporospatial orientation in four. The patients with focal ESES in the frontal region showed behavioral disturbances and/or motor deterioration, and in those with temporo-occipital involvement the dominant clinical manifestations were language and/or behavioral disturbances.	Our patients with typical clinical manifestations of ESES syndrome but with unusual EEG patterns may be variants of this syndrome.	
25456523	Analysis of brain recurrence (ABR) is a novel computational method that uses two variables for sleep depth and two for sleep fragmentation to quantify temporal changes in non-random brain electrical activity. We postulated that ABR of the sleep-staged EEG could identify an EEG signature specific for the presence of mental health symptoms. Using the Mental Health Inventory Questionnaire (MHI-5) as ground truth, psychological distress was assessed in a study cohort obtained from the Sleep Heart Health Study. Subjects with MHI-5 <50 (N=34) were matched for sex, BMI, age, and race with 34 subjects who had MHI-5 scores >50. Sixteen ABR markers derived from the EEG were analyzed using linear discriminant analysis to identify marker combinations that reliably classified individual subjects. A biomarker function computed from 12 of the markers accurately classified the subjects based on their MHI-5 scores (AUROC=82%). Use of additional markers did not improve classification accuracy. Subgroup analysis (20 highest and 20 lowest MHI-5 scores) improved classification accuracy (AUROC=89%). Biomarker values for individual subjects were significantly correlated with MHI-5 score (r=0.36, 0.54 for N=68, 40, respectively). ABR of EEGs obtained during sleep successfully classified subjects with regard to the severity of mental health symptoms, indicating that mood systems were reflected in brain electrical activity. 
25456469	Although sleep complaints are often reported in patients with fibromyalgia syndrome (FMS), there is no conclusive evidence that these complaints represent symptomatic disorders of sleep physiology. Thus, the question of the role of sleep disturbances as an etiological or maintenance factor in FMS remains open. This study identifies the subjective and objective characteristics of sleep disturbances in adult women diagnosed with FMS. We carried out a systematic review of publications since 1990, the publication year of the American College of Rheumatology criteria of FMS. We selected empirical studies comparing sleep characteristics of adult women with FMS and healthy women or women with rheumatic diseases. We identified 42 articles. Patients with FMS were more likely to exhibit sleep complaints and also a less efficient, lighter and fragmented sleep. The evidence of a FMS signature on objective measures of sleep is inconsistent, however, as the majority of studies lacks statistical power. Current evidence cannot confirm the role played by sleep physiology in the pathogenesis or maintenance of FMS symptoms; nonetheless, it is clear that sleep disturbances are present in this syndrome. 
25456245	This prospective study assessed the effects of a 12-wk. exercise program based on the Pilates method (2 one-hr. sessions per week) on 99 sedentary middle-aged volunteers (M age = 47.6 yr., SD = 0.8), using an accelerometry, the Pittsburgh Sleep Quality Index, and the SF-36 questionnaire to measure changes in physical activity, quality of life, sleep latency, and quantity. The variables (quality of life, sleep latency, and quantity) were compared before and after applying the Pilates program. All of the physical and emotional components of the SF-36 questionnaire showed significant improvement, and the latency and sleep quantity also showed significant increases. The results indicate that Pilates is an accessible, interesting exercise program that can generate important changes in middle age.
25455941	Extreme environmental conditions present challenges for thermoregulation in homoeothermic organisms such as mammals. Such challenges are exacerbated when two stressors are experienced simultaneously and each stimulus evokes opposing physiological responses. This is the case of cold, which induces an increase in thermogenesis, and hypoxia, which suppresses metabolism conserving oxygen and preventing hypoxaemia. As an initial approach to understanding the thermoregulatory responses to cold and hypoxia in a small mammal, we explored the effects of acclimation to these two stressors on the body temperature (Tb) and the daily and ultradian Tb variations of Sprague-Dawley rats. As Tb is influenced by sleep-wake cycles, these Tb variations reflect underlying adjustments in set-point and thermosensitivity. The Tb of rats decreased precipitously during initial hypoxic exposure which was more pronounced in cold (Tb=33.4 ± 0.13) than in room temperature (Tb=35.74 ± 0.17) conditions. This decline was followed by an increase in Tb stabilising at a new level ~0.5°C and ~1.4°C below normoxic values at room and cold temperatures, respectively. Daily Tb variations were blunted during hypoxia with a greater effect in the cold. Ultradian Tb variations exhibited daily rhythmicity that disappeared under hypoxia, independent of ambient temperature. The adjustments in Tb during hypoxia and/or cold are in agreement with the hypothesis that an initial decrease in the Tb set-point is followed by its partial re-establishment with chronic hypoxia. This rebound of the Tb set-point might reflect cellular adjustments that would allow animals to better deal with low oxygen conditions, diminishing the drive for a lower Tb set-point. Cold and hypoxia are characteristic of high altitude environments. Understanding how mammals cope with changes in oxygen and temperature will shed light into their ability to colonize new environments along altitudinal clines and increase our understanding of how Tb is regulated under stimuli that impose contrasting physiological constraints.
25455647	The Epworth Sleepiness Scale (ESS) is a questionnaire widely used in developed countries to measure daytime sleepiness and diagnose sleep disorders.This study aimed to develop an ESS questionnaire for the Arabic population (ArESS), to determine ArESS internal consistency, and to measure ArESS test-retest reproducibility. It also investigated whether the normal range of ESS scores of healthy people in different cultures are similar.	The original ESS questionnaire was translated from English to Arabic and back-translated to English. In both the English and Arabic translations of the survey, ESS consists of eight different situations. The subject was asked to rate the chance of dozing in each situation on a scale of 0-3 with total scores ranging between 0 (normal sleep) and 24 (very sleepy). An Arabic translation of the ESS questionnaire was administered to 90 healthy subjects.	Item analysis revealed high internal consistency within ArESS questionnaire (Cronbach's alpha=0.86 in the initial test, and 0.89 in the retest). The test-retest intra-class correlation coefficient (ICC) shows that the test-retest reliability was substantially high: ICC=0.86 (95% confidence interval: 0.789-0.909, p-value<0.001). The difference in ArESS scores between the initial test and retest was not significantly different from zero (average difference=-0.19, t=-0.51, df=89, p-value=0.611). In this study, the averages of the ESS scores (6.3 ± 4.7, range 0-20 in the initial test and 6.5 ± 5.3, range 0-20 in the retest) are considered high in Western cultures.	The study shows that the ArESS is a valid and reliable tool that can be used in Arabic-speaking populations to measure daytime sleepiness. The current study has shown that the average ESS score of healthy Arabian subjects is significantly higher than in Western cultures.	
25455580	The questions facing clinicians with patients with sleep disorder and epilepsy are addressed in this article. Both adult and child epilepsy are discussed in the context of the most typical questions a clinician would have, such as "Are parasomnias more common in people with epilepsy?", "Is sleep architecture abnormal in children with epilepsy", along with outcomes of numerous questionnaire-based, case-based, and double-blind placebo studies on such aspects as sleep duration, daytime sleepiness, anxiety and fears, limb movement, nocturnal seizures, agitation, behavioral disorders, and learning disorders. 
25454985	The Child Behavior Checklist (CBCL) is a commonly used measure of child and adolescent functioning, and a handful of items from the CBCL are often used to measure sleep functioning. The objective of this study was to examine the convergent, discriminant, and external validity of the individual CBCL sleep items and a CBCL sleep composite with validated measures of sleep functioning and youth adjustment as well as sleep disorder diagnoses.The participants were 383 youths (ages 6-18 years; 52.5% male; 80% non-Hispanic White) evaluated in a behavioral sleep medicine clinic. A sleep psychologist diagnosed sleep disorders following a comprehensive evaluation. Parents completed the CBCL in addition to the Children's Sleep Habits Questionnaire (CSHQ) and the Sleep Disorders Inventory for Students (SDIS). Adolescents completed the Adolescent Sleep-Wake Scale (ASWS).	Individual CBCL sleep items were generally associated with sleep scales on validated sleep measures and with sleep disorder diagnoses. The CBCL sleep composite was associated with total scores on each of the sleep-specific measures, as well as with the CBCL attention, social, internalizing, and externalizing problems scales.	Although the CBCL is inadequate for thoroughly assessing sleep problems and disorders, sleep items on the CBCL may be useful in epidemiological/archival studies that lack a more comprehensive sleep measure or to clinicians who do not use other validated sleep measures in their typical practice. Individual CBCL sleep items may be optimal when assessing specific facets of sleep functioning whereas the CBCL sleep composite may be optimal when examining overall sleep functioning and external correlates of sleep.	
25454982	The ethnic disparity in ischemic stroke between Mexican Americans (MAs) and non-Hispanic whites (NHWs) may be partly attributable to disparities in sleep and its disorders. We therefore assessed whether pre-stroke sleep apnea symptoms (SA risk) and pre-stroke sleep duration differed between MAs and NHWs.MA and NHW ischemic stroke survivors in the Brain Attack Surveillance in Corpus Christi (BASIC) project reported sleep duration and SA symptoms on the validated Berlin questionnaire, both with respect to their pre-stroke baseline. Log binomial and linear regression models were used to test the unadjusted and adjusted (demographics and vascular risk factors) associations of high-risk Berlin scores and sleep duration with ethnicity.	Among 862 subjects, 549 (63.7%) were MA and 514 (59.6%) had a high risk of pre-stroke SA. The MA and NHW subjects showed no ethnic difference, after adjustment for potential confounders, in pre-stroke SA risk (risk ratio (95% confidence interval (CI)): 1.06 (0.93, 1.20)) or in pre-stroke sleep duration (on average MAs slept 2.0 fewer minutes than NHWs, 95% CI: -18.8, 14.9 min).	Pre-stroke SA symptoms are highly prevalent, but ethnic differences in SA risk and sleep duration appear unlikely to explain ethnic stroke disparities.	
25454981	Sleep disturbances and fatigue are common in patients with multiple sclerosis (MS), but little is known about hypnotic use patterns in MS, or the relationship between these medications and fatigue. The objectives of this study were to investigate the prevalence of prescription and over-the-counter (OTC) hypnotic use among MS patients, and to assess the relationships between fatigue severity and hypnotic use among persons with MS.Data on hypnotic use frequency, hypnotic agents of choice, and clinical characteristics were extracted from medical records and a survey dataset from 190 MS patients who completed questionnaires regarding sleep quality, sleep quantity, nocturnal symptoms, sleepiness (Epworth Sleepiness Scale), obstructive sleep apnea risk (STOP-Bang questionnaire), insomnia (Insomnia Severity Index), and fatigue level (Fatigue Severity Scale - FSS).	Eighty-nine subjects (47%) endorsed hypnotic use occasionally, frequently, or always. OTC diphenhydramine-containing products accounted for the majority of utilization, reported by 47 (25%). The occurrence of occasional or more frequent hypnotic use correlated with daytime fatigue (Spearman rho = 0.28, P = 0.0002), but not sleepiness. Regression of FSS scores on hypnotic use confirmed the association [beta (SE) = 0.55 (0.21), P = 0.0092] after adjustment for clinical and sleep-related confounds. In separate, similarly adjusted models, the use of OTC hypnotics but not prescription hypnotics was independently associated with higher FSS scores [0.54 (0.22), P = 0.0159]. An analogous association was observed more specifically for the use of diphenhydramine-containing products (0.49 (0.24), P = 0.044).	Hypnotic use is highly prevalent among MS patients. Carryover effects from hypnotic agents, and in particular OTC diphenhydramine-containing products, could contribute to daytime fatigue.	
25454846	Recent studies have suggested that the onset of sleepwalking episodes may be preceded by fluctuations in slow-wave sleep electroencephalographic characteristics. However, whether or not such fluctuations are specific to sleepwalking episodes or generalized to all sleep-wake transitions in sleepwalkers remains unknown. The goal of this study was to compare spectral power for delta (1-4 Hz) and slow delta (0.5-1 Hz) as well as slow oscillation density before the onset of somnambulistic episodes versus non-behavioral awakenings recorded from the same group of sleepwalkers. A secondary aim was to describe the time course of observed changes in slow-wave activity and slow oscillations during the 3 min immediately preceding the occurrence of somnambulistic episodes.Twelve adult sleepwalkers were investigated polysomnographically during the course of one night.	Slow-wave activity and slow oscillation density were significantly greater prior to patients' somnambulistic episodes as compared with non-behavioral awakenings. However, there was no evidence for a gradual increase over the 3 min preceding the episodes.	Increased slow-wave activity and slow oscillation density appear to be specific to sleepwalking episodes rather than generalized to all sleep-wake transitions in sleepwalkers.	
25454592	Circadian clocks allow anticipation of daily environmental changes. The suprachiasmatic nucleus (SCN) houses the master clock, but clocks are also widely expressed elsewhere in the body. Although some peripheral clocks have established roles, it is unclear what local brain clocks do. We tested the contribution of one putative local clock in mouse histaminergic neurons in the tuberomamillary nucleus to the regulation of the sleep-wake cycle. Histaminergic neurons are silent during sleep, and start firing after wake onset; the released histamine, made by the enzyme histidine decarboxylase (HDC), enhances wakefulness. We found that hdc gene expression varies with time of day. Selectively deleting the Bmal1 (also known as Arntl or Mop3) clock gene from histaminergic cells removes this variation, producing higher HDC expression and brain histamine levels during the day. The consequences include more fragmented sleep, prolonged wake at night, shallower sleep depth (lower nonrapid eye movement [NREM] δ power), increased NREM-to-REM transitions, hindered recovery sleep after sleep deprivation, and impaired memory. Removing BMAL1 from histaminergic neurons does not, however, affect circadian rhythms. We propose that for mammals with polyphasic/nonwake consolidating sleep, the local BMAL1-dependent clock directs appropriately timed declines and increases in histamine biosynthesis to produce an appropriate balance of wake and sleep within the overall daily cycle of rest and activity specified by the SCN.
25452149	Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-h variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48h of baseline conditions with standard sleep-wake schedules and 40-50h of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-h rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-h rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles. These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function. 
25451855	The largest cluster of E200K familial Creutzfeldt-Jakob disease (fCJD) which occurs is in Jews of Libyan origin in Israel. Insomnia is a very common early complaint in those patients and may even be the presenting symptom. The aim of this study was to assess and characterize sleep pathology in E200K fCJD patients. To do so, sleep studies of 10 consecutive fCJD patients were compared with those of 39 age and gender-matched controls. All patients presented pathological sleep characterized by fragmentation of sleep, loss of sleep spindles and reduced REM sleep amount. Respiration was characterized by irregular rhythm, periodic breathing, apneas and hypopneas, either central or obstructive. EMG recordings revealed repeated movements in sleep, with loss of REM atonia. Comparing to controls, a significant decrease of total sleep time, sleep efficacy and slow-wave sleep as well as a significant increase in the number of awakenings, apnea-hypopnea index and mixed and central apneas were evident in CJD patients. Comparison of two sequential sleep studies in one patient revealed a 40 % reduction of the total sleep time, a 40 % reduction in sleep efficacy and a 40-fold increase of the number of arousals in the second study. A significant correlation was found between the disease severity, as reflected by the CJD Neurological Scale and Periodic leg movement index. These definite and characteristic sleep pathologies in patients with fCJD associated with the E200K mutation may serve as a new diagnostic tool in the disease. 
25451441	Disturbed sleep is associated with mood disorders. Both depression and insomnia may increase the risk of disability retirement. The longitudinal links among insomnia, depression and work incapacity are poorly known.We examined association of self-reported sleep quality with incident symptoms of depression and disability retirement due to depressive disorders in a longitudinal population-based sample of twins (n=12,063 individuals). These adults were categorized by their sleep quality in 1975 and 1981, excluding individuals with depressed mood in 1975/1981. The outcomes were the Beck Depression Inventory (BDItot) and its subscale Negative Attitudes Towards Self (BDINATS) in 1990 as dichotomized measures, and the incidence of disability retirement due to depressive disorder during 1991-2004.	Onset of poor sleep between 1975 and 1981 predicted incident depression (BDItot OR=4.5, 95% CI: 2.7-7.4, BDINATS OR=2.0, 95% CI: 1.4-2.7), while persistent poor sleep showed somewhat weaker effects (BDItot; OR=2.5, 95% CI: 1.0-6.0, BDINATS OR=1.9, 95% CI: 1.1-3.3). Among those with few recent stressful life events, onset of poor sleep predicted strongly depression (BDINATS OR=9.5, 95% CI: 3.7-24.2). Likewise onset of poor sleep by 1981 increased the risk of disability retirement due to depression (OR=2.9, 95% CI: 1.8-4.9) with a similar risk among those with persistent poor sleep (OR=2.7, 95% CI: 1.3-5.7).	Lack of baseline diagnostic interviews; sleep quality based on self-report.	Poor sleep is of importance in etiology of depression and disability retirement due to depression. This emphasizes the importance of early detection and treatment of sleep disturbances.	
25450415	Tasimelteon is a circadian regulator that resets the master clock in the suprachiasmatic nuclei of the hypothalamus by binding to both melatonin MT1 and MT2 receptors making it a dual melatonin receptor agonist. Tasimelteon has been approved by the United States Food and Drug Administration for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24). Two prospective, single-center, open-label studies evaluated the pharmacokinetics of tasimelteon and its main metabolites after a single 20 mg dose administered to subjects with mild or moderate hepatic impairment or severe renal impairment, including subjects on dialysis compared to healthy controls. In subjects with mild or moderate hepatic impairment, exposure to tasimelteon after a single 20 mg dose, as measured by area under the plasma concentration-time curve to infinity, was increased by approximately 2-fold. There was no apparent relationship between tasimelteon clearance and renal function. No safety concerns were apparent in either study. Based on these results, the changes in the pharmacokinetics of tasimelteon due to mild or moderate hepatic or severe renal impairment are not considered clinically relevant, and no dose adjustment is necessary in these patients. 
25450154	The goal of this study was to identify the prevalence and clinical correlates and severity of restless legs syndrome (RLS) among pregnant women in mainland China.This cross-sectional study enrolled 1584 women (18-40 years old) who came to a prenatal outpatient clinic to consult an obstetrician. Pregnant women were studied in each trimester, and assessments included interviews about RLS symptoms and related questions. Standardized questionnaires include the International Restless Syndrome Scale and the Pittsburgh Sleep Quality Questionnaire. Blood tests included levels of hemoglobin and mean corpuscular volume.	RLS was diagnosed in 177 of 1584 women (11.2%); 4.2% were categorized as having pre-existing RLS and 54.8% reported onset of RLS symptoms after the 24th week. Multivariate analysis revealed that anemia was positively correlated with RLS. For the participants who first experienced RLS in pregnancy, RLS severity in the third trimester was more severe when compared with the first and second trimesters. Sleep disorders occurred more frequently in the third trimester.	In our study, RLS was frequent in pregnant Chinese women, and anemia was identified as an independent predictor of the disease. Further, most participants reported their symptoms during the third trimester, and the severity of RLS and sleep disorders of participants was more prominent in the third trimester.	
25450136	To investigate self-report measures of sleep disturbances and sleep-related impairments in samples of individuals with multiple sclerosis (MS) or spinal cord injury (SCI).Cross-sectional survey.	Community based.	Adults (age ≥18y) (N=700) with either MS (n=461) or SCI (n=239) who were enrolled in a longitudinal survey of self-reported health outcomes and who completed self-report sleep measures at 1 time point.	None.	Medical Outcomes Study Sleep Scale (MOS-S), Patient Reported Outcomes Measurement Information System (PROMIS) sleep disturbance short form, and PROMIS sleep-related impairments short form.	Mean scores on the MOS-S sleep index II were significantly worse for both the MS and SCI samples than those of previously reported samples representative of the U.S. general population (P<.0001 for each group). The PROMIS sleep disturbance short form and PROMIS sleep-related impairments short form scores of the MS sample were also significantly different from those reported for the calibration cohort (P<.0001 on each scale). However, although the scores of the SCI sample were significantly different from those of the comparison cohort for the PROMIS sleep-related impairments short form (P=.045), the differences on the PROMIS sleep disturbance short form were not significant (P=.069).	Although the MOS-S scores for the MS and SCI cohorts clearly indicated significantly high levels of sleep-related problems and were consistent with existing literature, the more ambiguous findings from the PROMIS sleep disturbance short form and PROMIS sleep-related impairments short form suggest that not enough is currently known about how these instruments function when applied to those with chronic neurologic dysfunction.	
25449993	To explore the association of sleep patterns with bone mineral density (BMD) in pre- and post-menopausal women, we used a questionnaire to evaluate the sleep patterns and performed calcaneal quantitative ultrasound to estimate BMD, in 6,510 women aged 40 years or older, from June to November 2011 in Nanjing City. We found a 1.7-fold risk of osteoporosis in post-menopausalwomen with bedtime of ≥0:00 am (OR = 1.69, 95 % CI 1.39-2.13), compared to those whose bedtime of <0:00 am. post-menopausalwomen with excessive total sleep (>10 h vs. 8-9 h, OR = 1.54, 95 % CI 1.05-2.02) were shown to have a higher risk of osteoporosis, however, this high risk was not detected in those with excessive nocturnal sleep (>10 h vs. 8-9 h, OR = 0.85, 95 % CI 0.62-1.30). By contrast, post-menopausalwomen with inadequate nocturnal sleep (≤7 h vs. 8-9 h, OR = 1.68, 95 % CI 1.32-2.75), excessive daytime sleep (≥180 min vs. 0 min, OR = 1.52, 95 % CI 1.08-2.13), and noontime nap (>60 min vs. 0 min: OR = 1.37, 95 % CI 1.06-1.76) were demonstrated to have higher risk of bone loss. Nevertheless, these associations were not found in premenopausal women. We conclude that delayed bedtime, nocturnal sleep deprivation, excessive daytime sleep, and noontime nap, but not reduced total sleep duration, could promote bone loss in post-menopausalwomen, which might be related to circadian rhythm disturbances. However, they have limited influences to BMD in women who were still in menstruating. Mechanism responsible for the phenomena warrants further investigation.
25449825	Sleep disturbance is a common complaint for women going through the menopausal transition. A previous systematic review and meta-analysis of cross-sectional studies showed a small but significant relationship between self-reported sleep disturbance and menopausal stage and highlighted a possible influence of culture. However, the longitudinal relationship between self-reported sleep disturbance and menopausal transition has not been explored. This paper aimed to review literature on the longitudinal relationship between self-reported sleep disturbance and menopausal transition among community dwelling midlife women. Multiple electronic databases were systematically searched. Literature published prior to 2013 was reviewed. A narrative synthesis was used to analyse the results due to high level of heterogeneity across the included studies. Overall, review of eligible studies showed a small increased risk of self-reported sleep disturbance as women go through the menopausal transition after adjustment of potential confounders. Although the methodological quality of the majority of included studies was classified as high, the impact of culture on this relationship could not be explored, as all of the included studies were conducted in western countries. Like vasomotor symptoms, self-reported sleep disturbance is one of the core menopausal symptoms. Management strategies should be put in place to help women manage sleep disturbance to prevent complications and to improve health related quality of life. 
25449319	Although sleep is vital to all human functioning and poor sleep is a known problem in cancer, it is unclear whether the overall prevalence of the various types of sleep disorders in cancer is known. The purpose of this systematic literature review was to evaluate if the prevalence of sleep disorders could be ascertained from the current body of literature regarding sleep in cancer. This was a critical and systematic review of peer-reviewed, English-language, original articles published from 1980 through 15 October 2013, identified using electronic search engines, a set of key words, and prespecified inclusion and exclusion criteria. Information from 254 full-text, English-language articles was abstracted onto a paper checklist by one reviewer, with a second reviewer randomly verifying 50% (k = 99%). All abstracted data were entered into an electronic database, verified for accuracy, and analyzed using descriptive statistics and frequencies in SPSS (v.20) (North Castle, NY). Studies of sleep and cancer focus on specific types of symptoms of poor sleep, and there are no published prevalence studies that focus on underlying sleep disorders. Challenging the current paradigm of the way sleep is studied in cancer could produce better clinical screening tools for use in oncology clinics leading to better triaging of patients with sleep complaints to sleep specialists, and overall improvement in sleep quality. 
25446760	The selective CRF₁ (corticotropin releasing factor type 1) receptor antagonist SSR125543 has been previously shown to attenuate the long-term behavioral and electrophysiological effects produced by traumatic stress exposure in mice. Sleep disturbances are one of the most commonly reported symptoms by people with post-traumatic stress disorder (PTSD). The present study aims at investigating whether SSR125543 (10 mg/kg/day/i.p. for 2 weeks) is able to attenuate sleep/wakefulness impairment induced by traumatic stress exposure in a model of PTSD in mice using electroencephalographic (EEG) analysis. Effects of SSR125543 were compared to those of the 5-HT reuptake inhibitor, paroxetine (10 mg/kg/day/i.p.), and the partial N-methyl-d-aspartate (NMDA) receptor agonist, d-cycloserine (10 mg/kg/day/i.p.), two compounds which have demonstrated clinical efficacy against PTSD. Baseline EEG recording was performed in the home cage for 6h prior to the application of two electric foot-shocks of 1.5 mA. Drugs were administered from day 1 post-stress to the day preceding the second EEG recording session, performed 14 days later. Results showed that at day 14 post-stress, shocked mice displayed sleep fragmentation as shown by an increase in the occurrence of both non-rapid eye movement (NREM) sleep and wakefulness bouts. The duration of wakefulness, NREM and REM sleep were not significantly affected. The stress-induced effects were prevented by repeated administration of SSR125543, paroxetine and D-cycloserine. These findings confirm further that the CRF₁ receptor antagonist SSR125543 is able to attenuate the deleterious effects of traumatic stress exposure.
25446342	SWEDDs (Scans Without Evidence of Dopaminergic Deficits) was defined from a series of pharmaceutical trials on Parkinson's disease (PD). Non-motor features including sleep-related problems are common even in early-stage PD patients; however, little is known about the burden of the non-motor symptoms in SWEDDs patients.The Non-motor Symptoms Assessment Scale (NMSS), revised version of the Parkinson's Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS), and EuroQol 5-Dimension (EQ-5D) were applied to evaluate 17 SWEDDs patients and 28 de novo PD patients. The presence of clinically probable rapid eye movement sleep behavior disorder (cpRBD) was assessed using the International Classification of Sleep Disorders-Revised (ICSD-R) criteria.	The total NMSS score for the SWEDDs group was significantly lower than for the de novo PD group (p = 0.032). The most distinct difference was in taste or smell change (p < 0.000). Prevalence of cpRBD was higher in de novo PD patients than in SWEDDs patients (p = 0.030), though no significant differences in the PDSS-2 total score (p = 0.496) or the ESS score (p = 0.517) were found. The SWEDDs patients did not significantly differ from the de novo PD patients with regard to quality of life, as measured by the EQ-5D index score (p = 0.177).	The patients with SWEDDs have less non-motor problems than newly diagnosed untreated PD patients. Given the difficulty distinguishing between SWEDDs and early PD, identifying some of non-motor symptoms, such as RBD or olfactory impairment, could aid clinicians in their work.	


25443216	Aging is associated with a variety of physiological changes originating peripherally and centrally, including within the autonomic nervous system. Sleep-wake disturbances constitute reliable hallmarks of aging in several animal species and humans. Recent studies have been interested in N-acetylmannosamine (ManNAc) a potential therapeutic agent for improving quality of life, as well as preventing age-related cognitive decline. In this study, ManNAc (5.0 mg/ml) was administered in the drinking water of middle-aged male C57BL/6J mice (55 weeks old) for 7 days. Mice were housed under a 12:12 h light:dark cycle at 23-24 °C. We evaluated bio-behavioral activity using electrocardiogram, body temperature and locomotor activity recorded by an implanted telemetry transmitter. To estimate sleep-wake profile, surface electroencephalogram and electromyogram leads connected to a telemetry transmitter were also implanted in mice. Autonomic nervous activity was evaluated using power spectral analysis of heart rate variability. ManNAc-treated mice spent more time in a wakeful state and less time in slow wave sleep during the dark phase. Parasympathetic nervous activity was increased following ManNAc treatment, then the sympatho-vagal balance was shifted predominance of parasympathetic nervous system. Furthermore, improvement in sleep-wake pattern was associated with increased parasympathetic nervous activity. These results suggest that ManNAc treatment can improve bio-behavioral activity and sleep-wake quality in middle-aged mice. This may have implications for improving sleep patterns in elderly humans.
25442171	Adolescence is a time of marked changes across sleep, circadian rhythms, brain function, and alcohol use. Starting at puberty, adolescents' endogenous circadian rhythms and preferred sleep times shift later, often leading to a mismatch with the schedules imposed by secondary education. This mismatch induces circadian misalignment and sleep loss, which have been associated with affect dysregulation, increased drug and alcohol use, and other risk-taking behaviors in adolescents and adults. In parallel to developmental changes in sleep, adolescent brains are undergoing structural and functional changes in the circuits subserving the pursuit and processing of rewards. These developmental changes in reward processing likely contribute to the initiation of alcohol use during adolescence. Abundant evidence indicates that sleep and circadian rhythms modulate reward function, suggesting that adolescent sleep and circadian disturbance may contribute to altered reward function, and in turn, alcohol involvement. In this review, we summarize the relevant evidence and propose that these parallel developmental changes in sleep, circadian rhythms, and neural processing of reward interact to increase risk for alcohol use disorder (AUD).
25442116	Sleep disturbances and cognitive impairment are common non-motor manifestations of Parkinson's disease (PD). Recent studies suggest that sleep spindles and slow waves play a role in brain plasticity mechanisms and are associated with cognitive performance. However, it remains unknown whether these sleep parameters could serve as markers of cognitive decline in PD. Therefore, we examined whether alterations in sleep spindles and slow waves at baseline visit were associated with increased likelihood of developing dementia at follow-up in PD. Sixty-eight nondemented PD patients (64.9 ± 8.8 years old; 46 men) participated in the study, along with 47 healthy individuals (65.0 ± 10.6 years old; 30 men). All participants underwent baseline polysomnographic recording and a comprehensive neuropsychological assessment. Sleep spindles (12-15 Hz) and slow waves (>75 μV and <4 Hz) were automatically detected on all-night non-rapid eye movement sleep electroencephalography. At follow-up (mean: 4.5 years later), 18 PD patients developed dementia (70.2 ± 7.6 years old; 13 men) and 50 remained dementia-free (63.0 ± 8.5 years old; 33 men). Sleep spindle density and amplitude were lower in PD patients who converted to dementia compared with both patients who remained dementia-free and controls, mostly in posterior cortical regions (p < 0.05). Dementia-free PD patients were intermediate between dementia patients and controls, with lower baseline sleep spindle density in all cortical areas compared with controls (p < 0.01). In demented PD patients, lower sleep spindle amplitude in parietal and occipital areas was associated with poorer visuospatial abilities. Although slow wave amplitude was lower in PD patients compared with controls (p < 0.0001), no difference was observed between those who developed or did not develop dementia. Results demonstrate non-rapid eye movement sleep electroencephalographic abnormalities in PD patients. Sleep spindle activity was particularly impaired in PD patients who developed dementia, with a more posterior topographic pattern. Sleep spindle alterations are associated with later development of dementia in PD, and thus may serve as an additional marker of cognitive decline in these patients.
25441750	The aim of the study was to examine sleep, neurocognitive and behavioural functioning in children and adolescents with type 1 diabetes (T1D) compared to controls and to test whether sleep quality mediates the relationship between diabetes and neurocognitive and behavioural deficits.Participants include 49 children and adolescents with T1D (recruited from a hospital clinic) and 36 healthy controls (age range = 6-16 years). Parents completed a survey consisting of the Sleep Disturbances Scale for Children, the Behavior Rating Inventory of Executive Functions, and the Behavior Assessment System for Children-2. Diabetic and demographic parameters were collated from medical records. The survey was posted to participants.	Children with T1D compared to controls reported a higher frequency of sleep problems, and mild deficits in executive and behavioural functioning. Mediational analyses revealed that sleep quality fully mediated metacognitive functioning, externalised problematic behaviour, and internalised problematic behaviour, but not behavioural regulation.	Rather than the direct impact of T1D on daytime functioning, it is the consequent impact of T1D on sleep and the resulting sleep disruption which can explain much of the neurocognitive and behavioural deficits reported in children with T1D. Maintaining good nocturnal glycaemic control may play a much larger role than previously thought in regulating daytime functioning in children with T1D.	
25441749	Sleep is critical for adolescent health and well-being. However, there are a limited number of validated self-report measures of sleep for adolescents and no well-validated measures of sleep that can be used across middle childhood and adolescence. The Children's Report of Sleep Patterns (CRSP) has been validated in children aged 8-12 years. The purpose of this study was to examine the psychometric properties of the CRSP, a multidimensional, self-report sleep measure for adolescents.The participants included 570 adolescents 13-18 years, 60% female, recruited from pediatricians' offices, sleep clinics, children's hospitals, schools, and the general population. A multi-method, multi-reporter approach was used to validate the CRSP. Along with the CRSP, a subset of the sample completed the Adolescent Sleep Hygiene Scale (ASHS), with a different subset of adolescents undergoing polysomnography.	The CRSP demonstrated good reliability and validity. Group differences on the CRSP were found for adolescents presenting to a sleep or medical clinic (vs. a community sample), for older adolescents (vs. younger adolescents), for those who regularly napped (vs. infrequently napped), and for those with poor sleep quality (vs. good sleep quality). Self-reported sleep quality in adolescents was also associated with higher apnea-hypopnea index scores from polysomnography. Finally, the CRSP Sleep Hygiene Indices were significantly correlated with indices of the ASHS.	The CRSP is a valid and reliable measure of adolescent sleep hygiene and sleep disturbances. With a parallel version for middle childhood, the CRSP likely provides clinicians and researchers the ability to measure self-reported sleep across development.	
25441745	Chronotype characterizes individual differences in sleep/wake rhythm timing, which can also impact light exposure patterns. The present study investigated whether early and late chronotypes respond differently to controlled advancing and delaying light exposure patterns while on a fixed, advanced sleep/wake schedule.In a mixed design, 23 participants (11 late chronotypes and 12 early chronotypes) completed a 2-week, advanced sleep/wake protocol twice, once with an advancing light exposure pattern and once with a delaying light exposure pattern. In the advancing light exposure pattern, the participants received short-wavelength light in the morning and short-wavelength-restricting orange-tinted glasses in the evening. In the delaying light exposure pattern, participants received short-wavelength-restricting orange-tinted glasses in the morning and short-wavelength light in the evening. Light/dark exposures were measured with the Daysimeter. Salivary dim light melatonin onset (DLMO) was also measured.	Compared to the baseline week, DLMO was significantly delayed after the delaying light intervention and significantly advanced after the advancing light intervention in both groups. There was no significant difference in how the two chronotype groups responded to the light intervention.	The present results demonstrate that circadian phase changes resulting from light interventions are consistent with those predicted by previously published phase response curves (PRCs) for both early and late chronotypes.	
25441744	To examine associations of self-reported sleep disturbance and short sleep duration with the risk for academic failure.A cohort of ~40,000 adolescents (age range: 12-19 years) who were attending high school grades 7, 9, and 2nd year of upper secondary school in the Swedish Uppsala County were invited to participate in the Life and Health Young Survey (conducted between 2005 and 2011 in Uppsala County, Sweden). In addition to the question how many subjects they failed during the school year (outcome variable), subsamples of adolescents also answered questions related to subjective sleep disturbance (n = 20,026) and habitual sleep duration (n = 4736) (exposure variables). Binary logistic regression analysis was utilized to explore if self-reported sleep disturbances and habitual short sleep duration (defined as less than 7-8 h sleep per night) increase the relative risk to fail subjects during the school year (controlled for possible confounders, e.g. body-mass-index).	Adolescents with self-reported sleep disturbances had an increased risk for academic failure (i.e., they failed at least one subject during the school year; OR: boys, 1.68; girls, 2.05, both P < 0.001), compared to adolescents without self-reported sleep disturbances. In addition, adolescents who reported short sleep duration on both working and weekend days were more likely to fail at least one subject at school than those who slept at least 7-8 h per night (OR: boys, 4.1; girls, 5.0, both P < 0.001).	Our findings indicate that reports of sleep disturbance and short sleep duration are linked to academic failure in adolescents. Based on our data, causality cannot be established.	
25441742	A high rate of sleep disturbances has been reported in individuals with Williams syndrome (WS) but the underlying aetiology has yet to be identified. Melatonin and cortisol levels display circadian rhythmicity and are known to affect and regulate sleep/wake patterns. The current study examined the levels of these two endocrine markers and explored a possible relationship with sleep patterns in children with WS.Twenty-five children with WS and 27 typically developing age- and gender-matched comparison children were recruited. Saliva was collected from each child at three time points: 4-6 pm, before natural bedtime, and after awakening. The levels of salivary melatonin and cortisol were analysed by specific enzyme-linked immunoassays. Sleep patterns were examined using actigraphy and the Children's Sleep Habit Questionnaire.	The WS group had shallower drops in cortisol and less pronounced increase in melatonin at bedtime compared to the controls. Furthermore, they also had significantly higher levels of cortisol before bedtime.	Increased bedtime cortisol and less pronounced rise in melatonin levels before sleep may play a role in the occurrence of sleep disturbances, such as delayed sleep onset, observed in children with WS. As both markers play a significant role in our circadian rhythm and sleep/wake cycle, it is necessary to examine sleep using multi-system analysis.	
25441304	Recent scientific evidences have brought a paradigm shift in our approach towards the concepts of insomnia and its management. The differentiation between primary and secondary insomnia was proved more hypothetical than actual and based upon the current evidences insomnia subtypes described in earlier system have been lumped into one-insomnia disorder. Research in this field suggests that insomnia occurring during psychiatric or medical disorders has a bidirectional and interactive relationship with and coexisting medical and psychiatric illnesses. The new approach looks to coexist psychiatric or medical disorders as comorbid conditions and hence specifies two coexisting conditions. Therefore, the management and treatment plans should address both the conditions. A number of sleep disorders may present with insomnia like symptoms and these disorders should be treated efficiently in order to alleviate insomnia symptoms. In such cases, a thorough history from the patient and his/her bed-partner is warranted. Moreover, some patients may need polysomnography or other diagnostic tests like actigraphy to confirm the diagnosis of the underlying sleep disorder. DSM-5 classification system of sleep–wake disorders has several advantages, e.g., it has seen insomnia across different dimensions to make it clinically more useful; it focuses on the assessment of severity and guides the mental health professional when to refer a patient of insomnia to a sleep specialist; lastly, it may encourage the psychiatrists to opt for sleep medicine as a career.
25441252	Excessive daytime sleepiness (EDS) has been associated with singular independent symptoms of metabolic syndrome, such as insulin resistance and diabetes. The aim of this study was to assess whether this relationship is sustained among individuals who meet criteria for the whole syndrome.994 Women aged 21-94 years (median 50.2 years, IQR 34-65) and 840 men aged 24-92 years (median 60.4 years, IQR 47-73) who resided in the Barwon Statistical Division, South-Eastern Australia, and participated in the Geelong Osteoporosis Study (GOS) between the years of 2001 and 2008. Anthropometric measurements, lifestyle, mood, demographic and health-related factors were obtained. Sleep duration was categorized as short (<6 h), average (6-9 h) and long (>9 h). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and scores of ≥ 10 indicated EDS. The presence of metabolic syndrome was assessed using a modified version of criteria as outlined by the International Diabetics Federations recommendations (2005).	Women: 138 (14.0%) of the women reported EDS; those with EDS were heavier, had a greater body mass index (BMI) and were more likely to have metabolic syndrome. The association between EDS and metabolic syndrome was sustained following adjustment for age and hours sleep (adjusted OR=1.90, 95% CI 1.16-3.09), however BMI attenuated the relationship (adjusted OR=1.64, 95% CI =1.05-2.57). These findings were independent of smoking status, alcohol intake, medication use, socioeconomic status, physical activity and current diagnosis of a depressive illness. Men: 111 (13.2%) of the men reported EDS; those with EDS had a greater waist circumference and were more likely to have metabolic syndrome. Analysis of age-stratified data (<60 years vs. ≥60 years) revealed that the older men with EDS were more likely to have metabolic syndrome (OR=1.71, 95% CI 1.01-2.92), however, age explained this association (age adjusted OR=1.51, 95% CI 0.88-2.60). In the younger age group, no association was detected between EDS and metabolic syndrome. For both men and women, the prevalence of combined EDS and metabolic syndrome increased progressively with age.	For women, the association between EDS and metabolic syndrome appears to be driven by adiposity measures; while for men, the association is somewhat attributed to older age. Additional research is required to assess temporal associations with underlying sleep pathology.	
25439524	Insight concerning having a mental illness has been found to influence outcome and effectiveness of treatment. It has been studied mainly in the area of schizophrenia with few studies addressing other disorders. This study evaluates insight in individuals with bipolar disorder using the Scale to Assess Unawareness of Mental Disorder (SUMD), a comprehensive interview for evaluation of awareness of illness and attribution of symptoms. The hypothesis was that in bipolar disorder level of awareness may be associated with numerous factors including neurocognitive function, structural changes in the frontal lobes and hippocampus evaluated by MRI, neurocognitive status, severity of mania and other psychiatric symptoms and comorbid alcoholism.In order to evaluate this hypothesis 33 individuals with DSM-IV diagnosed bipolar disorder, some with and some without comorbid alcoholism, were administered the SUMD and a number of other procedures including a quantitative MRI measuring volume of the frontal lobes and hippocampus, a brief battery of neurocognitive tests, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. The data were analyzed by comparing participants with and without alcoholism on these procedures using t tests and by linear multiple regression, with SUMD ratings of awareness and attribution as the dependent variables and variable sets from the other procedures administered as multivariate independent variables.	The median score obtained from the SUMD for current awareness was in a range between full awareness and uncertainty concerning presence of a mental disorder. For attribution, the median score indicated that attribution was usually made to the illness itself. None of the differences between participants with and without comorbid alcoholism were significant for the SUMD awareness and attribution scores, neurocognitive or MRI variables. The multiple regression analyses only showed a significant degree of association between the SUMD awareness score and the Young Mania Rating Scale (r(2)=.632, p<.05). A stepwise analysis indicated that items assessing degree of insight, irritability, and sleep disturbance met criteria for entry into the regression equation. None of the regression analyses for the SUMD attribution item were significant.	Apparently unlike the case for schizophrenia, most of the participants, all of whom had bipolar disorder, were aware of their symptoms and correctly related them to a mental disorder. Hypotheses concerning the relationships between degree of unawareness and possible contributors to its development including comorbid alcoholism, cognitive dysfunction and structural reduction of gray matter in the frontal region and hippocampus, were not associated with degree of unawareness but symptoms of mania were significantly associated. The apparent reason for this result is that the sample obtained a SUMD modal awareness score of 1 or 2, reflecting the area between full awareness and uncertainty about having a mental disorder. None of the participants were rated as having a 5 response reflecting the belief that s/he does not have a mental disorder.	
25439287	The importance of the cerebellum in sleep disorders, and vice versa, is only beginning to be understood. Advanced neuroimaging modalities have revealed cerebellar changes in both common and rare sleep disorders. Sleep disorders in those with genetic cerebellar disease, such as spinocerebellar ataxia, Friedreich ataxia, Joubert syndrome, and ataxia-telangiectasia, include excessive daytime sleepiness, restless legs syndrome, periodic limb movements of sleep, obstructive apnea, central apnea, and rapid eye movement behavior disorder. Sleep medicine is an important and under-recognized part of the neurologic evaluation in those with cerebellar disease. 
25439176	Night float rotations (NF) have been developed as a means of achieving duty hour compliance among residency programs. These were initially pioneered in the late 1980s as a response to fatigue among residents. The NF experience had its genesis in work hour reform and providing hospital service moreso than education. However, as NF has become ubiquitous, it is not clear that we have adequately revisited the educational component of this experience. We systematically reviewed the literature on educational aspects of a night float experience.PubMed searches were conducted for the terms "night float" and "night, curriculum, residency." This yielded 320 articles. Concerning educational aspects of the NF reduced the total to 134 articles. Editorials and those concerning procedural volumes or handoffs were also excluded. Most articles used surveys as methodology, so formal statistical analysis was not possible.	In total, 42 independent articles were found that directly related to the educational value of NF rotations, spanning all of the medical disciplines. Each study was searched for interventions or strategies that may affect the educational value of the NF experience. These may be grouped broadly into 3 discrete categories: (1) attention to the sleep-wake cycle, (2) addition of personal to augment the experience and (3) incorporation of formal educational elements to night rotations. A summary of these strategies is presented in Table 3.	NF is a practical solution to the challenge of work hour restrictions in residency, and is likely to persist in the future. Some educational issues arise due to the altered physiology of a reversed sleep-wake cycle, which may be best resolved through structural limitations of the night rotations. Other deficiencies are based on lack of interactions, for which there are strategies to improving the NF educational experience.	
25438949	To study the association between self-reported sleep disturbances and dementia risk.Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n = 1574) and 70 (n = 1029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of β-amyloid (Aβ) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.	Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P < .05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P < .001). No group differences were found in Aβ levels.	Improving sleep quality may help reduce the neurodegenerative risk in older men.	
25437848	Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG) was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers), previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM) sleep and slow wave sleep concomitant with reduced power between 8-16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is linked to working memory independent of the timing of the sleep episode within the 24-h cycle. 
25437468	When it comes to health and fitness, there's an app for just about everything. Want to track how many steps you've taken today? There's an app for that. Want to track the calories you've consumed? There's an app for that, too. And, if you want to know if you got a good night's sleep last night, well, now there's also an app for that. 


25436776	Cancer and treatments may induce cognitive impairments in cancer patients, and the causal link between chemotherapy and cognitive dysfunctions was recently validated in animal models. New cancer targeted therapies have become widely used, and their impact on brain functions and quality of life needs to be explored. We evaluated the impact of everolimus, an anticancer agent targeting the mTOR pathway, on cognitive functions, cerebral metabolism, and hippocampal cell proliferation/vascular density in mice. Adult mice received everolimus daily for 2 weeks, and behavioral tests were performed from 1 week after the last treatment. Everolimus-treated mice displayed a marked reduction in weight gain from the last day of the treatment period. Ex vivo analysis showed altered cytochrome oxidase activity in selective cerebral regions involved in energy balance, food intake, reward, learning and memory modulation, sleep/wake cycle regulation, and arousal. Like chemotherapy, everolimus did not alter emotional reactivity, learning and memory performances, but in contrast to chemotherapy, did not affect behavioral flexibility or reactivity to novelty. In vivo hippocampal neural cell proliferation and vascular density were also unchanged after everolimus treatments. In conclusion, two weeks daily everolimus treatment at the clinical dose did not evoke alteration of cognitive performances evaluated in hippocampal- and prefrontal cortex-dependent tasks that would persist at one to four weeks after the end of the treatment completion. However, acute everolimus treatment caused selective CO modifications without altering the mTOR effector P70S6 kinase in cerebral regions involved in feeding behavior and/or the sleep/wake cycle, at least in part under control of the solitary nucleus and the parasubthalamic region of the hypothalamus. Thus, this area may represent a key target for everolimus-mediating peripheral modifications, which has been previously associated with symptoms such as weight loss and fatigue. 

25435285	This review focuses on the medicinal chemistry efforts directed toward the identification of competitive and noncompetitive antagonists of glutamate at group II metabotropic glutamate receptors (mGluRII: mGlu2/3 and mGlu2). This class of compounds holds promise for the treatment of CNS disorders such as major depression, cognitive deficits and sleep-wake disorders, and several pharmaceutical companies are advancing mGluRII antagonists from discovery research into clinical development.This review article covers for the first time the patent applications that were published on mGlu2/3 orthosteric and allosteric antagonists between January 2005 and September 2014, with support from the primary literature, posters and oral communications from international congresses. Patent applications published prior to 2005 for which compositions of matter were largely described in peer review articles are briefly discussed with main findings.	Recent advances in the prodrug approach of novel mGlu2/3 orthosteric antagonists combined with the design of novel mGlu2/3 and mGlu2 negative allosteric modulators provide new therapeutic opportunities for neurologic and psychiatric disorders.	
25434872	Melatonin secretion is usually increased during the daytime and decreased at night in Smith-Magenis syndrome (SMS) and consequently is not a pertinent marker of the circadian phase of the clock in these cases. No data on temperature rhythm is available in SMS, another reliable marker of circadian clock activity. For this reason, we assessed the 24h profiles of core temperature, sleep-wake cycle, hormones (plasma cortisol and melatonin) and plasma and urine 6sulfatoxy-melatonin, the main hepatic melatonin metabolism in a 31-year-old man diagnosed with a SMS. All circadian rhythms, especially temperature rhythm showed a phase-advance, associated with reverse melatonin secretion. Plasma and urine 6sulfatoxy-melatonin profiles showed normal melatonin catabolism and confirmed the reversed melatonin secretion. Taking in consideration the reverse melatonin secretion and the phase-advanced temperature rhythm, which is driven by the suprachiasmatic nucleus, we hypothesize that the central clock is more sensitive to afternoon than to morning melatonin. This different responsiveness to melatonin according to the time of the day (i.e. chronaesthesia) corroborates the phase response curve of melatonin secretion to exogenous melatonin. 
25434476	Niemann-Pick disease type C (NP-C) is a rare and progressive autosomal recessive disease leading to disabling neurological manifestation and premature death. The disease is prone to underdiagnosis because of its highly heterogeneous presentation. NP-C is characterized by visceral, neurological, and psychiatric manifestation, and its clinical picture varies according to age at onset. Although cataplexy is one of its characteristic symptoms, particularly in the late infantile and juvenile form, sleep disturbances are described only exceptionally. A combination of splenomegaly, vertical supranuclear gaze palsy, and cataplexy creates a most useful suspicion index tool for the disease. In adolescent and adult patients, when intellectual deterioration progresses and emotional reactions become flat, cataplexy usually disappears. Pathological findings in the brainstem in NP-C mouse model are compatible with the patients' symptoms including cataplexy. The authors observed cataplexy in 5 (3 with late infantile and 2 with juvenile form) out of 22 NP-C cases followed up in the past 20 years.
25433921	An association between fibromyalgia and hepatitis C virus (HCV) has been previously described. However, the relationship between nonalcoholic steatohepatitis (NASH) and fibromyalgia symptoms has not been assessed, though they share several risk factors.We aimed to assess the factors associated with fibromyalgia symptoms across etiologies of liver disease.	Patients with cirrhosis due to HCV, NASH, or alcohol were recruited from an outpatient hepatology clinic and administered the Hospital Anxiety and Depression Score, Pittsburgh Sleep Quality Index, and the modified 2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia. Serum inflammatory markers were measured with standard luminex assays.	Of 193 participants, 53 (27 %) met criteria for fibromyalgia. Fibromyalgia symptoms were significantly associated with etiology of liver disease (HCV: 35 %, NASH: 30 %, alcohol-related liver disease: 12 %, p < 0.01). Using logistic regression, mood symptoms (OR 1.14, 95 % CI 1.06, 1.22), sleep disturbance (OR 1.32, 95 % CI 1.16, 1.52), and etiology of liver disease (NASH vs. HCV not different, alcohol vs. HCV OR 0.19, 95 % CI 0.05, 0.63) were associated with fibromyalgia symptoms. If abdominal pain was included in the model, etiology became nonsignificant, indicating that it may be central sensitization due to abdominal pain in patients with chronic liver disease that explains fibromyalgia symptoms rather than the etiology of liver disease or inflammation.	Fibromyalgia symptoms were significantly associated with HCV and NASH cirrhosis and with psychiatric symptoms. Future work should focus on the underlying pathophysiology and management of widespread pain in patients with cirrhosis.	
25433906	Sleep coaches are an emerging group of pediatric providers whose scope of services and regional distribution have not been well characterized. This descriptive analysis used Internet data to identify sleep coaches and certification programs in the US; we found a sizeable diversity of backgrounds, training, services offered, and pricing. 
25433714	Parkinson's disease (PD) is a neurobehavioral disorder characterized by motor symptoms and signs, and non-motor abnormalities such as olfactory dysfunction, pain, sleep disorders and cognitive impairment. Amongst these alterations, sleep disturbances play an important role in the pathology, but presence of disturbed sleep is not currently considered in diagnosis. However, sleeping problems may precede by many years the classic motor abnormalities of PD and should be clinically evaluated as a potential marker before disease onset. The first disturbance reported with this potential was the disorder REM sleep behaviour and currently several other disturbances have gained importance as potential markers, such as excessive daytime sleepiness, restless legs syndrome and new evidence also points to changes in circadian rhythms. Here we present a brief review of the major evidence indicating that sleep disturbances precede the motor symptoms in PD and neurodegeneration occurs in regions that could underlie these phenomena in order to provide support for the conclusion that disturbances of sleep should be considered as valuable preclinical markers for PD. 
25433519	Multiple Sclerosis is a disease of the central nervous system involving a variety of debilitating physical, sensory, cognitive and emotional symptoms. This literature review evaluated the impact of psychological interventions on the physiological symptoms associated with the illness.A systematic literature search was conducted using Medline, PsycINFO, Scopus, and the Cochrane Library databases, as well as reference lists. Relevant studies were selected and assessed according to a preset protocol.	The search produced 220 articles, with 22 meeting inclusion criteria for the review. A total of 5,705 subjects with Multiple Sclerosis were analyzed. Results from the included studies indicate a general improvement in both psychological and physiological outcomes following psychological treatment. The most highly influenced physical symptoms include fatigue, sleep disturbances, pain, and physical vitality.	Findings from the review suggest a positive relationship between psychological interventions and physiological Multiple Sclerosis symptoms. Implications for future research are discussed.	
25432918	Is there an excess of sleep disturbances in women with polycystic ovary syndrome (PCOS) in a community-based sample?Sleep disturbances are almost twice as common in women with PCOS compared with women of similar age without PCOS, with the association slightly accounted for by body weight and, to a greater extent, by depressive symptoms.	There is an excess of sleep-disordered breathing in clinical samples of women with PCOS, after accounting for their profile of body weight. Poor sleep patterns increase insulin resistance and thus may exacerbate PCOS symptoms and longer-term risk of metabolic disease.	A cross-sectional study of 724 women, comprising 74% of a cohort study established retrospectively when women were around age 30 years.	Comparisons were made between 87 women with PCOS, diagnosed using the Rotterdam criteria, and 637 women without this diagnosis in Adelaide, South Australia. Differences in sleep disturbances, assessed using a modified version of the Jenkins questionnaire, were investigated using ordered logistic regression.	Sleep disturbances were twice as common in women with PCOS compared with those without. Specifically, PCOS was associated with increasing occurrence of difficulty falling asleep (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.28-2.95); this association was attenuated but still statistically significant after accounting for BMI and depressive symptoms. Increasing occurrence of difficulty maintaining sleep (OR 1.92 95% CI 1.12-3.31) was mediated by obesity and depressive symptoms, together. Other factors did not change these findings.	The cross-sectional nature of the study means that the direction of associations between PCOS and sleep disturbances is unclear, although bi-directionality for the mediators is likely based on data in the wider literature.	Our results indicate that assessment and management of both sleep and mental health problems in women with PCOS should be undertaken. Longitudinal data would be valuable to see how poor sleep affects longer-term health profiles.	
25431234	The purpose of this work was to examine the relationships between geographical coordinates and the prevalence of winter depression (SADW ), and to compare the sleep characteristics and chronotype of youths with and without SADW . We conducted a cross-sectional study of self-reported sleep characteristics, chronotype and winter depression in northern European Russia. Two questionnaires, the Munich Chronotype Questionnaire (MCTQ) and the Seasonal Pattern Assessment Questionnaire (SPAQ), were administered to a total of 3435 adolescents aged 10-20 years (1517 males and 1918 females). The prevalence of SADW in the study population was 8.4% and sub-SADW 11.8%. Four variables predicted the likelihood of SADW in youths: sex [higher in females: odds ratio (OR): 1.87, P < 0.0001], age (increases with age: OR: 1.09, P < 0.001), latitude (higher in the North: OR: 1.49, P < 0.029) and position in the time zone (higher in the West: OR: 1.61, P < 0.001). Later sleeping and waking, longer sleep latencies, more severe sleep inertia, shorter total sleep times and lower sleep efficiencies were observed in both males and females with SADW . The influence of SADW on sleep characteristics was more pronounced on school days. Significant phase delays of the sleep-wake rhythm and severe social jetlag (the difference between the mid-point of sleep phase at weekends and on workdays) were observed in females with SADW , but not in males. There are significant differences in sleep characteristics and chronotype between people with SADW and no-SAD. We demonstrate that both latitude of residence and location within the time zone are significant predictors of SADW in young inhabitants of the North.
25431022	The lack of timely access to diagnosis and treatment for sleep disorders is well described, but little attention has been paid to understanding how multiple system constraints contribute to long waiting times. The objectives of this study were to identify system constraints leading to long waiting times at a multidisciplinary sleep centre, and to use patient flow simulation modelling to test solutions that could improve access. Discrete-event simulation models of patient flow were constructed using historical data from 150 patients referred to the sleep centre, and used to both examine reasons for access delays and to test alternative system configurations that were predicted by administrators to reduce waiting times. Four possible solutions were modelled and compared with baseline, including addition of capacity to different areas at the sleep centre and elimination of prioritization by urgency. Within the model, adding physician capacity improved time from patient referral to initial physician appointment, but worsened time from polysomnography requisition to test completion, and had no effect on time from patient referral to treatment initiation. Adding respiratory therapist did not improve model performance compared with baseline. Eliminating triage prioritization worsened time to physician assessment and treatment initiation for urgent patients without improving waiting times overall. This study demonstrates that discrete-event simulation can identify multiple constraints in access-limited healthcare systems and allow suggested solutions to be tested before implementation. The model of this sleep centre predicted that investments in capacity expansion proposed by administrators would not reduce the time to a clinically meaningful patient outcome.
25430914	Sleep dysregulation is highly prevalent in bipolar disorders (BDs), with previous actigraphic studies demonstrating sleep abnormalities during depressive, manic, and interepisode periods. We undertook a meta-analysis of published actigraphy studies to identify whether any abnormalities in the reported sleep profiles of remitted BD cases differ from controls.A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis. Effect sizes for actigraphy parameters were expressed as standardized mean differences (SMD) with 95% confidence intervals (95% CI).	Nine of 248 identified studies met eligibility criteria. Compared with controls (N=210), remitted BD cases (N=202) showed significant differences in SMD for sleep latency (0.51 [0.28-0.73]), sleep duration (0.57 [0.30-0.84]), wake after sleep onset (WASO) (0.28 [0.06-0.50]) and sleep efficiency (-0.38 [-0.70-0.07]). Moderate heterogeneity was identified for sleep duration (I2=44%) and sleep efficiency (I2=44%). Post hoc meta-regression analyses demonstrated that larger SMD for sleep duration were identified for studies with a greater age difference between BD cases and controls (β=0.22; P=0.03) and non-significantly lower levels of residual depressive symptoms in BD cases (β=-0.13; P=0.07).	This meta-analysis of sleep in remitted bipolar disorder highlights disturbances in several sleep parameters. Future actigraphy studies should pay attention to age matching and levels of residual depressive symptoms.	
25429678	University students are exposed to many stressors. We assessed the associations between two stressors (educational related and general overall), socio-demographic characteristics (five variables), health behaviours/lifestyle factors (six variables), as well as religiosity and quality of life as independent variables, with self-reported symptoms/health complaints as dependent variables (eight health complaints). A sample of 2100 undergraduate students from nine institutions (six universities, three colleges) located in seven cities in Libya completed a general health questionnaire. The most prevalent symptoms were headaches, depressive mood, difficulties to concentrate and sleep disorder/insomnia that have been reported by 50%-60% of the students. The majority of students (62%) reported having had three or more symptoms sometimes or very often in the last 12 months. There was a positive association between perceived stressors and health symptoms, which remained significant after adjustment for gender and many other relevant factors for headache (OR 1.52; 95% CI 1.15-2.02), depressive mood (OR 2.20; 95% CI 1.64-2.94) and sleep disorder/ insomnia (OR 1.55, 95% CI 1.19-2.03). Other factors independently associated with most health symptoms were female gender and poor self-perceived health. Stress management programmes and a reduction of educational related stressors might help to prevent stress-related symptoms and health complaints in this student population. 
25424629	A study with 1050 people over the age of 50 years with mild to severe intellectual disabilities showed that the health of this group declined at a much younger age than in the general population of the same age. The cardiovascular risk was often higher and depression and sleep disorders were more common in people aged over 50 years with intellectual disabilities, but these were often not diagnosed. Recognising the underlying causes and determining which approach to take to them require specialist knowledge. The accumulation of unfavourable factors from childhood may lead to people becoming frail at an earlier age, which in this population is predictive of a decline in health and independence and a high risk of death within 3 years. The prevalences of multimorbidity and polypharmacy in people over 50 with intellectual disabilities are comparable to those of the Dutch nursing home population. In order to maintain the health and independence of people with an intellectual disability for longer, an improvement in vocational training for carers, development of multidisciplinary guidelines, and enhancement of the quality and availability of outpatient clinics with intellectual disability specialists are required.
25423589	The International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Project is a population-based, longitudinal study describing early growth and development in an optimally healthy cohort of 4607 mothers and newborns. At 24 months, children are assessed for neurodevelopmental outcomes with the INTERGROWTH-21st Neurodevelopment Package. This paper describes neurodevelopment tools for preschoolers and the systematic approach leading to the development of the Package.An advisory panel shortlisted project-specific criteria (such as multi-dimensional assessments and suitability for international populations) to be fulfilled by a neurodevelopment instrument. A literature review of well-established tools for preschoolers revealed 47 candidates, none of which fulfilled all the project's criteria. A multi-dimensional assessment was, therefore, compiled using a package-based approach by: (i) categorizing desired outcomes into domains, (ii) devising domain-specific criteria for tool selection, and (iii) selecting the most appropriate measure for each domain.	The Package measures vision (Cardiff tests); cortical auditory processing (auditory evoked potentials to a novelty oddball paradigm); and cognition, language skills, behavior, motor skills and attention (the INTERGROWTH-21st Neurodevelopment Assessment) in 35-45 minutes. Sleep-wake patterns (actigraphy) are also assessed. Tablet-based applications with integrated quality checks and automated, wireless electroencephalography make the Package easy to administer in the field by non-specialist staff. The Package is in use in Brazil, India, Italy, Kenya and the United Kingdom.	The INTERGROWTH-21st Neurodevelopment Package is a multi-dimensional instrument measuring early child development (ECD). Its developmental approach may be useful to those involved in large-scale ECD research and surveillance efforts.	
25423562	Insomnia is typified by a difficulty in sleep initiation, maintenance and/or quality (non-restorative sleep) resulting in significant daytime distress.This review summarizes the available efficacy and safety data for drugs currently in the pipeline for treating insomnia. Specifically, the authors performed MEDLINE and internet searches using the keywords 'Phase II' and 'insomnia'. The drugs covered target GABAA (zaleplon-CR, lorediplon, EVT-201), orexin (filorexant, MIN-202), histamine-H1 (LY2624803), serotonin 5-HT2A (ITI-007), melatonin/serotonin5-HT1A (piromelatine) and melatonin (indication expansions of prolonged-release melatonin and tasimelteon for pediatric sleep and circadian rhythm disorders) receptors.	Low-priced generic environments and high development costs limit the further development of drugs that treat insomnia. However, the bidirectional link between sleep and certain comorbidities may encourage development of specific drugs for comorbid insomnia. New insomnia therapies will most likely move away from GABAAR receptors' modulation to more subtle neurological pathways that regulate the sleep-wake cycle.	


25422900	Many individuals with total blindness can develop a circadian rhythm disorder-called non-24 sleep wake syndrome-because they cannot detect light to resynchronize their sleep-wake cycles. A new melatonin 1 and melatonin 2 agonist tasimelteon improves sleep in these patients, resetting their circadian sleep-wake clocks.
25422493	Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain. 
25421842	Multiple sclerosis (MS) and migraine are two common neurological disorders affecting women more than men. Sleep quality impairment has been reported in both diseases. The goal of this study was to compare sleep quality and depression between women with MS and migraine. Seventy women with migraine and 75 women with MS were enrolled in this study. Participants were asked to fill-out valid and reliable Persian versions of Pittsburg Sleep Questionnaire (PSQI) and Beck Depression Inventory (BDI). Mean age and duration of disease for MS group was 31.1 ± 7.6, 4.8 ± 5 and for second group 31.4 ± 5.6, 5.2 ± 4 years, respectively. Mean BDI score and number of patients with poor sleep (PSQI ≥5) were significantly higher in patients with migraine. There was significant positive correlation between PSQI and BDI scores in all participants (r=0.32, P<0.001), while correlation coefficient was 0.39, P=0.001 in patients with migraine and 0.35, P=0.002 in MS cases. Multiple linear regression analysis between the PSQI as a dependent variable and age, BDI and education level as independent variables showed that BDI is the independent predictors of PSQI in both groups. This study shows that patients with migraine suffer from poor sleep and depression more frequently than MS cases. 
25417593	Depression, anxiety, delirium, and other psychiatric symptoms are highly prevalent in the cancer setting, and pharmacological intervention is an important component in the overall psychosocial care of the patient. Psychopharmacology is also used as a primary or adjuvant treatment for the management of cancer-related symptoms stemming from the disease itself and/or its treatment, including sleep disturbance, loss of appetite, neuropathic pain, nausea, fatigue, and hot flashes. Psychiatrists, oncologists, and palliative care physicians working as members of a multidisciplinary team have the opportunity to target multiple symptoms that negatively affect a patient's quality of life with the strategic use of psychotropic medications when deemed appropriate. This article aims to review the indications for use of antidepressants, psychostimulants, anxiolytics, antipsychotics, and mood stabilizers in oncology. An updated review of the relevant literature is discussed and referenced in each section. 
25417408	To investigate the effects of the Sini San at different doses on each sleeping state [slow-wave sleep 1 (SWS 1), slow-wave sleep 2 (SWS2), rapid-eye-movement (REM), wakefulness (W)] in insomnia rats and to identify its mode of action for improving sleep.The insomnia rats were randomly divided into a high-, medium- or low-dose group of Sini San (equal to crude drug 8.8, 4.4, or 2.2 g/kg, respectively) for seven consecutive days.	Compared with pre-administration, SWS2 was significantly increased after administration of the low dose. Compared with pre-administration, W was significantly decreased and SWS1, SWS2, and the total sleeping time (TST) were markedly increased after administration of the medium dose. Compared with pre-administration, W was significantly decreased and SWS1, SWS2, rapid-eye-movement sleep, and TST were significantly longer after administration of the high dose. The effects of Sini San on sleep-wake cycle are dose-dependent.	The results suggest that Sini San extends SWS1 and SWS2, which increases the total sleeping time.	
25416458	Chronic daily headache (CDH) is a common neurological condition that affects 1-4 % of the general population. Most individuals with CDH originally suffered from episodic headaches, but over time, this developed into CDH. Although the pathophysiology of CDH is not fully understood, recent clinical and epidemiological studies suggest some risk factors that are associated with an increased risk of transformation from episodic headaches. If risk factors can be identified, they could provide a base for aggressive preventive intervention and thus decrease the transformation from episodic headaches to eventual CDH. In this article, we review and summarize the current data on risk factors for CDH. 
25416413	Impaired well-being and high work-family conflict are critical issues among GPs. This research examined an understudied psychosocial risk factor for these outcomes, namely GPs' perception that they invest more in the relationship with their patients than what they receive in return (i.e. lack of reward in their relationship with patients).To test the effect of lack of reward as a risk factor for poor well-being and work-family conflict among GPs.	Longitudinal study (12 months time lag). 272 GPs in Switzerland [mean age 54.5 (SD = 8.3), 73% male] volunteered to participate in the study. 270 participants completed the baseline survey and 252 completed the follow-up survey. Of these, six retired between the baseline and the follow-up survey, resulting in a sample size of 246 participants at t2. Outcome measures were burnout, sleep problems, self-perceived health and work-family conflict.	Strength and direction of prospective effects were tested using cross-lagged models. Lack of reward was related to an increase in emotional exhaustion (β = 0.15), sleep problems (β = 0.16) and work-family conflict (β = 0.19) and a decrease in self-perceived health (β = -0.17). Effects on depersonalization and personal accomplishment were not significant. Regarding reversed effects of impaired well-being on lack of reward, emotional exhaustion (β = 0.14) and self-perceived health (β = -0.13) predicted future level of lack of reward.	Lack of reward by patients is a risk factor in GPs' mental health.	
25411207	Nasopharyngeal cancer (NPC) survivors often sustain head-neck-shoulder impairments from conventional treatments, which could disturb sleep. This novel study aimed to examine the efficacy of Tai Chi (TC) Qigong in optimizing temporomandibular joint (TMJ), cervical, and shoulder joint mobility and reducing sleep problems in NPC survivors.Fifty-two NPC survivors participated in the study. The experimental group (n = 25) received 6 months of TC Qigong training (1.5 h/session; 4 sessions/wk including self-practice) while the control group (n = 27) received no training. Cervical side flexion and rotation, shoulder flexion and horizontal flexion range of motion (ROM), mouth opening capacity (interincisor distance), and sleep problems (Medical Outcomes Study Sleep Scale) were assessed at baseline, mid-intervention (3 months), immediately after TC Qigong training, and at 6-month follow-up.	Intention-to-treat analysis revealed improvement in cervical side flexion ROM only (P < .008) and unchanged shoulder and TMJ mobility (P > .008) after the TC Qigong training. Deterioration was observed in shoulder flexion ROM and mouth opening capacity in the no-training controls over time (P < .008). Sleep problems also decreased in the TC Qigong group (P < .008), and this effect was most profound during the follow-up period. In addition, improvement in cervical side flexion ROM was associated with a reduction in sleep problems in the experimental group after TC Qigong training (P < .05).	The 6-month TC Qigong intervention improved neck mobility, maintained TMJ and shoulder joint mobility, and reduced sleep problems for NPC survivors. TC Qigong could be an effective nonpharmacological intervention for managing progressive trismus, chronic neck and shoulder hypomobility, and reducing sleep problems among NPC survivors.	
25409860	Diabetes mellitus (DM) is highly prevalent and increasing in geriatric population. Depression and sleep disorders occur at a higher rate in patients with diabetes compared with controls.The purpose of this study was to demonstrate whether diabetic complications influence the sleep quality and depression in elderly patients.	154 geriatric diabetic patients (male/female: 69/85) were enrolled in this study. Patients were investigated for microvascular and macrovascular complications. The Pittsburgh Sleep Quality Index (PSQI) and Geriatric Depression Scale (GDS) were performed for assessment of sleep quality and depression, respectively. Linear regression analysis was performed to identify significant independent related factors for GDS and PSQI scores.	Microvascular and macrovascular complications were found in 47.4 % and 29.2 of study population. PSQI and GDS scores of patients with microvascular complications were significantly higher than those of patients without microvascular complications (8.23 ± 3.83 vs 5.76 ± 3.04, p 0.001; 11.07 ± 6.07 vs 6.94 ± 5.35, p 0.001), respectively. There was no difference in GDS scores between the patients with and without macrovascular complications. There was a positive correlation between DM duration and PSQI, GDS scores. Neuropathy was an independent variable for poor sleep quality (OR 1.362, 95 % CI 0.032-2.692, p 0.045) and depression (OR 2.909, 95 % CI 0.610-5.209, p 0.014).	Depression status and sleep quality are strongly influenced by diabetic complications and DM duration in elderly patients.	
25409323	The Iowa Gambling Task (IGT) is widely used to assess real life decision-making impairment in a wide variety of clinical populations. Our study evaluated how IGT learning occurs across two sessions, and whether a period of intervening sleep between sessions can enhance learning. Furthermore, we investigate whether pre-sleep learning is necessary for this improvement. A 200-trial version of the IGT was administered at two sessions separated by wake, sleep or sleep and wake (time-of-day control). Participants were categorized as learners and non-learners based on initial performance in session one. In session one, participants initially preferred the high-frequency reward decks B and D, however, a subset of learners decreased choice from negative expected value 'bad' deck B and increased choices towards with a positive expected value 'good' decks (decks C and D). The learners who had a period of sleep (sleep and sleep/wake control conditions) between sessions showed significantly larger reduction in choices from deck B and increase in choices from good decks compared to learners that had intervening wake. Our results are the first to show that post-learning sleep can improve performance on a complex decision-making task such as the IGT. These results provide new insights into IGT learning and have important implications for understanding the neural mechanisms of "sleeping on" a decision. 
25409112	The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control.
25409107	Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms.Video-electroencephalogram (EEG), electromyogram (EMG), and electrooculogram (EOG) recordings.	Rodent sleep laboratory.	Fourteen male Arvicanthis ansorgei, aged 3 mo.	12 h light (L):12 h dark (D) baseline condition, 24-h constant darkness, 6-h sleep deprivation.	Wake and rapid eye movement (REM) sleep showed similar electrophysiological characteristics as nocturnal rodents. On average, animals spent 12.9 h ± 0.4 awake per 24-h cycle, of which 6.88 h ± 0.3 was during the light period. NREM sleep accounted for 9.63 h ± 0.4, which of 5.13 h ± 0.2 during dark period, and REM sleep for 89.9 min ± 6.7, which of 52.8 min ± 4.4 during dark period. The time-course of sleep and waking across the 12 h light:12 h dark was overall inverted to that observed in rats or mice, though with larger amounts of crepuscular activity at light and dark transitions. A dominant crepuscular regulation of sleep and waking persisted under constant darkness, showing the lack of a strong circadian drive in the absence of clock reinforcement by external cues, such as a running wheel. Conservation of the homeostatic regulation was confirmed with the observation of higher delta power following sustained waking periods and a 6-h sleep deprivation, with subsequent decrease during recovery sleep.	Arvicanthis ansorgei is a valid diurnal rodent model for studying the regulatory mechanisms of sleep and so represents a valuable tool for further understanding the nocturnality/diurnality switch.	
25409106	There is limited research on racial/ethnic variation in sleep disturbances. This study aimed to quantify the distributions of objectively measured sleep disordered breathing (SDB), short sleep duration, poor sleep quality, and self-reported sleep disturbances (e.g., insomnia) across racial/ethnic groups.Cross-sectional study.	Six US communities.	Racially/ethnically diverse men and women aged 54-93 y in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (n = 2,230).	N/A.	Information from polysomnography-measured SDB, actigraphy-measured sleep duration and quality, and self-reported daytime sleepiness were obtained between 2010 and 2013. Overall, 15.0% of individuals had severe SDB (apnea-hypopnea index [AHI] ≥ 30); 30.9% short sleep duration (< 6 h); 6.5% poor sleep quality (sleep efficiency < 85%); and 13.9% had daytime sleepiness. Compared with Whites, Blacks had higher odds of sleep apnea syndrome (AHI ≥ 5 plus sleepiness) (sex-, age-, and study site-adjusted odds ratio [OR] = 1.78, 95% confidence interval [CI]: 1.20, 2.63), short sleep (OR = 4.95, 95% CI: 3.56, 6.90), poor sleep quality (OR = 1.57, 95% CI: 1.00, 2.48), and daytime sleepiness (OR = 1.89, 95% CI: 1.38, 2.60). Hispanics and Chinese had higher odds of SDB and short sleep than Whites. Among non-obese individuals, Chinese had the highest odds of SDB compared to Whites. Only 7.4% to 16.2% of individuals with an AHI ≥ 15 reported a prior diagnosis of sleep apnea.	Sleep disturbances are prevalent among middle-aged and older adults, and vary by race/ethnicity, sex, and obesity status. The high prevalence of sleep disturbances and undiagnosed sleep apnea among racial/ethnic minorities may contribute to health disparities.	
25409105	To assess adverse drug reaction reports of "abnormal sleep related events" associated with varenicline, a partial agonist to the α4β2 subtype of nicotinic acetylcholine receptors on neurones, indicated for smoking cessation.Twenty-seven reports of "abnormal sleep related events" often associated with abnormal dreams, nightmares, or somnambulism, which are known to be associated with varenicline use, were identified in the World Health Organisation (WHO) Global Individual Case Safety Reports Database. Original anonymous reports were obtained from the four national pharmacovigilance centers that submitted these reports and assessed for reaction description and causality.	These 27 reports include 10 of aggressive activity occurring during sleep and seven of other sleep related harmful or potentially harmful activities, such as apparently deliberate self-harm, moving a child or a car, or lighting a stove or a cigarette. Assessment of these 17 reports of aggression or other actual or potential harm showed that nine patients recovered or were recovering on varenicline withdrawal and there were no consistent alternative explanations. Thirteen patients experienced single events, and two had multiple events. Frequency was not stated for the remaining two patients.	The descriptions of the reports of aggression during sleep with violent dreaming are similar to those of rapid eye movement sleep behavior disorder and also nonrapid eye movement (NREM) sleep parasomnias in some adults. Patients who experience somnambulism or dreams of a violent nature while taking varenicline should be advised to consult their health providers. Consideration should be given to clarifying the term sleep disorders in varenicline product information and including sleep related harmful and potentially harmful events.	
25409030	During their development, Caenorhabditis elegans larvae go through four developmental stages. At the end of each larval stage, nematodes molt. They synthesize a new cuticle and shed the old cuticle. During the molt, larvae display a sleep-like behavior that is called lethargus. We wanted to determine how gene expression changes during the C. elegans molting cycle. We performed transcriptional profiling of C. elegans by selecting larvae displaying either sleep-like behavior during the molt or wake behavior during the intermolt to identify genes that oscillate with the molting-cycle. We found that expression changed during the molt and we identified 520 genes that oscillated with the molting cycle. 138 of these genes were not previously reported to oscillate. The majority of genes that had oscillating expression levels appear to be involved in molting, indicating that the majority of transcriptional changes serve to resynthesize the cuticle. Identification of genes that control sleep-like behavior during lethargus is difficult but may be possible by looking at genes that are expressed in neurons. 22 of the oscillating genes were expressed in neurons. One of these genes, the dopamine transporter gene dat-1, was previously shown in mammals and in C. elegans to control sleep. Taken together, we provide a dataset of genes that oscillate with the molting and sleep-wake cycle, which will be useful to investigate molting and possibly also sleep-like behavior during lethargus. 
25408116	Symptoms of fibromyalgia (FM)--chronic widespread pain, fatigue, unrefreshing sleep, dyscognition etcetera--present with varying degrees of severity in different individuals; however, studies reporting daily estimates of variability of symptoms are sparse. Given the limited literature on the stability and variability of FM symptoms, the purpose of the present study was to determine the feasibility of daily visual analogue, self-report measures to assess daily variability and time trends in core FM symptoms. Ten female patients completed daily assessments of common FM symptoms (pain, fatigue, anxiety, depression, stress, cognitive dysfunction, unrefreshing sleep and lightheadedness) for approximately 90 days. The completion rate was excellent (89.6%). The results demonstrated that average symptom intensity differs markedly across the different symptoms that were measured. Unrefreshing sleep, fatigue and pain are clearly higher in intensity than other symptoms and are followed by memory problems, stress, anxiety and depression. There is also notable average intra-individual change across time (10-15 points on a 100-point scale). Average symptom intensity does not appear to be related to the amount of symptom change within individuals. The results of the present study confirm that intensive longitudinal study, using comprehensive symptom assessment in patients with FM, is both possible and informative, in the sense that a rich description of the daily experience of living with FM can be obtained. Future work, utilizing larger samples, will offer the opportunity to investigate better the causes, consequences and correlates of the daily ups and downs of key symptoms that compromise quality of life in patients with FM.
25406272	We report the case of a 52-year-old female with spinocerebellar ataxia (SCA) 13. She presented with complaints of insomnia and had a history of restless legs syndrome. Her polysomnogram revealed that she had a significantly elevated periodic limb movement index, mild obstructive sleep apnea, and the absence of REM sleep. Sleep disorders have previously been described in patients with SCA 1, SCA 2, SCA 3, and SCA 6. To our knowledge, this is the first description of sleep disorders in a patient with SCA 13.
25406270	The prevalence of sleep disturbances and heart failure increases with age. We aimed to evaluate the associations of incident heart failure and cardiac dysfunction with changes in sleep quality.This prospective population-based study was conducted in the Rotterdam Study. Of the 3445 eligible persons (mean age 72.0±7.1 years) available for cross-sectional analyses, 8.9% (n = 307) had prevalent clinical heart failure. In longitudinal analyses, 1989 eligible persons (mean age 70.0±5.8 years) were followed for an average of 6.5±0.4 years, of which 4.6% (n = 91) had prevalent or incident clinical heart failure. Heart failure was assessed according to European Society of Cardiology criteria. To estimate cardiac function, we measured left ventricular fractional shortening, left ventricular systolic function, and E/A ratio by echocardiography. Heart failure and cardiac dysfunction were studied with linear regression in relation to sleep quality, assessed by the Pittsburgh Sleep Quality Index.	No associations between clinical heart failure and sleep quality were observed in cross-sectional analyses. Clinical heart failure predicted a reduction of sleep quality (B = 1.00 points on the Pittsburgh Sleep Quality Index; 95% CI 0.40, 1.60) in longitudinal assessment. This association was driven by the sleep onset latency and sleep quality components of the Pittsburgh Sleep Quality Index. Cardiac dysfunction was not related to sleep quality in cross-sectional or longitudinal analyses.	Clinical heart failure, but not cardiac dysfunction measured by echocardiography, increases the risk of poor sleep quality in the general population over time. These findings suggest that clinical manifestations of heart failure negatively affect sleep.	
25406269	The diagnosis of insomnia rests on self-report of difficulty initiating or maintaining sleep. However, subjective reports may be unreliable, and possibly may vary by the method of inquiry. We investigated this possibility by comparing within-individual response to direct versus indirect time queries after overnight polysomnography.We obtained self-reported sleep-wake times via morning questionnaires in 879 consecutive adult diagnostic polysomnograms. Responses were compared within subjects (direct versus indirect query) and across groups defined by apnea-hypopnea index and by self-reported insomnia symptoms in pre-sleep questionnaires. Direct queries required a time duration response, while indirect queries required clock times from which we calculated time durations.	Direct and indirect queries of sleep latency were the same in only 41% of cases, and total sleep time queries matched in only 5.4%. For both latency and total sleep, the most common discrepancy involved the indirect value being larger than the direct response. The discrepancy between direct and indirect queries was not related to objective sleep metrics. The degree of discrepancy was not related to the presence of insomnia symptoms, although patients reporting insomnia symptoms showed underestimation of total sleep duration by direct response.	Self-reported sleep latency and total sleep time are often internally inconsistent when comparing direct and indirect survey queries of each measure. These discrepancies represent substantive challenges to effective clinical practice, particularly when diagnosis and management depends on self-reported sleep patterns, as with insomnia. Although self-reported sleep-wake times remains fundamental to clinical practice, objective measures provide clinically relevant adjunctive information.	
25406112	To estimate the prevalence of nocturnal frontal lobe epilepsy (NFLE) in the adults of two areas of the Emilia-Romagna region (northeast Italy) and to describe the clinical features from a population-based perspective.Population-based retrospective cohort study including adults with NFLE.	Two areas of the Emilia-Romagna region: the city of Bologna (330,901 adult residents) and five districts of the province of Modena (424,007). Prevalence day: December 31, 2010.	Patients with NFLE collected from multiple databases of neurologic hub centers of the districts involved. Diagnostic criteria: clinical history of sleep related bizarre motor attacks and videopolysomnographic recording confirming the typical features of NFLE. Inclusion criteria for prevalence calculation: residence in one of the two geographic areas on the prevalence day and an "active" or "in remission with treatment" form of NFLE.	Six subjects from Bologna and eight from Modena were included. Crude prevalence (per 100,000 residents) was 1.8 (95% confidence interval 0.7-4.0) in Bologna and 1.9 (0.8-3.7) in Modena. Similarly, the main clinical features were consistent: onset during adolescence (median age 11-13 y), mainly hyperkinetic seizures, nonlesional form in more than two-thirds of cases, an active form of epilepsy in more than two-thirds of cases. A family history of epilepsy was reported only for two patients.	This epidemiologic study establishes that NFLE is a rare epileptic condition, fulfilling the definition for rare disease. Because of methodological limitations of our case ascertainment, the estimates we disclose must be considered the minimum prevalence.	
25405649	Sleep-wake disturbances are a highly prevalent and often disabling feature of Alzheimer's disease (AD). A cardinal feature of AD includes the formation of amyloid plaques, associated with the extracellular accumulation of the amyloid-β (Aβ) peptide. Evidence from animal and human studies suggests that Aβ pathology may disrupt the sleep-wake cycle, in that as Aβ accumulates, more sleep-wake fragmentation develops. Furthermore, recent research in animal and human studies suggests that the sleep-wake cycle itself may influence Alzheimer's disease onset and progression. Chronic sleep deprivation increases amyloid plaque deposition, and sleep extension results in fewer plaques in experimental models. In this review geared towards the practicing clinician, we discuss possible mechanisms underlying the reciprocal relationship between the sleep-wake cycle and AD pathology and behavior, and present current approaches to therapy for sleep disorders in AD.
25403789	The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective. 
25403523	Posttraumatic stress disorder (PTSD) has been associated with heightened nocturnal autonomic nervous system (ANS) arousal and sleep disturbances. It has been suggested that relationships between sleep and nocturnal ANS activity are influenced by insomnia; however, investigation of this relationship has been limited in PTSD. This study examined nocturnal ANS activity and its relationship to sleep in PTSD and resilience. Physically healthy young adult African Americans with current PTSD (n = 20) or who had never had PTSD despite exposure to a high-impact traumatic event (resilient, n = 18) were monitored with ambulatory electrocardiograms and actigraphy for 24-hr periods. Frequency-domain heart-rate variability measures, that is, low-frequency to high-frequency ratios (LF/HF), which index sympathetic nervous system activity, and normalized HF (nHF), which indexes parasympathetic nervous system activity were examined. Normalized HF during the time-in-bed period was lower for those with PTSD than those with resilience (p = .041). Total sleep time was strongly correlated with time-in-bed LF/HF (r = -.72) and nHF (r = .75) in the resilient group, but these were not correlated in the PTSD group. The results suggest elevated nocturnal ANS arousal and dissociation between ANS activity and total sleep time in PTSD. 
25403425	Despite robust associations between postpartum sleep difficulties and maternal psychopathology, little attention has been paid to the role of childhood trauma and posttraumatic stress disorder (PTSD). In the present study, we examined sleep complaints in postpartum women with a history of childhood trauma compared to postpartum women who were not exposed to childhood trauma. Participants (N = 173) completed questionnaires by telephone at 4-months postpartum. After adjusting for nuisance variables, there were significantly higher rates of sleep disturbance (falling asleep and staying asleep) for women with a past history of neglect (OR = 4.84, p = .036 and 5.78, p = .006, respectively), physical abuse (OR = 9.20, p = .002 and 3.84, p = .044, respectively), and physical abuse with sexual abuse (OR = 5.95, p = .011 and 3.56, p = .045, respectively). Current PTSD was significantly associated with trouble staying asleep (OR = 4.21, p = .032) whereas recovery from PTSD was associated with trouble falling (OR = 4.19, p = .015) and staying asleep (OR = 3.69, p = .011). Our findings affirm the contribution of childhood trauma and PTSD to postpartum sleep.
25403309	Neuropsychiatric symptoms (NPS) often occur in patients with dementia. Understanding the course of NPS in dementia is important for healthcare professionals for psycho-educational purposes and adequate and timely interventions to prevent or diminish NPS as much as possible.We conducted a systematic literature search in several electronic databases. We combined search strings for the terms dementia, community-dwelling, cohort studies and NPS. Screening titles and abstracts, assessing the methodological quality and data-extraction were independently conducted by at least two authors.	This literature search revealed 6605 unique records of which 23 studies were included in data synthesis. In total 7184 patients participated in the included studies with a mean number of 312. Sixty percent of the participants were female and the mean age of all participants was 74.8 years. Follow-up varied between 1 and 6 years; in 17 studies loss to follow-up was less than 20% per year. NPS are highly prevalent, incident and persistent although frequency parameters vary considerably across studies. Delusions/delusional misidentification, wandering/agitation, aberrant motor behavior/motor hyperactivity and apathy are the most common NPS. For hallucinations, delusions/delusional misidentification, paranoia, aggression, wandering/agitation, aberrant motor behavior/motor hyperactivity, disinhibition, apathy, and sleep disturbance increasing trends in point prevalence rates have been found.	NPS in community-dwelling patients are frequent and persistent. The increasing trends of several NPS in the course of dementia require a preventive approach of professional caretakers. For such an approach, a timely diagnosis and adequate professional support to prevent or diminish these problems is necessary.	
25402773	The Parkinson's Disease Sleep Scale (PDSS)-2 is a recently developed tool for evaluating disease-related nocturnal disturbances in patients with Parkinson's disease (PD). However, its cutoff score has not been clinically assessed. We determined the optimal cutoff score of the Japanese version of the PDSS-2.Patients with PD (n = 146) and controls (n = 100) completed the PDSS-2 and the Pittsburgh Sleep Quality Index (PSQI). Poor sleepers were defined as having global PSQI scores >5. Optimal cutoff scores for determining poor sleepers were assessed using the receiver operating characteristic curve.	A PDSS-2 total score ≥ 14 exhibited 82.0% sensitivity and 70.6% specificity, whereas a PDSS-2 total score ≥ 15 provided 72.1% sensitivity and 72.9% specificity in distinguishing poor sleepers (PSQI score >5) from good sleepers (PSQI ≤ 5). Nocturnal disturbances were more frequently observed in patients with PD than in controls (PDSS-2 total score ≥ 14 or ≥ 15; 51.4% vs 20%; 45.9% vs 19%). Nocturnal disturbances were associated with higher Hoehn and Yahr stages and Unified Parkinson's Disease Rating Scale motor scores, impaired quality of life, daytime sleepiness, and depressive symptoms.	We suggest that PDSS-2 total scores ≥ 15 are useful for detecting poor sleepers among patients with PD.	
25402604	Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 2 ± 11%; vibration time, 0.2 ± 0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13 ± 7% [P ≤ 0.0001]; vibration time, 1.2 ± 0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics.
25402367	Sleep and sleep disorders are related to cardiovascular disease, and microvascular function is an early cardiovascular disease marker. Therefore, the relationship of sleep (measured in sleep quality and duration) with microvascular function was examined in healthy adults. Sleep quality was assessed with the validated Sleep Wake Experience List (SWEL) questionnaire. Duration of sleep was self-reported in an additional question. Microvascular function was measured using nailfold capillaroscopy. Linear regression analyses were used to examine the relationship between sleep and microvascular function. Potential confounders included physical activity, smoking, blood pressure, body mass index and several biochemical parameters. Analyses were performed in 259 participants (116 men). For women reporting insufficient (<7 h) sleep duration, microvascular function (post-ischaemic capillary recruitment) was significantly lower (b = -11.17; P = 0.04) compared to women reporting sufficient sleep duration. There was no relationship between sleep quality and microvascular function in females. In males, a trend towards lower capillary recruitment was found in those reporting a combination of poor sleep quality and insufficient duration (b = -7.54; P = 0.09), compared to those reporting good sleep quality as well as sufficient duration. This study suggests an association between sleep and microvascular function. Which aspects of sleep exactly affect microvascular function, and if indeed the association is different between males and females in other samples, needs further research.
25399336	In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which is associated to an increased energy demand. Astrocytic glycogen depletion participates to an increase of extracellular adenosine release which influences sleep homeostasis. Here, we will review some evidence obtained by studies addressing the question of a key role played by glycogen metabolism in sleep regulation as proposed by this hypothesis or by an alternative hypothesis named "glycogenetic" hypothesis as well as the importance of the confounding effect of glucocorticoïds. Even though actual collected data argue in favor of a role of sleep in brain energy balance-homeostasis, they do not support a critical and direct involvement of glycogen metabolism on sleep regulation. For instance, glycogen levels during the sleep-wake cycle are driven by different physiological signals and therefore appear more as a marker-integrator of brain energy status than a direct regulator of sleep homeostasis. In support of this we provide evidence that blockade of glycogen mobilization does not induce more sleep episodes during the active period while locomotor activity is reduced. These observations do not invalidate the energy hypothesis of sleep but indicate that underlying cellular mechanisms are more complex than postulated by Benington and Heller. 
25399034	This study examined associations of sleep and minutes spent in moderate-vigorous physical activity (MVPA) with C-reactive protein (CRP) and interleukin (IL)-6 among persons living with HIV. Cross-sectional analyses (n = 45) focused on associations of inflammatory outcomes (i.e., CRP and IL-6) with actigraph-derived sleep duration, latency, and efficiency; sleep onset; wake time; and wake-after-sleep-onset; as well as MVPA. Least square means for CRP and IL-6 by levels of sleep and MVPA were computed from general linear models. Individuals below the median of sleep duration, above the median for sleep onset, and below the median of MVPA minutes had higher CRP or IL-6 levels. Generally, individuals with both low MVPA and poor sleep characteristics had higher inflammation levels than those with more MVPA and worse sleep. Understanding the combined impact of multiple lifestyle/behavioral factors on inflammation could inform intervention strategies to reduce inflammation and therefore, chronic disease risk.
25398202	The prevalence of obesity in adults and children has increased greatly in the past three decades, as have metabolic sequelae, such as insulin resistance and type 2 diabetes mellitus (T2DM). Sleep disturbances are increasingly recognized as contributors to this widespread epidemic in adults, and data are emerging in children as well. The categories of sleep disturbances that contribute to obesity and its glycemic co-morbidities include the following: (1) alterations of sleep duration, chronic sleep restriction and excessive sleep; (2) alterations in sleep architecture; (3) sleep fragmentation; (4) circadian rhythm disorders and disruption (i.e., shift work); and (5) obstructive sleep apnea. This article reviews current evidence supporting the contributions that these sleep disorders play in the development of obesity, insulin resistance, and T2DM as well as possibly influences on glycemic control in type 1 diabetes, with a special focus on data in pediatric populations. 
25398141	Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be the consequence of the inhibition of specific neuronal populations within the LH, i.e. the orexin and the MCH neurons, respectively. However, the interpretation of these results is limited by the lack of quantitative analysis of the electroencephalographic (EEG) activity that is critical for the assessment of NREM sleep quality and the presence of aborted NREM-to-REM sleep transitions. Furthermore, the lack of evaluation of the autonomic and thermoregulatory effects of the treatment does not exclude the possibility that the wake-sleep changes are merely the consequence of the autonomic, in particular thermoregulatory, changes that may follow the inhibition of LH neurons. In the present study, the EEG and autonomic/thermoregulatory effects of a prolonged LH inhibition provoked by the repeated local delivery of the GABAA agonist muscimol were studied in rats kept at thermoneutral (24°C) and at a low (10°C) ambient temperature (Ta), a condition which is known to depress sleep occurrence. Here we show that: 1) at both Tas, LH inhibition promoted a peculiar and sustained bout of NREM sleep characterized by an enhancement of slow-wave activity with no NREM-to-REM sleep transitions; 2) LH inhibition caused a marked transitory decrease in brain temperature at Ta 10°C, but not at Ta 24°C, suggesting that sleep changes induced by LH inhibition at thermoneutrality are not caused by a thermoregulatory impairment. These changes are far different from those observed after the short-term selective inhibition of either orexin or MCH neurons, suggesting that other LH neurons are involved in sleep-wake modulation. 
25396279	This study aimed to characterize sleep patterns and disturbances among Chinese urban kindergarten children and examine potentially associated factors. Caregivers of 513 children (47.96% male) aged 3-6 years (mean age = 4.46, SD = 0.9) completed the Children's Sleep Habits Questionnaire (CSHQ) and the Strengths and Difficulties Questionnaire (SDQ). Almost 80% (78.8%) of the children scored above the original CSHQ cutoff point for global sleep disturbance. Regression analysis indicated that child's age, and the presence of emotional problems, hyperactivity and peer problems, cosleeping, and interparental inconsistency of attitudes toward child rearing accounted for significant variance in the CSHQ total score (R(2) = 22%). These findings indicate that there is an apparently high prevalence of sleep disturbances in Chinese urban kindergarten children; and sleep disturbances are associated with both child-related and parenting practice variables. 
25395982	Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice.Sixteen male mice (age of 5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption protocol. Sleep-wake behaviors were checked every 5 min for a total duration of 15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and 10 days of recovery. During the dark cycle on the 16th experimental day, their general locomotor activities were measured in an open field for 120 minutes after an injection of quinpirole (0.5 mg/kg, s.c.).	The individual differences in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline cycle within 6 days after normalizing the LD cycle (early recovery group). The locomotor activities of mice that failed to recover within 6 days (delayed recovery group) were significantly higher (mean rank=12.25) than those of the early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test).	Given that the quinpirole-induced hyperactivity is an animal model of bipolar disorder, our results suggest individuals who have difficulties in recovery from circadian rhythm disruption may be vulnerable to bipolar disorder.	
25395965	People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression. 
25394829	We examined the role that serotonin has in the modulation of sleep and wakefulness across a 12-h:12-h light-dark cycle and determined whether temperature and motor activity are directly responsible for potential disruptions to arousal state. Telemetry transmitters were implanted in 24 wild-type mice (Tph2(+/+)) and 24 mice with a null mutation for tryptophan hydroxylase 2 (Tph2(-/-)). After surgery, electroencephalography, core body temperature, and motor activity were recorded for 24 h. Temperature for a given arousal state (quiet and active wake, non-rapid eye movement, and paradoxical sleep) was similar in the Tph2(+/+) and Tph2(-/-) mice across the light-dark cycle. The percentage of time spent in active wakefulness, along with motor activity, was decreased in the Tph2(+/+) compared with the Tph2(-/-) mice at the start and end of the dark cycle. This difference persisted into the light cycle. In contrast, the time spent in a given arousal state was similar at the remaining time points. Despite this similarity, periods of non-rapid-eye-movement sleep and wakefulness were less consolidated in the Tph2(+/+) compared with the Tph2(-/-) mice throughout the light-dark cycle. We conclude that the depletion of serotonin does not disrupt the diurnal variation in the sleep-wake cycle, motor activity, and temperature. However, serotonin may suppress photic and nonphotic inputs that manifest at light-dark transitions and serve to shorten the ultraradian duration of wakefulness and non-rapid-eye-movement sleep. Finally, alterations in the sleep-wake cycle following depletion of serotonin are unrelated to disruptions in the modulation of temperature. 
25392279	There is consistent evidence suggesting a relationship between individuals' sleep-wake rhythms and well-being. The indiscriminate demands from daily working routines, which do not respect this individual physiological rhythm, might be mediating this phenomenon. The aim of the present study was to evaluate the relationship between the characteristics of sleep routines during working days and psychological well-being. This was a cross-sectional study on 825 individuals from rural communities from southern Brazil. The study protocol included a questionnaire on demographic characteristics, working routines, health complaints, and habits; the Munich Chronotype Questionnaire for sleep-wake rhythm and; the WHO-Five well-being index. Since sex has been shown to affect sleep circadian rhythm and well-being, analysis was performed on men and women separately. In the proposed hierarchical regression models, different factors contributed to well-being according to sex. Among men, sleep-wake and work-related variables did not predict well-being scores. Among women, later midpoints of sleep on working days (B = -1.243, SE B = 0.315, β = -0.220), working more days per week (B = -1.507, SE B = 0.494, β = 0.150), having longer working journeys (B = -0.293, SE B = 0.105, β = -0.166), earlier working journey midpoints (B = 0.465, SE B = 0.222, β = 0.115), and being exposed to less sunlight (B = 0.140, SE B = 0.064, β = 0.103) predicted worse well-being. For the subgroup of women with days free from work, we have found a correlation between later midpoints of sleep during the week with worse well-being (Pearson's r = -0.159, p = 0.045) while the same relationship was not significantly observed with the midpoint of sleep on non-working days (Pearson's r = -0.153, p = 0.054). Considering WHO-Five as categorical, based on proposed clinical cut-offs, among women working 7-d/week, those with worst well-being (WHO-Five < 13) had the latest midpoint of sleep (F = 4.514, p = 0.012). Thus, the midpoint of sleep on working days represents the interaction between individuals' sleep-wake behavior and working routines. It plays an important role as a stress factor and may be a useful alternative variable related to chronodisruption. 
25390034	Electronic devices in the bedroom are broadly linked with poor sleep in adolescents. This study investigated whether there is a dose-response relationship between use of electronic devices (computers, cellphones, televisions and radios) in bed prior to sleep and adolescent sleep patterns.Adolescents aged 11-17 yrs (n = 1,184; 67.6% female) completed an Australia-wide internet survey that examined sleep patterns, sleepiness, sleep disorders, the presence of electronic devices in the bedroom and frequency of use in bed at night.	Over 70% of adolescents reported 2 or more electronic devices in their bedroom at night. Use of devices in bed a few nights per week or more was 46.8% cellphone, 38.5% computer, 23.2% TV, and 15.8% radio. Device use had dose-dependent associations with later sleep onset on weekdays (highest-dose computer adjOR  = 3.75: 99% CI  = 2.17-6.46; cellphone 2.29: 1.22-4.30) and weekends (computer 3.68: 2.14-6.32; cellphone 3.24: 1.70-6.19; TV 2.32: 1.30-4.14), and later waking on weekdays (computer 2.08: 1.25-3.44; TV 2.31: 1.33-4.02) and weekends (computer 1.99: 1.21-3.26; cellphone 2.33: 1.33-4.08; TV 2.04: 1.18-3.55). Only 'almost every night' computer use (: 2.43: 1.45-4.08) was associated with short weekday sleep duration, and only 'almost every night' cellphone use (2.23: 1.26-3.94) was associated with wake lag (waking later on weekends).	Use of computers, cell-phones and televisions at higher doses was associated with delayed sleep/wake schedules and wake lag, potentially impairing health and educational outcomes.	
25390000	Sleep duration is a risk factor for cardiovascular disease. Alteration in sleep pattern can induce the loss of circadian rhythmicity. Chronically, this desynchronization between endogenous rhythm and behavioral cycles can lead to an adverse metabolic profile, a proinflammatory condition and can increase the risk of cardiovascular disease. The circadian cycle can vary due to environmental cues. The circadian pacemaker is located in the suprachiasmatic nuclei; this central clock coordinates the circadian rhythm in the central nervous system and peripheral tissues. The mechanisms involved in sleep disturbance, circadian misalignment and adverse metabolic effects have yet to be fully elucidated. This review looks over the association among sleep alteration, circadian rhythm and the development of risk factors implicated in cardiovascular disease.
25387070	We performed a cross-sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18-month period. We used a clinical interview to evaluate a Chinese version of the nonmotor symptoms questionnaire (NMSQuest) as an instrument for measuring the nonmotor symptoms (NMS) in Chinese patients with PD. The patients' cognitive deficit, depression/sleep, disease severity and motor status were assessed based on the mini-mental state examination (MMSE), the Hamilton depression scale (HAMD)/Parkinson's disease sleep scale (PDSS), the modified Hoehn and Yahr staging scale (H&Y) and the unified Parkinson's disease rating scale part III (UPDRS III), respectively. Thirty items distributed in nine different domains of the NMSQuest were evaluated, and the association between the NMSQuest and MMSE, H&Y, UPDRS, HAMD and PDSS was identified. Significant correlations were observed between the NMSQuest and disease duration (rs = 0.272, p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p < 0.001) and UPDRS III (rs = 0.228, p = 0.039). Furthermore, the sleep disorder and mood (depression/anxiety) domain of the NMSQuest were significantly correlated with the PDSS (rs = -0.471, p < 0.001) and HAMD (rs = 0.687, p < 0.001), respectively. Our results indicate that the Chinese version of the NMSQuest, a useful screening tool, can be considered as a comprehensive, practical measure for NMS evaluation in Chinese PD patients. The NMSQuest highlights the prevalence of the wide range of NMS and indicated good responsiveness and interpretability. We strongly recommend routine use of the simplified Chinese version of NMSQuest in this country. 
25386163	Psychiatric disorders are often associated with metabolic and hormonal alterations, including obesity, diabetes, metabolic syndrome as well as modifications in several biological rhythms including appetite, stress, sleep-wake cycles, and secretion of their corresponding endocrine regulators. Among the gastrointestinal hormones that regulate appetite and adapt the metabolism in response to nutritional, hedonic, and emotional dysfunctions, at the interface between endocrine, metabolic, and psychiatric disorders, ghrelin plays a unique role as the only one increasing appetite. The secretion of ghrelin is altered in several psychiatric disorders (anorexia, schizophrenia) as well as in metabolic disorders (obesity) and in animal models in response to emotional triggers (psychological stress …) but the relationship between these modifications and the physiopathology of psychiatric disorders remains unclear. Recently, a large literature showed that this key metabolic/endocrine regulator is involved in stress and reward-oriented behaviors and regulates anxiety and mood. In addition, preproghrelin is a complex prohormone but the roles of the other ghrelin-derived peptides, thought to act as functional ghrelin antagonists, are largely unknown. Altered ghrelin secretion and/or signaling in psychiatric diseases are thought to participate in altered appetite, hedonic response and reward. Whether this can contribute to the mechanism responsible for the development of the disease or can help to minimize some symptoms associated with these psychiatric disorders is discussed in the present review. We will thus describe (1) the biological actions of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety and depression, and the physiological consequences of ghrelin invalidation on these parameters, (2) how ghrelin and ghrelin-derived peptides are regulated in animal models of psychiatric diseases and in human psychiatric disorders in relation with the GH axis. 
25385339	Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep-wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep-wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep-wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases. 
25384491	The purpose of this study was to assess state licensing and administrative regulations promoting healthy sleep practices in child care and to compare these regulations to national recommendations.We reviewed regulations related to healthy sleep practices for all states and territories for both child care centers (centers) and family child care homes (homes). We compared regulations with Institute of Medicine recommendations to promote sleep in child care, including (1) create environments that ensure restful sleep; (2) encourage sleep-promoting behaviors and practices; (3) encourage practices that promote child self-regulation of sleep; and (4) seek consultation yearly from a sleep expert. We used Cochran-Mantel-Haenszel trend tests to assess associations between geographic region and number of regulations consistent with the recommendations.	The mean number of regulations for states was 0.9 for centers and 0.8 for homes out of a possible 4.0. For centers, no state had regulations for all 4 recommendations; 11 states had regulations for 2 of the 4 recommendations. For homes, 9 states had regulations for 2 of the recommendations. States in the Northeast had the greatest mean number of regulations for centers (1.2) and homes (1.1), and states in the South had the fewest (0.7 and 0.7, respectively); these geographic differences were significant for centers (P = .03) but not homes (P = .14).	More states in the Northeast had regulations consistent with the Institute of Medicine sleep recommendations, but overall few states had regulations consistent with the recommendations.	
25384190	Sleep-wake cycle disruption and seasonal variation in mood and behavior have been associated with mood disorders. This study aimed to investigate the lifetime characteristics of the sleep-wake cycle and its association with the lifetime characteristics of seasonality in individuals with bipolar disorder. Circadian preference, regularity of bed-rise time, and seasonality were evaluated on a lifetime basis using the Composite Scale of Morningness, the Sleep Timing Questionnaire, and the Seasonal Pattern Assessment Questionnaire in clinically stable individuals with bipolar I/II disorders (n = 103/97) and healthy controls (n = 270). Bipolar groups were more likely to have evening preference and irregular bed-rise time. These characteristics were interrelated and, particularly, more prevalent in bipolar II disorder. Seasonality, which was also more prevalent in the bipolar groups, was associated with evening preference and irregularity of the weekday bed-rise time. 
25383556	Excessive daytime sleepiness (EDS) is often associated with increased adiposity, particularly when assessed in the context of samples of sleep-disordered patients; however, it is unclear if this relationship is sustained among non-clinical, population-based cohorts. This study aimed to investigate the relationship between EDS and a number of body composition markers among a population-based sample of men and women.This study assessed 1066 women aged 21-94 yr (median = 51 yr, IQR 35-66), and 911 men aged 24-92 yr (median = 60 yr, IQR 46-73) who participated in the Geelong Osteoporosis Study (GOS) between the years 2001 and 2008. Total body fat mass was determined from whole body dual-energy X-ray absorptiometry scans, and anthropometric parameters (weight, height, and waist circumference) were measured. Lifestyle and health information was collected via self-report. Sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Scores of ≥ 10 were considered indicative of EDS.	Women: After adjusting for age, alcohol intake, antidepressant medication use and physical activity, EDS was associated with greater waist circumference and body mass index (BMI). EDS was also associated with 1.5-1.6-fold increased odds of being overweight or obese. Men: After adjusting for age, alcohol use, physical activity and smoking status, EDS was associated with greater BMI. These findings were not explained by the use of sedative or antidepressant medication. EDS was also associated with 1.5-fold increased likelihood of being obese, independent of these factors. No differences in lean mass, %body fat, or %lean mass were detected between those with and without EDS for men or women.	These data suggest that EDS is associated with several anthropometric adiposity profiles, independent of associated lifestyle and health factors. Among women, symptoms of EDS are pervasive at both overweight and obese BMI classifications; suggesting a need for further clinical examination to assess possible temporal associations with underlying sleep pathology.	
25379877	This review highlights the current views on and differences and similarities between nocturnal enuresis (NE) in children and nocturia in adults, which might be a guidance to elucidate the missing links in our knowledge. In both conditions, a genetic factor is suspected. Reduced bladder capacity and nocturnal polyuria are the main underlying lower urinary tract-related conditions. There is a link with sleep disorders, although it is not clear whether this is a cause or consequence. Physical and mental health are comprised in both conditions, however, in different ways. In NE, constipation and attention deficit disorder are the most important comorbidities and the effect on mental health and quality of life is mainly through the negative impact on self-esteem. In nocturia, cardiovascular disease and fall injuries are important comorbidities, mainly affecting the older nocturia population; personal distress and depression are consequences of the related poor sleep quality. For both conditions, treatment is often inadequate and a more individualized approach seems to be necessary. The main difference between NE and nocturia seems to be the difference in arousal to bladder stimuli, suggesting that sleep characteristics might be a key factor in these conditions. 
25377647	Here, we review the prevalence and treatment of anxiety and depression among patients with breast cancer. Cancer-related symptoms include similarities to responses to traumatic stress. Well-developed screening devices for identifying and tracking psychiatric comorbidity are discussed. Basic principles of psychopharmacology, and individual and group psychotherapy are presented. Finally, effects of effective treatment of anxiety and depression on quality of life and overall survival are reviewed. 
25377292	In industrialisierten Gesellschaften klagen 10–15 % der Bevölkerung über Tagesschläfrigkeit. Neben der Schichtarbeit und der weit verbreiteten, sozial bedingten Schlafinsuffizienz, dürfte auch die zunehmende Zahl von Schlaf-Wachstörungen dazu beitragen. Die Folgen der Schläfrigkeit am Steuer sind Unaufmerksamkeit, „Tunnelblick“ und verlängerte Reaktionszeit. Die Unfälle beim Sekundenschlaf ereignen sich oft bei unverminderter Geschwindigkeit, was zu besonders schweren, und besonders oft zu tödlichen Unfällen führt. In der Schweiz werden zwar gemäß den offiziellen Statistiken lediglich ca. 1.5 % der Verkehrsunfälle durch Einschlafen am Steuer verursacht, was im Vergleich zu einem 10–30 % Anteil in der Fachliteratur massiv unterschätzt erscheint. Die Diskrepanz in den offiziellen statistischen Erhebungen entsteht wohl u. a. dadurch, dass Schläfrigkeit schwer zu erfassen ist. Die Unterschätzung des wahren Problems ist deswegen relevant, weil Gegenmaßnahmen im Straßenbau und die Abklärungen bei fehlbaren Fahrzeuglenkern immer noch zu wenig konsequent verfolgt werden. Zu den Risikofaktoren für schläfrigkeitsbedingte Verkehrsunfälle gehören junges Alter, geringe Fahrerfahrung, männliches Geschlecht, Risikoverhalten, Nachtfahrten, monotone Strecken, lange Fahrdauer, das sozial oder beruflich bedingte Schlafmanko, aber auch Schlaf-Wach-Krankheiten und sedierende Medikamente. Die Risikofaktoren und auch die typischen Merkmale von schläfrigkeitsbedingten Unfällen sind relativ gut bekannt, so dass prophylaktische Gegenmaßnahmen und gezielte Abklärungen von fehlbaren Lenkern möglich wären. Weil jeder Betroffene die Zeichen der Schläfrigkeit rechtzeitig, d. h. vor dem Auftreten eines Sekundenschlafes am Steuer erkennen kann, kommt der Aufklärung aller Verkehrsteilnehmer – und somit auch der Patienten – über das individuelle Risiko und über wirksame Gegenmaßnahmen wie anhalten, Kaffeetrinken und Turboschlaf einschalten, eine ganz besondere Bedeutung zu. Dieses Aufklärungsgespräch soll in der Krankengeschichte unbedingt bei der ersten Konsultation dokumentiert werden, was besonders wichtig ist bei der Verordnung von sedierenden Medikamenten. Bei allen Berufsfahrern mit Tagesschläfrigkeit und bei allen Fahrzeuglenkern, welche bereits einen Unfall erlitten haben, empfehlen wir eine Zuweisung an ein Zentrum für Schlafmedizin, um die Tagesschläfrigkeit zu objektivieren und damit die Compliance des Patienten zu verbessern. Bei uneinsichtigen Patienten hat der Arzt in der Schweiz das Recht, aber nicht die Pflicht, Anzeige bei den Behörden zu erstatten.Daytime sleepiness is reported by 10-15 % within the general population of industrialised countries. According to federal statistics in Switzerland, only ~1.5 % of motor vehicle crashes are caused by excessive daytime sleepiness, which is in sharp contrast to the scientific literature, indicating a figure of 10 to 30 %. This is most likely related to the difficulty to detect the underlying sleepiness by police officers and their low awareness of this cause in case of car accidents. As a consequence of this massively reduced figure, the real problem is underestimated and countermeasures as well as examinations of drivers at fault are inadequately realised in our country. The risk factors for sleepiness induced accidents are young age, male sex, driving at night or long distances and a number of diseases or sedative drugs. The most prevalent cause of sleepiness related accidents is the behaviourally induced sleep insufficiency syndrome or irregular sleep-wake rhythm in otherwise healthy subjects. Disease related sleepiness which may also cause motor vehicle accidents must be managed by physicians. In the diagnostic work-up sedative drugs, medical causes of sleepiness or tiredness as well as primary sleep-wake disorders must be considered. The most important duty of the treating physician, in addition to correct diagnosis and treatment, is to inform the affected patient of his or her responsibility not to drive while sleepy, about the theoretical legal consequences in case of an accident and about efficient countermeasures such as stopping in a rest area, drinking coffee, and taking a nap. For legal reasons, this information must be written in the patient's notes. Professional drivers suffering from sleep apnoea syndrome or other disorders with excessive daytime sleepiness, or private drivers who have already experienced a sleepiness induced accident, should be referred to a sleep-wake-centre for objective assessment of their sleepiness in the maintenance of wakefulness test or a driving simulator before they continue to drive. 	
25377291	Das Spektrum der schlafmedizinischen Erkrankungen umfasst eine Reihe von speziellen neurologischen Erkrankungen, die sich durch eine hohe Prävalenz kennzeichnen oder die Lebensqualität stark beeinträchtigen. Dem praktisch tätigen Arzt kommt eine Schlüsselrolle in der Erkennung und Behandlung dieser Erkrankungen zu und sollte deshalb mit den wichtigsten schlafmedizinischen neurologischen Erkrankungen vertraut sein. Im Folgenden werden als wichtigste Vertreter, das Restless Legs Syndrom (mit oder ohne Periodic Limb Movement im Schlaf), Bewegungsstörungen im Schlaf (v. a. nonREM- und REM-Schlaf-Parasomnien), epileptische Anfälle im Schlaf sowie die Narkolepsie vorgestellt. Die Narkolepsie gilt zwar als seltene Erkrankung, ermöglicht aber als Modellerkrankung physiologische bzw. pathophysiologische Vorgänge der Schlaf-/Wachregulation zu verstehen. Eine zunehmende Bedeutung gewinnt auch die REM-Schlafverhaltensstörung, die als Frühzeichen einer neurodegenerativen Erkrankung (z. B. Synukleinopathien wie Parkinson-Erkrankung) auftreten kann. Eine frühzeitige Diagnose eröffnet hier die Möglichkeit in Zukunft neuroprotektive Substanzen einzusetzen.Neurological sleep disorders are common in the general population and may have a strong impact on quality of life. General practitioners play a key role in recognizing and managing sleep disorders in the general population. They should therefore be familiar with the most important neurological sleep disorders. This review provides a comprehensive overview of the most prevalent and important neurological sleep disorders, including Restless legs syndrome (with and without periodic limb movements in sleep), narcolepsy, NREM- and REM-sleep parasomnias and the complex relationship between sleep and epilepsies. Although narcolepsy is considered as a rare disease, recent discoveries in narcolepsy research provided insight in the function of brain circuitries involved in sleep wake regulation. REM sleep behavioral parasomnia (RBD) is increasingly recognized to represent an early manifestation of neurodegenerative disorders, in particular evolving synucleinopathies. Early diagnosis may thus open new perspectives for developing novel treatment options by targeting neuroprotective substances. 	
25377289	Dieser Artikel gibt einen Überblick über mögliche Faktoren für altersbedingte Veränderungen, welche den Schlaf bei gesunden älteren Menschen beeinflussen. Ein wichtiger Beitrag wird hierbei durch die Selbstregulation des Schlaf-Wach Zyklus sowie die innere Uhr geleistet. Eine Quintessenz zeigt sich darin, dass ältere gesunde Erwachsene einen oberflächlicheren Schlaf und meistens frühere Bett- und Aufstehzeiten als noch in jüngeren Jahren haben, was auf altersbedingte Veränderungen in der Schlaf-Wach Homöostase und der inneren Uhr zurückzuführen ist. Zudem reagiert der Schlaf bei gesunden älteren Menschen empfindlicher auf Störungen, wie der circadianen Desynchronisation und einen Mangel an Zeitgebern [zu wenig Licht am Tage].This article gives an overview of factors underlying age-related changes in sleep wake behavior in healthy older humans. The self-regulation of the sleep-wake cycle [sleep-wake homeostasis] and the circadian clock, represent primary factors responsible for changes in sleep with age. As a matter of fact older healthy adults have a more superficial and less consolidated sleep and go to bed earlier compared to younger ages. Furthermore, sleep in healthy older people is more vulnerable to disturbances such as circadian desynchronisation and the lack of zeitgebers [insufficient light during the day]. 	
25377288	Schlafstörungen gehören zu den häufigsten Verhaltensauffälligkeiten im Kindesalter. In diesem Artikel werden die wichtigsten Erkenntnisse der kindlichen Schlafphysiologie zusammengefasst und unser entwicklungspädiatrisches Beratungskonzept vorgestellt, welches bei nicht-organischen (funktionellen) Schlafstörungen erfolgreich angewendet werden kann. Hauptbestandteil unserer fachlichen Beratung ist die Vermittlung von Kenntnissen über die normale Entwicklung des kindlichen Schlafs, seine Physiologie und über die große interindividuelle Variabilität einzelner Merkmale. Dieses Vorgehen ist von zentraler Bedeutung, damit Eltern die Schlafstörung ihres Kindes besser erkennen, einordnen und darauf reagieren können. Die Eltern der 18 Monate alten Nina werden vom Hausarzt überwiesen, da das Kind abends wie auch nach nächtlichem Erwachen nicht einschlafen kann. Nina ruft dann nach der Mutter und will in die Arme genommen werden. Manchmal gelingt es ihr dann das Kind durch Zureden und Streicheln zu beruhigen. Oft dauert es aber länger und die Mutter muss Nina herumtragen, bis sie schläft. Dies nimmt der Mutter ihren eigenen Schlaf und zehrt an ihren Kräften. Die Eltern haben schon alles versucht und wissen nicht mehr weiter.Sleep problems are among the most frequent behavioural issues during childhood. This article highlights some of the most important aspects of children's sleep physiology and presents a clinical approach for the management of behavioural sleep disorders in children. Our concept is based on developmental aspects of sleep physiology and also uses behavioural strategies for the parents and their child to handle maladaptive sleep behaviour. 	

25377051	The aim of this study was to examine the link between adolescent sleep and non-attendance in school.A large population-based study from Norway conducted in 2012, the youth@hordaland study, surveyed 8,347 adolescents aged 16-19 years (54% girls). Self-reported sleep measures included bedtime, rise time, sleep duration, sleep efficiency, sleep onset latency (SOL), wake after sleep onset (WASO), insomnia symptoms, tiredness, and sleepiness. School attendance was obtained from national administrative registries.	Most sleep parameters were associated with increased risk of school non-attendance. After adjusting for gender and socioeconomic status, short sleep duration and sleep deficiency were the sleep measures with the highest odds of non-attendance (OR=4.61, CI 95% 3.29-6.46) and (OR=3.26, CI 95% 2.67-3.99), respectively). Also, large bedtime discrepancies in weekend versus weekdays were associated with non-attendance (OR=2.43, CI 95% 1.93-2.02), as well as insomnia (OR=2.25, CI % 1.89-2.67) and daytime tiredness (OR=2.09, CI 95% 1.70-2.57). The associations were somewhat reduced after additional adjustment for depression, but remained significant in the fully adjusted model.	The demonstrated relationship between sleep problems and school absence suggests that careful assessment of sleep is warranted when adolescents present with extensive school absence future studies on how the sleep-school absence relationship in adolescence may impact later work affiliation in adulthood are needed.	
25376559	In addition to motor symptoms, patients with Parkinson's disease (PD) may experience non-motor symptoms (NMS), more often with more advanced disease stage. However, the clinical feature of the NMS and potential risk factors that affect NMS in idiopathic PD patients remain unclear. 493 PD patients diagnosed with PD via the UK. Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria and 93 healthy control subjects (CN) were recruited in the current study. Questionnaires were used to assess the NMS, motor symptoms, cognitive function, and disease severity in both groups. Levodopa daily dose was calculated in PD patients. Multivariate linear regression analysis was used to identify the risk factors that potentially affect NMS in PD patients. The results showed that, the NMS occurrence and positive endorsement rate of PD patients were significantly higher compared to CN subjects. Multiple stepwise regression analysis found the motor symptom was the only factor that affected NMS in PD patients within five years of the disease course, whereas motor symptoms, cognitive function, disease severity and Levodopa daily dose significantly affected NMS if the disease course was more than five years. These findings demonstrated that NMS are affected by several risk factors at different stages of PD. The distribution of difference NMS is associated with the severity of motor symptoms and the dosage of anti-PD medications in Chinese PD patients. 
25373558	The association of physical activity (PA) with sleep quality, perceived stress, and problematic Internet use was examined in a nationwide sample of Korean adolescents.Data from the 2010 Korean Youth Risk Behavior Web-based Survey collected from 73,238 Korean adolescents aged 12-18 years (mean age 15.06 ± 1.75 years) were analyzed. Participants were asked to rate the frequency with which they engaged in moderate and vigorous PA per week. The risk of problematic Internet use was assessed with the Korean Internet Addiction Proneness Scale for Youth-Short Form. Self-report questionnaires were used to assess levels of sleep satisfaction and perceived stress. The associations of PA with sleep satisfaction, perceived stress, and problematic Internet use were assessed with multiple logistic regression analysis. Then, the Sobel test was used to explore the mediation of the relationship between PA and problematic Internet use by sleep satisfaction and stress.	Physically active subjects were more likely to express satisfaction with their sleep (AOR = 1.13; 95% CI = 1.08, 1.18), less likely to feel stress in their lives (AOR = 0.89, 95% CI = 0.86, 0.93), and less likely to be a problematic Internet user (AOR = 0.78; 95% CI = 0.73, 0.82) compared to physically inactive subjects. The Sobel test revealed that the inverse association between PA and problematic Internet use was partially mediated by increased sleep satisfaction or decreased perceived stress (Z = -4.315, p = 0.001).	The results of the present study indicate a negative association between level of physical activity and risk of problematic Internet use via the mediation of sleep satisfaction and stress in Korean adolescents. Physical activity may be helpful to improve adolescent mental health.	
25373044	Mobile health (mHealth) refers to the use of mobile technology (e.g., smartphones) and software (i.e., applications) to facilitate or enhance health care. Several mHealth programs act as either stand-alone aids for Veterans with post-traumatic stress disorder (PTSD) or adjuncts to conventional psychotherapy approaches. Veterans enrolled in a Veterans Affairs outpatient treatment program for PTSD (N = 188) completed anonymous questionnaires that assessed Veterans' access to mHealth-capable devices and their utilization of and interest in mHealth programs for PTSD. The majority of respondents (n = 142, 76%) reported having access to a cell phone or tablet capable of running applications, but only a small group (n = 18) reported use of existing mHealth programs for PTSD. Age significantly predicted ownership of mHealth devices, but not utilization or interest in mHealth applications among device owners. Around 56% to 76% of respondents with access indicated that they were interested in trying mHealth programs for such issues as anger management, sleep hygiene, and management of anxiety symptoms. Findings from this sample suggest that Veterans have adequate access to, and interest in, using mHealth applications to warrant continued development and evaluation of mobile applications for the treatment of PTSD and other mental health conditions. 
25370891	This study was designed to detect the prevalence of poor sleep quality in cervical cancer patients before and after adjuvant therapy, determine whether the prevalence of poor sleep quality in cervical cancer patients is higher than that in the general population, and analyze the factors associated with poor sleep quality.A total of 76 stages I and II cervical cancer patients and 116 female residents completed the Pittsburgh Sleep Quality Index (PSQI). Patient Neurotoxicity Questionnaire (PNQ), Distress Thermometer (DT), Multidimensional Fatigue Inventory, and Hospital Anxiety and Depression Scale were used to measure the patients' chemotherapy-induced peripheral neurotoxicity (CIPN), psychological distress, fatigue, anxiety, and depression. Data on social support and exercise were collected by the questionnaire. Logistic regression was used to identify the factors associated with poor sleep quality.	Prevalence rates of poor sleep quality were 27.59 % for female residents, 52.63 % for patients before adjuvant therapy, and 64.50 % for patients after adjuvant therapy. The distributions of the PSQI scores of the patients before (Z = 3.814, P < 0.001) and after (Z = 5.957, P < 0.001) adjuvant therapy were different from those of the residents. The difference in the PSQI scores before and after adjuvant therapy among cervical cancer patients was significant (P = 0.007). The factors associated with poor sleep quality were high DT score (P = 0.045), depression (P = 0.028), anxiety (P = 0.027), high PNQ grade (P = 0.016), and chemotherapy + radiotherapy treatment (P = 0.017). Exercise was a protective factor for poor sleep quality (P =0.019).	The prevalence of poor sleep quality in stages I and II cervical cancer patients was approximately twice than that of women in the communities. Cancer treatment considerably affected sleep quality. Psychological distress, depression, anxiety, and high grade of CIPN during adjuvant therapy were factors associated with poor sleep quality. Exercise during adjuvant therapy could reduce the risk of poor sleep quality.	
25370592	Sleep is important for underlying neural plasticity, and children with developmental disabilities suffer behavioural, emotional, cognitive, and sensory-motor issues that affect their wake and sleep states. Problematic sleeping can be hypothesized to have adverse effects on both of these areas in children with developmental disabilities. With this review, we aim to provide a benchmark in managing problematic sleeping in children with developmental disabilities.A literature search was conducted and data on the study descriptives, patient characteristics, study design, study-related factors, criteria applied to operationalize sleep and developmental disability, and sleep 'management' were collected. Each management strategy was tabulated and analysed.	We identified 90 studies involving 1460 children with developmental disabilities, of whom 61.6% were male. The highest proportion of studies, almost half, were in children with syndromes (44.4%), followed by studies in children with intellectual disabilities (18.9%). Non-pharmacological sleep management was primarily aimed at improving sleep quality (86.7%), followed by sleep-wake schedules and, to a certain extent, sleep regularity (42.2%). About 56.7% of the studies reported more than one approach. Studies mostly focused on disorders of initiating and maintaining sleep through a diversity of strategies and relied heavily on subjective measures to identify and monitor problematic sleeping. Sleep management approaches were primarily delivered at the level of the individual in the home setting. The number of management approaches per study was unrelated to the number of sleep problems discussed.	Modifying sleep management strategies to meet the specific needs of children with developmental disabilities is encouraged, and studies that look beyond sleep quality or sleep quantity are required. It is also advocated that modifications to sleep hygiene, sleep regularity, and sleep ecology in a population with developmental disabilities are rigorously investigated. Finally, daytime somnolence should not be overlooked when aiming to optimize sleep in children with developmental disabilities across the ages and stages of their lives. There were several limitations in the research findings of problematic sleep in children with developmental disabilities. In general, the sleep problems and the developmental disabilities investigated were multicomponent in nature. It is likely that management approaches impacted those problems on multiple levels or through diverse 'therapeutic' pathways. There is a need for randomized controlled trials and more objective measures that quantify improved sleep or wake states.	
25369874	Excessive wandering in people in dementia is associated with a severe care burden. However, the quantification of excessive wandering has not been described, and its cause and treatment have not been evaluated with objective measurements to date. The purpose of this study was to evaluate pharmacological treatments and non-pharmacological interventions to reduce excessive wandering in an early-onset Alzheimer disease patient with objective indicators. Wandering was quantified using an integrated circuit monitoring system that measured the distance moved and the location of the patient. Monitoring was conducted in the dementia ward of a general hospital in 2012. Sleep quality was measured by non-wear actigraphy. The study was approved by the ethics committees of the Osaka University School of Allied Health Science, and of the study hospital. The case involved a 62-year-old woman diagnosed with early-onset Alzheimer disease and hospitalized in 2012 because of irritability and agitation; her Mini-Mental State Examination score was 5/30 and her Clinical Dementia Rating score was 3. When olanzapine (2.5 mg) was prescribed, she developed insomnia, and her wandering movements increased from 10 to 20 km/day. On some days, it exceeded 30 km/day, and she walked most of the night. She did not experience weight loss or physical exhaustion, but she sustained a minor injury in her left sole. Olanzapine was increased to 7.5 mg, but these problems persisted. Nursing staff discovered triggers for wandering and insomnia, including high sensitivity to odour and noise in the living room or her room. When the environment was changed to meet her needs, the distance moved per day decreased to <15 km and the sleep disturbances disappeared. This case demonstrated the difficulty in assessing the degree of ambulation and sleep disorder. Objective indicators are essential in evaluating the effectiveness of pharmacological and non-pharmacological interventions. 
25369213	The treatment of head and neck cancer (HNC) may cause substantial local and systemic symptomatic morbidities, but many patients have high symptom levels before treatment begins. Knowledge of disease-related (treatment-naive) symptom status would aid in the evaluation of the symptomatic benefit or burden of HNC therapies.The authors retrospectively examined symptoms, quality of life, and health status reported by patients with HNC who were naive to any treatment. Symptoms were explored by anatomical site and disease factors were correlated with symptom severity and interference. A clustering algorithm was used to identify a subset of highly symptomatic patients, and the effects of disease site, tumor stage, and demographic variables on membership in this high-symptom group were examined.	A total of 748 treatment-naive patients with mucosal (434 patients), nonmucosal (272 patients), or skull base (42 patients) tumors were identified who had rated their symptoms using the MD Anderson Symptom Inventory. The majority of patients were white non-Hispanic (82%) and male (68%), with a median age of 59 years. Approximately one-third the patients had a high pretreatment symptom burden. Pain, fatigue, distress, and disturbed sleep were the most severe symptoms reported, regardless of tumor stage or site. Symptom burden was found to be higher among patients with more advanced disease. Predictors of a high symptom burden included having a mucosal tumor and being female.	The high prevalence of moderate to severe symptoms found in the current study demonstrates the importance of assessing patient-reported symptoms routinely before treatment is initiated and emphasizes the need for symptom management in parallel with disease treatment. Baseline characterization of symptom status should be incorporated into clinical trials that may affect symptom burden.	
25369189	The focus of this case is a 78-year-old female who is being referred to an assisted living community following several episodes of excessive daytime sleepiness (EDS). EDS in the geriatric patient is widespread and is often underdiagnosed and inadequately treated. It can affect an older patient?s quality of life, as well as increasing physical, psychological, cognitive, and mortality risks. There are many different etiologies for EDS including coexisting medical conditions, circadian misalignment, medications affecting the sleep/wake cycle, and psychiatric or psychosocial circumstances. This case illustrates how the pharmacist can help patients with EDS by recognizing symptoms; performing a targeted medical history, sleep history, and medication review; and offering screening with validated tools to refer patients to sleep specialists. There are both pharmacological and nonpharmacological treatment options. The consultant pharmacist is a vital member of the interprofessional health care team and can play a major role in the education, monitoring, and management of EDS. 
25368585	Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by human beings, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to no, mild (10), or severe (100) acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced rapid eye movement (REM) and non-REM (NREM) sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep/wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep/wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders. 
25368503	To review circadian rhythm sleep disorders, including underlying causes, diagnostic considerations, and typical treatments.Literature review and discussion of specific cases.	Survey studies 1,2 suggest that up to 3% of the adult population suffers from a circadian rhythm sleep disorder (CRSD). However, these sleep disorders are often confused with insomnia, and an estimated 10% of adult and 16% of adolescent sleep disorders patients may have a CRSD 3-6. While some CRSD (such as jet lag) can be self-limiting, others when untreated can lead to adverse medical, psychological, and social consequences. The International Classification of Sleep Disorders classifies CRSD as dyssomnias, with six subtypes: Advanced Sleep Phase Type, Delayed Sleep Phase Type, Irregular Sleep Wake Type, Free Running Type, Jet Lag Type, and Shift Work Type. The primary clinical characteristic of all CRSD is an inability to fall asleep and wake at the desired time. It is believed that CRSD arise from a problem with the internal biological clock (circadian timing system) and/or misalignment between the circadian timing system and the external 24-hour environment. This misalignment can be the result of biological and/or behavioral factors. CRSD can be confused with other sleep or medical disorders.	Circadian rhythm sleep disorders are a distinct class of sleep disorders characterized by a mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep. If untreated, CRSD can lead to insomnia and excessive daytime sleepiness, with negative medical, psychological, and social consequences. It is important for physicians to recognize potential circadian rhythm sleep disorders so that appropriate diagnosis, treatment, and referral can be made.	
25367636	This study evaluated the effectiveness of a stress management intervention combining individual cognitive behavioral therapy (CBT) with a brief workplace intervention on self-reported measures of sleep and cognitive functioning among patients on sick leave due to work-related stress complaints.Participants were patients referred to the regional Department of Occupational Medicine. Inclusion criteria were (i) sick leave due to work-related stress complaints and (ii) a diagnosis of adjustment disorder/reactions to stress or mild depression. Participants (N=137) were randomized to either an intervention (N=57) or control (N=80) group. The intervention comprised six sessions with a psychologist and the offer of a small workplace intervention. Questionnaires were answered at baseline and after 4, and 10 months.	Symptoms were significantly reduced over time in both groups but there was no significant treatment effect on sleep or cognitive outcomes at any time point. From 0-4 months, there was a tendency for larger improvements in the intervention group with regards to sleep and cognitive failures in distraction. Although neither was significant, the results came close to significance depicting a small effect size (Cohen's d) on sleep complaints and distractions (but not memory).	The specific intervention was not superior to the control condition in reducing symptoms of sleep problems and cognitive difficulties at any time point during the 10-month follow-up period. Substantial improvements in symptoms over time were seen in both groups.	
25367475	The recently released third edition of the International Classification of Sleep Disorders (ICSD) is a fully revised version of the American Academy of Sleep Medicine's manual of sleep disorders nosology, published in cooperation with international sleep societies. It is the key reference work for the diagnosis of sleep disorders. The ICSD-3 is built on the same basic outline as the ICSD-2, identifying seven major categories that include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. Significant modifications have been made to the nosology of insomnia, narcolepsy, and parasomnias. Major features and changes of the manual are reviewed in this article. The rationales for these changes are also discussed. 
25367349	Respiratory muscle weakness is the major cause of early death in patients with adult Pompe disease. It first manifests as nocturnal hypercapnia, eventually leading to sleep disruption. Sleep-related symptoms along with motor performance, forced vital capacity (FVC) and respiratory symptoms were investigated in 65 adult patients with Pompe disease.Patients answered the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, the Fatigue Severity Scale, the Rotterdam Nine-item Handicap Scale, the SF-36 health-related quality of life questionnaire, and a respiratory symptom questionnaire. In all patients, the 6-min walk test was performed and FVC was obtained. Polysomnography and oxycapnometry results were available in 31 patients.	Sixty patients received enzyme replacement therapy, and 32 individuals were on home ventilatory support. Reduced sleep quality was highly prevalent (PSQI > 5; 43.1%) and correlated with both excessive daytime sleepiness (Epworth Sleepiness Scale > 10; 24.6%) and fatigue (Fatigue Severity Scale > 4; 72.3%). The SF-36 health-related quality of life questionnaire was reduced in the physical domains, and was inversely correlated with sleep quality, FVC and motor performance. In 11 out of 17 non-ventilated patients with polysomnography records, sleep-disordered breathing was present, and duration of nocturnal oxygen desaturation (SaO2 < 90%) was significantly correlated to the PSQI global score.	In adult Pompe disease, sleep disturbances are a common cause of excessive daytime sleepiness and fatigue. Sleep-related symptoms may be indicative of respiratory muscle weakness and should give rise to further work-up of sleep-disordered breathing.	
25366389	Polymyalgia rheumatica (PMR) is the commonest inflammatory disorder of older adults. Although not part of the recently published classification criteria, patients with PMR frequently complain of fatigue. We compared consultation for fatigue and sleep problems between individuals with and without PMR.Consulters receiving a Read-coded diagnosis of PMR at nine general practices between 2000 and 2009 were matched by age, gender, general practice, and year of consultation to four patients without PMR. Fatigue and sleep problems were defined using Read codes. Cox regression was used to determine the association between PMR diagnosis and consultation for a fatigue/sleep problem.	In total, 549 PMR patients were identified. Their mean (SD) age was 73.9 (8.6) years and 71% of the participants were female. Prior to the index date, 33 PMR patients and 80 matched non-PMR patients consulted with fatigue (0.43 vs. 0.25 consultations per 10 000 person-years, p = 0.006). PMR was associated with significantly more multiple fatigue consultations in the 12 months before PMR diagnosis [hazard ratio (HR) 1.95, 95% confidence interval (CI) 1.23-3.08]; no significant difference was seen in rates of consultations for sleep problems between patients with and without PMR.	PMR patients were significantly more likely to have had multiple fatigue consultations before being diagnosed with PMR. Given the overproduction of inflammatory cytokines seen in PMR, this fatigue may represent a prodromal phase prior to consulting with more classical musculoskeletal symptoms. This suggests that clinicians should consider PMR as a potential diagnosis in older patients consulting with fatigue.	
25365961	Acne is a common disease among young people, which could have a serious impact on quality of life. Based on a survey using the quotas method on a large sample of the French population, we studied the impact of acne on feelings of stress, fatigue upon waking, sleep disorders and sexual activity. We did not establish any relationship to sleep disorders, but clearly ascertained that people with acne (n = 1,375) feel more stressed and have less sexual intercourse. Hence, 18% of people from acne group declared to be stressed every day (13.9% in control group) and 37.5% had no sexual intercourse (20.4% in control group; n = 891). To our knowledge, this is the first study to show that fatigue upon waking is strongly associated with the presence of acne (65.4% versus 58.4%). This study emphasises the fact that acne could have a deep resounding impact on the lives of people suffering from the disease.
25364076	To examine relationships among gastroesophageal reflux disease (GERD) symptoms, dietary behaviors, and sleep duration in the general population.Cross-sectional.	Community-based.	There were 9,643 participants selected from the general population (54 ± 13 y).	None.	Sleep duration, sleep habits, and unfavorable dietary behaviors of each participant were assessed with a structured questionnaire. Participants were categorized into five groups according to their sleep duration: less than 5 h, 5 to less than 6 h, 6 to less than 7 h, 7 to less than 8 h, and 8 or more h per day. GERD was evaluated using the Frequency Scale for the Symptoms of GERD (FSSG) and participants having an FSSG score of 8 or more or those under treatment of GERD were defined as having GERD. Trend analysis showed that both the FSSG score and the number of unfavorable dietary habits increased with decreasing sleep duration. Further, multiple logistic regression analysis showed that both the presence of GERD (odds ratio = 1.19, 95% confidence interval (CI) = 1.07-1.32) and the number of unfavorable dietary behaviors (odds ratio = 1.19, 95% CI = 1.13-1.26) were independent and potent factors to identify participants with short sleep duration even after controlling for other confounding factors.	The current study showed that both GERD symptoms and unfavorable dietary behaviors were significant correlates of short sleep duration independently of each other in a large sample from the general population.	
25359533	Bipolar disorder is a common psychiatric disease characterized by mood disturbances with alternating episodes of mania and depression. Moreover, disturbances in the sleep/wake cycle are prevalent. We tested a hypothesis that the function of the circadian system, which drives the sleep/wake cycle, may differ in patients with bipolar disorder depending on whether they are experiencing an episode of mania or depression.To assess the functional state of the central circadian clock, daily profiles of melatonin levels in saliva were determined. The functional state of the peripheral clocks was assessed by determining daily profiles of Per1 and Nr1d1 clock gene expression in buccal mucosa cells. Sixteen patients with bipolar disorder in a manic episode, 22 patients in a depressive episode, and 19 healthy control subjects provided samples at regular intervals during a 24-hour cycle.	During episodes of mania, the daily profiles of melatonin differed compared with healthy controls and patients in an episode of depression, mainly due to elevated melatonin levels during the daytime. No difference was found between melatonin profiles of control subjects and patients in depression. The Per1 and Nr1d1 profiles were advanced in patients in mania compared with those in depression. Compared with controls, a trend toward an advance was apparent in the profiles of patients during an episode of mania but not depression. The amplitude of the Nr1d1 expression profile was higher in mania than in depression.	The data revealed differences in the functional state of the circadian system in patients with bipolar disorder depending on whether they were experiencing a manic or a depressive episode.	
25359419	Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) experience high rates of sleep problems and are also at increased risk for experiencing comorbid mental health problems. This study provides an initial examination of the 1-year prospective association between sleep problems and comorbid symptoms in youth diagnosed with ADHD. Participants were 81 young adolescents (75 % male) carefully diagnosed with ADHD and their parents. Parents completed measures of their child's sleep problems and ADHD symptoms, oppositional defiant disorder (ODD) symptoms, and general externalizing behavior problems at baseline (M age = 12.2) and externalizing behaviors were assessed again 1 year later. Adolescents completed measures of anxiety and depression at both time-points. Medication use was not associated with sleep problems or comorbid psychopathology symptoms. Regression analyses indicated that, above and beyond demographic characteristics, ADHD symptom severity, and initial levels of comorbidity, sleep problems significantly predicted greater ODD symptoms, general externalizing behavior problems, and depressive symptoms 1 year later. Sleep problems were not concurrently or prospectively associated with anxiety. Although this study precludes making causal inferences, it does nonetheless provide initial evidence of sleep problems predicting later comorbid externalizing behaviors and depression symptoms in youth with ADHD. Additional research is needed with larger samples and multiple time-points to further examine the interrelations of sleep problems and comorbidity.
25358428	Most literature on the relationship between video gaming and sleep disturbances has looked at children and adolescents. There is little research on such a relationship in adult samples. The aim of the current study was to investigate the association of video game volume with sleep quality in adults via face-to-face interviews using standardized questionnaires. Adults (n = 844, 56.2% women), aged 18-94 years old, participated in the study. Sleep quality was measured using the Pittsburgh Sleep Quality Index, and gaming volume was assessed by asking the hours of gaming on a regular weekday (Mon-Thurs), Friday and weekend day (Sat-Sun). Adjusting for gender, age, educational level, exercise and perceived stress, results of hierarchical regression analyses indicated that video gaming volume was a significant predictor of sleep quality (β = 0.145), fatigue (β = 0.109), insomnia (β = 0.120), bedtime (β = 0.100) and rise time (β = 0.168). Each additional hour of video gaming per day delayed bedtime by 6.9 min (95% confidence interval 2.0-11.9 min) and rise time by 13.8 min (95% confidence interval 7.8-19.7 min). Attributable risk for having poor sleep quality (Pittsburgh Sleep Quality Index > 5) due to gaming >1 h day was 30%. When examining the components of the Pittsburgh Sleep Quality Index using multinomial regression analysis (odds ratios with 95% confidence intervals), gaming volume significantly predicted sleep latency, sleep efficiency and use of sleep medication. In general, findings support the conclusion that gaming volume is negatively related to the overall sleep quality of adults, which might be due to underlying mechanisms of screen exposure and arousal.
25358390	Sleep disorders for patients on dialysis are significant causes of a poorer quality of life and increased morbidity and mortality. No study has evaluated patients undergoing automated peritoneal dialysis (APD) to assess their sleep disorders compared to hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). A total of 166 clinically stable patients who had been on dialysis for at least 3 months were randomly selected for the study and divided into HD, CAPD or APD. Socio-demographic, clinical and laboratory parameters and self-administered questionnaires were collected for the investigation of insomnia, restless legs syndrome (RLS), bruxism, rapid eye movement sleep behavior disorder, excessive daytime sleepiness (EDS), obstructive sleep apnea syndrome (OSAS), sleepwalking, sleep hygiene, depression and anxiety. Insomnia was detected in more than 80 % of patients on the three modalities. OSAS was lower for patients on HD (36 %) than on CAPD (65 %) (p < 0.01) or APD (60 %) (p < 0.04). Patients on APD were more likely to have RLS compared to those on HD or CAPD (p < 0.04) (50 vs. 23 vs. 33 %). No differences among the modalities were found in bruxism, EDS, sleepwalking, sleep hygiene, depression or anxiety. ESRD patients undergoing any one of the three dialysis modalities studied had a high prevalence of sleep disorders. Patients on HD had a lower proportion of OSAS than those on CAPD and APD, which is most likely attributed to their lower body mass indices. The possible causes of higher RLS rates in APD patients have not been established.
25356730	The brain endocannabinoid system is a potential target for the treatment of psychiatric and metabolic conditions. Here, a novel CB1 receptor antagonist (ABD459) was synthesized and assayed for pharmacological efficacy in vitro and for modulation of food consumption, vigilance staging and cortical electroencephalography in the mouse. ABD459 completely displaced the CB1 agonist CP99540 at a Ki of 8.6 nmol/l, and did not affect basal, but antagonized CP55940-induced GTPγS binding with a KB of 7.7 nmol/l. Acute ABD459 (3-20 mg/kg) reliably inhibited food consumption in nonfasted mice, without affecting motor activity. Active food seeking was reduced for 5-6 h postdrug, with no rebound after washout. Epidural recording of electroencephalogram confirmed that ABD459 (3 mg/kg) robustly reduced rapid eye movement (REM) sleep, with no alterations of wakefulness or non-REM sleep. Effects were strongest during 3 h postdrug, followed by a progressive washout period. The CB1 antagonist AM251 (3 mg/kg) and agonist WIN-55,212-2 (WIN-2: 3 mg/kg) also reduced REM, but variously affected other vigilance stages. WIN-2 caused a global suppression of normalized spectral power. AM251 and ABD459 lowered delta power and increased power in the theta band in the hippocampus, but not the prefrontal cortex. The neutral antagonist ABD459 thus showed a specific role of endocannabinoid release in attention and arousal, possibly through modulation of cholinergic activity. 
25356522	We have previously reported that maternal separation (MS) for 3 h daily during the first two postnatal weeks increases wakefulness, whereas it reduces sleep in rats. Oleamide, an agonist of the cannabinoid receptor type 1, increases sleep in MS rats to such a level that we cannot differentiate their sleep patterns from those of their non-MS (NMS) siblings. However, 2-arachidonoylglycerol (2-AG), an endocannabinoid, infused into the lateral hypothalamus of NMS rats at the beginning of the dark phase of the cycle increases rapid eye movement sleep and the expression of c-Fos on the rapid eye movement sleep promoting melanin-concentrating hormone neurons. We recorded the sleep-wake cycle of adult rats subjected to MS for 3 h daily from postnatal days 2 to 16, as well as in their NMS siblings. Besides the electrodes for recording the sleep-wake cycle, a couple of cannulae aimed bilaterally to the lateral hypothalamus were implanted to infuse 2-AG. We found that administration of 2-AG into the lateral hypothalamus of MS rats at the beginning of the light phase of the cycle restores sleep, whereas sleep and wakefulness of NMS rats under 2-AG infusion do not show any significant change.
25355824	To objectively measure daytime sleepiness and to assess for clinical and polysomnographic determinants of mean sleep latency in adult patients with somnambulism (sleepwalking [SW]) or sleep terrors (ST) compared with controls.Thirty drug-free adult patients with primary SW or ST, and age-, sex-, and body mass index-matched healthy controls underwent a standardized clinical interview, completed questionnaires including the Epworth Sleepiness Scale, and underwent one night of video polysomnography followed by the Multiple Sleep Latency Test (MSLT).	Excessive daytime sleepiness defined as Epworth Sleepiness Scale score >10 was reported in 66.7% of patients and 6.7% of controls. The temporal pattern of sleep latencies in individual MSLT trials differed between patients and controls, with progressive increased sleep latency in patients across the trials in contrast to a "U curve" for controls. We did not find between-group differences regarding the mean sleep latency on the 5 MSLT trials, but did observe reduced sleep latencies in patients for the first 2 trials. Despite increased slow-wave sleep disruptions found in patients (i.e, more micro-arousals and hypersynchronous high-voltage delta waves arousals), we did not find polysomnographic characteristic differences when comparing sleepy patients for either subjective or objective daytime sleepiness on the MSLT compared with alert patients.	Excessive daytime sleepiness is a common complaint in subjects with SW or ST and shorter sleep latencies in the early morning hours. Despite an increased slow-wave sleep fragmentation found in these patients, we did not identify any association with the level of daytime sleepiness.	
25355211	Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. 
25354470	Our objective was to review how meditation could comfort the terminally ill.Our methodology was a literature search, which included books, journals, papers in collections, and online databases. The main search engines employed were Google Scholar and the Durham University Library. The main databases consulted were the Christian Meditation Centre, Project Meditation, and Stress-Related Facts and Well-Being at Monash. We were specifically interested in data acquired from clinical and nonclinical trials. The arguments needed to be based on qualitative and quantitative scientific data. Papers were published between 1985 and 2014. We then subdivided the review into three subcategories: physical, emotional, and self-awareness. When reviewing each category, we put our results into tabular form. In each table, we noted the percentage of terminally ill patients (TIPs) and non-terminally ill patients (NTIPs), and whether meditation had comforted them.	Our review demonstrated that there are many areas that have yet to be researched. First, very little work has been done on how meditation affects the physical health of TIPs, including such variables as blood pressure, chronic pain, and sleeping patterns. However, no research has been done on heart disease, hypertension, depression, among others. Second, virtually no research has been conducted on how meditation affects the mental health of TIPs. Notably neglected areas include anxiety, compliance, depression, and stress. Third, no research has been done on whether meditation increases self-awareness in TIPs. In each of these cases, most NTIPs reacted positively; however, no research has been done on why TIPs reacted differently.	Our results demonstrate the need for further research on how meditation affects terminally ill patients. In turn, this would enrich the debate on whether meditation should be prescribed for the dying.	
25353103	Sleep is a fundamental physiological process necessary for recovery from acute illness. Unfortunately for hospitalized patients, sleep is often short, fragmented, and poor in quality, and may be associated with adverse outcomes including inpatient delirium. Many factors contribute to poor sleep in the hospital setting, including preexisting sleep deprivation, sleep disordered breathing, environmental noise and light, patient care activities, and medications. Sleep disordered breathing increases the risk of potentially life-threatening cardiovascular, respiratory, and metabolic consequences, and therefore should be diagnosed and treated in hospitalized patients. Mitigating the sequelae associated with poor sleep quality and sleep disordered breathing requires early identification of modifiable factors impacting a patient's sleep, including engagement of a multidisciplinary team. In this article, we review the current knowledge of sleep in hospitalized patients with a detailed focus on patients with sleep disordered breathing. 
25351854	To investigate the quality of sleep of patients with primary burning mouth syndrome (BMS) compared with a control group.A total of 70 patients with primary BMS and 70 control subjects were enrolled in the study. The severity of pain was evaluated with a Visual Analogue Scale (VAS). Four validated questionnaires were used to investigate the psychological profile of each patient: the Hospital Anxiety and Depression Scale, the Oral Health Impact Profile-14 (OHIP-14), the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (EES).	Poor sleep quality was present in 67.1% patients with BMS vs. 17.1% in control subjects (P ≤ 0.001). For patients with BMS, total data resulting from the PSQI correlated with results obtained by the EES (P ≤ 0.001), VAS pain (P ≤ 0.001), localization (P = 0.01), HAD-A (P = 0.001) and HAD-D (P = 0.001). Logistic regression analysis showed that an increase of one point in each depression score (HAD-D) made the chances of PSQI 1.26 times more likely, with a 95% confidence interval (CI = 1.03-1.55).	Patients with primary BMS exhibited significant decreases in sleep quality compared with the control group.	
25351230	The aim of the present study was to measure the test-retest validity of Parkinson's Disease Sleep Scale 2nd version (PDSS-2) on PD patients with stable medication and motor symptoms over the period of 4 weeks.The subject population consisted of 92 PD patients. Besides PDSS-2, Unified PD rating scale, Montgomery-Asberg Depression Rating Scale and EQ-5D were assessed at baseline and 4 weeks later.	The total score of PDSS-2 decreased from 19.06 ± 10.78 points to 18.00 ± 9.34 points (p > 0.05). For the total score of PDSS-2 the Intra-class and Lin's Concordance Correlation Coefficients were 0.782 and 0.799. The average difference between the baseline and follow-up total PDSS-2 scores was -1.06 points with the 95% confidence interval of -7.96 and +5.84 points.	Our data supports that the items and the total score of PDSS-2 have acceptable test-retest reliability over a four week period on patients with stable PD symptoms and pharmacological therapy.	

25348241	Poor sleep quality, particularly insomnia, has been identified as a frequent problem among individuals with mental health difficulties. Comorbid sleep difficulties adversely affect quality of life and functioning, and have been associated with the causation and maintenance of a number of psychiatric disorders, as well as increasing the risk of relapse. The study objectives were to ascertain clinician knowledge related to insomnia, investigate sleep quality among service users in a community mental health setting in the UK, and evaluate service provision of evidence-based interventions for sleep difficulties.A cross-sectional design was used. Nineteen clinicians completed a questionnaire on their clinical practice. Seventy-three service users completed the Pittsburgh Sleep Quality Index and provided self-report data on interventions received and associated satisfaction.	Clinical staff demonstrated deficits in knowledge of insomnia symptomatology. Sixty-four percent (95% CI 54% to 74%) of service users were identified as poor sleepers on the PSQI. Sixty-one percent of poor sleepers had not been offered support for sleep difficulties. The most common support received was prescribed psychotropic medication (32%). Cognitive behavioral therapy was the intervention rated as most helpful but was only received by 6%.	This study highlights inadequaciesin providing evidence-based interventions for sleep difficulties. Key recommendations include training clinicians in the identification of sleep difficulties and provision of evidence-based interventions, provision of cost-effective transdiagnostic group interventions, and formalizing assessment and treatment pathways for service users with sleep difficulties.	
25348124	Blood pressure (BP) may be adversely affected by a variety of sleep disturbances, including sleep fragmentation, hypoxemia, respiratory disturbances, and periodic limb movements. We aim to identify which polysomnography indices are most strongly and consistently associated with systolic and diastolic blood pressure (SBP, DBP) levels in a population-based sample.Cross-sectional analysis of data from 2,040 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent polysomnography at MESA Exam 5 in 2011-2013.	Multisite cohort study.	Participants were mean age 68 y (54% females; 28% African American, 24% Hispanic, 11% Chinese).	Thirty-two candidate polysomnography predictors were identified representing the domains of breathing disturbance frequency, hypoxemia, sleep architecture, and periodic limb movements. Cluster analysis was used for variable reduction. Statistical models, adjusted for potential confounders, were derived using stepwise regression. Final models were selected using cross-validation techniques.	The apnea-hypopnea index (AHI) defined using a 4% desaturation hypopnea criterion (AHI4P) was most consistently associated with SBP level. The AHI and periodic limb movement index (associated with arousals; PLMIA) were significantly associated with DBP. Estimated adjusted differences in SBP and DBP levels between an individual with no sleep apnea (AHI4P = 0) and one with moderately severe sleep apnea (AHI4P = 30) were 2.2 mm Hg and 1.1 mm Hg, respectively. Each 10-unit increase in the PLMIA was associated with an increase in DBP of 1.2 mm Hg.	Our results support the use of a currently recommended apnea-hypopnea index definition as a marker of blood pressure risk and indicate that measurement of limb movements with arousals is also independently associated with diastolic blood pressure.	

25347156	Circadian rhythms are associated with the preference for sleep-wake timing, also known as morningness-eveningness (ME). Both circadian rhythms and ME are influenced by genetic factors. Studies show an association between eveningness and depression. This study investigates the heritability of ME and whether ME and depression share common genetic influences. Study participants (n = 1237) were from the Vietnam Era Twin Study of Aging, a longitudinal study of aging with a baseline in midlife. Participants received the Morningness-Eveningness Questionnaire (MEQ) and the Center for Epidemiologic Studies Depression (CES-D) Scale as part of an extensive neurocognitive and psychosocial assessment. MEQ correlations between members of twin pairs were 0.41 (95% CI 0.31-0.49) for monozygotic (MZ) twins and 0.28 for dizygotic (DZ) twins (95% CI 0.19-0.41). CES-D correlations were 0.38 (95% CI 0.28-0.46) for MZ twins and 0.24 (95% CI 0.14-0.36) for DZ twins. Greater eveningness (i.e. lower MEQ scores) was significantly related to more depression symptoms (phenotypic correlation = -0.15 (95% CI -0.21 to -0.09). In the best fitting model, the heritability estimates are 0.42 for the MEQ and 0.37 for the CES-D. A significant genetic correlation of -0.21 indicated that ME and depression share a significant amount of their underlying genetic variance. The genetic covariance between ME and depression accounted for 59.1% of the phenotypic correlation. Of the CES-D sub-scales, Depressed Mood and Interpersonal Difficulties were significantly heritable, while only Well-Being had a significant genetic correlation with ME. ME and depression are both heritable (ME 0.42, depression 0.37) and share common genetic factors, suggesting an overlap in etiology and the relevance of circadian rhythms to depression. Further study of this relationship may help elucidate etiological factors in depression and targets for treatment. 

25342922	A need exists, from both a clinical and a research standpoint, for objective sleep measurement systems that are both easy to use and can accurately assess sleep and wake. This study evaluates the output of an automated sleep-wake detection algorithm (Z-ALG) used in the Zmachine (a portable, single-channel, electroencephalographic [EEG] acquisition and analysis system) against laboratory polysomnography (PSG) using a consensus of expert visual scorers.Overnight laboratory PSG studies from 99 subjects (52 females/47 males, 18-60 years, median age 32.7 years), including both normal sleepers and those with a variety of sleep disorders, were assessed. PSG data obtained from the differential mastoids (A1-A2) were assessed by Z-ALG, which determines sleep versus wake every 30 seconds using low-frequency, intermediate-frequency, and high-frequency and time domain EEG features. PSG data were independently scored by two to four certified PSG technologists, using standard Rechtschaffen and Kales guidelines, and these score files were combined on an epoch-by-epoch basis, using a majority voting rule, to generate a single score file per subject to compare against the Z-ALG output. Both epoch-by-epoch and standard sleep indices (eg, total sleep time, sleep efficiency, latency to persistent sleep, and wake after sleep onset) were compared between the Z-ALG output and the technologist consensus score files.	Overall, the sensitivity and specificity for detecting sleep using the Z-ALG as compared to the technologist consensus are 95.5% and 92.5%, respectively, across all subjects, and the positive predictive value and the negative predictive value for detecting sleep are 98.0% and 84.2%, respectively. Overall κ agreement is 0.85 (approaching the level of agreement observed among sleep technologists). These results persist when the sleep disorder subgroups are analyzed separately.	This study demonstrates that the Z-ALG automated sleep-wake detection algorithm, using the single A1-A2 EEG channel, has a level of accuracy that is similar to PSG technologists in the scoring of sleep and wake, thereby making it suitable for a variety of in-home monitoring applications, such as in conjunction with the Zmachine system.	
25341374	Sleep disorders are commonly observed in patients with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease and often represent an early manifestation of the underlying degenerative process. The pathophysiology of sleep dysfunction in these conditions is complex and incompletely understood. However, in recent years, functional imaging in vivo with SPECT and PET has significantly improved our understanding of the possible molecular mechanisms. These include dysfunction of both dopaminergic and non-dopaminergic pathways involved in sleep/wakefulness control. This paper summarizes the main findings of the imaging studies performed to elucidate the aetiology of sleep disorders in Alzheimer's disease and Parkinson's disease. 
25340654	Exposure to electromagnetic field (EMF) emitted by mobile phone and other machineries concerns half the world's population and raises the problem of their impact on human health. The present study aims to explore the effects of electromagnetic field exposures on sleep quality and sleep duration among workers from electric power plant.A cross-sectional study was conducted in an electric power plant of Zhejiang Province, China. A total of 854 participants were included in the final analysis. The detailed information of participants was obtained by trained investigators using a structured questionnaire, which including socio-demographic characteristics, lifestyle variables, sleep variables and electromagnetic exposures. Physical examination and venous blood collection were also carried out for every study subject.	After grouping daily occupational electromagnetic exposure into three categories, subjects with long daily exposure time had a significantly higher risk of poor sleep quality in comparison to those with short daily exposure time. The adjusted odds ratios were 1.68 (95%CI: 1.18, 2.39) and 1.57 (95%CI: 1.10, 2.24) across tertiles. Additionally, among the subjects with long-term occupational exposure, the longer daily occupational exposure time apparently increased the risk of poor sleep quality (OR (95%CI): 2.12 (1.23∼3.66) in the second tertile; 1.83 (1.07∼3.15) in the third tertile). There was no significant association of long-term occupational exposure duration, monthly electric fee or years of mobile-phone use with sleep quality or sleep duration.	The findings showed that daily occupational EMF exposure was positively associated with poor sleep quality. It implies EMF exposure may damage human sleep quality rather than sleep duration.	
25340473	Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2. 

25335517	Fragestellung: Wie eine Vielzahl von Studien belegen, ist Körperkontakt entscheidend für Gesundheit, Regulation und Entwicklung des Säuglings sowie die Eltern-Kind-Interaktion. Daher wäre gerade für Säuglinge mit Regulationsstörungen (wie exzessivem Schreien, Schlaf- und Fütterproblemen) ein qualitativ hochwertiger Körperkontakt wünschenswert. Vorausgegangene Beobachtungen im Rahmen der Elternberatung deuteten darauf hin, dass gerade diese Säuglinge eher einen schlechten Körper- und Blickkontakt aufweisen. Dies war der Ausgangspunkt der vorliegenden Studie, in der Säuglinge mit und ohne Regulationsstörung bezüglich ihres Körper- und Blickkontakts miteinander verglichen wurden. Methodik: Die Qualität des Körper- und die Dauer des Blickkontakts wurden anhand von Videoaufzeichnungen der Mutter-Kind-Interaktion mittels Rating ausgewertet. Zusätzlich wurde die tägliche Dauer von Schreien, Schlafen, Füttern, Unruhe und ruhiger Beschäftigung mit Hilfe eines Tagebuchs erfasst. Ergebnisse: Säuglinge mit einer Regulationsstörung zeigten einen schlechteren Körperkontakt (p < .01) und weniger Blickkontakt (p < .01). In nahezu allen Tagebuchvariablen zeigten sich signifikante Gruppenunterschiede. Schlussfolgerungen: Offensichtlich können Körper- und Blickkontakt, grundlegende kommunikative Fähigkeiten, bei Säuglingen mit Regulationsstörungen blockiert sein. Dies kann sich ungünstig auf die Regulationsproblematik auswirken. Therapeutische Maßnahmen mit betroffenen Kindern und ihren Eltern sollten daher auch auf eine Verbesserung der Fähigkeit zu Körper- und Blickkontakt abzielen.Numerous studies have emphasized the importance of body contact for health, regulation, and development of infants as well as for parent-child interaction. Especially for infants with regulatory disorders (such as excessive crying, sleeping, and feeding problems), high-quality physical contact would be desirable. Observations in the context of parental counseling suggest that precisely these infants have a poor quality of body and eye contact. The present study compares infants with and without regulatory disorders with respect to their body and eye contact.	Quality of body contact and amount of eye contact were examined by means of video ratings of the mother-child interaction. In addition, we measured the daily amount of crying, sleeping, feeding, being fussy, and quiet play in an infant behavior diary.	Infants with regulatory disorders scored worse in body contact (p < .01) and gaze contact (p < .001). There were also significant differences in most of the diary variables.	Body and eye contact - basic communication skills - may be disturbed in infants with regulatory disorders, which could have an adverse effect on the regulation problems. Therapeutic interventions with affected children and their parents should aim at improving the ability of body and eye contact.	
25333682	To determine which SBP measure best predicts cardiovascular events (CVEs) independently, a systematic review was conducted for cohorts with all patients diagnosed with hypertension, 1+ years follow-up, and coronary artery disease and stroke outcomes. Lead investigators provided ad hoc analyses for each cohort. Meta-analyses gave hazard ratios from clinic SBP (CSBP), daytime SBP (DSBP), and night-time SBP (NSBP). Coefficients of variation of SBP measured dispersion. Nine cohorts (n = 13,844) were from Europe, Brazil, and Japan. For sleep-wake SBP classification, seven cohorts used patient-specific information.Overall, NSBP's dispersion exceeded DSBP's dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for CSBP and DSBP. For each comparison, P = 0.004 that this occurred by chance. Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22-1.29), 1.20 (1.15-1.26), and 1.11 (1.06-1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20-1.31), 1.01 (0.94-1.08), and 1.00 (0.95-1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night-day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP: P = 0.023 and 0.012, respectively, that this occurred by chance.	In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP, increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely.	
25332703	Hintergrund: Heutzutage sind Serotonin-Wiederaufnahmehemmer (SSRI) aufgrund ihrer verglichen mit trizyklischen Antidepressiva oder Monoamino-Oxidase-Inhibitoren überlegenen klinischen Wirksamkeit, Verträglichkeit und Sicherheit die meistverschriebenen Antidepressiva. Dennoch sind trotz dieser Vorteile SSRIs mit einer Vielzahl an unerwünschten Arzneimittelnebenwirkungen verbunden, insbesondere im frühen Stadium der Behandlung, was in manchen Fällen zu einem verfrühtem Therapieabbruch führen kann. Das Ziel der vorliegenden Studie war es die meisten unerwünschten Arzneimittelnebenwirkungen von SSRIs zu erfassen sowie die Auswirkung auf die Behandlungsabbruchrate in einer großen Population zu ermitteln.Patienten und Methoden: Daten von 50.824 Patienten mit einer SSRI-Erstbehandlung einer schweren depressiven Störung wurden über die IMS (R) Disease Analyzer Datenbank (IMS Health) retrospektiv analysiert, wobei Informationen über unerwünschte SSRI-Nebenwirkungen und deren Einfluss auf einen verfrühten Therapieabbruch über Regressionsanalysen ermittelt wurden. Das Auftreten von bestimmten Co-Morbiditäten wurden ebenfalls registriert.Ergebnisse: Das mittlere Alter war 54.5 (±19) Jahre, zwei Drittel der Population waren weiblich. Die meist dokumentierten unerwünschten Nebenwirkungen waren: Beschwerden des Verdauungssystems (10%), Schlafstörung (8.6%) und Herzrhythmusstörung (4%); diese waren allerdings von erträglichem Ausmaß, da dadurch die Drop-Out-Rate nicht signifikant beeinflusst wurde. Hingegen erhöht insbesondere Somnolenz als Nebenwirkung und jüngeres Alter (≤50 Jahre) die Wahrscheinlichkeit eines vorzeitigen Therapieabbruchs, während Patienten mit kardiovaskulären Risikofaktoren oder Osteoporose die Tendenz aufweisen die Therapie aufrechtzuerhalten. Schlussfolgerung: Insgesamt wurde eine gute Verträglichkeit der SSRI-Behandlung nachgewiesen, wohingegen das Auftreten von Somnolenz zu einem Therapieabbruch führte.Nowadays, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants due to their superior clinical efficacy, effectiveness, tolerability, and safety as compared to tricyclic antidepressants or monoamino oxidase inhibitors. However, despite these advantages SSRIs are still associated with a number of adverse drug reactions, especially in the early stages of treatment, which may lead to premature discontinuation of therapy in some cases. The aim of the present study was to assess the most common adverse drug reactions of SSRIs as well as their impact on dropout rate in a large study population.	Data for 50,824 patients treated for major depressive disorder with SSRIs for the first time was accessed via the Disease Analyzer database (IMS Health, Germany), providing information on SSRI adverse drug reactions and their influence on premature treatment discontinuation calculated by regression analysis. The presence of certain co-morbidities was also registered.	The mean age was 54.5 ± 19 years, two-thirds of the study population being female. The adverse effects mentioned most frequently were: "discomfort" of the digestive system (10%), sleep disorders (8.6%), and heart rhythm disorders (4%); however, these were of tolerable severity as they did not significantly influence the dropout rate. Contrary to that, somnolence and younger age (≤50 years) in particular increased the chance of premature treatment discontinuation, while patients suffering from cardiovascular risk factors or osteoporosis tended to adhere to the therapy.	Overall, there is high tolerability for early SSRI treatment, whereas the occurrence of somnolence leads to discontinuation.	
25331353	Patients frequently report sleep disruptions or insomnia during their hospital stay, particularly after a traumatic brain injury (TBI). The consequences of these sleep disturbances on everyday activities are not well documented and are therefore not considered in the evaluation of independence in activities of daily living (ADLs). The goal of this narrative review is to explore the consequences of poor sleep quality on cognition and ADLs in the acute and subacute stages of a moderate and severe TBI, when patients are in acute care or inpatient rehabilitation.We will present an overview of normal sleep and its role in cognitive functioning, and then present the findings of studies that have investigated sleep characteristics in hospital settings and the consequences of sleep disturbances on ADLs.	During hospitalisation, TBI patients present severe sleep disturbances such as insomnia and sleep fragmentation, which are probably influenced by both the medical condition and the hospital or rehabilitation environment. Sleep disruption is associated with several cognitive deficits, including attention, memory and executive function impairments. Poor quality and/or insufficient quantity of sleep in acute TBI probably affect general functioning and ADLs calling for these cognitive functions.	The cognitive impairments present following TBI are probably exacerbated by poor sleep quality and sleep deprivation during hospitalisation, which in turn impact ADLs among this population. Health-care personnel should further consider sleep disturbances among people with TBI and a sleep protocol should be established.	
25330404	Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients.	The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated.	University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination.	Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD.	
25329625	We examined 2 sleep-wake parameters as moderators of the associations between exposure to family stressors and adolescent cognitive functioning. Participants were 252 school-recruited adolescents (M = 15.79 years; 66% European American, 34% African American). Youths reported on 3 dimensions of family stress: marital conflict, harsh parenting, and parental psychological control. Cognitive functioning was indexed through performance on the Woodcock-Johnson III Tests of Cognitive Abilities. Sleep minutes and efficiency were measured objectively using actigraphy. Toward identifying unique effects, path models controlled for 2 family stress variables while estimating the third. Analyses revealed that sleep efficiency moderated the associations between negative parenting (harsh parenting and parental psychological control) and adolescents' cognitive functioning. The highest level of cognitive performance was predicted for adolescents with higher levels of sleep efficiency in conjunction with lower levels of either harsh parenting or psychological control. The effects of sleep were more pronounced at lower levels of negative parenting, in which adolescents with higher sleep efficiency performed better than their counterparts with poorer sleep. At higher levels of either harsh parenting or psychological control, similar levels of cognitive performance were observed regardless of sleep. Results are discussed in comparison with other recent studies on interrelations among family stress, sleep, and cognitive performance in childhood and adolescence.
25329537	The concept of health literacy has been widened to include higher order aspects such as patient decision-making skills while its measurement continued to rely narrowly on reading and numeracy skills, known as functional health literacy. We developed a Judgment Skills measure, designed to assess patients' ability to make appropriate decisions with regard to their condition. The measure offers scenarios with answer options ranked for biomedical adequacy. This study aims to examine the psychometric properties and the functional validity of the Judgment Skills measure. A self-administered survey among 87 primary insomnia patients in the Italian-speaking part of Switzerland was conducted. The extensive path model included variables such as functional health literacy, coping with the medical condition, experience of the scenario, sleep quality, duration suffering, education, and age. Correlation analyses were conducted to link the variables. The Judgment Skills measure showed the expected significant correlations. In general, higher Judgment Skills were related to coping strategies leading to better health outcomes. Functional health literacy correlated highly with education, while Judgment Skills did not, which confirmed the conceptual difference of these skills. The findings propose a model for conducting research that does embrace the broader conceptualization of health literacy. 
25329499	Sedentary behavior (including sitting) is negatively associated with physical health, independent from physical activity (PA). Knowledge on the associations with mental health is less elaborated. Therefore this study aims to investigate the relationship between sitting and 5 indices of mental health in adults (psychological distress, depression, anxiety, somatization, and sleeping problems), and between sitting interactions (sitting×gender, sitting×age, sitting×education, and sitting×PA) and these mental health indices.A cohort of Belgian adults (25-64 years; n = 4344) provided self-reported data on sitting and PA and on 5 mental health indices. Cross-sectional associations were examined using multiple linear regression analyses.	Analyses adjusted for gender, age, education, and PA showed significant positive associations between sitting and the 5 mental health indices (P < .05). All associations were true for both men and women, and for low and high educated individuals, while some were only found in older individuals (somatization, P < .001) and those being insufficiently active (psychological distress, P = .007; depression, P = .002; and anxiety, P = .014).	More sitting seems to be associated with poorer mental health, independently of gender, age, education, and PA. Moderation analyses showed that these associations may differ according to age and PA levels.	
25328844	In addition to their cognitive and motor deficits, R6/2 mice show a progressive disintegration in circadian rhythms that mirrors the problems associated with sleep-wake disturbances experienced by patients with Huntington's disease (HD). It has been shown previously that motor and cognitive performance, as well as survival, can be improved in transgenic mouse models of HD through the provision of environmental enrichment.We compared the effect of two different overnight entrainment paradigms presented either separately or in combination. The first was environmental enrichment, the second was temporal food-entrainment. Environmental enrichment was provided in the dark period (the natural active period for mice) in the form of access to a Perspex playground containing running wheels, tunnels, climbing frame, ropes and chew blocks. Food entrainment was imposed by allowing access to food only during the dark period. We assessed a number of different aspects of function in the mice, measuring general health (by SHIRPA testing, body temperature and body weight measurements), cognitive performance in the touchscreen and locomotor behavior in the open field.	There were no significant differences in cognitive performance between groups on different schedules. Environmental enrichment delayed the onset of general health deterioration, while food entrainment slowed the loss of body weight, aided the maintenance of body temperature and improved locomotor behavior. Effects were limited however, and in combination had deleterious effects on survival.	Our results support previous studies showing that environmental enrichment can be beneficial and might be used to enhance the quality of life of HD patients. However, improvements are selective and 'enrichment' per se is likely to only be useful as an adjunct to a more direct therapy.	
25328021	This study aimed to describe the somatic, social, psychological, and work-related factors that characterize participants with a duration of sick leave over and under one year.During 2012, 181 patients on long-term sick leave were consecutively recruited and asked to answer an extensive survey. Several outcomes were reported, addressing work-related factors and somatic, psychological, and social symptoms. In cross-sectional analyses, sick leave duration was dichotomized as > or < one year, based on Norwegian legislation. Linear and logistic regressions were used to estimate population probabilities and means.	The estimated prevalence of pain, fatigue, anxiety, and depression was overall high. There was a tendency towards a higher prevalence of fatigue, anxiety, and depression in those with sick leave duration less than one year, with the exception of sleep problems, which was more frequent in the population with longer duration. Relationship with friends, family, co-workers, and the last workplace were worse in the population with longer duration.	Cross-sectional analyses indicated that social and work-related problems are more adverse in patients with longer duration of sick leave, while psychological and somatic symptoms appear less adverse. This is one of the first studies quantitatively demonstrating these differences through comprehensive, simultaneously measured self-report questionnaires.	
25325607	Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease.We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances.	Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration.	Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology.	
25325604	To characterize the nature and impact of sleep disturbances on quality of life (QOL) in women with interstitial cystitis/bladder pain syndrome (IC/BPS).Participants were 3,397 women from a telephone probability survey who met IC/BPS symptom criteria. Sleep quality, duration, and IC/BPS nocturnal symptoms (i.e., trouble sleeping due to bladder pain, urgency, or needing to use the bathroom), general QOL (mental and physical health and sexual functioning), and IC/BPS QOL impairment were assessed via self-report during telephone interview.	Over half of the sample reported poor sleep quality, sleep duration ≤ 6 hours, or trouble sleeping due to IC/BPS symptoms. After covariate adjustment, short sleep duration was significantly associated with greater IC/BPS QOL impairment (β = -0.04; p < 0.001) and poorer self-reported physical health (β = 1.86; p < 0.001). Poor sleep quality was significantly associated with greater IC/BPS QOL impairment (β = 0.06; p < 0.001), poorer self-reported physical health (β = -2.86; p < 0.001), and greater sexual dysfunction (β = -0.04; p < 0.05). IC/BPS nocturnal symptoms were significantly associated with greater IC/BPS impairment (β = 0.14; p < 0.001), poorer physical health (β = -2.76; p < 0.001) and mental health (β = 0.52; p < 0.01), and greater sexual dysfunction (β = -0.10; p < 0.001), after covariate adjustment. After further adjustment for IC/BPS nocturnal symptoms, we found that poor sleep quality and short sleep duration were independent correlates of poor self-reported physical health.	Poor sleep quality and short sleep duration, as well as disorder-specific sleep disturbances, are highly prevalent in women with IC/BPS and are associated with poorer disease-specific and general QOL.	
25325592	In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS).Reference databases were searched for randomized controlled trials using IRT or prazosin for nightmares, sleep disturbance, and/or PTSS. Effect sizes were calculated by subtracting the mean posttest score in the control group from the mean posttest score in the treatment group, and dividing the result by the pooled standard deviation of both groups. Mixed effects models were performed to evaluate effects of treatment characteristics, as well as sample characteristics (veteran vs. civilian) on treatment efficacy.	Four studies used prazosin, 10 used IRT alone or in combination with another psychological treatment, and 1 included a group receiving prazosin and another group receiving IRT. Overall effect sizes of both treatments were of moderate magnitude for nightmare frequency, sleep quality, and PTSS (p < 0.01). Effect size was not significantly different with type of treatment (psychological vs. pharmacological) on nightmare frequency (p = 0.79), sleep quality (p = 0.65), or PTSS, (p = 0.52). IRT combined with CBT for insomnia showed more improvement in sleep quality compared to prazosin (p = 0.03), IRT alone (p = 0.03), or IRT combined with another psychological intervention, (p < 0.01).	Although IRT interventions and prazosin yield comparable acute effects for the treatment of nightmares, adding CBT for insomnia to IRT seems to enhance treatment outcomes pertaining to sleep quality and PTSS. More randomized clinical trials with long-term follow-up are warranted.	A commentary on this article appears in this issue on page 9.	



25325580	The impact of hospitalization on sleep in late-life is underexplored. The current study examined patterns of sleep quality before, during, and following hospitalization, investigated predictors of sleep quality patterns, and examined predictors of classification discordance between two suggested clinical cutoffs used to demarcate poor/good sleep.This study included older adults (n = 163; mean age 79.7 ± 6.9 years, 31% female) undergoing inpatient post-acute rehabilitation. Upon admission to inpatient post-acute rehabilitation, patients completed the Pittsburgh Sleep Quality Index (PSQI) retrospectively regarding their sleep prior to hospitalization. They subsequently completed the PSQI at discharge, and 3 months, 6 months, 9 months, and 1 year post discharge. Patient demographic and clinical characteristics (pain, depression, cognition, comorbidity) were collected upon admission.	Using latent class analysis methods, older adults could be classified into (1) Consistently Good Sleepers and (2) Chronically Poor Sleepers based on patterns of self-reported sleep quality pre-illness, during, and up to 1 year following inpatient rehabilitation. This pattern was maintained regardless of the clinical cutoff employed (> 5 or > 8). Logistic regression analyses indicated that higher pain and depressive symptoms were consistently associated with an increased likelihood of being classified as a chronic poor sleeper. While there was substantial classification discordance based on clinical cutoff employed, no significant predictors of this discordance emerged.	Clinicians should exercise caution in assessing sleep quality in inpatient settings. Alterations in the cutoffs employed may result in discordant clinical classifications of older adults. Pain and depression warrant detailed considerations when working with older adults on inpatient units when poor sleep is a concern.	
25325503	Because work demands and lack of social support seem to be prospectively linked to sleep problems, and sleep problems are linked to depression, sleep problems may play a role in the relationship between these work characteristics and depressive symptoms. In order to shed more light on this relationship, the current study investigated whether disturbed sleep is a mediator in the longitudinal relationships between work demands, social support, and depression.Longitudinal cohort study with repeated survey measures on four occasions.	Swedish workforce.	2,017 working participants from the Swedish Longitudinal Occupational Survey of Health in 2006, 2008, 2010, and 2012.	Work demands (four items) and social support (six items) were assessed with the Demand Control Questionnaire, disturbed sleep (four items) with the Karolinska Sleep Questionnaire, and depressive symptoms with a brief subscale (six items) from the Symptom Checklist. Autoregressive longitudinal mediation models using structural equation modeling were tested. The work characteristics, and disturbed sleep, were found to be separately associated with depressive symptoms in subsequent waves. However, only demands were found to be longitudinally related to subsequent disturbed sleep. The longitudinal autoregressive models supported a weak mediating role of disturbed sleep in the relationship between demands and depressive symptoms (standardized beta 0.008, P < 0.001), but not between support and depressive symptoms.	These results indicate that higher demands at work might cause an increase in depressive symptoms, in part, by increasing disturbed sleep, although the mediated effect was relatively small compared to the total effect.	
25325495	Human error is defined as an unintended error that is attributable to humans rather than machines, and that is important to avoid to prevent accidents. We aimed to investigate the association between sleep quality and human errors among train drivers.Cross-sectional.	Population-based.	A sample of 5,480 subjects who were actively working as train drivers were recruited in South Korea. The participants were 4,634 drivers who completed all questionnaires (response rate 84.6%).	None.	The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Impact of Event Scale-Revised (IES-R), the State-Trait Anxiety Inventory (STAI), and the Korean Occupational Stress Scale (KOSS).	Of 4,634 train drivers, 349 (7.5%) showed more than one human error per 5 y. Human errors were associated with poor sleep quality, higher PSQI total scores, short sleep duration at night, and longer sleep latency. Among train drivers with poor sleep quality, those who experienced severe posttraumatic stress showed a significantly higher number of human errors than those without. Multiple logistic regression analysis showed that human errors were significantly associated with poor sleep quality and posttraumatic stress, whereas there were no significant associations with depression, trait and state anxiety, and work stress after adjusting for age, sex, education years, marital status, and career duration.	Poor sleep quality was found to be associated with more human errors in train drivers, especially in those who experienced severe posttraumatic stress.	
25325476	The carotid bodies are thought to play an important role in sleep-dependent autonomic changes. Patients who underwent resection of bilateral carotid body tumors have chronically attenuated baroreflex sensitivity. These subjects provide a unique opportunity to investigate the role of the baroreflex during sleep.One-night ambulatory polysomnography (PSG) recording.	Participants' homes.	Nine patients with bilateral carotid body tumor resection (bCBR) (four women, mean age 50.4 ± 7.2 years) and nine controls matched for age, gender, and body mass index.	N/A.	Sleep parameters were obtained from PSG. Heart rate (HR) and its variability were calculated using 30-s epochs.	In bCBR patients, HR was slightly but not significantly increased during wake and all sleep stages. The effect of sleep on HR was similar for patients and controls. Low frequency (LF) power of the heart rate variability spectrum was significantly lower in bCBR patients in active wakefulness, sleep stage 1 and REM sleep. No differences were found between patients and controls for high frequency (HF) power and the LF/HF ratio.	Bilateral carotid body tumor resection (bCBR) is associated with decreased low frequency power during sleep, suggesting impaired baroreflex function. Despite this, sleep-related heart rate changes were similar between bCBR patients and controls. These findings suggest that the effects of sleep on heart rate are predominantly generated through central, non-baroreflex mediated pathways.	
25325444	The goal of this study was to describe sleep patterns and accomplishment of daily life habits in children with Down syndrome (DS) and to investigate the relationship between subjective indicators of sleep disturbance with functional outcomes in daily life.Cross-sectional study with an Internet sample.	Online survey filled out at home.	110 parents of children with DS and 29 parents of children with typical development (TD), age 5 to 18 years.	N/A.	Children's Sleep Habits Questionnaire was employed to collect information about sleep disturbances in 8 domains (subscales) and a total score. The Life Habits (Life-H) questionnaire sampled information about daily life habits in 11 domains. Multivariable regression modeling was used to assess the associations between sleep disturbances and the accomplishment of daily life habits. Sleep disordered breathing (SDB) was a significant explanatory factor in 10 of 11 daily life habits and the total Life-H score. Sleep anxiety and parasomnias significantly influenced the accomplishment of life habits in children with DS as compared to children with typical development. When evaluated in multivariable models in conjunction with the other 7 domains of sleep disturbances, SDB was the most dominant explanatory factor for accomplishment of life habits.	Sleep disturbances are negatively related to accomplishment of daily life functions. Prevention and treatment of sleep problems, particularly sleep disordered breathing, in children with DS may lead to enhanced accomplishment of daily life habits and activities.	
25323624	Evidence is emerging that positive and negative modulation of the metabotropic glutamate (mGluR5) receptors has the potential for treating cognitive deficits and neuroprotection associated with psychiatric and neurodegenerative diseases, respectively. Sleep and synchronisation of disparate neuronal networks are critically involved in neuronal plasticity, and disturbance in vigilance states and cortical network connectivity contribute significantly to cognitive deficits described in schizophrenia and Alzheimer's disease. Here, we examined the circadian changes of mGluR5 density and the functional response to modulation of mGluR5 signaling.The current study carried out in Sprague-Dawley rats quantified the density of mGluR5 across the light-dark cycle with autoradiography. The central activity of mGluR5 negative allosteric modulators (2-methyl-6-(phenylethynyl)pyridine (MPEP) and [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and positive allosteric modulators (S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone (ADX47273) and (7S)-3-tert-butyl-7-[3-(4-fluoro-phenyl)-1,2,4-oxadiazol-5-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine (LSN2814617) was examined on sleep-wake architecture. The functional effect of mGluR5 modulation on cortical networks communication was described in freely moving animals.	The density of mGluR5 in the striatal, cortical, hippocampal and thalamic structures was unchanged across the light-dark cycle. Allosteric blockade of mGluR5 consistently consolidated deep sleep, enhanced sleep efficiency and elicited prominent functional coherent network activity in slow theta and gamma oscillations. However, allosteric activation of mGluR5 increased waking, decreased deep sleep and reduced functional network connectivity following the activation of slow alpha oscillatory activity.	This functional study differentiates the pharmacology of allosteric blockade of mGluR5 from that of allosteric activation and suggests that mGluR5 blockade enhances sleep and facilitates oscillatory network connectivity, both processes being known to have relevance in cognition processes.	
25322735	The aim of this study was to investigate sleep quality in patients with chronic low back pain (CLBP) and its relationship with pain, functional status, and health-related quality of life (HRQOL).Two hundred patients with CLBP aged 20-78 years (mean: 50.2 years) and 200 sex- and age-matched pain-free healthy controls (HCs) aged 21-73 years (mean: 49.7 years) were included in this study. After lumbar region examination, in patients, pain was evaluated with the Short Form-McGill Pain Questionnaire (SF-MPQ), functional capacity with the Functional Rating Index (FRI), and health-related quality of life with the Short Form-36 (SF-36). The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality of both groups.The sleep quality was compared between the patients and HCs. In patients with CLBP, its relations with pain, functional status and HRQOL were also investigated.	The patients had significantly higher total scores (8.1 ± 4.3, 4.6 ± 3.4, P< 0.001, respectively) and subscale scores (P< 0.001) for PSQI compared to HCs. The groups were only similar in use of sleeping medication (P> 0.05) Among the patients, sleep quality was worse in women, in the patients with complaints more than 11 years, in the patients with low back and two leg pain (P< 0.05). Mean scores of the FRI, SF-MPQ, and visual analog scale in the patients were 8.5 ± 3.0, 16.7 ± 8.0, 6.9 ± 1.2, respectively. The PSQI total scores of patients were positively related with both SF-MPQ and FRI scores (P< 0.001). Also, there were negative relationships between the physical component summary score of the SF-36 and all subscale scores of the PSQI, without sleep duration of PSQI (P< 0.001).	The sleep quality of patients with CLBP was worse compared to HCs, and there were positive relations between the sleep quality with pain and functional status. Also, the poor sleep quality had negative effect on the physical component of quality of life.	
25322206	Nocturnal sleep disruption develops in Alzheimer disease (AD) owing to the derangement of the sleep-wake cycle regulation pathways. Orexin contributes to the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness.To study cerebrospinal fluid levels of orexin in patients with AD, to evaluate the relationship of orexin cerebrospinal fluid levels with the degree of dementia and the cerebrospinal fluid AD biomarkers (tau proteins and β-amyloid 1-42), and to analyze potentially related sleep architecture changes measured by polysomnography.	We conducted a case-control study from August 1, 2012, through May 31, 2013. We included 48 drug-naive AD patients referred to the Neurological Clinic of the University Hospital of Rome Tor Vergata. Based on the Mini-Mental State Examination score, 21 patients were included in mild AD group (score, ≥21), whereas 27 were included in the moderate to severe AD group (score, <21). The control group consisted of 29 nondemented participants of similar age and sex.	Laboratory assessment of cerebrospinal fluid levels of orexin, tau proteins, and β-amyloid 1-42 and polysomnographic assessment of sleep variables.	Levels of orexin, tau proteins, and β-amyloid 1-42; macrostructural variables of nocturnal sleep (total sleep time, sleep efficiency, sleep onset and rapid eye movement [REM] sleep latencies, non-REM and REM sleep stages, and wakefulness after sleep onset); and Mini-Mental State Examination scores.	Patients with moderate to severe AD presented with higher mean (SD) orexin levels compared with controls (154.36 [28.16] vs 131.03 [26.55]; P < .01) and with more impaired nocturnal sleep with respect to controls and patients with mild AD. On the other hand, in the global AD group, orexin levels were positively correlated with total tau protein levels (r = 0.32; P = .03) and strictly related to sleep impairment. Finally, cognitive impairment, as measured by the Mini-Mental State Examination, was correlated with sleep structure deterioration.	Our results demonstrate that, in AD, increased cerebrospinal fluid orexin levels are related to a parallel sleep deterioration, which appears to be associated with cognitive decline. Therefore, the orexinergic system seems to be dysregulated in AD, and its output and function appear to be overexpressed along the progression of the neurodegenerative process. This overexpression may result from an imbalance of the neurotransmitter networks regulating the wake-sleep cycle toward the orexinergic system promoting wakefulness.	
25320100	To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels.Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay.	Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients.	DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.	
25319438	Sleep deprivation may adversely affect host defenses against infection while infection may impact sleep. We studied sleep quality in hospitalized patients with infection-related diagnoses.This was an observational study in a 900-bed tertiary care community teaching hospital involving consecutive patients seen by an infectious disease consultant from June 26, 2008 to December 31, 2011. During routine part of their care, patients were enquired about their sleep quality, categorized into either "sound" or "unsound" sleep and the reason(s) for experiencing unsound sleep.	Of 1,238 unique patients (mean age, 59 years), 592 (47.8%) reported unsound sleep. Patients of 50 years or younger were more likely to report unsound sleep compared with those in the age groups of 50 to 79 years (57.1% versus 45.7%) and 80 years or older (57.1% versus 36.5%) (OR: 1.58 [95% CI: 1.23-2.0] and OR: 2.32 [95% CI: 1.59-3.38], respectively). Skin and soft tissue infections, central nervous system infections, osteomyelitis/diskitis and the head and neck infections were associated with ≥ 50% rates of unsound sleep. Staff disruptions, pain and anxiety were the most commonly cited reasons for unsound sleep (28.9%, 26.4% and 9.6%, respectively). Patients receiving sedating and/or hypnotic medications were no more likely to report sound sleep, compared with those not receiving such medications (50.7% versus 58.7%, respectively, OR: 0.71 [95% CI: 0.5-1.00]).	Self-reported unsound sleep is common among hospitalized patients with an infection-related diagnosis, is associated with less advanced age and is often attributed to staff disruptions, pain and/or anxiety. Interventions at improving sleep quality in this patient population seem warranted.	
25319339	Psychological positive health and health complaints have long been ignored scientifically. Sleep plays a critical role in children and adolescents development. We aimed at studying the association of sleep duration and quality with psychological positive health and health complaints in children and adolescents from southern Spain.A randomly selected two-phase sample of 380 healthy Caucasian children (6-11.9 years) and 304 adolescents (12-17.9 years) participated in the study. Sleep duration (total sleep time), perceived sleep quality (morning tiredness and sleep latency), psychological positive health and health complaints were assessed using the Health Behaviour in School-aged Children questionnaire.	The mean (standard deviation [SD]) reported sleep time for children and adolescents was 9.6 (0.6) and 8.8 (0.6) h/day, respectively. Sleep time ≥10 h was significantly associated with an increased likelihood of reporting no health complaints (OR 2.3; P = 0.005) in children, whereas sleep time ≥9 h was significantly associated with an increased likelihood of overall psychological positive health and no health complaints indicators (OR ~ 2; all P < 0.05) in adolescents. Reporting better sleep quality was associated with an increased likelihood of reporting excellent psychological positive health (ORs between 1.5 and 2.6; all P < 0.05). Furthermore, children and adolescents with no difficulty falling asleep were more likely to report no health complaints (OR ~ 3.5; all P < 0.001).	Insufficient sleep duration and poor perceived quality of sleep might directly impact quality of life in children, decreasing general levels of psychological positive health and increasing the frequency of having health complaints.	
25319020	Freezing of gait (FOG) is a disabling motor symptom experienced by a large proportion of patients with Parkinson's disease (PD). While it is known that FOG contributes to lower health-related quality of life (HRQoL), previous studies have not accounted for other important factors when measuring the specific impact of this symptom. The aim of this study was to examine FOG and HRQoL while controlling for other factors that are known to impact patient well-being, including cognition, motor severity, sleep disturbance and mood. Two hundred and three patients with idiopathic PD (86 with FOG) were included in the study. All patients were between Hoehn and Yahr stages I-III. A forced entry multiple regression model evaluating the relative contribution of all symptoms was conducted, controlling for time since diagnosis and current dopaminergic treatment. Entering all significantly correlated variables into the regression model accounted for the majority of variance exploring HRQoL. Self-reported sleep-wake disturbances, depressive and anxious symptoms and FOG were individually significant predictors. FOG accounted for the highest amount of unique variance. While sleep-wake disturbance and mood have a significant negative impact on HRQoL in PD, the emergence of FOG represents the most substantial predictor among patients in the earlier clinical stages of disease. This finding presumably reflects the disabling loss of independence and fear of injury associated with FOG and underlines the importance of efforts to reduce this common symptom. 

25317096	To characterize the clinical, polysomnographic and treatment responses of patients with disruptive nocturnal behaviors (DNB) and nightmares following traumatic experiences.A case series of four young male, active duty U.S. Army Soldiers who presented with DNB and trauma related nightmares. Patients underwent a clinical evaluation in a sleep medicine clinic, attended overnight polysomnogram (PSG) and received treatment. We report pertinent clinical and PSG findings from our patients and review prior literature on sleep disturbances in trauma survivors.	DNB ranged from vocalizations, somnambulism to combative behaviors that injured bed partners. Nightmares were replays of the patient's traumatic experiences. All patients had REM without atonia during polysomnography; one patient had DNB and a nightmare captured during REM sleep. Prazosin improved DNB and nightmares in all patients.	We propose Trauma associated Sleep Disorder (TSD) as a unique sleep disorder encompassing the clinical features, PSG findings, and treatment responses of patients with DNB, nightmares, and REM without atonia after trauma.	
25317095	Disturbed sleep during pregnancy is associated with adverse obstetric outcomes and less mental well-being. In pregnant women with a mental disorder, who frequently suffer from sleep problems, it is unknown whether predominantly objective or subjective sleep quality is more affected. To clarify this, we compared objective and subjective parameters of sleep quality between patients and healthy controls during pregnancy.This observational study was embedded in an ongoing study among pregnant women with a mental disorder at the department of Psychiatry of Erasmus University Medical Center Rotterdam, the Netherlands. We compared 21 pregnant women with a confirmed mental disorder with 33 healthy controls (gestational age, 23-29 weeks). To measure objective parameters of sleep quality, all participants continuously wore a wrist actigraph for 7 days and nights. Subjective sleep quality was retrospectively assessed using the Pittsburgh Sleep Quality Index (PSQI) and on a daily basis with the Subjective Sleep Quality-scale (SSQ). Differences in parameters of sleep between patients and controls were tested using a multivariate linear regression analysis adjusted for parity, gestational age, educational level, and employment status.	Objective parameters of sleep quality and subjective sleep quality as assessed by the PSQI did not differ significantly between patients and controls. Daily sleep reports showed that, relative to controls, patients had a significantly worse average SSQ-score (5.2 vs. 7.6, adjusted β = 0.12, 95%CI = 0.03-0.53, p < 0.01).	Our exploratory study suggests that perceived sleep quality reported on a daily basis by pregnant women with a mental disorder is worse than the sleep quality as measured by wrist actigraphy.	
25317093	To longitudinally examine sleep patterns, habits, and parent-reported sleep problems during the first year of life.Seven hundred four parent/child pairs participated in a longitudinal cohort study. Structured interview recording general demographic data, feeding habits, intercurrent diseases, family history, sleep habits, and parental evaluation of the infant's sleep carried out at 1, 3, 6, 9, and 12 months.	Nocturnal, daytime, and total sleep duration showed a high inter-individual variability in the first year of life associated with changes in the first 6 months and stability from 6 to 12 months. Bedtime was at around 22:00 and remained stable at 6, 9, and 12 months of age. Approximately 20% of the infants had more than 2 awakenings and slept more often in the parent bed. Nearly 10% of the infants were considered as having a problematic sleep by parents and this significantly correlated with nocturnal awakenings and difficulties falling asleep.	Sleep patterns change during the first year of life but most sleep variables (i.e., sleep latency and duration) show little variation from 6 to 12 months. Our data provide a context for clinicians to discuss sleep issues with parents and suggest that prevention efforts should focus to the first 3-6 months, since sleep patterns show stability from that time point to 12 months.	
25316334	Lesions of the globus pallidus externa (GPe) produce a profound sleep loss (∼45%) in rats, suggesting that GPe neurons promote sleep. As GPe neuronal activity is enhanced by dopamine (DA) from the substantia nigra pars compacta (SNc), we hypothesized that SNc DA via the GPe promotes sleep. To test this hypothesis, we selectively destroyed the DA afferents to the caudoputamen (CPu) using 6-hydroxydopamine and examined changes in sleep-wake profiles in rats. Rats with 80-90% loss of SNc neurons displayed a significant 33.7% increase in wakefulness (or sleep reduction). This increase significantly correlated with the extent of SNc DA neuron loss. Furthermore, these animals exhibited sleep-wake fragmentation and reduced diurnal variability of sleep. We then optogenetic-stimulated SNc DA terminals in the CPu and found that 20-Hz stimulation from 9 to 10 PM increased total sleep by 69% with high electroencephalograph (EEG) delta power. We finally directly optogenetic-stimulated GPe neurons and found that 20-Hz stimulation of the GPe from 9 to 10 PM increased total sleep by 66% and significantly increased EEG delta power. These findings elucidate a novel circuit for DA control of sleep and the mechanisms of abnormal sleep in BG disorders such as Parkinson's disease and Huntington's disease. 
25316292	Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load (AL), which is a measure of systemic wear and tear of multiple body systems, as well as with individual risk markers within the cardiac, metabolic, anthropometric, and immune system.A cross-sectional population-based study of 5226 men and women from the Danish Copenhagen Aging and Midlife Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions.	Long sleep (mean difference 0.23; 95% confidence interval, 0.13, 0.32) and disturbed sleep (0.14; 0.06, 0.22) were associated with higher AL as well as with high-risk levels of risk markers from the anthropometric, metabolic, and immune system. Sub-analyses suggested that the association between disturbed sleep and AL might be explained by underlying disorders. Whereas there was no association between short sleep and AL, the combination of short and disturbed sleep was associated with higher AL (0.19; 0.08, 0.30) and high-risk levels of immune system markers.	Our study suggests small but significant differences in the distribution of allostatic load, a pre-clinical indicator of disease risk and premature death, for people with impaired relative to normal sleep. Impaired sleep may be a risk factor for developing disease and be a risk marker for underlying illness or sleep disorders.	
25314798	The relationship between sleep disturbances and sexual dysfunctions still remains unclear. The links which indicate the importance of central nervous system and sleep mechanisms in regulations of the endocrine system seem to have bilateral character; the nature of such associations is not fully understood. The aim of the paper is to describe the influence of androgens on the relations between sexual functioning and sleep functions in patients of both sexes. The physiological role of the androgens is described with the emphasis put on the specific action of these hormones in sleep regulation, as well as the mutual relations between the regulatory role of sleep on the sexual apparatus. The newest data suggest that the androgenic hormonal profile is linked to the sleep rhythm, but not to the chronobiological diurnal rhythm in male patients. This may constitute the purpose for further research on the role of androgens in the connections between sexual and sleep disturbances. Up to date there is little known about androgens' role in sleep regulation in women. The influence of sexual activity disturbances as behavioral factors influencing the severity and the persistence of insomnia as well as their position among other factors important for the triggering of insomnia requires further scientific exploration.
25314578	Elite athletes frequently undergo periods of intensified training (IT) within their normal training program. These periods can lead athletes into functional overreaching, characterized by high perceived fatigue, impaired sleep, and performance. Because whole-body cryostimulation (WBC) has been proven to be an effective recovery method in the short term (<76 h), we investigated whether daily WBC sessions during IT could prevent exercise and sleep-related signs of overreaching.After a normal training week (BASE), 10 elite synchronized swimmers performed two 2-wk IT periods in a randomized crossover fashion using WBC daily (ITWBC) or not (ITCON), separated by 9 d of light training. Swim time trials (400 m) were performed at BASE and after each IT to quantify blood lactate ([La]B), HR (HR400), salivary alpha amylase ([α-amylase]s400), and cortisol ([cortisol]s400) responses. Swimmers wore a wrist actigraph nightly to monitor sleep patterns.	Swim speed (400 m), [La]B400, and [α-amylase]s400 decreased from BASE to ITCON, although no significant changes were found after ITWBC. Decreased swim speed was correlated to decreased HR400 and [cortisol]s400. During ITCON, significant decreases in actual sleep duration (-21 ± 7 min) and sleep efficiency (-1.9% ± 0.8%) were observed, with increased sleep latency (+11 ± 5 min) and fatigue compared with BASE, although these variables did not change during ITWBC. Using a qualitative statistical analysis, we observed that daily WBC use resulted in a 98%, 59%, 66%, and 78% chance of preserving these respective variables compared with ITCON.	WBC use during IT helped mitigate the signs of functional overreaching observed during ITCON, such as reduced sleep quantity, increased fatigue, and impaired exercise capacity. These results support the daily use of WBC by athletes seeking to avoid functional overreaching during key periods of competition preparation.	
25313639	A sample of 844 adults, aged 18-94 years old, was queried about media habits and sleep behavior in face-to-face interviews with standardized questionnaires. A substantial proportion of this sample reported using books (39.8%), television (31.2%), music (26.0%), Internet (23.2%), and videogames (10.3%) as a sleep aid. The use of media as sleep aids was associated with increased fatigue and higher scores on the Pittsburgh Sleep Quality Index (PSQI), indicating poorer sleep quality. There was no relationship with sleep duration. Finally, results suggest that media use coincides with later bedtimes, but also later rise times, a process called time shifting. 
25312049	The present study examined the association between objective measures of sleep quality and performance-based measures of physical function in community-dwelling oldest old Japanese.This cross-sectional study included 207 community-dwelling adults aged 80 years or older (92 men, 115 women; age 83.5 ± 2.6 years [range 80-95 years]). Participants wore an accelerometer (ActiGraph GT3X+) on their non-dominant wrist for 24 h per day over seven consecutive nights. Sleep parameters included total sleep time, sleep efficiency and wake after sleep onset during the night for a week. Performance-based physical function measures were handgrip strength, knee extension strength, and usual and maximum walking speeds. Multivariable linear regression was carried out to determine the associations between weekly sleep parameter averages and physical function measures.	Approximately 24% of participants had a total sleep time of less than 6 h a night, and 13% had greater than 8 h a night. Overall, average daily physical activity was 1771.8 ± 520.6 (counts/min/day). In multiple linear regression, sleep efficiency and wake after sleep onset were significantly associated with maximum walking speed (β = 0.277; 95% confidence interval [CI] 0.103 to 0.351 and β = -0.214; 95% CI -0.339 to -0.082, respectively) and usual walking speed (β = 0.200, 95% CI 0.035 to 0.305 and β = -0.174; 95% CI -0.341 to -0.064, respectively), after adjusting for potential confounding factors including daily physical activity. Both sleep qualities were also independently associated with knee extension strength. However, wake after sleep onset was not associated with handgrip strength.	Objectively measured sleep quality was associated with physical function in the oldest old. Further research is required to identify the temporality of associations between sleep and physical function.	
25312027	Medications promoting wakefulness are currently used in psychopharmacology in different contexts and with different objectives. In particular, they may be used for the treatment of syndromes that primarily show significant impairment in alertness/wakefulness (e.g., excessive sleepiness and other sleep disorders) as well as for the symptomatic treatment of different neuropsychiatric disorders that, in turn, are not exclusively characterized by sleep-wake disturbances (like mood disorders, for instance). In addition, several psychotropic compounds, including some antipsychotics, mood stabilizers, antidepressants, and anxiolytics have well-established sedating side effects that may go beyond the therapeutic target and require the symptomatic use of wake-promoting agents. Even though such a clinical scenario reflects millions of individuals affected (alterations of wakefulness have a prevalence rate of 20-43% in the general population), relatively few pharmacotherapies are available, mainly including compounds with psychostimulating effects, such as methylphenidate, modafinil, and armodafinil and some amphetaminic agents. In light of their side effects and potential for abuse, such compounds have received FDA approval only for a limited number of psychiatric disorders. Nonetheless, their clinical application has recently become more widespread, including attention deficit hyperactivity disorder, narcolepsy, treatment-resistant depression, bipolar disorder, shift work sleep disorder, schizophrenia, and addictions. Wake-promoting agents have different mechanisms of action, peculiar clinical strengths and specific limitations, with novel drugs in the field under extensive investigation. The present review is aimed to provide an updated overview of the aforementioned compounds as well as investigational drugs in the field, in terms of mechanism of action, indications and use in clinical practice.
25311836	Deployed military personnel are vulnerable to chronic sleep disturbance, which is highly comorbid with post-traumatic stress disorder (PTSD) and depression, as well as declines in health-related quality of life (HRQOL). Inflammation is associated with HRQOL declines and sleep-related comorbidities; however, the impact of sleep changes on comorbid symptoms and inflammation in this population is unknown.In this observational study, we examined the relationship between reported sleep changes and concentrations of inflammatory biomarkers, interleukin 6 (IL-6), and C-reactive protein (CRP) in peripheral blood. The sample was dichotomized into two groups: (1) decrease in Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (2) no change or increase in PSQI (no change). Mixed between-within subjects analysis of variance tests were used to determine group differences on changes of inflammation and comorbid symptoms.	In our sample of 66 recently deployed military personnel with insomnia, 34 participants reported restorative sleep whereas 32 reported no sleep changes. The two groups did not differ in demographic or clinical characteristics, with the exception of PTSD diagnosis at baseline. The restorative sleep group had significant reductions in CRP concentrations and depression symptoms, as well as reduced fatigue and improvements in emotional well-being, social functioning, and physical functioning at follow-up.	Military personnel who report sleep restoration after deployment have reduced CRP concentrations, decreased severity of depression, and improved HRQOL. These findings suggest that treatment for sleep disturbances may be associated with improvements in mental and physical health, thereby supporting continued study in this line of research.	
25311835	We and others have reported that experimentally induced short sleep does not affect resting metabolic rate and leads to increased laboratory-measured 24-h energy expenditure. Here, we aimed to determine if sleep timing and/or quality are related to physical activity (PA) levels.Measures of PA via waist actigraphy, sleep diary, and sleep quality questionnaires were collected over a 7-18-day period in 22 adults (mean age ± standard deviation (SD): 35.8 ± 4.6 years, and mean body mass index ± SD: 23.8 ± 1.1 kg/m(2)) who were on their habitual sleep-wake and activity schedules.	During the recording period, mean (±SD) bedtime and wake times were 00:17 ± 1:07 h (range: 22:02-02:07 h) and 08:20 ± 1:14 h (range: 06:30-10:11 h), respectively. After controlling for sleep duration, later bedtime, wake time, and midpoint of sleep were associated with less time spent in moderate-to-vigorous PA (p = 0.013, p = 0.005, and p = 0.007, respectively), and increased time in sedentary PA (p = 0.016, p = 0.013, and p = 0.013, respectively).	Current results suggest that even relatively small alterations in sleep timing may influence PA. However, causality cannot be inferred from this cross-sectional study. Clinical intervention studies should be conducted to assess the relationship between sleep timing and energy balance.	
25311831	To compare the prevalence of self-reported abnormal sleep duration and excessive daytime sleepiness in pregnancy among Māori (indigenous New Zealanders) and non-Māori women versus the general population, and to examine the influence of socio-demographic factors.Self-reported total sleep time (TST) in 24-hrs, Epworth Sleepiness Scale scores and socio-demographic information were obtained from nullipara and multipara women aged 20-46 yrs at 35-37 weeks pregnant (358 Māori and 717 non-Māori), and women in the general population (381 Māori and 577 non-Māori).	After controlling for ethnicity, age, socio-economic status, and employment status, pregnant women average 30 min less TST than women in the general population. The distribution of TST was also greater in pregnant women, who were 3 times more likely to be short sleepers (≤6 h) and 1.9 times more likely to be long sleepers (>9 h). In addition, pregnant women were 1.8 times more likely to report excessive daytime sleepiness (EDS). Pregnant women >30 years of age experienced greater age-related declines in TST. Identifying as Māori, being unemployed, and working at night increased the likelihood of reporting abnormal sleep duration across all women population in this study. EDS also more likely occurred among Māori women and women who worked at night.	Pregnancy increases the prevalence of abnormal sleep duration and EDS, which are also higher among Māori than non-Māori women and those who do night work. Health professionals responsible for the care of pregnant women need to be well-educated about the importance of sleep and discuss sleep issues with the women they care for.	
25311289	Although a small number of studies characterized cross-sectional associations between sleep hygiene and insomnia severity, no prior study has examined their relationships prospectively. Further, the relationship between sleep hygiene and insomnia severity among college students has rarely been examined. This study examined the prevalence of diverse sleep hygiene behaviors and their associations with insomnia severity in two independent samples of college students from a cross-sectional (N=548; mean age=19; 59% female; 71% White) and a two-wave short-term prospective (N=157; mean age=19; 71% female; 76% White) study. A total of 12% to 13% of students reported clinically significant insomnia. On average, students reported frequent engagement in inconsistent sleep-wake schedules and lounging and worrying/thinking about important matters in the bed. Improper sleep scheduling, behaviors that promote arousal near bedtime, and uncomfortable sleeping environments were positively associated with cross-sectional insomnia severity. After controlling for other well-established risk factors, only improper sleep scheduling remained significant. Prospectively, baseline improper sleep scheduling predicted insomnia severity at a 2-month follow-up after controlling for baseline insomnia severity and other well-established risk factors. Together, findings suggest a potential unique role of improper sleep scheduling in insomnia among college students. 
25311104	Pituicytoma is a rare tumor arising from the neurohypophysis or pars intermedia of the adenohypophysis.A 36 year old male came to our observation presenting polydipsia, polyuria, polyphagia, decreased libido and altered sleep-wake rhythm. The biochemical tests showed hypotonic urine, mild hyperprolactinemia, hypogonadotropic hypogonadism, central hypothyroidism. Magnetic resonance revealed an expansive lesion of the suprasellar region (slightly isointense on T1, hyperintense on T2, impregnating contrast medium), that was partially removed by trans-cranial neurosurgical approach. The histopathological diagnosis was pituicytoma. After surgery, in addition to endocrine disorders, the patient presented severe neurological sequelae and hyperthermia, likely due to damage of the hypothalamus, followed by a progressive metabolic syndrome. The residual tumor was monitored by MRI, and, due to the early gradual increase in volume, was treated by stereotactic radiosurgery.	Pituicytomas are often difficult to distinguish from other hypothalamic or pituitary lesions. However, their identification would be preferable in a pre-operative setting in order to optimize the work-up and to initiate a proactive management of the expected complications.	
25310204	Sleep disturbances play a fundamental role in the pathophysiology posttraumatic stress disorder (PTSD), and are not only a secondary feature. The aim of this study was to validate and assess the psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A-BR), a self-report instrument designed to assess the frequency of seven disruptive nocturnal behaviors, in a sample of participants with and without PTSD.PSQI-A was translated into Brazilian Portuguese and applied to a convenience sample of 190 volunteers, with and without PTSD, who had sought treatment for the consequences of a traumatic event.	The PSQI-A-BR displayed satisfactory internal consistency (Cronbach's coefficient of 0.83 between all items) and convergent validity with the Clinician Administered PTSD Scale (CAPS), even when excluding sleep-related items (r = 0.52). Test-retest yielded high agreement in the global PSQI-A-BR, with good stability over time (r = 0.88). A global PSQI-A-BR cutoff score of 7 yielded a sensitivity of 79%, specificity of 64%, and a global score of 7 yielded a positive predictive value of 93% for discriminating participants with PTSD from those without PTSD.	The PSQI-A-BR is a valid instrument for PTSD assessment, applicable to both clinical and research settings.	
25309500	Subcortical circuits mediating sleep-wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine-Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep-wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep-wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders. 
25307946	Sleep disturbances are highly prevalent in women with breast cancer; side effects of cancer treatment may worsen pre-existing sleep problems and have been pointed to as important determinants of their incidence. Therefore, we aimed to assess the association between different types of breast cancer treatment and sleep disturbances, through a systematic review. Medline (using PubMed), CINAHL Plus with full text, PsycINFO and Cochrane Central Register of Controlled Trials (Central) were searched from inception to January 2014. Studies that evaluated samples of women with breast cancer, assessed sleep disturbances with standardized sleep-specific measures, and provided data for different cancer treatments were eligible. A total of 12 studies met the inclusion criteria. Three studies evaluated insomnia, five studies assessed sleep quality, two provide data on general sleep disturbances and two analysed specific sleep parameters. Women submitted to chemotherapy, or radiotherapy, tended to report higher levels of sleep disturbances. More heterogeneous findings were observed regarding the effect of surgical treatment and hormonal therapy. However, a sound assessment of the impact of these treatments was hampered by differences across studies regarding the outcomes assessed, reporting bias and the fact that most studies did not control for the effect of potential confounders. The present review highlights the potential relation between breast cancer treatments and sleep disturbances, particularly of chemotherapy, though more robust evidence is needed for a proper understanding of these associations. 
25307588	Alcohol acts as a sedative that interacts with several neurotransmitter systems important in the regulation of sleep. Acute administration of large amounts of alcohol prior to sleep leads to decreased sleep-onset latency and changes in sleep architecture early in the night, when blood alcohol levels are high, with subsequent disrupted, poor-quality sleep later in the night. Alcohol abuse and dependence are associated with chronic sleep disturbance, lower slow-wave sleep, and more rapid-eye-movement sleep than normal, that last long into periods of abstinence and may play a role in relapse. This chapter outlines the evidence for acute and chronic alcohol effects on sleep architecture and sleep electroencephalogram, evidence for tolerance with repeated administration, and possible underlying neurochemical mechanisms for alcohol's effects on sleep. Also discussed are sex differences as well as effects of alcohol on sleep homeostasis and circadian regulation. Evidence for the role of sleep disruption as a risk factor for developing alcohol dependence is discussed in the context of research conducted in adolescents. The utility of sleep-evoked potentials in the assessment of the effects of alcoholism on sleep and the brain and in abstinence-mediated recovery is also outlined. The chapter concludes with a series of questions that need to be answered to determine the role of sleep and sleep disturbance in the development and maintenance of problem drinking and the potential beneficial effects of the treatment of sleep disorders for maintenance of abstinence in alcoholism. 
25304131	Pain, fatigue, sleep disturbance, and depression are common and frequently co-occurring symptoms in oncology patients. This symptom cluster is often attributed to the release of proinflammatory cytokines. The purposes of this study were to determine whether distinct latent classes of patients with breast cancer (n = 398) could be identified based on their experience with this symptom cluster, whether patients in these latent classes differed on demographic and clinical characteristics and whether variations in cytokine genes were associated with latent class membership. Three distinct latent classes were identified: "all low" (61.0%), "low pain and high fatigue" (31.6%), "all high" (7.1%). Compared to patients in the all low class, patients in the all high class were significantly younger, had less education, were more likely to be non-White, had a lower annual income, were more likely to live alone, had a lower functional status, had a higher comorbidity score, and had more advanced disease. Significant associations were found between interleukin 6 (IL6) rs2069845, IL13 rs1295686, and tumor necrosis factor alpha rs18800610 and latent class membership. Findings suggest that variations in pro- and anti-inflammatory cytokine genes are associated with this symptom cluster in breast cancer patients. 
25303963	Diabetes has previously been linked to mental health problems in adolescents, but more recent studies have yielded mixed findings. The aim of the current study was to compare symptoms of mental health problems, sleep and eating disturbances in adolescents with and without Type 1 diabetes in a population based sample.Data were taken from the youth@hordaland study, a large population based study in Hordaland County in Norway conducted in 2012. In all, 9883 adolescents aged 16-19 years (53% girls) provided self-reported data on both diabetes and a range of instruments assessing mental health symptoms, including depression, anxiety, obsessive-compulsive behaviours, hyperactivity, impulsivity, inattention, perfectionism, resilience, sleep problems and eating behaviour.	40 adolescents were classified as having Type 1 diabetes (prevalence 0.4%). We found that adolescents with Type 1 diabetes did not differ from their peers on any of the mental health measures.	This is one of the first population-based studies to examine mental health of adolescents with Type 1 diabetes. There was no evidence of increased psychopathology across a wide range of mental health measures. These findings contradict previous studies, and suggest that Type 1 diabetes is not associated with an increased risk of psychosocial problems.	
25300874	Sleep is an essential component of good physical and mental health. Previous studies have reported that poor quality sleep is associated with an increased risk of hypertension and cardiovascular disease. Hypertension is the most common and important risk factor for cardiovascular disease, and even modest reductions in blood pressure can result in significant reductions in the risk of stroke and myocardial infarction. In this trial, we will determine the efficacy of an online sleep intervention in improving blood pressure, in participants with hypertension and poor sleep quality.	Randomized-controlled, two-group, parallel, blinded, single-center, Phase II trial of 134 participants. Population and recruitment: Primary prevention population of participants with hypertension (systolic blood pressure, 130 to 160 mm Hg; diastolic blood pressure, <110 mm Hg) and poor sleep quality in a community setting.	Multicomponent online sleep intervention consisting of sleep information, sleep hygiene education, and cognitive behavioral therapy. Comparator: Standardized cardiovascular risk factor and lifestyle-education session (usual care).	Change in mean 24-hour ambulatory systolic blood pressure between baseline and 8-week follow-up. Hypertension has been selected as the primary outcome measure because of its robust association with both poor sleep quality and cardiovascular disease.	Intention-to-treat analysis by using a linear mixed model.	
25300105	The purpose of the research was a comparative assessment of the level of diet nutrients, characteristics of higher nervous activity, specificity of chronobiological changes of the sleep-wake cycle, the daily dynamics of cortisol level and total antioxidant activity in saliva in students with the presence of night eating compared with students who do not eat at night. The participants were 72 university students aged 17-22 years (59 females and 13 males), a self-administered diet diary for a week was used to acquire dietary pattern and nutrient content. All participants were divided into two groups: group 1--students with food consumption from 06.00 am to 10.00 pm without night meals (n = 34), and group 2--students, whose food consumption include all day period and night snaking from 10.00 pm to 06.00 am (n = 38). High nervous activity parameters were detected according to the Eysenck questionnaire, Spielberg and Taylor anxiety tests, the test "Stress", the three-factor eating questionnaire; chronobiological state was evaluated according to sleep quality, sleep hygiene, daily sleepiness, chronotype. Levels of cortisol and total antioxidant activity were estimated in saliva twice a day: in the morning and in the evening. In both groups, the majority of students (97%) have reduced consumption of vitamins and minerals such as biotin, vitamin D, choline, iodine, cobalt, manganese, sulfur, fluorine and zinc. Deficit of carbohydrates was found in 93% of respondents. The number of students with calcium deficiency was increased in the group 2 compared to the group 1 and reached 27.8% vs 3% (p < 0.05), niacin insufficiency was revealed in 41.7% vs 18.2% (p < 0.05) and proteins insufficiency frequency reached 30.6% vs 0% (p < 0.05). The students from the group 2 had a significantly lower (p < 0.05) intake of vitamins A, B6 and C. In the group 2 it was detected the time shift of food consumption acrophase (15.1 h vs. 13.8 h; p < 0.05), decrease of persons with morning chronotype (5.55% vs 24.24%; p < 0.05), increase of anxiety and daily sleepiness (26 vs 20; p < 0.01, and 10 vs 6; p < 0.03 respectively); decrease of sleep quality (13 vs 15; p < 0.01), increase of evening saliva cortisol level [9.41 (6.96; 13.11) vs 6.51 (5.61; 9.88) ng/ml; p < 0.005) and decrease of saliva total antioxidant activity in the morning [13.00 (9.82; 14.98) vs 16.41 (15.21; 17.51) mg/l; p < 0.001] and in the evening [11.11 (7.85; 12.89)vs 14.32 (13.27; 15.29) mg/l; p < 0.001].
25299689	Sleep disturbances and psychological distress are the most common adverse effects associated with cancer diagnosis and treatment. The aim of this study was to examine sleep and psychological characteristics in patients with local-advanced nasopharyngeal carcinoma (NPC) following completion of intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy, and to describe the predictors of post-test psychological symptoms after treatment. Sleep quality and psychological symptoms were measured using Pittsburgh sleep-quality index (PSQI) and symptom checklist-90 in 60 local-advanced NPC patients treated with IMRT and concurrent chemotherapy, respectively. After treatment, the subscores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction increased significantly compared with their pre-test scores. Similar results were observed for the mean PSQI global score. However, for psychological symptoms, only subscores of somatization and depression were higher than their baseline level. Multivariate analysis revealed that concurrent chemotherapy cycle was the only predictor of depression after treatment among all of the psychological symptoms assessed. These findings indicate that sleep disturbance and psychological distress are significant problems in NPC patients treated with IMRT and concurrent chemotherapy. Patients who receive many cycles of concurrent chemotherapy may be at an increased risk of depression after completion of IMRT. 
25299477	The prevalence of musculoskeletal chronic pain in adolescents is estimated to be approximately 4% to 40%. The development of musculoskeletal pain during teenage years could have a marked impact on physical, psychological and social well-being.To examine whether sleep problems during adolescence are associated with musculoskeletal pain, particularly chronic regional pain and chronic widespread pain.	Using data from the Avon Longitudinal Study of Children, the relationship between sleep problems at 15 years of age and the presence of chronic regional and widespread pain at 17 years of age was explored. Pain data were not available at 15 years of age. A total of 2493 participants with complete data were identified. Relationships among sleep problems and musculoskeletal pain were examined using logistic regression. ORs were calculated after adjusting for sex, ethnicity, socioeconomic position and depression (15 years of age).	Sleep disturbance (usually wakes up more than two or three times), difficulties with hypersomnolence and poor subjective sleep perception were associated with the presence of both musculoskeletal regional and widespread pain. Finally, using ordered logistic regression, poor subjective sleep perception was also found to be associated with greater pain severity in participants with chronic musculoskeletal regional and widespread pain.	The results of the present study suggest an association between sleep problems during adolescence and the presence of musculoskeletal pain at a later stage. These findings are consistent with adult literature suggesting a link between sleep problems and musculoskeletal pain. Given these associations, sleep problems in adolescence may be an important risk factor for musculoskeletal pain.	
25299145	Older adults with cancer reporting fatigue and sleep disorders often have coexisting geriatric syndromes and are at high risk of further functional decline. This review summarizes special considerations in the diagnosis and treatment of sleep disorders and fatigue when older persons with cancer present with multiple comorbidities, polypharmacy, dementia, delirium, and/or falls. Physicians caring for these older adults need to be aware of the unique diagnostic and treatment concerns in this population so that these patients can receive optimal care. 
25299144	Sleep disturbances are common in patients with cancer, occurring throughout the disease trajectory and sometimes well after treatment has concluded. Insomnia often does not occur in isolation; it may be associated with pain, fatigue, depression, and medication usage. Screening for sleep disturbances is an essential part of caring for oncologic patients. The criterion standard for nonpharmacologic treatment of insomnia in these patients is cognitive-behavioral therapy, a multimodal approach using sleep hygiene and education, stimulus control, sleep restriction, and relaxation. Exercise and complementary and integrative medicine have been studied with varying results, and no firm recommendation can be made about their efficacy. 
25299139	Sleep disorders are highly prevalent among cancer patients. These disorders can include disorders of sleep onset or maintenance or disorders of excessive sleepiness. A broad differential diagnosis is required to adequately treat these disorders. This review discusses current diagnoses and treatment associated with sleep difficulties that may be seen in cancer patients. With appropriate diagnosis and treatment, the prognosis is good for sleep improvement and improvements in quality of life. 
25299138	It is well known that cancer patients experience lack of sleep, which affects their symptoms and decrease their much needed energy, particularly while undergoing treatment. Insomnia, which is defined as a predominant complaint of dissatisfaction with sleep quantity or quality during different phases of the sleep cycle, could easily affect patients' quality of life and even cancer treatment outcomes. In this article, we review the current research on and treatments for insomnia, as well as explore cancer-related fatigue and its connections to sleep disorders. 
25297871	Previous studies have documented the involvement of the central nervous system serotonin in promoting wakefulness. There are few and conflicting results over whether there is an actual association between bearing the short allele of serotonin transporter promoter polymorphism (5-HTTLPR) and worse sleep quality. This study examined whether sleep onset latency complaint is associated with the 5-HTTLPR triallelic polymorphism in the SLC6A4 gene promoter and whether this polymorphism influences the relationship between sleep onset latency complaint and depressive symptoms in elderly people. A total of 1321 community-dwelling individuals aged 70-74 years were interviewed for sleep onset latency complaint and for sleep medication consumption. Participants' genomic DNA was typed for 5-HTTLPR and rs25531 polymorphisms. Depressive symptoms were evaluated with the Geriatric Depression Scale Short form and general medical comorbidity was assessed by the Cumulative Illness Rating Scale. The presence of a past history of depression was recorded. The S' allele of the 5-HTTLPR triallelic polymorphism was associated with sleep onset latency complaint. This association was maintained after adjusting for depressive symptoms, sex, age, history of depression and medical comorbidity. After stratification for 5-HTTLPR/rs25531, only in S'S' individuals high depressive symptoms were actually associated with sleep onset latency complaint. These data indicate that the low-expressing 5-HTTLPR triallelic polymorphism is an independent risk factor for sleep onset latency disturbance. Furthermore, the 5-HTTLPR genotype influences the association between depressive symptoms and sleep onset latency complaint.
25297618	Enzyme-treated asparagus extract (ETAS) has been developed as a novel anti-stress functional food ingredient that is produced from asparagus. Two human intervention trials with ETAS were conducted in healthy adult male volunteers. Study 1 was a randomized, double-blind, placebo-controlled study to assess the effects of ETAS on expression of heat shock protein 70 (HSP70) mRNA in blood and the autonomic nervous system (ANS). The ETAS group showed a tendency to enhance HSP70 mRNA expression level compared to the placebo group. Several ANS condition parameters were significantly improved in the ETAS group when compared to the placebo group. In Study 2, a randomized, double-blind, placebo-controlled, crossover trial investigated the influence on stress-related hormones and sleep. Serum and salivary cortisol levels were significantly elevated compared to baseline during the placebo period, but remained unchanged during the ETAS period. The salivary chromogranin A level was significantly decreased in the ETAS-treated subjects compared to their baseline levels. The actual sleep time was not significantly different between ETAS and placebo. However, when the subjects were divided into two categories based on sleep efficiency or the average of night sleeping time, ETAS intake was effective to modulate the sleep state among those with low sleep efficiency or excess sleep time. 
25297467	Insomnia is highly prevalent in people who are affected by cancer. However, options available to receive support for insomnia are limited. Telephone-based help services, such as cancer helplines, may be ideally placed to meet unmet needs regarding insomnia after cancer. The present study describes the prevalence and predictors of insomnia in patients and caregivers who call cancer helplines seeking support.Participants (N = 500 patients, N = 234 caregivers) were recruited through an Australian state-based telephone-delivered cancer helpline. In addition to routine screening with the Distress Thermometer, participants were administered the Insomnia Severity Index.	Most participants were female, older than 50 years of age, and were three (caregivers) to four (patients) months post-diagnosis. Insomnia symptoms were reported by 59.4 % of patients and 62.9 % of caregivers, with moderate to severe levels of insomnia reported by 27 % of patients and 30 % of caregivers. Insomnia was predicted by distress level for both patients (β = .31, p < .001) and caregivers (β = .32, p < .001) and age for patients only (β = -.13, p < .01).	Insomnia symptoms are common in patients and caregivers who call cancer helplines and appear to be related to distress. Telephone-based helplines have the potential to act as the first line of support in a stepped care approach addressing insomnia.	
25297322	Sleep is essential for children's physical and mental recovery and it is indispensable for their growth, for endocrine and for immune function, and for the development of cognitive behavioral skills. The purpose of this study is to describe the impact of hospitalization on the sleep patterns of newborns, infants and toddlers, as well as mothers' perceptions of any changes in their children's sleep patterns.This was a single-centre cross-sectional study. The study included children aged up to 2 years who had been hospitalized for more than two days, selected by accidental sampling. Data were collected using an anonymous questionnaire with open and closed questions administered to mothers.	Two hundred and one children aged on average 11.2 months (SD 10.3) were enrolled in the study. The percentage of children who at home used to sleep less than 5 hours a night increased by 4.7% in hospital, while the percentage of children sleeping 9 to 11 hours at home decreased by 5.9% in hospital. In hospital mothers put their children to bed later than at home. Indeed, the number of individuals going to bed between 9 and 10 p.m. decreased by 9.8% in hospital, while the number of children going to bed between 10 and 11 p.m. increased by 10.1%. The number of children who had 2 to 4 awakenings per night increased by 13.9% and the number of those who had 4 to 6 nocturnal awakenings increased by 4.8%; 50.5% of mothers reported that their children's sleep was interrupted by nurses to provide care. Mothers generally perceived their children's sleep as adequate, even if they noticed that their children were more restless and irritable. Mothers with only one child reported that they had more difficulty helping their children fall asleep (P=0.02).	The study highlights the need to review the routine in paediatric wards on the basis of the sleep needs of children. Further studies are needed to estimate the effectiveness of the specific measures suggested by mothers.	

25296015	Murine gammaherpesvirus (MuGHV) is a natural pathogen of wild rodents that has been studied extensively in terms of host immune responses to herpesviruses during acute infection, latency, and reactivation from latency. Although herpesvirus infections in people can be associated with fatigue and excessive sleepiness during both acute and latent infection, MuGHV has not been assessed extensively as a model for studying the behavioral consequences of chronic latent herpesvirus infections. To assess MuGHV infection as a model for evaluating fatigue and assessing potential mechanisms that underlie the exacerbation of fatigue during chronic viral disease, we evaluated sleep, temperature, and activity after exposure of healthy and latently MuGHV-infected mice to sleep fragmentation and social interaction. Neither treatment nor infection significantly affected temperature. However, at some time points, latently infected mice that underwent sleep fragmentation had less locomotor activity and more slow-wave sleep than did mice exposed to social interaction. In addition, delta-wave amplitude during slow-wave sleep was lower in infected mice exposed to sleep fragmentation compared with uninfected mice exposed to the same treatment. Both reduced locomotor activity and increased time asleep could indicate fatigue in infected mice after sleep fragmentation; reduced delta-wave amplitude during slow-wave sleep indicates a light plane of sleep from which subjects would be aroused easily. Identifying the mechanisms that underlie sleep responses of mice with chronic latent MuGHV infection may increase our understanding of fatigue during infec- tions and eventually contribute to improving the quality of life for people with chronic viral infections. 
25295652	Insomnia affects one-third of the adult population. Ten percent of adults surveyed in America consider it a serious problem. Chronic insomnia is associated with poor quality of life and the potential for various psychiatric and medical conditions, notably depression and cardiovascular disease. Since most patients with insomnia are unlikely to disclose obvious sleeping difficulties, the first step in diagnosing and managing patients is having a high index of suspicion in patients with specific complaints, comorbidities, and risk factors. This is followed by a complete evaluation of the patient's medical and physical history to determine if the insomnia is primary or comorbid with another disease. The management of insomnia should consider the extent of impairment associated with the disorder, as well as duration, causes, and comorbidities. In some cases, referral to a specialist is warranted. Recently, there have been new definitions of insomnia proposed; elucidation of the role of orexin-mediated hyperarousal brain neural pathway in the sleep-wake cycle; and new drugs available that target this system. Thus, a review and update for today's primary care physician is warranted. 
25295522	The suprachiasmatic nuclei (SCN) coordinate the daily sleep-wake cycle by generating a circadian rhythm in electrical impulse frequency. While period and phase of the SCN rhythm have been considered as major output parameters, we propose that the waveform of the rhythm of the SCN also has significance. Using implanted micro-electrodes, we recorded SCN impulse frequency in freely moving mice and manipulated its circadian waveform by exposing mice to light-dark (LD) cycle durations ranging from 22 hours (LD 11:11) to 26 hours (LD 13:13). Adaptation to long T-cycles (>24 h) resulted in a trough in electrical activity at the beginning of the night while in short T-cycles (<24 h), SCN activity reached a trough at the end of night. In all T-cycle durations, the intensity of behavioral activity was maximal during the trough of SCN electrical activity and correlated negatively with increasing levels of SCN activity. Interestingly, small changes in T-cycle duration could induce large changes in waveform and in the time of trough (about 3.5 h), and accordingly in the timing of behavioral activity. At a smaller timescale (minutes to hours), we observed a negative correlation between SCN activity and behavioral activity, and acute silencing of SCN neurons by tetrodotoxin (TTX) during the inactive phase of the animal triggered behavioral activity. Thus, the SCN electrical activity levels appear crucially involved in determining the temporal profile of behavioral activity and controls behavior beyond the circadian time domain.
25294429	Sleep disorders can occur in many neurodegenerative disorders; in a previous paper we constructed a scale investigating sleep discontinuity/fragmentation with the aim to obtain a rapidly and easily administered tool suitable for early identification and longitudinal monitoring of sleep disturbances in Alzheimer's disease (AD). We introduced this instrument in the daily clinical practice in a center for dementia; here we present the results of our experience. Two hundred and sixteen AD outpatients referred to the Alzheimer's Disease Assessment Unit at the IRCCS C. Mondino National Neurological Institute, Pavia, Italy, in the period October 2012 to March 2014 were administered the scale. The questionnaire global score was correlated with measures of cognitive, functional and behavioral impairment; a significant association was found with Mini-Mental State (p = 0.005), Activities of Daily Living (p = 0.01), Neuropsychiatric Inventory (p = 0.01) and Clinical Dementia Rating (p = 0.0005). The present data indicate that the previously validated questionnaire proves to be a suitable, rapid and easy to use tool in investigating sleep quality in AD in daily clinical practice. An early identification and longitudinal monitoring of sleep disturbances in AD may improve pharmacological and non-pharmacological interventions.
25294264	A lot of data were reported about monitoring patients with inflammatory bowel disease, with varying degrees of practical applicability. Concerning the evaluation of disease activity, it was established that objective assessments are needed. Among the techniques that we use, although endoscopy is undoubtedly the reference standard, a lot of data were presented regarding less invasive techniques. The importance of MRIs, CTs and ultrasounds (with some variations) was thus reiterated. The importance of fecal calprotectin is also reiterated, not only for colon disease, but probably small intestine disease as well. Regarding treatment monitoring, a great deal was reported about anti-TNF therapy, demonstrating again its potential role when properly used. In addition to results with infliximab, results with adalimumab were reported as very consistent. For colon cancer prevention, it seems that the clinical guidelines are achieving their objective. It also seems clear that we must improve conventional endoscopic techniques. Finally, there are other aspects that need to be considered when monitoring our patients, such as adequate sleeping patterns, anxiety or depression. 
25293637	This annotation discusses definitions of 'sleep problems', the impacts of infant sleep on maternal and paternal well-being, and the evidence behind two areas of current controversy - the role of attachment versus behaviourally based parenting in infant sleep and management strategies for sleep problems in infants aged less than 6 months. 
25291726	Sleep disturbance is a problem for many children; however, it remains an underevaluated factor when assessing behavior. The purpose of the current article is to explore sleep problems in children, as well as the effects that disrupted sleep patterns have on child behavior. The authors recommend strategies to guide the assessment of sleep and improve children's sleep quality.
25290525	Sleep-wake disturbances are prevalent in patients with lung cancer yet are infrequently studied over time. This article reports on the qualitative results of a mixed-methods study of newly diagnosed patients' narratives over 6 months.The objective of this study was to gain an understanding of the treatment and illness trajectory related to sleep-wake disturbances as well as the beliefs and practices of patients while seeking optimal treatment outcomes.	Longitudinal interview narratives of 26 patients' experiences with advanced lung cancer diagnosis (at baseline, pre-second and third treatment, and 6 months) were obtained from participants recruited from Veterans Administration Hospital Center and a Comprehensive Cancer Center in Northeast United States. Analysis of illness narratives used interpretive phenomenology based on Heideggarian hermeneutic traditions.	At diagnosis, participants described poor sleep such as trouble falling asleep and frequent awakenings. Over time, as the treatment worsened their sleep symptoms, these participants still maintained hope for more time with treatment. This focus enabled them to tolerate the sleep-wake disturbances and treatment adverse effects. As the treatment effectiveness declined, their focus changed to spiritual meanings for the future and to keep living life with a purpose.	By explicating lung cancer patients' experiences with sleep-wake disturbances, nurses will gain insight into potential interventions to improve sleep and support effective outcomes as well as open a dialogue about hope.	Findings offer insight for oncology nurses to provide opportunities for dialogue about treatment options and techniques to improve sleep, which will facilitate patients living their lives.	
25288753	The mammalian circadian system synchronizes daily timing of activity and rest with the environmental light-dark cycle. Although the underlying molecular oscillatory mechanism is well studied, factors that influence phenotypic plasticity in daily activity patterns (temporal niche switching, chronotype) are presently unknown. Molecular evidence suggests that metabolism may influence the circadian molecular clock, but evidence at the level of the organism is lacking. Here we show that a metabolic challenge by cold and hunger induces diurnality in otherwise nocturnal mice. Lowering ambient temperature changes the phase of circadian light-dark entrainment in mice by increasing daytime and decreasing nighttime activity. This effect is further enhanced by simulated food shortage, which identifies metabolic balance as the underlying common factor influencing circadian organization. Clock gene expression analysis shows that the underlying neuronal mechanism is downstream from or parallel to the main circadian pacemaker (the hypothalamic suprachiasmatic nucleus) and that the behavioral phenotype is accompanied by phase adjustment of peripheral tissues. These findings indicate that nocturnal mammals can display considerable plasticity in circadian organization and may adopt a diurnal phenotype when energetically challenged. Our previously defined circadian thermoenergetics hypothesis proposes that such circadian plasticity, which naturally occurs in nocturnal mammals, reflects adaptive maintenance of energy balance. Quantification of energy expenditure shows that diurnality under natural conditions reduces thermoregulatory costs in small burrowing mammals like mice. Metabolic feedback on circadian organization thus provides functional benefits by reducing energy expenditure. Our findings may help to clarify relationships between sleep-wake patterns and metabolic phenotypes in humans. 
25287985	Adolescents prefer sleep and wake times that are considerably delayed compared with younger children or adults. Concomitantly, multimedia use in the evening is prevalent among teenagers and involves light exposure, particularly in the blue-wavelength range to which the biological clock and its associated arousal promotion system is the most sensitive. We investigated whether the use of blue light-blocking glasses (BB) during the evening, while sitting in front of a light-emitting diode (LED) computer screen, favors sleep initiating mechanisms at the subjective, cognitive, and physiological level.The ambulatory part of the study comprised 2 weeks during which the sleep-wake cycle, evening light exposure, and multimedia screen use were monitored in thirteen 15- to 17-year-old healthy male volunteers. BB or clear lenses as control glasses were worn in a counterbalanced crossover design for 1 week each, during the evening hours while using LED screens. Afterward, participants entered the laboratory and underwent an evening blue light-enriched LED screen exposure during which they wore the same glasses as during the preceding week. Salivary melatonin, subjective sleepiness, and vigilant attention were regularly assayed, and subsequent sleep was recorded by polysomnography.	Compared with clear lenses, BB significantly attenuated LED-induced melatonin suppression in the evening and decreased vigilant attention and subjective alertness before bedtime. Visually scored sleep stages and behavioral measures collected the morning after were not modified.	BB glasses may be useful in adolescents as a countermeasure for alerting effects induced by light exposure through LED screens and therefore potentially impede the negative effects modern lighting imposes on circadian physiology in the evening.	
25287534	Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the external environment, we studied the effects of PRS on circadian rhythms, including the sleep-wake cycle, that are parameters altered in depression. Using a restraint stress during gestation, we showed that PRS induced phase advances in hormonal/behavioral circadian rhythms in adult rats, and an increase in the amount of paradoxical sleep, positively correlated to plasma corticosterone levels. Plasma corticosterone levels were also correlated with immobility in the forced swimming test, indicating a depressive-like profile in the PRS rats. We observed comorbidity with anxiety-like profile on PRS rats that was correlated with a reduced release of glutamate in the ventral hippocampus. Pharmacological approaches aimed at modulating glutamate release may represent a novel therapeutic strategy to treat stress-related disorders. Finally, since depressed patients exhibit changes in HPA axis activity and in circadian rhythmicity as well as in the paradoxical sleep regulation, we suggest that PRS could represent an original animal model of depression. 
25287067	Psychometric properties of the Korean versions of three sleep evaluation questionnaires were described to provide tools for practitioners and researchers interested in transcultural studies in Korea. The Pittsburgh Sleep Quality Index (PSQI), the General Sleep Disturbance Scale (GSDS), and the Leeds Sleep Evaluation Questionnaire (LSEQ) were analyzed using data from 959 community-dwelling adults in Korea. Furthermore, cut-off points and prevalence of sleep disturbance were identified. Reliability and concurrent validity for all measures were acceptable. Optimal cut-off points of PSQI, GSDS, and LSEQ with highest Youden's index were 5, 33, and 66, and prevalence of sleep disturbance was 22.1%, 26.3%, and 25.8%, respectively. The Korean PSQI, GSDS, and LSEQ are all valid and reliable tools for detecting sleep disturbance. We provide suggestions for selecting the right tools according to the purpose, setting, and participants of transcultural studies. 

25283955	It is known that osteoarthritis (OA) increases the risk of sleep disturbance, and that both pain and sleep problems may trigger functional disability and depression. However, studies examining all 4 variables simultaneously are rare. The aim of this study was to examine cross-sectional and longitudinal associations of self-reported sleep disturbance with OA-related pain and disability and depressive symptoms.At baseline, 367 persons with physician-diagnosed knee OA reported sleep disturbances, pain, functional limitations, and depressive symptoms. At 1-year followup, all measures were repeated in 288 of the subjects. Baseline analyses examined the independent and interactive associations of sleep disturbance with pain, disability, and depression, net of demographics and general health. Longitudinal analyses used baseline sleep disturbance to predict the 1-year change in pain, disability, and depression.	At baseline, sleep was independently associated with pain and depression but not disability. The sleep-pain relationship was mediated by depressive symptoms; sleep interacted with pain to exacerbate depression among persons with high levels of pain. Baseline sleep disturbance predicted increased depression and disability, but not pain, at followup.	These data confirm known cross-sectional relationships between sleep disturbance and pain and depression and provide new insights regarding longitudinal associations among those variables. Depression appears to play a strong role in the sleep-pain linkage, particularly when pain is severe. The unique predictive role of sleep in the progression of disability requires further study but may be an important point of intervention to prevent OA-related functional decline among persons whose sleep is disrupted by OA-related pain.	

25282356	This study aimed to develop an algorithm for determining sleep/wake states by using chronological data on the amount of physical activity (activity intensity) measured with the FS-750 actigraph, a device that can be worn at the waist, allows for its data to be downloaded at home, and is suitable for use in both sleep research and remote sleep medicine.Participants were 34 healthy young adults randomly assigned to two groups, A (n =17) and B (n =17), who underwent an 8-hour polysomnography (PSG) in the laboratory environment. Simultaneous activity data were obtained using the FS-750 attached at the front waist. Sleep/wake state and activity intensity were calculated every 2 minutes (1 epoch). To determine the central epoch of the sleep/wake states (x), a five-variable linear model was developed using the activity intensity of Group A for five epochs (x-2, x-1, x, x+1, x+2; 10 minutes). The optimal coefficients were calculated using discriminant analysis. The agreement rate of the developed algorithm was then retested with Group B, and its validity was examined.	The overall agreement rates for group A and group B calculated using the sleep/wake score algorithm developed were 84.7% and 85.4%, respectively. Mean sensitivity (agreement rate for sleep state) was 88.3% and 90.0% and mean specificity (agreement rate for wakeful state) was 66.0% and 64.9%, respectively. These results confirmed comparable agreement rates between the two groups. Furthermore, when applying an estimation rule developed for the sleep parameters measured by the FS-750, no differences were found in the average values between the calculated scores and PSG results, and we also observed a correlation between the two sets of results. Thus, the validity of these evaluation indices based on measurements from the FS-750 is confirmed.	The developed algorithm could determine sleep/wake states from activity intensity data obtained with the FS-750 with sensitivity and specificity equivalent to that determined with conventional actigraphs. The FS-750, which is smaller, less expensive, and able to take measurements over longer periods than conventional devices, is a promising tool for advancing sleep studies at home and in remote sleep medicine.	
25279939	Academic exam stress is known to compromise sleep quality and alter drug consumption in university students. Here we evaluated if sleeping problems and changes in legal drug consumption during exam stress are interrelated. We used the Pittsburgh Sleep Quality Index (PSQI) to survey sleep quality before, during, and after an academic exam period in 150 university students in a longitudinal questionnaire study. Self-reports of alcohol, caffeine, and nicotine consumption were obtained. The Perceived Stress Questionnaire (PSQ-20) was used as a measure of stress. Sleep quality and alcohol consumption significantly decreased, while perceived stress and caffeine consumption significantly increased during the exam period. No significant change in nicotine consumption was observed. In particular, students shortened their time in bed and showed symptoms of insomnia. Mixed model analysis indicated that sex, age, health status, as well as the amounts of alcohol and caffeine consumed had no significant influence on global sleep quality. The amount of nicotine consumed and perceived stress were identified as significant predictors of diminished sleep quality. Nicotine consumption had a small-to-very-small effect on sleep quality; perceived stress had a small-to-moderate effect. In conclusion, diminished sleep quality during exam periods was mainly predicted by perceived stress, while legal drug consumption played a minor role. Exam periods may pose an interesting model for the study of stress-induced sleeping problems and their mechanisms. 

25276051	Obstructive sleep apnea (OSA) is associated with growth impairment that usually improves following effective treatment. In this study we investigated the mechanisms underlying the growth processes in young children diagnosed with OSA, before and after adenotonsillectomy (T&A).Young children (6-36 months old) were enrolled and evaluated before and several months after T&A surgery for height, weight, circulating high sensitive C-reactive protein (CRP), and insulin-like growth factor 1 (IGF-1) levels. Caloric intake was assessed by a validated Short Food Frequency Questionnaire (SFFQ).	Following T&A, children added 4.81 cm and 1.88 kg to their height and weight, respectively (P < 0.001 for both) and had a significant increase in BMI Z score (P = 0.002). Increased caloric intake of 377 kcal/day was noted (P < 0.001), with increased protein and decreased fat intake. The decrease in CRP levels correlated with the increase in body weight in boys (P < 0.05, adjusted for caloric intake).	Adenotonsillectomy results in enhanced somatic growth in young children that correlates with a decrease in systemic inflammation and caloric intake increment. Our findings imply that systemic inflammation may have an important role in this OSA-related morbidity.	
25275933	Sleep disturbance after mild traumatic brain injury (mTBI) is commonly reported as debilitating and persistent. However, the nature of this disturbance is poorly understood. This study sought to characterize sleep after mTBI compared with a control group. A cross-sectional matched case control design was used. Thirty-three persons with recent mTBI (1-6 months ago) and 33 age, sex, and ethnicity matched controls completed established questionnaires of sleep quality, quantity, timing, and sleep-related daytime impairment. The mTBI participants were compared with an independent sample of close-matched controls (CMCs; n = 33) to allow partial internal replication. Compared with controls, persons with mTBI reported significantly greater sleep disturbance, more severe insomnia symptoms, a longer duration of wake after sleep onset, and greater sleep-related impairment (all medium to large effects, Cohen's d > 0.5). No differences were found in sleep quantity, timing, sleep onset latency, sleep efficiency, or daytime sleepiness. All findings except a measure of sleep timing (i.e., sleep midpoint) were replicated for CMCs. These results indicate a difference in the magnitude and nature of perceived sleep disturbance after mTBI compared with controls, where persons with mTBI report poorer sleep quality and greater sleep-related impairment. Sleep quantity and timing did not differ between the groups. These preliminary findings should guide the provision of clearer advice to patients about the aspects of their sleep that may change after mTBI and could inform treatment selection.
25275619	In China, spouse caregivers of cancer patients (SCCPs) are involved in all aspects of patient care and experience psychological distress which could result in sleep disturbance and fatigue. However, few studies have explored the differences between SCCPs and the general population, or what factors affect SCCPs' sleep. This study aims to (1) Compare the differences in sleep disturbances and fatigue severity between SCCPs and the age- and gender-matched general population, and (2) Identify selected personal characteristics, including coping style that affect sleep disturbances in SCCPs.The Stress and Coping Model was used to guide this study. Participants were recruited from the northeast part of China and included 600 people from the general population and 300 SCCPs. Participants completed a socio-demographic form, Fatigue Scale-14, trait Coping Style Questionnaire, and Symptom Checklist-90.	The majority of the participants were middle age, most of whom (78.7%) spent more than 8 hours each day taking care of their spouses. Compared to the general population, the SCCPs experienced significant sleep disturbances with a mean of 7.30 (SD = 1.27), and fatigue severity with a mean of 8.11 (SD = 3.25). Among the selected SCCPs' personal characteristics, current poor health status (β = 0.14, P<0.001), having a spouse under mixed treatment (β = 0.13, p<0.001), and financial burden (β = 0.14, P<0.001) are the significant predictors for sleep disturbances. Positive coping is the predictor for fewer sleep disturbances (β = 0.27, P<0.001). Those who reported sleep disturbances also experienced higher physical and mental fatigue severity (P<0.001).	Intervention to improve coping style in SCCPs is needed. Further research is also needed to explore the other mediators and moderators that regulate sleep disturbance and health outcomes in the SCCPs.	
25275515	In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slowwave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity--a typical 1/f complex pattern--while for large time intervals there is anti-correlation. High correlation of short intervals (0.01 s to 2 s: waking state and 0.01 s to 0.1 s: SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales (30 s to 300 s: waking state and 0.3 s to 5 s: SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anticorrelation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better understanding of neuroautonomic regulation mechanisms.
25274449	Visual impairment (VI) is associated with increased mortality and health factors such as depression and cardiovascular disease. Epidemiologic studies consistently show associations between sleep duration with adverse health outcomes, but these have not systematically considered the influence of VI. The aim of this study was to ascertain the independent association between VI and sleep duration using the National Health Interview Survey (NHIS) data. We also examined whether race/ethnicity influenced these associations independently of sociodemographic and medical characteristics.Our analysis was based on the 2009 NHIS, providing valid sleep and vision data for 29,815 participants. The NHIS is a cross-sectional household interview survey utilizing a multistage area probability design. Trained personnel from the US census bureau gathered data during face-to-face interview and obtained socio-demographic, self-reported habitual sleep duration and physician-diagnosed chronic conditions.	The mean age of the sample was 48 years and 56% were female. Short sleep and long sleep durations were reported by 49% and 23% of the participants, respectively. Visual impairment was observed in 10%. Multivariate-adjusted logistic regression models showed significant associations between VI and short sleep (OR = 1.6, 95% CI = 1.5-1.9 and long sleep durations (OR = 1.6, 95% CI = 1.3-1.9). These associations persisted in multivariate models stratified by race-ethnic groups.	Visual impairment was associated with both short and long sleep durations. Analysis of epidemiologic sleep data should consider visual impairment as an important factor likely to influence the amount of sleep experienced habitually.	
25274228	Although gastroesophageal reflux disease (GERD) is known to cause sleep disturbances, the relationships between other abdominal symptoms and sleep disorders have not been clarified. In the present study, we examined the relationships between daytime sleepiness and various abdominal symptoms in a non-clinical population.We enrolled 2,936 subjects who visited Matsue Red Cross Hospital for an annual health check examination during a 10-month consecutive period after excluding those with organic gastrointestinal diseases. The Izumo scale abdominal symptom and Epworth Sleepiness Scale (ESS) questionnaires were employed to evaluate the presence of abdominal symptoms and daytime sleepiness.	Among the 2,936 subjects, 233 (7.9%), 254 (8.6%) and 528 (18%) had GERD-like, functional dyspepsia (FD)-like and irritable bowel syndrome (IBS)-like symptoms, respectively. The ESS scores in the subjects with GERD-, FD- and IBS-like symptoms were significantly higher than those observed in the asymptomatic subjects. The subjects with multiple abdominal symptoms tended to have higher ESS scores than those with single symptoms. A multiple logistic regression analysis revealed a younger age and the presence of FD- and IBS-like symptoms to be significant influencing factors for sleep disturbances.	The presence of FD and IBS symptoms in addition to GERD symptoms exhibits a strong relationship with sleep disturbances from the viewpoint of daytime sleepiness.	
25273932	Fatigue and quality of sleep are the main factors that contribute to a poor quality of life among patients on long-term haemodialysis. Studies have also emphasised the importance of exercise for improving the wellbeing of dialysis patients. This study aimed to determine the effectiveness of a predialysis low-to-moderate-intensity exercise programme for reducing fatigue and improving sleep disorders among long-term haemodialysis patients.In this quasi-experimental study, an exercise programme was conducted three times a week for 12 weeks before long-term haemodialysis patients underwent dialysis at two centres. The patients were categorised into either the exercise group (n = 28) or control group (n = 27). The latter was asked to maintain their current lifestyles. Assessments of fatigue and sleep disorder levels were performed for both groups using self-reported questionnaires at baseline and after intervention. The patients' perception of the exercise programme was also determined using self-reported questionnaires.	Paired sample t-test indicated improvements in fatigue level in the exercise group (mean fatigue score: post-treatment 40.5 ± 7.9 vs. pre-treatment 30.0 ± 10.9). Improvements in sleep disorders were also observed in the exercise group (mean score: post-treatment 7.6 ± 3.3 vs. pre-treatment 10.1 ± 3.8). However, sleep quality deteriorated in the control group (mean score: post-treatment 10.7 ± 2.9 vs. pre-treatment 9.3 ± 2.9).	Simple low-to-moderate-intensity exercise is effective for improving fatigue, sleep disorders and the overall quality of life among haemodialysis patients.	
25273079	Sleep disturbance is a prominent complaint of cancer patients. Most studies have focused on insomnia and cancer-related fatigue. Obstructive sleep apnea (OSA) has been reported in small studies and case reports.In a retrospective review of patients who underwent formal sleep evaluation and polysomnography (PSG) from 2006 to 2011, 56 patients with tumors in the head and neck region were identified. Clinical characteristics, sleep-related history, and PSG data were reviewed.	Most patients had active cancer (80%), and the majority had squamous pathology (68%). Prominent symptoms included daytime fatigue (93%), daytime sleepiness (89%), and snoring (82%). Comorbid conditions primarily included hypertension (46%) and hypothyroidism (34%). Significant sleep-related breathing disorder was noted in 93% of patients, and 84% met clinical criteria for OSA. A male predominance (77%) was noted, and patients were not obese (body mass index <30 kg/m(2) in 52%). The majority of patients (79%) underwent radiation prior to sleep study, of which 88% had OSA, and in the group without prior radiation, 67% had OSA. Adherence to positive airway pressure (PAP) therapy was slightly better when compared with the general population. A subset of patients with persistent hypoxia despite advanced forms of PAP required tracheostomy. Multivariate analysis revealed that patients with active disease and radiation prior to PSG were more likely to have OSA.	Sleep-related breathing disorder was common in patients with tumors in the head and neck region referred for evaluation of sleep disruption, and most met clinical criteria for OSA. Daytime fatigue and sleepiness were the most common complaints. OSA was prevalent in male patients, and most with OSA were not obese. Architectural distortion from the malignancy and/or treatment may predispose these patients to OSA by altering anatomic and neural factors. A heightened clinical suspicion for sleep-related breathing disorder and referral to a sleep specialist would be beneficial for patients with these complaints.	
25273034	Children with disabilities are more likely to have sleep disturbances than children without disabilities. Identifying attitudes, beliefs, knowledge, and perceptions of caregivers and health professionals is essential in developing effective intervention programs to improve disabled children's sleep health. However, no such qualitative data about adults who have key roles in the life and daytime activities of children with disabilities are available. This qualitative study aimed to understand attitudes, beliefs, knowledge, and perceptions about disabled children's sleep hygiene among caregivers and rehabilitation providers of children with disabilities.Twenty seven adults, including nine primary caregivers and eighteen rehabilitation providers, participated in five focus group discussions between September and December 2012 at the Rehabilitation Center in Punta Arenas, Chile. A trained facilitator guided focus group discussions using a semi-structured script. Audiotapes and transcripts of focus group discussions were reviewed and analyzed for recurrent themes.	Participants identified seven themes related to children's sleep hygiene: lifestyle behaviors, family factors, children's disabilities and/or comorbidities, environmental factors, adults' responsibilities for children's sleep, perception of good sleep, and parental distress about children's sleep problems. While both caregivers and rehabilitation providers recognized the importance of sleep for children's health and functioning, they differed in their understanding of how sleep hygiene practices influence sleep. Rehabilitation providers recognized the negative influence of electronics on sleep and the positive influence of sleep routines. In contrast, caregivers reported use of television/movie watching and stimulants as coping strategies for managing children's sleep problems.	Caregivers may benefit from better understanding the influence of electronics and stimulant use on child sleep health. Rehabilitation providers are well positioned to provide educational messages to both children and caregivers in order to change their attitudes, perceptions, and practices surrounding sleep. These qualitative data are valuable in developing intervention programs aimed at improving sleep health among children with disabilities.	
25272094	Pregabalin has been shown to be a safe, effective treatment for neuropathic pain associated with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), with average time to reduction in pain of 2 days. Pain-related sleep interference is commonly reported in both painful DPN and PHN. These post hoc analyses examined the time to improvement in sleep with pregabalin in patients with painful DPN or PHN, measured by reduction in daily sleep interference (DSI) scores on an 11-point numeric rating scale. A total of 4527 patients from 16 placebo-controlled trials of pregabalin for treatment of painful DPN or PHN were included in the analysis. In these trials, there were a total of 16 pregabalin treatment arms for painful DPN (75-600 mg/d), 10 for PHN (150-600 mg/d), and 3 for painful DPN/PHN (150-600 mg/d). Time to improvement in DSI scores was calculated for all treatment arms that demonstrated statistically significant reductions in DSI scores during the first 14 days of treatment compared with placebo (23 of 29; 79.3%) and was defined as the first day DSI scores for that day and the following day were significantly lower than placebo (P < 0.001). Mean (SD) time to improvement in DSI scores was 1.6 (1.3) days. Sustained improvement (≥1-point improvement in mean DSI score) was seen significantly earlier for pregabalin DSI responders than patients receiving placebo. These findings demonstrate that statistically significant and sustained improvement in sleep occurs rapidly (within 1 day for some patients) in response to treatment with pregabalin. 

25271675	Narcolepsy is characterized by abnormal sleep-wake regulation, causing sleep episodes during the day and nocturnal sleep disruptions. The transitions between sleep and wakefulness can be identified by manual scorings of a polysomnographic recording. The aim of this study was to develop an automatic classifier capable of separating sleep epochs from epochs of wakefulness by using EEG measurements from one channel. Features from frequency bands α (0-4 Hz), β (4-8 Hz), δ (8-12 Hz), θ (12-16 Hz), 16 to 24 Hz, 24 to 32 Hz, 32 to 40 Hz, and 40 to 48 Hz were extracted from data by use of a wavelet packet transformation and were given as input to a support vector machine classifier. The classification algorithm was assessed by hold-out validation and 10-fold cross-validation. The data used to validate the classifier were derived from polysomnographic recordings of 47 narcoleptic patients (33 with cataplexy and 14 without cataplexy) and 15 healthy controls. Compared with manual scorings, an accuracy of 90% was achieved in the hold-out validation, and the area under the receiver operating characteristic curve was 95%. Sensitivity and specificity were 90% and 88%, respectively. The 10-fold cross-validation procedure yielded an accuracy of 88%, an area under the receiver operating characteristic curve of 92%, a sensitivity of 87%, and a specificity of 87%. Narcolepsy with cataplexy patients experienced significantly more sleep-wake transitions during night than did narcolepsy without cataplexy patients (P = 0.0199) and healthy subjects (P = 0.0265). In addition, the sleep-wake transitions were elevated in hypocretin-deficient patients. It is concluded that the classifier shows high validity for identifying the sleep-wake transition. Narcolepsy with cataplexy patients have more sleep-wake transitions during night, suggesting instability in the sleep-wake regulatory system. 
25271587	This is a descriptive cross-sectional study, which aimed to identify the perception of nursing home elderly residents related to the chronological organization of their daily routines and to their sleep quality. The study was conducted with 37 elderly (14 women and 23 men, mean age of 75 years) who lived in a long term care facility located in the municipality of Campinas-SP, Brazil. The results showed that 81% of the elderlies had complaints compatible with poor sleep, but 70% of them reported that they had good sleep quality when directly questioned about it. All elderlies adequately realized the chronological organization of their routines, but this perception did not appear to contribute to the good sleep quality, as most of them had complaints compatible with poor sleep. It becomes evident that nurses should perform detailed assessment of sleep quality in order to minimize or prevent these problems and their possible consequences.
25271396	This randomised trial tested (i) whether a home-based expressive writing (EW) intervention improves quality of life in patients with colorectal cancer (CRC) and (ii) whether the intervention is more beneficial for men or for people who feel constrained in disclosing cancer-related concerns and feelings.Patients treated for CRC were randomised to an EW (n = 101) or control writing (CW; n = 92) group. Assessments were completed at 1 month pre- and post-intervention. Sex and perceived social constraints on disclosure were evaluated as moderators.	Primary outcomes were depressive symptoms, sleep problems and quality of life indicators.	Eighty-one per cent of participants completed all writing assignments. Consistent with hypotheses, relative to the CW group, participants in the EW group expressed more negative emotion in writing and rated their writings as more meaningful, personal and emotionally revealing. There were no significant main effects of EW or moderating effects of sex or social constraints on outcomes.	Although EW is feasible to use with persons who have CRC, it was not effective as a stand-alone psychotherapeutic intervention. Neither was it more effective for men nor for people who felt they could not freely disclose cancer-related concerns and feelings.	
25271084	Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders. 
25270130	Object In the last decade the indications for the endoscopic endonasal approach have been progressively expanded to include lesions that have not been traditionally considered amenable to resection through the transsphenoidal route. In this study, the authors analyze their experience with hypothalamic gliomas treated via the endoscopic endonasal approach. Methods Consecutive cases of hypothalamic gliomas treated since 2007 via an endoscopic endonasal approach were reviewed. Preoperative and postoperative neuroimaging as well as endocrinological, neurological, and visual symptoms were analyzed to assess the surgical outcome. Signs and symptoms of hypothalamic dysfunction including body mass index (BMI), memory, sleep-wake rhythm, and polyphagia were prospectively collected pre- and postoperatively to assess hypothalamic function. Quality of life was evaluated using the Katz scale. Results In the initial phase the endoscopic endonasal approach was adopted in 3 cases with a palliative intent, to obtain a biopsy sample or for debulking of the mass followed by radio- or chemotherapy. In 2 later cases it was successfully adopted to achieve gross-total tumor resection. Complications consisted of 2 postoperative CSF leaks, which required an endoscopic endonasal reintervention. Visual deficit improved in 3 cases and normalized in the other 2. Four patients developed diabetes insipidus, and 3 an anterior panhypopituitarism. All patients had a moderate increase in BMI. No patients presented with any other signs of hypothalamic damage, and their quality of life at follow-up is normal. Conclusions Despite the limitations of a short follow-up and small sample, the authors' early experience with the endoscopic endonasal approach has revealed it to be a direct, straightforward, and safe approach to third ventricle astrocytomas. It allowed the authors to perform tumor resection with the same microsurgical technique: dissecting the tumor with 2 hands, performing a central debulking, and controlling the bleeding with bipolar coagulation. The main limitations were represented by some anatomical conditions, such as the position of the chiasm and the anterior communicating artery complex and, finally, by the challenge of watertight plastic repair. To definitively evaluate the role of this approach in hypothalamic gliomas, a comparison with transcranial series would be necessary, but due to the rarity of these cases such a study is still lacking. The authors observed that more aggressive surgery is associated with a worse endocrinological outcome; thus they consider it to be an open question (in particular in prepubertal patients) whether radical removal is an advisable goal for hypothalamic gliomas. 
25269754	Recently, we have developed a simple method that uses two electro-oculography (EOG) electrodes for the automatic scoring of sleep-wake in normal subjects. In this study, we investigated the usefulness of this method on 284 consecutive patients referred for a suspicion of sleep apnea who underwent a polysomnography (PSG).We applied the AASM 2007 scoring rules. A simple automatic sleep-wake classification algorithm based on 18-45 Hz beta power was applied to the calculated bipolar EOG channel and was compared to standard polysomnography. Epoch by epoch agreement was evaluated.	Eighteen patients were excluded due to poor EOG quality. One hundred fifty-eight males and 108 females were studied, their mean age was 48 (range 17-89) years, apnea-hypopnea index 13 (range 0-96) /h, BMI 29 (range 17-52) kg/m(2), and sleep efficiency 78 (range 0-98) %. The mean agreement in sleep-wake states between EOG and PSG was 85% and the Cohen's kappa was 0.56. Overall epoch-by-epoch agreement was 85%, and the Cohen's kappa was 0.57 with positive predictive value of 91% and negative predictive value of 65%.	The EOG method can be applied to patients referred for suspicion of sleep apnea to indicate the sleep-wake state.	
25268092	Sleep is a vital function for human beings, which can be affected by several factors. Chronic pain is one of these factors where it is the most frequent cause for seeking medical care in combination with insomnia. The aim of this study is to examine the prevalence and relationship between sleep disturbance and chronic pain.After approval, a total of 85 Family Medicine Units from over 170 in Tokat were randomly selected using a 50% sampling. A sample of 2635 subjects, over the age of 19 years, who were registered with the selected Family Medicine Units, were assessed due to gender, age group, and the urban/rural population size of Tokat using the stratified sampling method. The sample size distribution was calculated as 1515 urban subjects, 1120 rural subjects; 1345 female subjects, 1290 male subjects; 1123 subjects between 20-39 years of age, 1103 subjects between the ages of 40-64, and 409 subjects over 64 years of age. After sampling, subjects were invited to participate in the study via an invitation letter, and agreeing individuals were taken to the Family Medicine Unit for face-to-face meetings. Written, informed consent was obtained, along with demographic data. The presence of chronic pain was recorded. According to the presence of chronic pain, all subjects were separated into two groups as Group Chronic Pain and Group Non-Chronic Pain. The visual analog scale for pain intensity, and Pittsburgh Sleep Quality Index for sleep quality, were performed with all subjects. A multiple linear regression model was used to assess the predictors of sleep quality. Analyses were conducted using the Statistical Package for Social Sciences program (SPSS Inc., Chicago, IL, USA), version 20.0. The statistical significance for all analyses was set at p < 0.05.	The mean global Pittsburgh Sleep Quality Index score of Group Chronic Pain (5.30 ± 4.29) was significantly higher than in Group Non-Chronic Pain (3.22 ± 3.30; p < 0.01). The mean Pittsburgh Sleep Quality Index scores of females (5.69 ± 4.40) were significantly higher than males (4.54 ± 3.96) in Group Chronic Pain (p = 0.000045). A total of 40.7% of patients in Group Chronic Pain, and 21.9% in Group Non-Chronic Pain demonstrated poorer sleep quality according to the Pittsburgh Sleep Quality Index scores, with a cut-off level > 5. A moderate positive correlation was found between the global Pittsburgh Sleep Quality Index and Visual Analog Scale scores (r = 0.310, p < 0.01). A multiple linear regression analysis showed that age, gender, income, Visual Analog Scale, and presence of depression were the significant predictors for Pittsburgh Sleep Quality Index score.	The current study revealed that chronic pain and pain intensity are important predictors of sleep quality.	
25266180	The main objectives of this cross-sectional study were (1) to examine chronic pain using the Multidimensional Pain Inventory-Spinal Cord Injury (MPI-SCI) version and (2) to assess the relationship between chronic pain and functional status, depression, and sleep quality among patients with SCI.This was a cross-sectional study of all eligible patients admitted to the Ministry of Health Ankara Diskapi Yildirim Beyazit Education and Research Hospital Physical Therapy and Rehabilitation Clinic between January 2007 and July 2010.	Forty-four patients (33 male, 11 female) with traumatic SCI, aged >=18 years, who had pain continuing for >=6 months and were hospitalized in the physical therapy and rehabilitation clinic were included in this cross-sectional study. Chronic pain intensity, functional status, depression, and sleep quality were assessed according to the MPI-SCI, Functional Independence Measure (FIM), Hamilton Rating Scale for Depression (HAM-D), and Pittsburg Sleep Quality Index (PSQI), respectively.	A positive correlation was observed between "Pain Severity" (one of the subscales of the MPI-SCI) and HAM-D (r=0.487, P=.001) and PSQI (r=0.312, P=.039). "Pain Severity" was significantly higher in the "impaired sleep" group (P < .05) than in the "normal sleep" group and in the "depression" group (P < .05) than in the "no depression" group.	We identified a strong interrelationship between SCI-related "Pain Severity" and both depression and sleep quality. Hence, a comprehensive pain examination and management strategies including psychosocial interventions should be given particular consideration to address the critical issue of chronic pain in individuals with SCI.	
25264973	Posttraumatic stress disorder (PTSD) has been linked to reduced heart rate variability (HRV), which is in turn a risk factor for cardiovascular disease and death. Although hyperarousal and anxiety are thought to underlie this association, behavioral health risks, including smoking, alcohol dependence, obesity, and sleep disturbance, represent potential mechanisms linking PTSD and HRV.To test this hypothesis, short-term laboratory-based and 24-hour ambulatory measures of HRV were collected from 227 young adults (18-39 years), 107 of whom were diagnosed as having PTSD. Latent variable modeling was used to assess the relationship of PTSD symptoms with HRV along with potential behavioral health mediators.	PTSD symptoms were associated with reduced HRV (β = -0.21, p = .002). However, this association was reduced in models that adjusted for cigarette consumption and history of alcohol dependence and was rendered nonsignificant in a model adjusting for sleep disturbance. Independent mediation effects were deemed significant via bootstrapping analysis. Together, the three behavioral health factors (cigarette consumption, history of alcohol dependence, and sleep disturbance) accounted for 94% of the shared variance between PTSD symptoms and HRV. Abdominal obesity was not a significant mediator.	These results indicate that behavioral factors-specifically smoking, alcohol overuse, and sleep disturbance-mediate the association between PTSD and HRV-based indices of autonomic nervous system dysregulation. Benefits from psychiatric and psychological interventions in PTSD may therefore be enhanced by including modification of health behaviors.	
25262787	Although sleep disorder is one of the most serious comorbidities of refractory chronic pain, it is usually assessed only from the patients' subjective point of view. Therefore, we aimed to objectively evaluate the sleep efficiency of patients with chronic pain.Using an actigraph, a highly sensitive accelerometer, we assessed the sleep efficiency of six patients with chronic pain before and after the introduction of spinal cord stimulation (SCS).	While pain improved in only five out of six patients after SCS, sleep efficiency improved in all cases. Interestingly, in one case, sleep efficiency improved even though pain intensity remained unchanged.	With the use of an actigraph, improvements in sleep of patients with chronic pain undergoing SCS were demonstrated. One case showing improvement in sleep despite pain palliation may suggest that SCS might have independently affected the sleep system, although further studies are necessary.	
25261385	Sleep disturbances and depression are costly and potentially disabling conditions that affect a considerable proportion of older adults. The purpose of this study was to test the effectiveness of 6 months of elastic band exercises on sleep quality and depression of wheelchair-bound older adults in nursing homes.One hundred twenty-seven older adults from 10 nursing homes participated in this cluster randomized controlled trial, and 114 completed the study. Participants were randomly assigned to two groups: experimental group (five nursing homes, n = 59) and control group (five nursing homes, n = 55). A 40-minute wheelchair-bound senior elastic band exercise program was implemented 3 times per week for 6 months. Sleep quality and depression of the participants were examined at baseline, after 3 months, and at the end of the 6-month study.	Participants in the experimental group had longer sleep durations, better habitual sleep efficiencies, and less depression than the control group at 3 months of the study and maintained them throughout the rest of the 6-month study.	Nursing home directors could recruit volunteers to learn the program and lead the elderly residents in wheelchairs in practicing the wheelchair-bound senior elastic band exercises regularly in the facilities.	
25260431	There is a need for comprehensive studies on adolescents' sleep habits in the Middle Eastern region. The aim of this study was to investigate the sleep-wake patterns, prevalence of excessive daytime sleepiness (EDS), and disturbed sleep among adolescents in Saudi Arabia and to identify the associated factors.The study was a cross-sectional survey done on a random sample of 1035 high school students, ages 14-23 years, in Jeddah, Saudi Arabia. The response rate was 91%. Students filled a self-reported questionnaire that included sleep-wake questions, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Perceived Stress Scale, academic performance, and personal data.	Students slept an average of 7.0 hours on school nights, with an average delay of 2.8 and 6.0 hours in weekend sleep and rise times, respectively. Around 1 in 10 students stayed up all night and slept after returning from school (exhibiting a reversed sleep cycle) on weeknights. This pattern was more prevalent among boys and students with lower grade point averages. The prevalence of sleep disturbance was 65%, and EDS was found in 37% of the students. Predictors of EDS were school type, stress, napping and caffeine use, while gender was a predictor of disturbed sleep.	Adolescents in Saudi Arabia showed a high percentage of poor sleep quality. Compared with adolescents from other countries, they had a larger delay in weekend sleep and rise times. An alarming reversed sleep cycle on weekdays is present and highlights the need for further assessment.	
25260261	Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain.One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM).	Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration.	Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development.	
25260230	Sleep disturbances are common following traumatic brain injury (TBI). The Pittsburgh Sleep Quality Index (PSQI) is a widely used measure of sleep quality that has been used in numerous populations. Although this measure has been used in TBI research, there are few studies examining the psychometric properties in this population.The current study examined the factor structure of the PSQI in a sample of persons with TBI and tested the one, two, and three factor models derived from previous studies in other populations.	A telephone interview was conducted with 243 individuals who had sustained a TBI. All participants were approximately one year post-injury. Factor analyses were conducted (exploratory and confirmatory) to examine the factor structure of the PSQI.	Results confirm the fit of models previously tested in the literature but also reveal an alternative conceptualization of sleep containing both qualitative and quantitative factors.	While the 3-factor model best fits the data in this TBI sample, the use of a 2-factor model is acceptable and may be more clinically relevant due to the grouping of time-related variables that could provide important information with regard to circadian rhythm disorders.	
25258560	Melatonin (N-acetyl-5-methoxytryptamine) is widely known as "the darkness hormone". It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review. 
25258123	Genetic variations in clock-related genes were hypothesized to be involved to in the susceptibility of mood disorders MD (both unipolar (UPD) and bipolar (BPD) disorders). In our work we investigated role of gene variants form four core period proteins: CLOCK, ARNTL, TIM and PER3. The total sample comprised from 744 mood disorders inpatients (UPD = 229, BPD = 515) and 635 healthy voluntary controls. The 42 SNPs from four genes of interest were genotyped. We used single polymorphisms, haplotypes, SNPs interactions and prediction analysis using classical statistical and machine learning methods. We observed association between two polymorphisms of CLOCK (rs1801260 and rs11932595) with BPDII and two polymorphisms of TIM (rs2291739, rs11171856) with UPD. We also detected ARNTL haplotype variant (rs1160996C/rs11022779G/rs1122780T) to be associated with increased risk of MD, BPD (both types). We established significant epistatic interaction between PER3 (rs2172563) and ARNTL (rs4146388 and rs7107287) in case of BPD. Additionally relation between PER3 (rs2172563) and CLOCK (rs1268271 and rs3805148) appeared in case of UPD. Classification and Regression Trees (C and RT) showed significant predictive value for 10 polymorphisms in all analyzed genes. However we failed to obtain model with sufficient predictive power. During analyses of sleep disturbances sample, we found carriers of homozygote variants (ARNTL: rs11022778 TT, rs1562438 TT, rs1982350 AA and PER3: rs836755 CC) showing more frequent falling asleep difficulties when compare to other genotypes carriers. Our study suggested a putative role of the CLOCK, TIM, ARNTL and PER3 and polymorphisms in MD susceptibility. In our analyses we showed association of specific gene variants with particular types of MD. We also confirmed necessity of performing separate analyzes for BPD and UPD patients. Comprehensive statistical approach is required even with individual symptoms analyses.
25257545	A study was carried out on the effects of unilateral microinjection of melanin-concentrating hormone (MCH) into the right locus coeruleus (LC) on the sleep-wake cycle in rats prepared for chronic sleep recordings. MCH 200 ng significantly augmented rapid-eye-movement sleep (REMS) time during the first, second and third 2-h of recording. Furthermore, MCH 100 ng induced a significant increase of REMS during the first 2-h period after treatment. The increment of the behavioral state was related to a greater number of REMS episodes. It is suggested that MCH deactivation of noradrenergic neurons located in the LC facilitates the occurrence of REMS.
25256933	To quantify the impact of objectively recorded hot flashes on objective sleep in perimenopausal women.Cross-sectional study. Participants underwent 1-5 laboratory-based polysomnographic recordings for a total of 63 nights, including sternal skin-conductance measures, from which 222 hot flashes were identified according to established criteria. Data were analyzed with hierarchical mixed-effect models and Spearman's rank correlations.	Sleep laboratory.	Thirty-four perimenopausal women (age ± SD: 50.4 ± 2.7 years).	None.	Perceived and polysomnographic sleep measures (sleep quality, amount of time spent awake after sleep onset, and number of awakenings). Subjective (frequency and level of bother) and objective (frequency and amount of hot flash-associated awake time) hot-flash measures.	Women had an average of 3.5 (95% confidence interval: 2.8-4.2, range = 1-9) objective hot flashes per night. A total of 69.4% of hot flashes were associated with an awakening. Hot flash-associated time awake per night was, on average, 16.6 minutes (95% confidence interval: 10.8-22.4 minutes), which accounted for 27.2% (SD 27.1) of total awake time per night. Hot flash-associated time awake, but not hot flash frequency, was negatively associated with sleep efficiency and positively associated with waking after sleep onset. In addition, self-reported wakefulness correlated with hot flash-associated waking, suggesting that women's estimates of wakefulness are influenced by the amount of time spent awake in association with hot flashes during the night. Having more perceived and bothersome hot flashes was correlated with more perceived wakefulness and awakenings and more objective hot flash-associated time awake and hot-flash frequency.	The presence of physiological hot flashes accounts for a significant proportion of total objective time awake during the night in perimenopausal women.	
25256878	Patients with polycystic ovarian syndrome (PCOS) have a high prevalence of sleep disorders. Metformin is an antidiabetic drug that may have a role in treatment of the manifestations of PCOS. The aim of this study was to assess the presence of sleep disorders in adolescent girls with PCOS and to study the effects of using metformin on sleep disorders in these girls.This study was carried out on 90 adolescent girls aging from 12 to 18 years who were divided into 3 equal groups: control untreated group, untreated PCOS group, and PCOS + metformin group. Body weight, height, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, Homeostatic Model Assessment (HOMA) index, sleep disturbances scale, and Epworth sleepiness scale were measured.	Metformin administration resulted in significant decrease in the body weight, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, HOMA index, sleep disturbances scale, and Epworth sleepiness scale compared to the untreated PCOS group.	Metformin can reduce the incidence of sleep disorders and excessive daytime sleepiness in adolescent girls with PCOS.	
25256020	The case study reports on the effect of pharmacological, complementary, and alternative medicine including acupuncture, Applied Kinesiology, and respiratory exercises in a boy with attention-deficit hyperactivity disorder (ADHD) on methylphenidate. A nine-year-old male patient was referred to treatment with a three-year diagnosis of ADHD, sleeping troubles, and dissatisfaction with methylphenidate. Examination included Applied Kinesiology, the coachman׳s test, assessment of breathing pattern disorders, and traditional chinese medicine (TCM) diagnosis. Muscle weakness related to thoracic breathing was found in the coachman׳s test. Respiratory exercises, acupuncture with permanent needles, and Applied Kinesiology treatments were given. Within the first treatment, muscle function as assessed by the coachman׳s test normalized. After two treatments, sleep behavior improved rapidly, and with further treatments, handwriting was improving. Methylphenidate continues to be given. The results were stable after 15 months. A multimodal approach to ADHD integrating pharmacological treatment and complementary and alternative medicine (CAM) including Applied Kinesiology, breathing exercises, and acupuncture. 
25255355	Midface fractures commonly occur following trauma to the face and may cause changes in the normal sinus outflow system. To the best of our knowledge, no study has examined the incidence of rhinosinusitis following midface fractures. We report the incidence of chronic rhinosinusitis in patients who underwent surgical repair of a midface fracture. Our evaluation tool was the 20-item Sino-Nasal Outcome Test quality-of-life survey (SNOT-20). We mailed a demographic survey and the SNOT-20 questionnaire to 486 eligible patients who had undergone surgical repair of either a midface (n = 234) or mandible (n = 252) fracture; we had intended to use the latter cohort as a control group. Of the 234 midface patients, 34 (14.5%) returned a usable survey, but only 7 of the 252 mandibular patients (2.8%) did so, which was not a sufficient number for analysis; therefore we used normative data obtained from another study for comparison purposes. The mean SNOT-20 score in our cohort was 24.15, which was similar to the 28.7 mean score in the control cohort of patients with rhinosinusitis. The highest mean scores for the individual components of the SNOT-20 were for "Wake up at night," "Lack of a good night's sleep," "Wake up tired," and "Frustrated/restless/irritable." The components that the most patients found bothersome were "Facial pain/pressure," "Need to blow nose," "Runny nose," and "Lack of a good night's sleep." We conclude that patients who experience a midface fracture have a much higher risk of developing chronic rhinosinusitis that negatively affects their long-term quality of life. These patients should be monitored with long-term follow-up and treated appropriately. 
25254979	Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.
25253755	To determine in a population-based study whether long sleep duration was associated with increased risk of dementia mortality.In this prospective, population-based study of 3,857 people without dementia aged 65 years and older (NEDICES [Neurological Disorders in Central Spain]), participants reported their daily sleep duration. The average daily total sleep duration was grouped into 3 categories: ≤5 hours (short sleepers), 6-8 hours (reference category), and ≥9 hours (long sleepers). Community-dwelling elders were followed for a median of 12.5 years, after which the death certificates of those who died were examined.	A total of 1,822 (47.2%) of 3,857 participants died, including 201 (11.0%) deaths among short sleepers, 832 (45.7%) among long sleepers, and 789 (43.3%) among those participants in the reference category. Of 1,822 deceased participants, 92 (5.1%) had a dementia condition reported on the death certificate (49 [53.3%] were long sleepers, 36 [39.1%] reported sleeping between 6 and 8 hours, and 7 [7.6%] were short sleepers). In an unadjusted Cox model, risk of dementia-specific mortality was increased in long sleepers (hazard ratio for dementia mortality in long sleepers = 1.58, p = 0.04) when compared with the reference group. In a Cox model that adjusted for numerous demographic factors and comorbidities, the hazard ratio for dementia mortality in long sleepers was 1.63 (p = 0.03).	Self-reported long sleep duration was associated with 58% increased risk of dementia-specific mortality in this cohort of elders without dementia. Future studies are required to confirm these findings.	
25253260	Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at first and the free-running cycle stopped after treatment day 15. Triazolam was added from the day 25 to promote earlier sleep onset. And the sleep-wake schedule was normalized by the day 34. Patient 2 (33-year-old male) had suffered from FRT for nearly 8 months after starting to take a leave of absence from his job. He was given sleep hygiene education and was treated with ramelteon and methylcobalamin. His sleep-wake schedule was normalized from the first treatment day. By the combined treatment with ramelteon, both patients have maintained favorable sleep-wake schedules. The agonist action of ramelteon at the melatonin 2 receptor may have primarily contributed to the cessation of the free-running cycle in these patients. 
25253105	Patients with cancer tend to suffer sleep-wake disturbances at a higher rate than the general population. Insomnia and fatigue should be regarded as a significant patient safety issue, as poor sleep can elevate patients' risks of falls, motor vehicle accidents, and acute infectious illnesses. To alleviate those risks, oncology nurses should be familiar with effective evidence-based practices for assessing and improving patients' sleep quality. 
25252988	Participation in the ONS Foundation-supported Breast Cancer Care Quality Measures Set pilot study was an opportunity for staff at a National Cancer Institute-designated comprehensive cancer center to improve their process for introducing a change in practice. The institution's treatment area revised a documentation tool, and the medical practice area embarked on an education project based on evidence-based practice from the Oncology Nursing Society's Putting Evidence Into Practice initiative. After implementation, an increase in the number of patients being assessed for the quality measures of fatigue and sleep-wake disturbances was noted. In addition, the number of patients being educated on neutropenia using evidence-based information increased. 
25252986	As a participant in the ONS Foundation-supported Breast Cancer Care Quality Measures Set in 2010, the Edward Cancer Center (ECC) identified gaps in patient assessment. Sleep-wake disturbance and distress were two common areas that were lacking consistent assessment when nurses saw patients during their visits. Another issue is the lack of standard methods of practice or a standardized tool. The ECC, in collaboration with Edward Diabetes Center, Linden Oaks Hospital, and other outpatient offices, adopted the use of the Patient Health Questionnaire-9 depression screening tool. The ECC also modified the intervention recommendations to meet the needs of the oncology population. As a result of the findings in the pilot, the ECC was able to implement an evidence-based practice change to improve the overall quality of patient care and provide earlier intervention in an effort to further improve patient outcomes. 
25252985	The Anne Arundel Medical Center (AAMC) DeCesaris Cancer Institute (DCI) began its participation in the ONS Foundation-supported Breast Cancer Care Quality Measures Set pilot study in 2010. The design and measures of the project were intriguing, paving a path for DCI to define quality measures and outcomes that were of value to the AAMC's oncology population and system. As the pilot program was getting underway, measurement instruments were selected for fatigue, distress, and sleep-wake disturbances. These were used as quality measures for care of patients receiving chemotherapy, to be reported to the Oncology Quality Council, AAMC DCI's Executive Quality Council, and the AAMC Board of Directors. Scores for these quality measures, as well as patient satisfaction scores for the Outpatient Infusion Center, have increased markedly since the 2010 pilot test. The increases in scores inspired nursing leadership, in conjunction with AAMC DCI's Medical Oncology Executive Committee, to develop an innovative nursing model, the advanced oncology nurse practitioner-led symptom management clinic, to systematically and efficiently treat the needs of patients with cancer. 
25252861	Functional dyspepsia is one of the most common gastrointestinal disorders encountered in clinical practice. Functional dyspepsia is currently defined by Rome III criteria as the chronic dyspeptic symptoms (postprandial fullness, early satiety, epigastric pain or burning) in the absence of underling structural or metabolic disease that readily explain the symptoms. According to the Rome III consensus, functional dyspepsia can be subdivided into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Although the Rome III criteria have been published more than 8 years ago, not much effort has been put into validating these criteria and direct scientific evidence supporting the validity of the subdividing functional dyspepsia into PDS and EPS are lacking. This article is intended to review the validity of the Rome III criteria on the subdivisions of functional dyspepsia, i.e. PDS and EPS. The impact of sleep disorder, Helicobacter pylori-associated dyspepsia, and the emerging drug therapies in functional dyspepsia will also be discussed in this article.
25250774	Alzheimer's disease (AD) involves selective loss of basal forebrain cholinergic neurons, particularly in the nucleus basalis (NB). Similarly, Parkinson's disease (PD) might involve the selective loss of pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore, lesions of these functionally distinct cholinergic centers in rats might serve as models of AD and PD cholinergic neuropathologies. Our previous articles described dissimilar sleep/wake-state disorders in rat models of AD and PD cholinergic neuropathologies. This study further examines astroglial and microglial responses as underlying pathologies in these distinct sleep disorders. Unilateral lesions of the NB or the PPT were induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by using stereotaxically guided microinfusion of the excitotoxin ibotenic acid (IBO). Twenty-one days after the lesion, loss of cholinergic neurons was quantified by nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry, and the astroglial and microglial responses were quantified by glia fibrillary acidic protein/OX42 immunohistochemistry. This study demonstrates, for the first time, the anatomofunctionally related astroglial response following unilateral excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT lesions similarly enhanced local astroglial and microglial responses, astrogliosis in the PPT was followed by a remote astrogliosis within the ipslilateral NB. Conversely, there was no microglial response within the NB after PPT lesions. Our results reveal the rostrorostral PPT-NB astrogliosis after denervation of cholinergic neurons in the PPT. This hierarchically and anatomofunctionally guided PPT-NB astrogliosis emerged following cholinergic neuronal loss greater than 17% throughout the overall rostrocaudal PPT dimension.
25248582	The diurnal variation of the geophysical position of the earth in relation to the sun has imposed considerable evolutionary pressure. The suprachiasmatic nucleus, which serves as the central biological clock, receives the input regarding light-dark through the optic nerves. This nucleus in turn conveys output in a diurnal fashion to other hypothalamic nuclei and to the autonomic nervous system. Sleep is the most extreme phenotypical adaptation to this diurnal light-dark cycle. In recent years, sleep duration has been reduced and sleep deprivation has become endemic in our modern 24/7 society, either by voluntary sleep restriction and/or through sleep disorders. Experimental studies in humans have documented that sleep deprivation induces insulin resistance in multiple metabolic pathways in both healthy subjects and patients with type 1 diabetes. Epidemiological studies have documented that sleep duration is an important risk factor for development of insulin resistance and type 2 diabetes. Several potential pathways have been suggested to contribute to insulin resistance after sleep restriction, including altered function of the autonomic nervous system, endocrine changes, and an altered inflammatory state. Nonetheless, the causal factors explaining the relation between altered sleep characteristics and insulin resistance in multiple organs need additional study, and most likely include central autonomic pathways. 
25247458	Extensive scientific efforts have been made in an attempt to identify early markers of behavioral and emotional problems. In this context, sleep has received considerable research attention, as it appears to be closely linked to developmental psychopathology. The present review synthesizes some of the most recent findings regarding the concurrent and longitudinal associations between psychopathology and behavioral manifestations of sleep in childhood and adolescence.Recent evidence suggests that compromised sleep is associated with both internalizing and externalizing problems in childhood and adolescence. Moreover, sleep problems have been shown to predict the development of various emotional and behavioral problems, including depression, anxiety, attention-deficit hyperactivity disorder, risk-taking and aggression. Yet, inconsistencies are apparent, particularly among findings that are based on objective sleep measurement.	Taken together, most recent findings suggest that poor sleep in childhood and adolescence constitutes a risk factor for psychopathological symptoms. Accordingly, the importance of early detection and intervention should be a primary goal in clinical settings. In the research domain, the underlying mechanism of these associations should receive future research attention, in an attempt to broaden the understanding of the relationship between sleep and psychopathology.	
25246779	Light therapy has shown great promise as a nonpharmacological method to improve symptoms associated with Alzheimer's disease and related dementias (ADRD), with preliminary studies demonstrating that appropriately timed light exposure can improve nighttime sleep efficiency, reduce nocturnal wandering, and alleviate evening agitation. Since the human circadian system is maximally sensitive to short-wavelength (blue) light, lower, more targeted lighting interventions for therapeutic purposes, can be used.The present study investigated the effectiveness of a tailored lighting intervention for individuals with ADRD living in nursing homes. Low-level "bluish-white" lighting designed to deliver high circadian stimulation during the daytime was installed in 14 nursing home resident rooms for a period of 4 weeks. Light-dark and rest-activity patterns were collected using a Daysimeter. Sleep time and sleep efficiency measures were obtained using the rest-activity data. Measures of sleep quality, depression, and agitation were collected using standardized questionnaires, at baseline, at the end of the 4-week lighting intervention, and 4 weeks after the lighting intervention was removed.	The lighting intervention significantly (P<0.05) decreased global sleep scores from the Pittsburgh Sleep Quality Index, and increased total sleep time and sleep efficiency. The lighting intervention also increased phasor magnitude, a measure of the 24-hour resonance between light-dark and rest-activity patterns, suggesting an increase in circadian entrainment. The lighting intervention significantly (P<0.05) reduced depression scores from the Cornell Scale for Depression in Dementia and agitation scores from the Cohen-Mansfield Agitation Inventory.	A lighting intervention, tailored to increase daytime circadian stimulation, can be used to increase sleep quality and improve behavior in patients with ADRD. The present field study, while promising for application, should be replicated using a larger sample size and perhaps using longer treatment duration.	
25246026	Shift work comprises work schedules that extend beyond the typical "nine-to-five" workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2-5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers' health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers' impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts.
25245897	We evaluated ocular outcomes in a 14-d head-down tilt (HDT) bed rest (BR) study designed to simulate the effects of microgravity on the human body.Healthy subjects were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented (e.g., strict sleep-wake cycle, standardized diet, 24-hour-a-day BR, continuous video monitoring). Subjects maintained a 6° HDT position for 14 consecutive days. Weekly ophthalmological examinations were performed in the sitting (pre/post-BR) and HDT (in-bed phase) positions. Equivalency tests with optimal-alpha techniques evaluated pre/post-BR differences in best-corrected visual acuity (BCVA), spherical equivalent, intraocular pressure (IOP), Spectral-domain OCT retinal nerve fiber layer thickness (RNFLT), optic disc and macular parameters.	16 subjects (12 men and 4 women) were enrolled. Nearly all ocular outcomes were within our predefined clinically relevant thresholds following HDTBR, except near BCVA (pre/post-BR mean difference: -0.06 logMAR), spherical equivalent (-0.30 D), Tonopen XL IOP (+3.03 mmHg) and Spectralis OCT average (+1.14 μm), temporal-inferior (+1.58 μm) and nasal-inferior RNFLT (+3.48 μm). Modified Amsler grid, red dot test, confrontational visual field, and color vision were within normal limits throughout. No changes were detected on stereoscopic color fundus photography.	A few functional and structural changes were detected after 14-d HDTBR, notably an improved BCVA possibly due to learning effect and RNFL thickening without signs of optic disc edema. In general, 6° HDTBR determined a small nonprogressive IOP elevation, which returned to baseline levels post-BR. Further studies with different BR duration and/or tilt angle are warranted to investigate microgravity-induced ophthalmological changes.	


25244637	Reports of higher stress responsivity, altered sleep-wake cycle and a melatonin deficit in autism have stimulated interest in the cortisol circadian rhythm in individuals with autism.The study was conducted on 55 low-functioning children and adolescents with autism (11.3 ± 4.1 years-old) and 32 typically developing controls (11.7 ± 4.9 years-old) matched for age, sex and puberty. Behavioral assessment was performed using the Autism Diagnostic Observation Schedule (ADOS). Salivary samples for measurement of cortisol were collected during a 24-h period (at least 0800 h-Day 1, 1600 h, 0800 h-Day 2 for 46 individuals with autism and 27 controls, and 0800 h-Day 1, 1100 h, 1600 h, 2400 h, 0800 h-Day 2 for 13 individuals with autism and 20 controls). Overnight (2000 h-0800 h) urinary cortisol excretion was also measured.	The autism group displayed significantly higher levels of salivary cortisol at all time-points, flatter daytime and nighttime slopes, higher 0800 h cortisol levels on Day 2 compared to Day 1, and greater variances of salivary and urinary cortisol. There was a significant relationship between salivary cortisol levels and impairments in social interaction and verbal language. Overnight urinary cortisol excretion was similar in the autism and control groups.	Anticipation of the stressful collection procedure appears to contribute to the higher 0800 h-Day 2 versus 0800 h-Day 1 salivary cortisol levels in autism. This sensitization to stressors might be as, or even more, important clinically than exposure to novelty in autism. The similar group means for overnight urinary cortisol excretion indicate that basal HPA axis functioning is unaltered in low-functioning autism. The elevated salivary cortisol levels observed in autism over the 24-h period in a repeated stressful condition, flattened diurnal cortisol patterns and the apparent effect of anticipation are consistent with prior findings in high trait anxiety.	
25242371	Traumatic brain injury (TBI) can cause sleep-wake disturbances and excessive daytime sleepiness. The pathobiology of sleep disorders in TBI, however, is not well understood, and animal models have been underused in studying such changes and potential underlying mechanisms. We used the rat lateral fluid percussion (LFP) model to analyze sleep-wake patterns as a function of time after injury. Rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wake bouts during light and dark phases were measured with electroencephalography and electromyography at an early as well as chronic time points after LFP. Moderate TBI caused disturbances in the ability to maintain consolidated wake bouts during the active phase and chronic loss of wakefulness. Further, TBI resulted in cognitive impairments and depressive-like symptoms, and reduced the number of orexin-A-positive neurons in the lateral hypothalamus. 
25237837	Excessive daytime sleepiness (EDS) is one of the main symptoms of several sleep related disorders and has a great impact on patients' lives. While many studies have been carried out in order to assess daytime sleepiness, automatic EDS detection still remains an open problem. In this work, a novel approach to this issue based on correntropy function analysis of EEG signals was proposed in order to detect patients suffering from EDS. Multichannel EEG signals were recorded during five Maintenance of Wakefulness Tests (MWT) and Multiple Sleep Latency Tests (MSLT) alternated throughout the day for patients suffering from sleep disordered breathing (SDB). A group of 20 patients with EDS was compared with a group of 20 patients without daytime sleepiness (WDS), by analyzing 60 s EEG windows in a waking state. Measures obtained from the cross-correntropy function (CCORR) and auto-correntropy function (ACORR) were calculated in the EEG frequency bands: δ, 0.1-4 Hz; θ, 4-8 Hz; α, 8-12 Hz; β, 12-30 Hz; total band TB, 0.1-45 Hz. These functions permitted the quantification of complex signal properties and the non-linear couplings between different areas of the scalp. Statistical differences between EDS and WDS groups were mainly found in the β band during MSLT events (p-value < 0.0001). The WDS group presented more complexity in the occipital zone than the EDS group, while a stronger nonlinear coupling between the occipital and frontal regions was detected in EDS patients than in the WDS group. At best, ACORR and CCORR measures yielded sensitivity and specificity above 80% and the area under ROC curve (AUC) was above 0.85 in classifying EDS and WDS patients. These performances represent an improvement with respect to classical EEG indices applied in the same database (sensitivity and specificity were never above 80% and AUC was under 0.75). 


25234509	Although cardiovascular disease is typically associated with middle or old age, the atherosclerotic process often initiates early in childhood. The process of atherosclerosis appears to be occurring at an increasing rate, even in pre-adolescents, and has been linked to the childhood obesity epidemic. This study will investigate the relationships between obesity, lifestyle behaviours and cardiometabolic health in pre-pubescent children aged 8-10 years, and investigates whether there are differences in the correlates of cardiometabolic health between Māori and Caucasian children. Details of the methodological aspects of recruitment, inclusion/exclusion criteria, assessments, statistical analyses, dissemination of findings and anticipated impact are described.Phase 1: a cross-sectional study design will be used to investigate relationships between obesity, lifestyle behaviours (nutrition, physical activity/fitness, sleep behaviour, psychosocial influences) and cardiometabolic health in a sample of 400 pre-pubescent (8-10 years old) children. Phase 2: in a subgroup (50 Caucasian, 50 Māori children), additional measurements of cardiometabolic health and lifestyle behaviours will be obtained to provide objective and detailed data. General linear models and logistic regression will be used to investigate the strongest correlate of (1) fatness; (2) physical activity; (3) nutritional behaviours and (4) cardiometabolic health.	Ethical approval will be obtained from the New Zealand Health and Disabilities Ethics Committee. The findings from this study will elucidate targets for decreasing obesity and improving cardiometabolic health among preadolescent children in New Zealand. The aim is to ensure an immediate impact by disseminating these findings in an applicable manner via popular media and traditional academic forums. Most importantly, results from the study will be disseminated to participating schools and relevant Māori health entities.	
25233688	Sleep disorders and psychological disturbances are common in end-stage renal disease (ESRD) patients. However, despite their frequency and importance, such conditions often go unnoticed, since all patients do not clearly manifest fully expressed symptoms.This study aimed to determine the prevalence of depression and poor sleep quality and to examine the association between these disorders and demographic, clinical and treatment-related characteristics of ESRD patients on hemodialysis (HD).	The study included 222 patients (132 men and 90 women), mean age 57.3 +/- 11.9 years, from 3 HD centers in Central Serbia, which provided us with biochemical parameters and demographic data. Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI), respectively.	The average BDI was 16.1 +/- 11.3. Depressed patients were significantly older (p=0.041), had a significantly lower dialysis adequacy (p=0.027) and a significantly worse quality of sleep (p < 0.001), while they did not show significant difference as regarding sex, employment, marital status, comorbidities, dialysis type, dialysis vintage, shift and laboratory parameters.The average PSQI was 7.8 +/- 4.5 and 64.2% of patients were poor sleepers. Poor sleepers were significantly older (p = 0.002), they were more often females (p = 0.027) and had a significantly higher BDI (p < 0.001), while other investigated variables were. not correlated with sleep quality. A statistically significant positive correlation was found between BDI and PSQI (r = 0.604; p < 0.001).	Depression and poor sleep quality are frequent and interrelated among HD patients.	

25233249	Research into the physiologic underpinnings of epilepsy has revealed reciprocal relationships between seizures and the activity of several regulatory systems in the brain. This review highlights recent progress in understanding and using the relationships between seizures and the arousal or consciousness system, the sleep-wake and associated circadian system, and the central autonomic network. 
25233248	Characterize the polysomnographic (PSG) and quantitative EEG (qEEG) features of fibromyalgia and determine whether fibromyalgia patients differ in these measures when compared with a control sleep disorder population.All undergoing all-night PSG for evaluation of a sleep disorder were evaluated for fibromyalgia. The PSGs were interpreted for routine sleep measures, and qEEG was performed to measure the delta and alpha frequency power during non-rapid eye movement sleep. Measures and qEEG were analyzed according to fibromyalgia diagnosis.	Community-based sleep medicine center.	All patients undergoing PSG over a 2-year period.	None.	Of the 385 patients in the study population, 133 had fibromyalgia according to American College of Rheumatology criteria. The population's average Epworth Sleepiness Score was 10.5, the average sleep efficiency was 78%, and the Periodic Limb Movement disorder prevalence was 15%. None of these sleep measures differed significantly between the fibromyalgia and non-fibromyalgia groups. Obstructive sleep apnea was present in 45% of the fibromyalgia group. Significant differences were present in the qEEG ratio of delta to alpha frequency power, which was 95% specific for fibromyalgia when ≤1. A qEEG ratio ≤10.5 was 85% sensitive for fibromyalgia, and a qEEG ratio >10.5 had an 89% negative predictive value for fibromyalgia. Among patients with fibromyalgia who were not taking a benzodiazepine or benzodiazepine agonist, a qEEG ratio ≤10.5 was 84% specific and had a 78% positive predictive value.	Sleep disorders identified by routine PSG, including obstructive sleep apnea, are common in fibromyalgia, but periodic leg movement disorder and poor sleep efficiency are not. A qEEG low delta/alpha ratio during non-rapid eye movement sleep can differentiate patients with fibromyalgia from others who are referred for PSG. Consideration of benzodiazepine and benzodiazepine agonist use is important when interpreting the delta/alpha ratio.	
25233147	Parkinson's disease (PD) involves a variety of motor and non-motor symptoms, several of which, including gait abnormalities and sleep disorders, are generally not adequately managed with standard therapy. This study aimed to determine the impact of Qigong as a potential complementary therapy in the management of gait and sleep-related symptoms in PD.Seven subjects (aged 66.9 ± 8.1 years) with PD participated in a six-week Qigong exercise intervention. Pre- and post-intervention testing was performed to assess sleep quality, cognitive function, fatigue, quality of life, gait performance (stride time, stride length, double support time, and velocity), and gait variability (stride time and length variability).	Following Qigong, subjects showed improvement in some aspects of sleep quality. Fatigue remained unchanged. Gait function was improved by a significant reduction of stride time and a slight increase in stride length. Together these changes resulted in significant improvements to gait velocity. In addition, time spent in double limb support was reduced following the intervention. Overall gait variability improved significantly, particularly in the reduction of stride time variability.	These results suggest that Qigong may provide benefit for gait performance and sleep quality in PD patients. However, larger, controlled studies are required to determine the immediate and long-term benefits of Qigong for PD sleep and gait problems as well as the impact on other aspects of the disease.	
25231936	The normal sleep patterns of the spider monkey (Ateles geoffroyi) have not been described yet. The objective of this study was to characterize the electrophysiological patterns, sleeping postures, and sleep-wake cycle in semi-restricted spider monkeys. Continuous 24-hr polysomnographic (PSG) recordings, involving simultaneous recording of non-invasive electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activities, were carried out in captive monkeys living in outdoor rainforest enclosures. Electrode placement was done according to the human international 10-20 system. Specific behaviors displayed by monkeys during the sleep-wake cycles were correlated with the PSG recordings. The nycthemeral distribution of the sleep-wake cycle was also calculated. The results show that electrophysiological N-REM sleep patterns in spider monkeys are similar to those observed in other primates, including human beings. Furthermore, a vertical semi-fetal posture was observed during N-REM and REM sleep phases. The amount of nocturnal sleep was significantly higher than that of the diurnal period, showing that the spider monkey is a diurnal primate. An outstanding finding was the absence of muscular atonia during the spider monkey's REM sleep, which suggests that arboreal primates have developed a neuromuscular mechanism specialized for sleeping in a vertical posture.
25231857	Although sleep is an important risk factor for suicidal behavior, research has yet to examine the association between sleep problems and suicidality across the course of inpatient treatment. This study examined the relationship among sleep-related symptoms and suicidal ideation across inpatient treatment.To examine whether poor sleep at admission longitudinally predicts less improvement in suicidal ideation over the course of treatment. Further, to examine whether suicidal ideation is reduced in patients whose sleep does not improve.	The study utilized the Beck Depression Inventory (BDI)-II, which contains items measuring depressive symptoms, sleep-related symptoms, and suicidal ideation. The study sample consisted of 1,529 adult psychiatric inpatients. Patients were assessed at admission, biweekly, and at treatment termination.	Admission fatigue, loss of energy, and change in sleep pattern were associated with higher levels of suicidal ideation at admission and discharge. Fatigue at admission predicted suicidal ideation at termination independent of admission depression and suicidal ideation. Individuals whose sleep did not improve over the course of treatment had significantly higher suicidal ideation scores at termination relative to those whose sleep symptoms improved, after controlling for sleep, depression, and suicidal ideation scores at admission.	These findings suggest that persistence of sleep-related symptoms warrants clinical attention in the treatment of suicidal patients.	
25231559	Patients with psychiatric disorders, including schizophrenia, are reported to suffer from sleep disorders. In this study, we investigated the effects of lurasidone, an atypical antipsychotic, on sleep architecture in rats using sleep electroencephalography. The course of sleep in rats was classified into 3 stages: WAKE, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Lurasidone shortened REM duration and prolonged the mean duration of one bout in WAKE and NREM. Quantitative frequency band analysis during NREM sleep revealed that lurasidone increases slow waves and decreases fast waves. These results suggest that lurasidone ameliorates sleep disorders associated with psychosis. 
25231524	Sleep disturbances and cognitive impairment are common in older adults. Mounting evidence points to a potential connection between sleep and cognitive function. Findings from observational studies support a role for sleep disturbances (particularly for sleep duration, sleep fragmentation, and sleep-disordered breathing) in the development of cognitive impairment. Less consistent evidence exists for associations of insomnia and circadian rhythm dysfunction with cognition. These findings suggest that the sleep-wake cycle plays a crucial part in brain ageing, pointing to a potential avenue for improvement of cognitive outcomes in people at risk of cognitive decline and dementia. Several biological mechanisms might underlie the association between sleep and cognition, but these pathways are not completely understood. Future studies that aim to clarify the association between sleep and cognition might help to identify people at risk of cognitive disorders and to facilitate the development of novel therapies to treat and potentially prevent both sleep disturbances and cognitive impairment.
25231054	The development of sleep-wake regulation in infants depends upon brain maturation as well as various environmental factors. The aim of the present study was to evaluate sleep duration and quality as a function of child attachment to the mother. One hundred and thirty-four mother-child dyads enrolled in the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) project were included in this study. Attachment was assessed with the Strange Situation procedure at 36 months and maternal sleep reports were collected at 6, 12, 24 and 36 months. Differences in sleep characteristics were assessed with mixed models with one factor (attachment group) and one repeated measure (age). Children classified as disorganized had a significantly lower duration of nocturnal sleep, went to bed later, signaled more awakenings, had shorter periods of uninterrupted sleep (only at 12 months) and had shorter periods of time in bed (only at 6 months) than children classified as secure and/or ambivalent (p < 0.05). This is the first study to show that children with insecure disorganized attachment present a distinct sleep pattern in comparison with those with secure or ambivalent attachment between 6 and 36 months of age. Sleep disturbances could exacerbate difficulties in these families that are already considered vulnerable.
25230991	This study examined reactivity to social-evaluative stress in the parasympathetic (PNS) and sympathetic (SNS) branches of the autonomic nervous system (ANS) as prospective predictors of sleep in middle childhood. Participants included 339 children (M age = 9 years and 5 months at T1; 54% female; 64% European American, 36% African American). Sleep efficiency, sleep minutes, and variability in sleep onset time were assessed with actigraphy for seven consecutive nights at T1 and 1 year later at T2. Respiratory sinus arrhythmia reactivity (RSAR) and skin conductance level reactivity (SCLR) were assessed in response to a developmentally salient social-evaluative stress task at T1. Controlling for demographic variables and the respective sleep parameter at T1, the interaction between RSAR and SCLR predicted T2 sleep efficiency and sleep minutes. Consistent with the hypothesized role of reciprocal sympathetic activation (higher SCLR) and parasympathetic withdrawal (higher RSAR), higher RSAR predicted higher sleep efficiency and sleep minutes among children with higher SCLR but not lower SCLR.
25228562	Cancer patients belonging to the adolescent and young adult (AYA) age group have unique and very specific needs, which require special attention from the caring staff. The difficulty in maintaining the personal and professional development at this age is both natural and normal. Adding to this, coping with a life-threatening disease turns this stage in life into a period with many dilemmas and challenges of quite a complex nature. AYA patients have to deal with issues above and beyond the disease itself, which create a very complex coping picture. On top of that, prognosis for this age group has not improved in recent years, unlike the situation in other age groups like children and adults. The literature on this subject is extensive and comprehensive. However, most of the papers on this subject are very specific and narrow in their approach, each dealing with a specific topic. In this article, we bring together many different papers which make a wide and comprehensive picture of the subject of AYAs coping with cancer, coupled with recommendations for the caring staff. In this review we focus on the various aspects of the disease and treatments in AYAs, based on the conceptual model of quality of life proposed by Ferrell and colleagues [Cancer Nurs 1992;15:153-160; Cancer Nurs 1992;15:247-253], including physical, social, emotional and spiritual aspects. From the psychological standpoint, most of the papers discuss the negative aspects; however, in this article we try to include some articles from the positive psychology school of thought. From our findings it is apparent that there is an opportunity and need to further explore research in this regard. It is apparent that taking a unique approach to AYA cancer patients is needed in order to deal with the unique needs of this age group. This article aims at putting a framework around this issue, with actionable recommendations for the caring staff.
25228080	There were two objectives in this study: (1) to identify, among women and men with MS, the extent to which different MS-related symptoms, including fatigue, pain, sleep disturbance, depression, anxiety, irritability, cognitive impairment, spasticity, and poor balance, cluster and (2) to compare the contribution of generated symptom clusters to MS consequences including functional walking capacity, perceived health, illness intrusiveness, and quality of life (QOL).This was a cross-sectional study. A center-stratified random sample comprising 139 women and 49 men was recruited from three major MS clinics in Montreal. Subjects completed several self-report and performance-based measures that assessed symptoms and downstream MS consequences. Hierarchical and K-means cluster analyses were used to create clusters.	Three symptom clusters were identified. Cluster 1, labeled the "emotional/cognitive symptom cluster," comprised of depression, anxiety, cognitive impairments, and irritability. The second cluster, labeled the "physical symptom cluster," included pain, fatigue, and sleep disorders. Cluster 3, labeled the "motor symptom cluster," included spasticity and poor balance. Furthermore, the motor symptom cluster had a strong effect on functional walking capacity, while it did not affect significantly illness intrusiveness and QOL. On the other hand, the physical symptom clusters and emotional/cognitive symptom clusters showed a significant contribution to prediction of illness intrusiveness and QOL. All symptom clusters showed a significant effect in predicting the overall variability of perceived health status.	The findings of this study provide useful information to help healthcare professionals, clinicians, and researchers to target symptoms that are often in the same cluster when one or two of them are present. Identification of the strength of the contributions of each symptom clusters to the targeted MS consequences would further help to prioritize treatment approaches for the MS population.	
25227218	Sleep EEG spectral patterns were investigated in eight newly diagnosed, non-depressed, non-demented, drug-naïve Parkinson's disease patients compared to nine controls.Mean relative spectral power density calculated for 0.25 Hz frequency bins and for classical EEG frequency bands.	Differences between patients and controls were most prominent in non-REM sleep, specially around 8.6 Hz (slow alpha), 12.5 Hz (fast alpha/slow sigma) and 15 Hz (fast sigma). Slow alpha showed lower p-values over frontal and occipital electrodes, whereas fast sigma activity was more important on central and parietal sites. Significantly increased NREM sleep alpha activity was found in left and right frontal (Mann-Whitney U=12,000, p=.021; U=14,000, p=.036), left and right central (U=14,000, p=.036), left parietal and left occipital (U=13,000, p=.027; U=15,000, p=.046) areas. Increased sigma activity was found in right frontal (U=14,000, p=.036), left central (U=12,000, p=.021), left and right parietal (U=12,000, p=.021; U=13,000, p=.027) and left occipital (U=15,000, p=.046) areas.	Concomitantly increased scalp EEG alpha and sigma activity was found during NREM sleep in initial Parkinson's disease.	These non-REM sleep microstructure changes may represent evidence for altered electrophysiological mechanisms leading to sleep-wake instability in early disease stages.	
25225371	Many animals regulate their activity over a 24-h sleep-wake cycle, concentrating their peak periods of activity to coincide with the hours of daylight, darkness, or twilight, or using different periods of light and darkness in more complex ways. These behavioral differences, which are in themselves functional traits, are associated with suites of physiological and morphological adaptations with implications for the ecological roles of species. The biogeography of diel time partitioning is, however, poorly understood. Here, we document basic biogeographic patterns of time partitioning by mammals and ecologically relevant large-scale patterns of natural variation in "illuminated activity time" constrained by temperature, and we determine how well the first of these are predicted by the second. Although the majority of mammals are nocturnal, the distributions of diurnal and crepuscular species richness are strongly associated with the availability of biologically useful daylight and twilight, respectively. Cathemerality is associated with relatively long hours of daylight and twilight in the northern Holarctic region, whereas the proportion of nocturnal species is highest in arid regions and lowest at extreme high altitudes. Although thermal constraints on activity have been identified as key to the distributions of organisms, constraints due to functional adaptation to the light environment are less well studied. Global patterns in diversity are constrained by the availability of the temporal niche; disruption of these constraints by the spread of artificial lighting and anthropogenic climate change, and the potential effects on time partitioning, are likely to be critical influences on species' future distributions. 
25225088	Although it is considered to be the most complex organ in the body, the brain can be broadly classified into two major types of cells, neuronal cells and glial cells. Glia is a general term that encompasses multiple types of non-neuronal cells that function to maintain homeostasis, form myelin, and provide support and protection for neurons. Astrocytes, a major class of glial cell, have historically been viewed as passive support cells, but recently it has been discovered that astrocytes participate in signalling activities both with the vasculature and with neurons at the synapse. These cells have been shown to release D-serine, TNF-α, glutamate, atrial natriuretic peptide (ANP) and ATP among other signalling molecules. ATP and its metabolites are well established as important signalling molecules, and astrocytes represent a major source of ATP release in the nervous system. Novel molecular and genetic tools have recently shown that astrocytic release of ATP and other signalling molecules has a major impact on synaptic transmission. Via actions at the synapse, astrocytes have now been shown to regulate complex network signalling in the whole organism with impacts on respiration and the sleep-wake cycle. In addition, new roles for astrocytes are being uncovered in psychiatric disorders, and astrocyte signalling mechanisms represents an attractive target for novel therapeutic agents.
25224987	Sleep disturbance is a common symptom of multiple sclerosis (MS) and knowledge about factors that contribute to poor sleep quality is scarce.The aim was to explore the differences in the prevalence and determinants of poor sleep quality in a sample of patients with MS with disease duration ≤ 5 years and >5 years.	We collected data from 152 consecutive patients with MS; 66 patients (78% women, averaged 37.35 ± 10.1 years) were in the group with disease duration ≤ 5 years and 86 patients (73.3% women, averaged 42.10 ± 9.4 years) in the group with disease duration >5 years. Patients filled out the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, the Multidimensional Fatigue Inventory, one item of the Incapacity Status Scale regarding bladder problems and one item of the Short Form-36 regarding pain. Multiple linear regression was used to analyze the relationship between the study variables.	The prevalence of poor sleep is significantly higher in patients with longer disease duration (34.8 vs. 51.2%). Anxiety, reduced motivation and mental fatigue (all p < 0.05) were associated with poor sleep quality in patients with disease duration ≤5 years, whereas pain (p < 0.01), depression and mental fatigue (both p < 0.05) were in patients with disease duration >5 years.	Sleep problems are present in patients with MS with both short and long disease duration, but these problems are associated with different factors. These should be recognized and managed in addition to the treatment of sleep disorders.	
25224151	To explore the possible impact factors on daytime sleepiness among peritoneal patients from a single center in China. A cross-sectional study was conducted in 98 prevalent peritoneal dialysis (PD) patients using both the Pittsburgh Sleep Quality Index (PSQI) questionnaire of sleep quality and the Epworth Sleepiness Scale (ESS) questionnaire of excessive daytime sleepiness (EDS). Biochemical differences between daytime sleepiness and non-daytime sleepiness population were evaluated, following univariate and multivariable analysis to find the risk factors on sleep disturbance. The prevalence of "poor sleep quality" (PSQI > 5) was 74.49%, while daytime sleepiness (ESS ≥ 9) occurred in 22.45%. Mean PSQI was 9.06 ± 4.60 and EES was 6.31 ± 4.98. Compared to non-EDS cases, patients with ESS ≥ 9 had worse residual renal function (RRF), higher serum creatinine, higher serum magnesium and elevated serum ferritin. In univariate analysis, ESS correlated with serum albumin (r = 0.346, p = 0.015), phosphate (r = 0.313, p = 0.029), magnesium (r = 0.376, p = 0.008) and urinary Kt/V (r = -0.341, p = 0.029). Finally, multivariable linear regression indicated that urinary Kt/V, PSQI and magnesium were independent predictors of ESS score. EDS does exist in PD patients and is associated both with poor nighttime sleep quality and lower RRF. Hypermagnesemia may be a treatable risk factor to improve daytime tiredness.
25224072	This study evaluated the relationship between sleep disorders (SDs) and osteoporosis risk in Taiwan.From the Taiwan National Health Insurance data, we identified 44,690 newly diagnosed SD patients (846 with apnea and 43,844 without) from 1998 to 2001 and 89,380 comparisons without SD in the same period frequency matched by sex, age and diagnosis year. Incident osteoporosis was measured by the end of 2010.	Patients with apnea-SD and nonapnea SD exhibited a higher osteoporosis incidence rate than did the comparisons (9.97 and 13.3 vs. 6.77 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratio (HR) of osteoporosis was 2.98 (95% confidence interval [CI] = 2.36-3.74) in apnea-SD patients, compared with 2.76 (95% CI = 2.64-2.88) in nonapnea-SD patients after controlling for sex, age, comorbidities, and treatment. Greater HRs of osteoporosis were observed for female patients (4.00, 95% CI = 3.72-4.29) and those aged >64 years (42.0, 95% CI = 33.5-52.7) in the apnea SD sub-cohort. Apnea SD was associated with the highest risk of osteoporosis without fracture compared with both the nonapnea SD sub-cohort and comparisons.	Patients with sleep disorders have an elevated risk of osteoporosis, especially for women and the elderly.	
25223586	Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf by sleep or sleep deprivation. Here we investigated whether 5-methylcytosine (5mC) DNA modification at Bdnf promoters p1, p4 and p9 influences Bdnf1, Bdnf4 and Bdnf9a expression during the normal inactive phase or after sleep deprivation (SD) (3, 6 and 12 h, end-times being ZT3, ZT6 and ZT12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical Bdnf expression: Bdnf1 expression was highest at ZT6 and Bdnf4 lowest at ZT12. Such variation was not observed in the basal forebrain. Also Bdnf p1 and p9 methylation levels differed only in the cortex, while Bdnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced Bdnf1 and Bdnf4 with the similar pattern for Bdnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5mC levels at the cortical Bdnf p4 and p9. Regression analysis between the 5mC promoter levels and the corresponding Bdnf transcript expression revealed significant negative correlations for the basal forebrain Bdnf1 and cortical Bdnf9a transcripts in only non-deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that Bdnf transcription during the light phase of undisturbed sleep-wake cycle but not after SD is regulated at least partially by brain site-specific DNA methylation.
25222348	Extended wakefulness, sleep loss, and circadian misalignment are factors associated with an increased accident risk in shiftwork. Splitting shifts into multiple shorter periods per day may mitigate these risks by alleviating prior wake. However, the effect of splitting the sleep-wake schedule on the homeostatic and circadian contributions to neurobehavioural performance and subjective assessments of one's ability to perform are not known. Twenty-nine male participants lived in a time isolation laboratory for 13 d, assigned to one of two 28-h forced desynchrony (FD) schedules. Depending on the assigned schedule, participants were provided the same total time in bed (TIB) each FD cycle, either consolidated into a single period (9.33 h TIB) or split into two equal halves (2 × 4.67 h TIB). Neurobehavioural performance was regularly assessed with a psychomotor vigilance task (PVT) and subjectively-assessed ability was measured with a prediction of performance on a visual analogue scale. Polysomnography was used to assess sleep, and core body temperature was recorded to assess circadian phase. On average, participants obtained the same amount of sleep in both schedules, but those in the split schedule obtained more slow wave sleep (SWS) on FD days. Mixed-effects ANOVAs indicated no overall difference between the standard and split schedules in neurobehavioural performance or predictions of performance. Main effects of circadian phase and prior wake were present for both schedules, such that performance and subjective ratings of ability were best around the circadian acrophase, worst around the nadir, and declined with increasing prior wake. There was a schedule by circadian phase interaction for all neurobehavioural performance metrics such that performance was better in the split schedule than the standard schedule around the nadir. There was no such interaction for predictions of performance. Performance during the standard schedule was significantly better than the split schedule at 2 h of prior wake, but declined at a steeper rate such that the schedules converged by 4.5-7 h of prior wake. Overall, the results indicate that when the total opportunity for sleep per day is satisfactory, a split sleep-wake schedule is not detrimental to sleep or performance. Indeed, though not reflected in subjective assessments of performance capacity, splitting the schedule may be of some benefit, given its reduction of neurobehavioural impairment at night and its association with increased SWS. Therefore, for some industries that require operations to be sustained around the clock, implementing a split work-rest schedule may be of assistance. 
25222347	In any sport, successful performance requires a planned approach to training and recovery. While sleep is recognized as an essential component of this approach, the amount and quality of sleep routinely obtained by elite athletes has not been systematically evaluated. Data were collected from 70 nationally ranked athletes from seven different sports. Athletes wore wrist activity monitors and completed self-report sleep/training diaries for 2 weeks during normal training. The athletes also recorded their fatigue level prior to each training session using a 7-point scale. On average, the athletes spent 08:18 ± 01:12 h in bed, fell asleep at 23:06 ± 01:12 h, woke at 6:48 ± 01:30 h and obtained 06:30 ± 01:24 h of sleep per night. There was a marked difference in the athletes' sleep/wake behaviour on training days and rest days. Linear mixed model analyses revealed that on nights prior to training days, time spent in bed was significantly shorter (p = 0.001), sleep onset and offset times were significantly earlier (p < 0.001) and the amount of sleep obtained was significantly less (p = 0.001), than on nights prior to rest days. Moreover, there was a significant effect of sleep duration on pre-training fatigue levels (p ≤ 0.01). Specifically, shorter sleep durations were associated with higher levels of pre-training fatigue. Taken together, these findings suggest that the amount of sleep an elite athlete obtains is dictated by their training schedule. In particular, early morning starts reduce sleep duration and increase pre-training fatigue levels. When designing schedules, coaches should be aware of the implications of the timing of training sessions for sleep and fatigue. In cases where early morning starts are unavoidable, countermeasures for minimizing sleep loss - such as strategic napping during the day and correct sleep hygiene practices at night - should be considered. 
25221914	This study examined sleep hygiene practices and bedtime resistance and tested whether associations differed by child temperament. Parents of Head Start preschoolers (n = 374, 56% non-Hispanic white) completed the Going to Bed subscale of the Children's Sleep-Wake Scale (GTB; higher score reflects less bedtime resistance), Children's Sleep Hygiene Scale (CSHS; higher score reflects better sleep hygiene), and Child Behavior Questionnaire (Anger, Activity, Impulsivity subscales indicated difficult temperament). Monte Carlo simulation adjusted for demographic covariates tested associations of CSHS with GTB in children with more- vs. less-difficult temperaments. Children with more- vs. less-difficult temperaments experienced worse sleep hygiene (p < .0001) and had more bedtime resistance (p < .0001). Among children with more difficult temperaments, better sleep hygiene was linearly associated with less bedtime resistance (β = 1.28, 95% CI 0.77, 1.78). Among children with less difficult temperaments, the association followed a piecewise linear trend: sleep hygiene was not associated with bedtime resistance when CSHS scores were < 4.1 (β = 0.15, 95% CI -4.87, 3.13), but for CSHS scores ≥ 4.1, an increase in CSHS was associated with lower bedtime resistance (β = 1.33, 95% CI 1.00, 1.79). Consistent sleep hygiene is associated with less bedtime resistance and may be helpful in reducing bedtime resistance among children with more difficult temperaments.



25219940	Rett syndrome is a rare neurodevelopmental disorder usually affecting females, and is associated with a mutation in the MECP2 gene. Sleep problems occur commonly and we investigated the trajectories and influences of age, mutation and treatments. Data were collected at six time points over 12 years from 320 families registered with the Australian Rett Syndrome Database. Regression analysis was used to investigate relationships between sleep disturbances, age, mutation type and use of treatment, and latent class growth analysis was performed to identify sleep problem phenotypes and model the effect of mutation type. The age range of subjects was 2.0-35.8 years. The study showed that sleep problems occurred in more than 80% of individuals and the prevalence decreased with age. Night laughing and night screaming occurred in 77 and 49%, respectively, when younger. Those with a large deletion had a higher prevalence of night laughing, which often occurred frequently. Treatment was associated with a 1.7% reduction in risk of further sleep problems. High and low baseline prevalence groups were identified. Approximately three-quarters of girls and women with sleep disturbances were in the high baseline group and problems persisted into adulthood. Conversely, 57% with night laughing and 42% with night screaming in the high baseline group exhibited mild improvement over time. Mutation type was not found to be a significant predictor of group membership. In conclusion, the evolution of sleep problems differed between subgroups of girls and women with Rett syndrome, in part explained by age and genotype. Treatment was not associated with improvement in sleep problems.

25218899	Alzheimer's disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHR(lit/lit) mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHR(lit/lit) mice was significantly smaller than that in PS1APP/GHRHR(lit/+) mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition. 

25216071	Within sample female nurses/nurse assistants in three shift work, we explored the association of job strain with heart rate variability before and during sleep. The participants (n = 95) were recruited from the Finnish Public Sector Study, from hospital wards that belonged either to the top (high job strain [HJS], n = 42) or bottom quartiles on job strain (low job strain [LJS], n = 53) as rated by Job Content Questionnaire responses. A further inclusion criterion was that participants' own job strain was at least as high (HJS group) or low (LJS group) as their ward's average estimation. Three-week field measurements included sleep diary and actigraphy to study the participants' sleep patterns and sleep-wake rhythm. A subset of three pre-selected, circadian rhythm and recovery controlled measurement days, one morning shift, one night shift and a day off, included 24-h heart rate variability (HRV) measurements. The bootstrapped HRV parameters (HR, HF, LF, LF-to-HF-ratio and RMSSD) 30 min before and during 30 min of sleep with lowest average heart rate showed no statistically significant job strain group differences. No association of exposure to stressful work environment and HRV before and during sleep was found. 
25215524	Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis.Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily.	Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn.	Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.	
25213642	Sleep disorders in physicians who perform shift work can result in increased risks of health problems that negatively impact performance and patient safety. Even those who cope well with shift work are likely to suffer from sleep disorders. The aim of this manuscript is to discuss possible causes, contributing factors and consequences of sleep disorders in physicians and to identify measures that can improve adaptation to shift work and treatment strategies for shift work-associated sleep disorders. The risk factors that influence the development of sleep disorders in physicians are numerous and include genetic factors (15 % of the population), age (> 50 years), undiagnosed sleep apnea,, alcohol abuse as well as multiple stress factors inherent in clinical duties (including shift work), research, teaching and family obligations. Several studies have reported an increased risk for medical errors in sleep-deprived physicians. Shift workers have an increased risk for psychiatric and cardiovascular diseases and shift work may also be a contributing factor to cancer. A relationship has been reported not only with sleep deprivation and changes in food intake but also with diabetes mellitus, obesity, hypertension and coronary heart disease. Nicotine and alcohol consumption are more frequent among shift workers. Increased sickness and accident rates among physicians when commuting (especially after night shifts) have a socioeconomic impact. In order to reduce fatigue and to improve performance, short naps during shiftwork or naps plus caffeine, have been proposed as coping strategies; however, napping during adverse circadian phases is less effective, if not impossible when unable to fall asleep. Bright and blue light supports alertness during a night shift. After shiftwork, direct sunlight exposure to the retina can be avoided by using dark sunglasses or glasses with orange lenses for commuting home. The home environment for daytime sleeping after a night shift should be very dark to allow endogenous melatonin secretion, which is a night signal and supports continuous sleep. Sleep disorders can be treated with timed light exposure, as well as behavioral and environmental strategies to compensate for sleep deprivation. Fatigue due to sleep deprivation can only be systematically treated with sleep.
25213135	Problematic sleep can be detrimental to the development of important cognitive functions, such as working memory, and may have the potential for negative behavioral consequences, such as risk-taking. In this way, sleep problems may be particularly harmful for youth-whose cognitive abilities are still developing and who are more susceptible to risky behavior. Using data from a large, national, longitudinal study, continuity and change in sleep problems were examined from 2 to 15 years of age and associated with deficits in working memory at age 15 and risk taking behaviors at age 18. Participants (N = 1,364 children; 48.3% female) were assessed for sleep problems (parent-report), working memory (behavioral task), and risk taking behavior (youth self-report). The sample was predominantly White (80.4%); additional races represented in the sample included Black/African American (12.9%), Asian/Pacific Islander (1.6%), American Indian/Eskimo/Aleut (.4%), and Other (4.7%). The findings suggest that sleep problems are likely to cascade across development, with sleep problems demonstrating continuity from infancy to early childhood, early childhood to middle childhood, and middle childhood to adolescence. Although sleep problems in infancy, early childhood, and middle childhood were not directly related to adolescent working memory, sleep problems during adolescence were associated with poorer adolescent working memory. In turn, these deficits in working memory were related to greater risk taking in late adolescence. In summary, the present results suggest that sleep problems in earlier periods are indicative of risk for sleep problems later in development, but that sleep problems in adolescence contribute uniquely to deficits in working memory that, in turn, lead to risky behavior during late adolescence.
25213049	There is a need to understand more about modifiable health behaviors that may be related to asthma control. Sleep is one such health behavior that has received little attention in pediatric asthma research.To examine sleep duration, sleep hygiene, and insomnia in adolescents with and without asthma.	Adolescents (n = 298; 51% boys; age range, 12-17 years; 48% with asthma) from the general community completed an online survey that included the International Study of Asthma and Allergies in Childhood questionnaire, the Children's Report of Sleep Patterns, and the Insomnia Severity Index.	Sleep duration did not differ between the asthma severity groups, yet more adolescents with severe asthma reported insufficient weekday sleep (44%) versus adolescents without asthma (31%). Significant asthma group differences were found for sleep hygiene, with adolescents with severe asthma reporting poorer sleep hygiene. Almost twice as many adolescents with severe asthma reported clinically significant insomnia than adolescents with mild or no asthma. Sleep hygiene variables were correlated with insomnia, although these associations did not differ between adolescents with and without severe asthma. Finally, both insomnia severity and asthma severity were significant predictors of daytime sleepiness; however, asthma severity accounted for only 2% of the variance compared with 28% of the variance accounted for by insomnia severity.	Many adolescents with severe asthma regularly obtain insufficient sleep, have poor sleep hygiene, and experience clinically significant insomnia. It is important to ask adolescents with asthma about sleep duration, sleep hygiene, and insomnia because there are effective interventions that can improve sleep for these youths.	
25211024	It has not hitherto been clarified whether there is an association between dietary behavior and circadian variation in autonomic nervous system activity among shift workers. This study examines diurnal 24-h rhythm in heart rate variability (HRV) and dietary behavior among rotating shift workers, while taking into account the sleep-wake cycle and physical activity. The subjects were 11 female and 2 male nurses or caregivers working in a rotating 2-shift system at a health care facility. All the subjects were asked to undergo 24-h electrocardiograph and step count recordings, and to record the time of each meal and the amounts of each food and beverage consumed. Coarse graining spectral analysis was used for approximately 10-min segments of HRV to derive the total power (TOT: >0.04 Hz) of the periodic components and the integrated power of periodic components in the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: >0.15 Hz) ranges. Then the ratio of HF power to TOT (HF nu) and the ratio of LF power to HF power (LF/HF) were calculated to assess cardiac vagal tone and cardiac sympathovagal balance, respectively. Single cosinor analysis was used to obtain 24-h period variations in both variables of HRV. Acrophases of HF nu and LF/HF expressed in time since awakening were significantly (p<0.05) delayed for subjects having breakfast at a later time after awakening. Multivariable regression analysis indicated that the timing of breakfast, the ratio of energy intake at dinner to total energy intake, and total energy intake were correlated to the acrophases of HF nu and/or LF/HF. These results suggest that the phase angle between circadian variation in cardiac autonomic nervous system activity and the sleep-wake cycle may be associated with dietary behavior in shift workers. 
25210880	In a cohort of 17 patients treated for nonfunctioning pituitary macroadenoma (NFMA), we observed alterations in polysomnographic sleep characteristics and actigraphic sleep-wake rhythmicity, and subjective fatigue, daytime somnolence, and low sleep quality. We aimed to confirm the actigraphic data in a larger scale cohort of NFMA patients, powered to address risk factors for altered rhythmicity, including the effects of hydrocortisone replacement.Sleep-wake rhythmicity in treated NFMA patients was measured using actigraphy for 7 days, and subjective sleep quality and quality of life (QoL) with validated questionnaires. To assess the influence of hydrocortisone dependency, we additionally studied patients with Addison's disease (AD). The results were compared with matched healthy controls.	We included 69 NFMA patients in long-term remission after trans-sphenoidal surgery on stable replacement therapy for hypopituitarism, 21 AD patients, and 58 controls. NFMA patients reported severely impaired QoL, sleep quality, and increased daytime sleepiness. The day-night dichotomy of activity was fragmented, with decreased daytime activity and a tendency for increased nighttime activity. Preoperative visual field defects (VFD) were associated with this fragmentation, and vasopressin deficiency with decreased sleep efficiency, independent of age, hypopituitarism, or radiotherapy. AD patients showed similar decreases in daytime functioning, but normal subjective and objective sleep, and no daytime sleepiness.	NFMA patients suffer from altered sleep-wake rhythmicity. Hydrocortisone dependency may explain part of the decreased daytime functioning, but the independent influence of VFD and differences between AD and NFMA patients point towards a role for dysfunction of the adjacent suprachiasmatic nucleus (SCN).	
25209268	Extrasynaptic δ-subunits containing GABAA receptors (δGABAARs) are sensitive targets for several commonly used hypnotic agents and mediate tonic neuronal inhibition. δGABAARs are highly expressed within the thalamus and their activation promotes a switch from tonic to burst firing in vitro. Here we test two hypotheses in vivo. (1) Activation of thalamic δGABAARs will elicit electrocortical signatures consistent with widespread thalamocortical burst firing such as increased delta oscillations (1-4 Hz) and reciprocal changes in spindle-like oscillations (7-14 Hz). (2) These signatures will be recapitulated by the general anesthetic etomidate, if the electrocortical effects of etomidate at the thalamus are mediated by δGABAARs. Microperfusion of the δGABAAR-preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; 10 and 50 μM) into the ventrobasal complex produced significant effects on electrocortical activity in wild-type mice, but not in mice lacking δGABAARs (Gabrd(-/-)), i.e., the effects with THIP were dependent on δGABAARs. THIP (1) increased 1-4 Hz power in wakefulness and nonrapid-eye movement (NREM) sleep; (2) reduced spindle-like oscillations in NREM sleep; and (3) increased the speed of stable transitions into NREM sleep, indicating effects on state-space dynamics. In contrast, microperfusion of etomidate (10 and 30 μM) into the ventrobasal complex produced effects on electrocortical activity that were independent of δGABAARs, i.e., effects occurred in wild-type and Gabrd(-/-) mice. Etomidate (1) decreased 1-4 Hz power, increased 8-12 Hz, and/or 12-30 Hz power in all sleep-wake states; (2) increased spindle-like oscillations; and (3) increased REM sleep expression. These results indicate that thalamic δGABAARs promote electrocortical signatures of deep NREM sleep, but do not mediate the effects of etomidate at the thalamus in vivo.
25207930	To examine longitudinal change in cardiorespiratory fitness and odds of incident sleep problems.A cohort of 7368 men and 1155 women, age 20-85 yr, was recruited from the Aerobics Center Longitudinal Study. The cohort did not complain of sleep problems, depression, or anxiety at their first clinic visit. Cardiorespiratory fitness assessed at four clinic visits between 1971 and 2006, each separated by an average of 2-3 yr, was used as a proxy measure of cumulative physical activity exposure. Sleep complaints were made to a physician during follow-up.	Across visits, there were 784 incident cases of sleep complaints in men and 207 cases in women. After adjusting for age, time between visits, body mass index, smoking, alcohol use, chronic medical conditions, complaints of depression or anxiety at each visit, and fitness at visit 1, each minute of decline in treadmill endurance (i.e., a decline in cardiorespiratory fitness of approximately 0.5 MET) between the ages of 51 and 56 yr increased the odds of incident sleep complaints by 1.7% (range = 1.0%-2.4%) in men and by 1.3% (range = 0.0%-2.8%) in women. Odds were ∼8% higher per minute decline in people with sleep complaints at visits 2 and 3.	The results indicate that maintenance of cardiorespiratory fitness during middle age, when decline in fitness typically accelerates and risk of sleep problems is elevated, helps protect against the onset of sleep complaints made to a physician.	
25207602	Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. The efficacy and safety profiles of these compounds in the treatment of the indicated disorders are reviewed. Accumulating evidence indicates that sleep-wake disorders and co-existing medical conditions are mutually exacerbating. This understanding has now been incorporated into the new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Therefore, when evaluating the risk/benefit ratio of sleep drugs, it is pertinent to also evaluate their effects on wake and comorbid condition. Beneficial effects of melatonin receptor agonists on comorbid neurological, psychiatric, cardiovascular and metabolic symptomatology beyond sleep regulation are also described. The review underlines the beneficial value of enhancing physiological sleep in comorbid conditions. 
25204612	Those suffering insomnia symptoms generally report daytime impairments. However, research has not assessed whether this relationship holds on a nightly basis, despite the strongly held belief that a night of poor sleep impairs mood and functioning the following day. The objective of this study was to test this relationship in a group of older poor sleepers with insomnia symptoms compared with good sleepers. This study utilized a within-subjects design to investigate day-to-day subjective daytime functioning and its relation to the previous night's sleep. Seventeen older individuals (mean age: 67.5 years) were identified with a retrospective questionnaire and 2 weeks of sleep-wake diary to have poor sleep consistent with insomnia. Seventeen good sleepers (mean age: 67.8 years) were selected using the same measures. Participants reported their beliefs about sleep and daytime functioning on the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16). One week later they commenced a 14-day period of sleep-wake diaries and concurrent responses to a modified Daytime Insomnia Symptom Scale (DISS). Results showed significant night-to-day covariation between sleep efficiency and daytime functioning for individuals with poor sleep (r = 0.34), but not for good sleepers (r = 0.08). Those poor sleepers who held this covariation belief most strongly were those who subsequently showed this night-to-day relationship the most strongly (r = 0.56). This was not true for good sleepers. For those suffering insomnia, these findings demonstrate their belief that a poor sleep is followed by an impaired daytime, consistent with their experience.
25204464	To examine the efficacy of tasimelteon for the treatment of non-24-hour sleep-wake disorder using evidence from controlled clinical trials.Citations in Google Scholar and PubMed from January 1, 2008, to May 31, 2014, were identified using tasimelteon as the search term.	Results were limited to human trials published in English. Trials that compared tasimelteon with placebo were included.	A phase II trial (n = 39) evaluated the effects of tasimelteon versus placebo on improvements in sleep efficiency and the ability to shift circadian rhythms over 3 days. Significant shifts in circadian rhythm were only observed for 100-mg tasimelteon. A phase III trial (n = 412) evaluated the effects of tasimelteon versus placebo on assessment of latency to persistent sleep and wake after sleep onset; significant advantages were observed in tasimelteon recipients. The SET (Safety and Efficacy of Tasimelteon) trial (n = 84) enrolled blind men and women with Non-24. They received placebo or tasimelteon 20 mg daily. Tasimelteon recipients had significantly (P = 0.0025) better entrainment and N24CRS scores. The RESET (Randomized Withdrawal Study of the Efficacy and Safety of Tasimelteon) trial (n = 20) enrolled entrained participants from the SET trial who received 20 mg of tasimelteon or placebo daily for 8 weeks. The primary objective was to evaluate the maintenance of effect of tasimelteon to entrain circadian rhythms. Tasimelteon was associated with significantly (P = 0.0055) greater entrainment than placebo.	Tasimelteon improves sleep initiation and maintenance in patients with Non-24 who have a shift in endogenous circadian rhythms. However, the cost of this agent limits its use.	
25203899	The nature of sleep-wake abnormalities in individuals with mental disorders remains unclear. The present study aimed to examine the differences in objective ambulatory measures of the sleep-wake and activity cycles across young people with anxiety, mood or psychotic disorders.Participants underwent several days of actigraphy monitoring. We divided participants into 5 groups (control, anxiety disorder, unipolar depression, bipolar disorder, psychotic disorder) according to primary diagnosis.	We enrolled 342 participants aged 12-35 years in our study: 41 healthy controls, 56 with anxiety disorder, 135 with unipolar depression, 80 with bipolar disorder and 30 with psychotic disorders. Compared with the control group, sleep onset tended to occur later in the anxiety, depression and bipolar groups; sleep offset occurred later in all primary diagnosis groups; the sleep period was longer in the anxiety, bipolar and psychosis groups; total sleep time was longer in the psychosis group; and sleep efficiency was lower in the depression group, with a similar tendency for the anxiety and bipolar groups. Sleep parameters were significantly more variable in patient subgroups than in controls. Cosinor analysis revealed delayed circadian activity profiles in the anxiety and bipolar groups and abnormal circadian curve in the psychosis group.	Although statistical analyses controlled for age, the sample included individuals from preadolescence to adulthood. Most participants from the primary diagnosis subgroups were taking psychotropic medications, and a large proportion had other comorbid mental disorders.	Our findings suggest that delayed and disorganized sleep offset times are common in young patients with various mental disorders. However, other sleep-wake cycle disturbances appear to be more prominent in broad diagnostic categories.	
25203719	Adenosine A2A antagonists are believed to have therapeutic potential in the treatment of Parkinson's disease (PD). We have characterized the dual adenosine A2A/A1 receptor antagonist JNJ-40255293 (2-amino-8-[2-(4-morpholinyl)ethoxy]-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one). JNJ-40255293 was a high-affinity (7.5 nM) antagonist at the human A2A receptor with 7-fold in vitro selectivity versus the human A1 receptor. A similar A2A:A1 selectivity was seen in vivo (ED50's of 0.21 and 2.1 mg/kg p.o. for occupancy of rat brain A2A and A1 receptors, respectively). The plasma EC50 for occupancy of rat brain A2A receptors was 13 ng/mL. In sleep-wake encephalographic (EEG) studies, JNJ-40255293 dose-dependently enhanced a consolidated waking associated with a subsequent delayed compensatory sleep (minimum effective dose: 0.63 mg/kg p.o.). As measured by microdialysis, JNJ-40255293 did not affect dopamine and noradrenaline release in the prefrontal cortex and the striatum. However, it was able to reverse effects (catalepsy, hypolocomotion, and conditioned avoidance impairment in rats; hypolocomotion in mice) produced by the dopamine D2 antagonist haloperidol. The compound also potentiated the agitation induced by the dopamine agonist apomorphine. JNJ-40255293 also reversed hypolocomotion produced by the dopamine-depleting agent reserpine and potentiated the effects of l-dihydroxyphenylalanine (L-DOPA) in rats with unilateral 6-hydroxydopamine-induced lesions of the nigro-striatal pathway, an animal model of Parkinson's disease. Extrapolating from the rat receptor occupancy dose-response curve, the occupancy required to produce these various effects in rats was generally in the range of 60-90%. The findings support the continued research and development of A2A antagonists as potential treatments for PD.

25201715	Sleep disorders are among the most common non-motor symptoms in Parkinson's disease.The prevalence of parasomnias and their association with other symptoms were studied in a questionnaire study among 1447 randomly selected Parkinson patients, aged 43 to 89 years. The response rate was 59.0% and of these 77% had answered to all questions that were used in the analyses (N = 661).	The prevalence of REM sleep behavior disorder (RBD) evaluated by the RBDSQ ≥ 6 was 39.0%. The occurrences of other parasomnias (≥ 1/week) in patients with PD were: nightmares 17.2%, night terrors 3.9%, sleepwalking 1.8%, enuresis 21.0%, and hallucinations 15.3%. Occurrences (≥ 1/week) of the isolated sleep symptoms were: nocturnal sweating 28.8%, bruxism 4.7%, and sleep talking 21.7%. Association of RBD with sleepwalking (parasomnia overlap disorder) was found in 1.7% of all PD patients. Adjusted logistic regression analysis showed that weekly nightmares (OR 12.5; 95% CI 5.3 to 29.7), hallucinations (OR 5.1; 2.1 to 12.4), sleep talking (OR 11.6; 5.9 to 22.8), male gender (OR 1.9; 1.1 to 3.1), and restless legs syndrome (OR 4.7; 1.7 to 13.2) associated with the presence of RBD.	Parkinson patients with RBD have often also other parasomnias and/or isolated sleep symptoms.	
25201169	People with severe asthma experience significant respiratory symptoms and suffer adverse effects of oral corticosteroids (OCS), including disturbed mood and physical symptoms. OCS impacts on health-related quality of life (HRQoL) have not been quantified. Asthma HRQoL scales are valid as outcome measures for patients requiring OCS only if they assess the deficits imposed by OCS.The aim of this study was to compare the burden of disease and treatment in patients with severe asthma with items in eight asthma-specific HRQoL scales.	Twenty-three patients with severe asthma recruited from a severe asthma clinic were interviewed about the impact of their respiratory symptoms and the burden of their treatment. The domains from a thematic analysis of these interviews were compared with the items of eight asthma-specific HRQoL scales.	In addition to the burden caused by symptoms, ten domains of OCS impact on HRQoL were identified: depression, irritability, sleep, hunger, weight, skin, gastric, pain, disease anxiety, and medication anxiety. Some patients experienced substantial HRQoL deficits attributed to OCS. Although all HRQoL scales include some OCS-relevant items, all eight scales fail to adequately assess the several types of burden experienced by some patients while on OCS.	The burden of OCS in severe asthma is neglected in policy and practice because it is not assessed in outcome studies. Existing asthma HRQoL scales provide an overly positive estimation of HRQoL in patients with frequent exposure to OCS and underestimate the benefit of interventions that reduce OCS exposure. Changes to existing measurement procedures are needed.	
25201053	A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes. 
25199126	Flight timing is expected to influence pilot fatigue because it determines the part of the circadian body clock cycle that is traversed during a flight. However the effects of flight timing are not well-characterized because field studies typically focus on specific flights with a limited range of departure times and have small sample sizes. The present project combined data from four studies, including 13 long-range and ultra-long range out-and-back trips across a range of departure and arrival times (237 pilots in 4-person crews, 730 flight segments, 1-3 d layovers).All studies had tripartite support and underwent independent ethical review. Sleep was monitored (actigraphy) from 3 d prior to ≥ 3 d post-trip. Preflight and at top of descent (TOD), pilots rated their sleepiness (Karolinska Sleepiness Scale) and fatigue (Samn-Perelli scale), and completed a psychomotor vigilance task (PVT) test. Mixed model ANOVA identified independent associations between fatigue measures and operational factors (domicile times of departure and arrival, flight duration and direction, landing versus relief crew).	Preflight subjective fatigue and sleepiness were lowest for flights departing 14:00-17:59. Total in-flight sleep was longest on flights departing 18:00-01:59. At TOD, fatigue and sleepiness were higher and PVT response speeds were slower on flights arriving 06:00-09:59 than on flights arriving later. PVT response speed at TOD was also faster on longer flights.	The findings indicate the influence of flight timing (interacting with the circadian body clock cycle), as well as flight duration, on in-flight sleep and fatigue measures at TOD.	
25198548	Excessive daytime sleepiness is a frequent complaint in Parkinson's disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson's disease (PD) using a wide range of potential predictors.One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.	Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.	We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.	
25197895	Airplane emergency medical services (AEMS) operators use fixed-wing airplanes to undertake rapid response, round-the-clock medical transport missions. This paper explores the structure of long-range, multileg AEMS missions and the sleep and sleepiness of the pilots who work them.During nine long-range AEMS missions, pilots kept a sleep and sleepiness logbook and wore a wrist activity monitor to evaluate the timing of sleep/wake.	Missions had a mean duration of 20 h 00 min ± 2 h 39 min, involved two to four flight legs, and were crewed by three or four pilots who rotated between operating and sleeping in curtained-off bunks. The pilots obtained a mean of 15 h 26 min ± 4 h 51 min and 7 h 54 min ± 1 h 33 min of sleep in the 48 h and 24 h prior to checking in for duty, respectively. During missions, a mean of 3 h 33 min ± 1 h 46 min of sleep was taken, usually across two in-flight sleep periods. Karolinska Sleepiness Scores (KSS) at top of climb and top of descent were typically less than 5 ('neither alert nor sleepy'). A small number of individual higher KSS scores were recorded on the longest missions and on flights between 02:00 and 06:00.	These findings suggest that despite the long duration, timing, and multileg nature of AEMS missions, it is possible via careful design and management to operate these missions with appropriate levels of pilot alertness.	
25197810	To assess how the characteristics of slow waves and spindles change in the falling-asleep process.Participants undergoing overnight high-density electroencephalographic recordings were awakened at 15- to 30-min intervals. One hundred forty-one falling-asleep periods were analyzed at the scalp and source level.	Sleep laboratory.	Six healthy participants.	Serial awakenings.	The number and amplitude of slow waves followed two dissociated, intersecting courses during the transition to sleep: slow wave number increased slowly at the beginning and rapidly at the end of the falling-asleep period, whereas amplitude at first increased rapidly and then decreased linearly. Most slow waves occurring early in the transition to sleep had a large amplitude, a steep slope, involved broad regions of the cortex, predominated over frontomedial regions, and preferentially originated from the sensorimotor and the posteromedial parietal cortex. Most slow waves occurring later had a smaller amplitude and slope, involved more circumscribed parts of the cortex, and had more evenly distributed origins. Spindles were initially sparse, fast, and involved few cortical regions, then became more numerous and slower, and involved more areas.	Our results provide evidence for two types of slow waves, which follow dissociated temporal courses in the transition to sleep and have distinct cortical origins and distributions. We hypothesize that these two types of slow waves result from two distinct synchronization processes: (1) a "bottom-up," subcorticocortical, arousal system-dependent process that predominates in the early phase and leads to type I slow waves, and (2) a "horizontal," corticocortical synchronization process that predominates in the late phase and leads to type II slow waves. The dissociation between these two synchronization processes in time and space suggests that they may be differentially affected by experimental manipulations and sleep disorders.	
25197809	To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation.Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake.	Sleep laboratory.	Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT.	Thirty-eight hours of continuous wakefulness.	We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] < 5%). Biological pathways were enriched for biosynthetic processes during sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR < 5%). The main change with sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes.	Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity.	
25196321	In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo-controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug-free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep-wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non-significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate.

25195152	Recent studies in troops deployed to Iraq and Afghanistan have shown that combat exposure and exposure to deployment-related stressors increase the risk for the development of mental health symptoms. The aim of this study is to assess the prevalence of mental health symptoms in a cohort of Dutch military personnel prior to and at multiple time-points after deployment.Military personnel (n=994) completed various questionnaires at 5 time-points; starting prior to deployment and following the same cohort at 1 and 6 months and 1 and 2 years after their return from Afghanistan.	The prevalence of symptoms of fatigue, PTSD, hostility, depression and anxiety was found to significantly increase after deployment compared with pre-deployment rates. As opposed to depressive symptoms and fatigue, the prevalence of PTSD was found to decrease after the 6-month assessment. The prevalence of sleeping problems and hostility remained relatively stable.	The prevalence of mental health symptoms in military personnel increases after deployment, however, symptoms progression over time appears to be specific for various mental health symptoms. Comprehensive screening and monitoring for a wide range of mental health symptoms at multiple time-points after deployment is essential for early detection and to provide opportunities for intervention.	This project was funded by the Dutch Ministry of Defence.	
25194823	Sleep length and architecture are potential markers of progressive cognitive impairment, while neuropsychiatric symptoms and APOE4- haplotypes have been associated with more sleep complaints in patients with dementia due to Alzheimer's disease (AD). In this cross-sectional study, we sought to investigate which factors might be related to sleep satisfaction in patients with AD. A total of 217 consecutive patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functional impairment for activities of daily living, caregiver burden, APOE haplotypes, self-reported sleep satisfaction and length of sleep. Statistical comparisons were conducted with significance at p<0.05. Concerning sleep complaints, 179 patients (82.5%) reported satisfactory sleep, while 38 (17.5%) were unsatisfied, with no relation to age, sex, APOE haplotypes, obesity, education, marital status, alcohol consumption or smoking found. Length of sleep (p=0.011) and behavioural symptoms (p=0.009) had significant associations with sleep satisfaction. Length of sleep was positively correlated with apathy (p=0.014) and scores on the Clock Drawing Test (p=0.015), and inversely correlated with anxiety (p=0.015) and independence for instrumental activities of daily living (p=0.003). Patients who were treated with memantine (p=0.02) or anti-psychotics (p<0.01) had longer duration of sleep. In conclusion, behavioural symptoms had strong associations with sleep satisfaction, which is highly correlated with length of sleep in patients with AD. Functional independence, apathy, anxiety, use of memantine or anti-psychotics, and scores on the Clock Drawing Test were significantly associated with length of sleep in this sample. 
25194583	Behavioral sleep problems are common in children with attention-deficit/hyperactivity disorder (ADHD), yet their persistence or otherwise is unknown. We examined behavioral sleep problem trajectories, types of sleep problems experienced, and associated risk/protective factors.	Prospective cohort study.	Twenty-one pediatric practices across Victoria, Australia.	A total of 195 children with ADHD (5-13 years).	Sleep problem trajectories classified as never, transient, or persistent on the basis of sleep problem severity measured at baseline, 6, and 12 months. Explanatory variables: Types of sleep problems, internalizing and externalizing comorbidities, ADHD symptom severity and medication use, autism spectrum disorder, caregiver mental health, and sociodemographic factors.	Multinomial logistic regression models.	Sleep problems fluctuated over 12 months, but for 10% of children they persisted. In adjusted analyses, co-occurring internalizing and externalizing comorbidities were a risk factor for persistent (odds ratio (OR) 9.2, 95% confidence interval (CI) 1.6, 53.9, p = 0.01) and transient (OR 3.7, 95% CI 1.5, 8.8, p = 0.003) sleep problems, while greater ADHD symptom severity and poorer caregiver mental health were risk factors for persistent and transient sleep problems, respectively.	Sleep problems in children with ADHD are commonly transient, but in a subgroup they are characterized as persistent. Early preventive/intervention strategies should target children at risk of persistent sleep problems.	
25194193	Upper airway muscle motoneurons, as assessed at the level of the motor unit, have a range of different discharge patterns, varying as to whether their activity is modulated in phase with the respiratory cycle, are predominantly inspiratory or expiratory, or are phasic as opposed to tonic. Two fundamental questions raised by this observation are: how are synaptic inputs from premotor neurons distributed over motoneurons to achieve these different discharge patterns; and how do different discharge patterns contribute to muscle function? We and others have studied the behavior of genioglossus (GG) and tensor palatini (TP) single motor units at transitions from wakefulness to sleep (sleep onset), from sleep to wakefulness (arousal from sleep), and during hypercapnia. Results indicate that decreases or increases in GG and TP muscle activity occur as a consequence of derecruitment or recruitment, respectively, of phasic and tonic inspiratory-modulated motoneurons, with only minor changes in rate coding. Further, sleep-wake state and chemical inputs to this "inspiratory system" appear to be mediated through the respiratory pattern generator. In contrast, phasic and tonic expiratory units and units with a purely tonic pattern, the "tonic system," are largely unaffected by sleep-wake state, and are only weakly influenced by chemical stimuli and the respiratory cycle. We speculate that the "inspiratory system" produces gross changes in upper airway muscle activity in response to changes in respiratory drive, while the "tonic system" fine tunes airway configuration with activity in this system being determined by local mechanical conditions. 
25193739	This cross-sectional study evaluated the influence of sleep quality and pain perceptions on different dimensions of quality of life in community-dwelling persons with dementia. Evaluations of pain were collected using Visual Analog Scale (VAS), sleep disruption using Pittsburg Sleep Quality Index (PSQI) items, and quality of life indicators using the DemQOL-Proxy in 88 persons with dementia and their family caregivers. Lower overall quality of life was associated with the presence of pain and symptoms of sleep disruption when controlling for mental status, age, and number of health conditions. Pain and sleep symptoms were differentially associated with different aspects of QoL. As symptoms negatively impact quality of life but are modifiable, better clinical procedures are needed to prevent and also identify and treat symptoms of pain and sleep disturbance in community-dwelling persons with dementia. 
25193423	Limited data exist on the association of symptom burden, daily activity impairment, and work productivity (WP) in patients with advanced breast cancer. This cross-sectional analysis evaluated baseline patient-reported outcomes (PROs) in patients with locally recurrent or metastatic breast cancer (MBC) receiving first-line hormonal therapy or chemotherapy and/or targeted therapy in the VIRGO observational study. The primary PRO study endpoint, symptom severity and interference score, was measured using the MD Anderson Symptom Inventory (MDASI). Secondary endpoints included Activity Level Scale (ALS), health-related quality of life (HRQOL), and Work Productivity and Activity Impairment Questionnaire (WPAI:SHP) scores. Overall, 152 patients (chemotherapy cohort, 104; hormonal therapy cohort, 48) answered questionnaires. Fatigue, decreased sexual interest, disturbed sleep, emotional distress, and drowsiness were the most common severe symptoms, and were of moderate-to-severe intensity in 38.8%-52.0% of patients. Mean percent daily activity impairment was 30% for study patients, and WP impairment ranged from 20% to 40% across indices in employed patients (n, 58). Significant positive correlations existed for MDASI severity and interference scores with activity impairment and WP indices (Pearson correlation coefficients [R] = 0.47-0.82; p < 0.0001). ALS and overall HRQOL correlated negatively with these indices (R = -0.41 to -0.60; p ≤ 0.001). After adjustment for potential confounders, MDASI symptom interference and ALS were significant predictors of activity and WP impairment. Our results indicate patients receiving treatment for MBC are symptomatic with significant daily activity and/or WP impairment. Symptom severity and interference, functional status, and overall HRQOL were moderately correlated with perceived work-related ability.
25193034	The retina is the only part of the central nervous system that is exposed to light radiation between 400 and 780 nm. Short wavelength light (SWL) ranging between 400 and 480 nm are absorbed maximally by chromophores located in mitochondria. An abundance of mitochondria are located in retinal ganglion cell (RGC) intraocular axons and photoreceptor inner segments and as a consequence SWL will impact these organelles. The purpose of this article is to summarise the experimental evidence for the possible negative effects of SWL on RGC mitochondria, in situ. The threat of damage to photoreceptor mitochondria may be less than to RGCs, since macular carotenoid, located chiefly in Henle's layer of the photoreceptor inner segment absorbs SWL. The article underlines the hypothesis that SWL contributes to RGC death when these neurones are not in an optimum homoeostatic state as is likely to occur in conditions such as glaucoma and possibly other types of pathologies and even old age. A case therefore exists for the idea that shielding RGCs to slow down visual loss in certain circumstances. This can theoretically be achieved with lenses that reduce transmission of SWL but specifically allow for maximal transmission of 479 nm light to stimulate melanopsin and maintain an optimum sleep/wake cycle.
25192629	The purpose of this study is to identify factors that are associated with poor quality of life (QOL) among cervical cancer survivors.Patients identified through the California Cancer Registry were recruited to participate in a randomized counseling intervention. Patient-reported outcomes (PROs) were collected at study baseline (9-30 months post-diagnosis) and subsequent to the intervention. Multivariable linear models were used to identify independent factors associated with poor baseline QOL.	Non-Hispanic (N=121) and Hispanic (N=83) women aged 22-73 completed baseline measures. Approximately 50% of participants received radiation therapy with or without chemotherapy. Compared to the US population, cervical cancer patients reported lower QOL and significantly higher levels of depression and anxiety (26% and 28% >1 SD above the general population means, respectively). Among those in the lowest quartile for QOL, 63% had depression levels >1 SD above the mean. In addition, treatment with radiation±chemotherapy (p=0.014), and self-reported comorbidities predating the cancer diagnosis (p<0.001) were associated with lower QOL. Sociodemographic characteristics explained only a small portion of variance in QOL (r(2)=0.23). Persistent gynecologic problems, low social support, depression, somatization, less adaptive coping, comorbidities, sleep problems and low education were all independently associated with low QOL in multivariate analysis (r(2)=0.74).	We have identified key psychological and physical health factors that contribute significantly to poor quality of life subsequent to definitive cancer treatment. The majority of these factors are amenable to supportive care interventions and should be evaluated at the time of primary treatment.	
25192605	We aimed to measure the diurnal changes of critical flicker frequency in healthy subjects and cirrhotic patients and to investigate their relationship with sleep disturbance.Cirrhotic patients and healthy volunteers were included. All groups completed the Pittsburgh Sleep Quality Index and a simple sleep questionnaire. Sleep disturbance was defined as a Pittsburgh Sleep Quality Index score of >5. Critical flicker frequency was measured twice a day to detect diurnal abnormalities.	Overall, 59 cirrhotic patients (54.2% males, Mean Age 59 ± 11 years) and 18 controls (39.9% males, Mean Age 58 ± 9 years) were included. Sleep disturbances were more common in cirrhotics (66.1%) than controls (38.9%, p<0.05). In cirrhotics, the critical flicker frequency was not related to decompensation. The nocturnal values were higher than the morning values in cirrhotics (64.4%), but not in controls (p<0.0001). Additionally, sleep disturbances were more common in cirrhotics who had higher nocturnal values (p<0.05).	Changes in the diurnal critical flicker frequency were observed in cirrhotics but not in controls. Sleep disturbances in cirrhotics appear to be associated with deviations of the diurnal rhythm of critical flicker frequency rather than with clinical parameters such as the clinical stages of cirrhosis and the Model For End-Stage Liver Disease and Child-Pugh scores.	
25192320	The factors associated with persistent delirium, in contrast to resolved delirium, have not been studied well. The aim of our present study was to identify the factors associated with delirium resolution as measured by the Memorial Delirium Assessment Scale (MDAS) and functional improvement as measured by the Karnofsky Performance Status (KPS) scale.All subjects were recruited from psychiatric referrals at the Memorial Sloan Kettering Cancer Center (MSKCC). The two study instruments were performed at baseline (T1), at 2-3 days (T2), and at 4-7 days (T3). Subjects with persistent delirium were compared to those with resolved delirium in respect to sociodemographic and medical variables.	Overall, 26 out of 111 patients had persistent delirium. These patients were older, predominantly male, and had more frequently preexisting comorbid dementia. Among cancer diagnoses and stage of illness, brain cancer and terminal illness contributed to persistent delirium or late response, whereas gastrointestinal cancer was associated with resolved delirium. Among etiologies, infection responded late to delirium management, usually at one week. Furthermore, delirium was more severe in patients with persistent delirium from baseline through one week. At baseline, MDAS scores were 20.1 in persistent delirium compared to 17 to 18.8 in resolved delirium (T2 and T3), and at one week of management (T3), MDAS scores were 15.2 and 4.7 to 7.4, respectively. At one week of management, persistent delirium manifested in more severe impairment in the domains of consciousness, cognition, organization, perception, psychomotor behavior, and sleep-wake cycle. In addition, persistent delirium caused more severe functional impairment.	In this delirium sample, advanced age and preexisting dementia, as well as brain cancer, terminal illness, infection, and delirium severity contributed to persistent delirium or late response, indicating a prolonged and refractory course of delirium, in addition to more severe functional impairment through one week of management.	
25191304	Hypnagogic and hypnopompic hallucinations are characteristic symptoms of narcolepsy, as are excessive daytime sleepiness, cataplexy, and sleep paralysis. Narcolepsy patients may also experience daytime hallucinations unrelated to sleep-wake transitions. The effect of medication on hallucinations is of interest since treatment of narcolepsy may provoke psychotic symptoms. We aim to analyze the relation between sodium oxybate (SXB) treatment and psychotic symptoms in narcolepsy patients. Furthermore, we analyze the characteristics of hallucinations to determine their nature as mainly psychotic or hypnagogic and raise a discussion about whether SXB causes psychosis or if psychosis occurs as an endogenous complication in narcolepsy.We present altogether four patients with narcolepsy who experienced psychotic symptoms during treatment with SXB. In addition, we searched the literature for descriptions of hallucinations in narcolepsy and similarities and differences with psychotic symptoms in schizophrenia.	Three out of four patients had hallucinations typical for psychosis and one had symptoms that resembled aggravated hypnagogic hallucinations. Two patients also had delusional symptoms primarily associated with mental disorders. Tapering down SXB was tried and helped in two out of four cases. Adding antipsychotic treatment (risperidone) alleviated psychotic symptoms in two cases.	Psychotic symptoms in narcolepsy may appear during SXB treatment. Hallucinations resemble those seen in schizophrenia; however, the insight that symptoms are delusional is usually preserved. In case of SXB-induced psychotic symptoms or hallucinations, reducing SXB dose or adding antipsychotic medication can be tried.	
25191278	Actigraphy as an objective measure of sleep and wakefulness in infants and children has gained popularity over the last 20 years. However, the field lacks published guidelines for sleep-wake identification within pediatric age groups. The scoring rules vary greatly and although sensitivity (sleep agreement with polysomnography) is usually high, a significant limitation remains in relation to specificity (wake agreement). Furthermore, accurate algorithm output and sleep-wake summaries usually require prior entry from daily logs of sleep-wake periods and artifact-related information (e.g., non-wear time), involving significant parent co-operation. Scoring criteria for daytime naps remains an unexplored area. Many of the problems facing accuracy of measurement are inherent within the field of actigraphy itself, particularly where sleep periods containing significant movements are erroneously classified as wake, and within quiet wakefulness when no movements are detected, erroneously classified as sleep. We discuss the challenges of actigraphy for pediatric sleep, briefly describe the technical basis and consider a number of technological approaches that may facilitate improved classification of errors in sleep-wake discrimination. 
25190261	Sleep disorders (SD), including apnea and nonapnea, and burning mouth syndrome (BMS) have been mutually associated with systemic diseases. Based on our research, the association between BMS and SD has not been elucidated. We determined whether SD patients have an increased risk of BMS.We used information from health insurance claims obtained from the Taiwanese National Health Insurance (NHI) program. We identified patients newly diagnosed with sleep apnea syndrome between 1998 and 2001 as the apnea SD cohort, and newly diagnosed patients with nonapnea SD as the nonapnea SD cohort. The non-SD cohort was 1:2 frequency matched the case group according to sex, age, and index year. We analyzed the risks of BMS by using Cox proportional hazards regression models.	Compared with the non-SD cohort, both of the apnea SD (adjusted HR = 2.56, 95% CI = 1.30-5.05) and nonapnea SD (adjusted HR = 2.89, 95% CI = 2.51-3.34) were associated with a significantly higher risk of BMS. The hazard ratio (HR) increased with increased age in the apnea SD cohort and in the nonapnea SD cohort compared with patients younger than 40 years of age. Female apnea SD patients (IRR = 4.63, 95% CI = 3.82-5.61) had a higher risk of developing BMS than did male patients (IRR = 1.76, 95% CI = 1.39-2.24).	Based on our research, SD might increase the risk of BMS.	

25189053	Sleep-wake disturbances, in particular insomnia, are experienced by 30%-75% of oncology patients, yet no effective interventions have been designed to address this distressing symptom in the ambulatory setting. In response to an identified gap in care, I share the development and evaluation of an innovative sleep intervention designed specifically for the ambulatory setting. Preliminary findings, as well as an informative blueprint for conducting point-of-care research, are described. As a "bedside" nurse it is possible and within our moral imperative and social justice mandate to take action to find evidence-informed solutions to improve care for populations of patients experiencing gaps in care. The "I" used throughout the article refers to the lead author Surya.
25188896	Trouble falling or staying asleep, poor sleep quality, and short or long sleep duration are gaining attention as potential risk factors for cognitive decline and dementia, including Alzheimer's disease. Sleep-disordered breathing has also been linked to these outcomes. Here, we review recent observational and experimental studies investigating the effect of poor sleep on cognitive outcomes and Alzheimer's disease, and discuss possible mechanisms.Observational studies with self-report and objective sleep measures (e.g. wrist actigraphy, polysomnography) support links between disturbed sleep and cognitive decline. Several recently published studies demonstrate associations between sleep variables and measures of Alzheimer's disease pathology, including cerebrospinal fluid measures of Aβ and PET measures of Aβ deposition. In addition, experimental studies suggest that sleep loss alters cerebrospinal fluid Aβ dynamics, decrements in slow-wave sleep may decrease the clearance of Aβ from the brain, and hypoxemia characteristic of sleep-disordered breathing increases Aβ production.	Findings indicate that poor sleep is a risk factor for cognitive decline and Alzheimer's disease. Although mechanisms underlying these associations are not yet clear, healthy sleep appears to play an important role in maintaining brain health with age, and may play a key role in Alzheimer's disease prevention.	
25188718	The relevance of sleep instability is poorly appreciated among the metrics of sleep physiology. The cyclic alternating pattern (CAP) is a periodic electroencephalogram activity of non-REM sleep, characterized by sequences of transient electrocortical events that are distinct from the tonic background and recur at up to 1-min intervals. In the dynamic organization of sleep, CAP expresses a condition of instability that reflects the brain's effort in preserving and regulating the physiological structure of sleep.CAP quantification is a topical feature in the evaluation of sleep quality. In addition to duration, depth, and continuity, sleep restorative properties depend on the brain's capacity to determine the periods of sustained stable sleep. This issue is not confined only to the electroencephalogram activities but reverberates upon the ongoing autonomic and behavioral functions, which are mutually entrained in a synchronized oscillation. As a master clock involved in the dynamic organization of sleep, CAP plays a crucial role in numerous sleep disorders and is powerfully influenced by medication and appropriate treatment.	This article reviews the scoring, significance, and clinical applications of CAP.	

25186656	To examine whether day-to-day variations in sleep behaviors, ongoing sleep disturbance, and fatigue predict the cortisol diurnal rhythm in women recently diagnosed as having early-stage breast cancer.Women (N = 130, mean [standard deviation] age = 55.6 [9.4] years) collected saliva 5×/day/2 days for cortisol. Diaries were used to assess prior-day nap duration, nocturnal awakenings, sleep latency, and morning restfulness. Ongoing fatigue and sleep disturbance were measured using the Multidimensional Fatigue Symptom Inventory and the Pittsburg Sleep Quality Inventory. Data were analyzed using a multilevel growth curve modeling.	Greater ongoing fatigue (b = 0.035, p = .032), or sleep disturbance (b = 0.026, p = .006) predicted a slower cortisol decline. Greater ongoing fatigue also predicted higher awakening cortisol (b = 0.154, p = .030) and lower cortisol awakening response (CAR; b = -0.146, p = .005). Longer prior-day naps predicted higher CAR (b = 0.042, p = .050) and a steeper cortisol decline (b = -0.035, p = .003). Longer sleep latency predicted both a greater cortisol linear decline (b = -0.013, p < .001) and a greater quadratic slope curvature (b = 0.0007, p < .001). Feeling less rested in the morning predicted lower awakening cortisol (b = -0.187, p = .004), higher CAR (b = 0.124, p = .016), and a slower cortisol decline (b = 0.023, p = .042).	Both daily variations in sleep behaviors and ongoing sleep disturbance and fatigue are associated with a disrupted cortisol rhythm. In contrast, prior-day napping is associated with a more robust cortisol rhythm. These findings are particularly relevant to women with breast cancer who often experience sleep disturbance and fatigue. Additional research is needed to determine causal pathways between sleep disturbance and dysregulation of the hypothalamic-pituitary-adrenal axis in patients with breast cancer.	
25186268	Although commonly observed in clinical practice, the heterogeneity of obstructive sleep apnoea (OSA) clinical presentation has not been formally characterised. This study was the first to apply cluster analysis to identify subtypes of patients with OSA who experience distinct combinations of symptoms and comorbidities. An analysis of baseline data from the Icelandic Sleep Apnoea Cohort (822 patients with newly diagnosed moderate-to-severe OSA) was performed. Three distinct clusters were identified. They were classified as the "disturbed sleep group" (cluster 1), "minimally symptomatic group" (cluster 2) and "excessive daytime sleepiness group" (cluster 3), consisting of 32.7%, 24.7% and 42.6% of the entire cohort, respectively. The probabilities of having comorbid hypertension and cardiovascular disease were highest in cluster 2 but lowest in cluster 3. The clusters did not differ significantly in terms of sex, body mass index or apnoea-hypopnoea index. Patients with OSA have different patterns of clinical presentation, which need to be communicated to both the lay public and the professional community with the goal of facilitating care-seeking and early identification of OSA. Identifying distinct clinical profiles of OSA creates a foundation for offering more personalised therapies in the future. 
25185212	To compare the influence of low-frequency (10-25 Hz) versus higher (60-80 Hz) frequency stimulation of the pedunculopontine nucleus area (PPNa) on akinaesia, freezing of gait and daytime sleepiness.We included nine patients with Parkinson's disease (PD) and severe gait disorders. In this double-blind randomised cross-over study, patients were assessed after 24 h of PPNa stimulation. Assessments included the motor part of the Unified Parkinson's Disease Rating Scale, the Epworth Sleepiness Scale and a behavioural gait assessment.	Compared with 60-80 Hz, 10-25 Hz PPNa stimulation led to decreased akinaesia, gait difficulties and daytime sleepiness in 7/9 patients. In one patient, these symptoms were aggravated under 10-25 Hz stimulation compared with 60-80 Hz.	These results are in keeping with the benefits of chronic PPNa stimulation for gait and postural difficulties in patients with PD, and with regard to the influence of patients' clinical characteristics, differential neuronal loss in the PPNa and electrode location. We conclude that in patients with PPNa stimulation, low frequency provides a better outcome than high-frequency stimulation.	
25183726	Disturbance of the sleep-wake cycle is a characteristic of delirium. In addition, changes in melatonin rhythm influence the circadian rhythm and are associated with delirium. We compared the effect of melatonin and placebo on the incidence and duration of delirium.We performed this multicentre, double-blind, randomized controlled trial between November 2008 and May 2012 in 1 academic and 2 nonacademic hospitals. Patients aged 65 years or older who were scheduled for acute hip surgery were eligible for inclusion. Patients received melatonin 3 mg or placebo in the evening for 5 consecutive days, starting within 24 hours after admission. The primary outcome was incidence of delirium within 8 days of admission. We also monitored the duration of delirium.	A total of 452 patients were randomly assigned to the 2 study groups. We subsequently excluded 74 patients for whom the primary end point could not be measured or who had delirium before the second day of the study. After these postrandomization exclusions, data for 378 patients were included in the main analysis. The overall mean age was 84 years, 238 (63.0%) of the patients lived at home before admission, and 210 (55.6%) had cognitive impairment. We observed no effect of melatonin on the incidence of delirium: 55/186 (29.6%) in the melatonin group v. 49/192 (25.5%) in the placebo group; difference 4.1 (95% confidence interval -0.05 to 13.1) percentage points. There were no between-group differences in mortality or in cognitive or functional outcomes at 3-month follow-up.	In this older population with hip fracture, treatment with melatonin did not reduce the incidence of delirium.	Netherlands Trial Registry, NTR1576: MAPLE (Melatonin Against PLacebo in Elderly patients) study; www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576.	
25183509	Sleep deprivation affects the homeostasis of the physiological functions in the human organism. Beer is the only beverage that contains hops, a plant which has a sedative effect. Our objective is to determine the improvement of subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The sample was conducted among a population of 30 university students. The study took place during a period of 3 weeks, the first 7 days were used for the Control, and during the following 14 days the students ingested beer (were asked to drink non-alcoholic beer) while having dinner. The results revealed that Subjective Sleep Quality improved in the case of those students who drank one beer during dinner compared to the Control, this is corroborated by the fact that Sleep Latency decreased (p < 0.05) compared to their Control. The overall rating Global Score of Quality of Sleep also improved significantly (p < 0.05). These results confirm that the consumption of non-alcoholic beer at dinner time helps to improve the quality of sleep at night. 


25181729	Many service members suffer from chronic pain that can be difficult to adequately treat. Frustration has led to more openness among service members to complementary and alternative medicine modalities. This report follows JK, a Marine with chronic pain related to an injury while on combat deployment through participation in a 6-week self-care-based Mind Body Medicine program and for 7 months after completion of the program. JK developed and sustained a regular meditation practice throughout the follow-up period. JK showed a noticeable reduction in perceived disability and improvements in psychological health, sleep latency/duration and quality of life. This report supports further study into the efficacy and feasibility of self-care-based mind body medicine in the treatment of chronic pain in the military medical setting. 
25179226	The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. 
25179036	Depressive symptoms in patients with heart failure can affect the relationship between physical signs and symptoms and inflammation.To examine the relationship between soluble tumor necrosis factor receptor I and physical signs and symptoms and the effects of depressive symptoms on this relationship in patients with heart failure.	Data on physical signs and symptoms (Symptom Status Questionnaire-Heart Failure), depressive symptoms (Beck Depression Inventory-II), and levels of the receptor (blood samples) were collected from 145 patients with heart failure. Data on the receptor were square root transformed to achieve normality. Patients were divided into 2 groups according to their scores for depressive symptoms (nondepressed <14 and depressed ≥14). Hierarchical multiple regression was used to analyze the data.	In the total sample, with controls for covariates, higher levels of the receptor were significantly related to more severe physical signs and symptoms (F = 7.915; P < .001). In subgroup analyses, with controls for covariates, levels of the receptor were significantly related to physical signs and symptoms only in the patients without depression (F = 3.174; P = .005).	Both depressive symptoms and inflammation should be considered along with physical signs and symptoms in patients with heart failure. Further studies are needed to determine the effects of improvement in inflammation on improvement in physical signs and symptoms, with consideration given to the effects of depressive symptoms.	
25178705	Specific developmental and aging trajectories characterize sleep electroencephalogram (EEG) of typically developing (TD) subjects. Williams syndrome (WS) is marked by sleep alterations and accelerated aging of several anatomo-functional and cognitive measures. Here we test the hypothesis of a premature aging of sleep in WS. Age-related changes of home recorded sleep EEG of 42 subjects (21 WS, 21 age- and gender matched TD subjects, age: 6-29 years) were tested by Pearson correlations and homogeneity-of-slopes analysis. Typical developmental/aging effects of sleep EEGs were observed in TD subjects. Accelerated aging in WS was confirmed by overall sleep/wake measures. Specifically, premature aging was evident in accelerated age-dependent declines in WS subjects' sleep efficiency, as well as in steeper age-related rises in wakefulness and wake after sleep onset (WASO) of the WS group. In contrast, NREM sleep-related measures indicated atypical decelerations of the developmental trends of WS subjects, characterized by the slowing down of the age-related slow wave sleep (SWS) declines mirrored by the lack of age-dependent increase in Stage 2 (S2) sleep. Age-effects in sleep EEG power spectra were not different among the groups. Objectively measured sleep disruption of subjects with WS is age-dependent and increasing with age. Moreover, these data suggest atypical pre- and postpubertal neural development in WS, with sleep/wake balance and REM sleep time indicating accelerated aging while NREM sleep composition revealing signs of an as yet unidentified, perhaps compensatory developmental delay. 
25178401	Abstract Background: Continence care commonly disrupts sleep in residential aged care facilities, however, little is known about what staff do when providing continence care, and the factors that inform their practice. Aims: To describe nurses' and personal care workers' beliefs and experiences of providing continence care at night in residential aged care facilities. Methods/design: Eighteen nurses and personal care workers were interviewed about continence care, and 24 hours of observations were conducted at night in two facilities. Results/Findings: Most residents were checked overnight. This practice was underpinned by staffs' concern that residents were intractably incontinent and at risk of pressure injuries. Staff believed pads protected and dignified residents. Decisions were also influenced by beliefs about limited staff-to-resident ratios. Conclusion: Night-time continence care should be audited to ensure decisions are based on residents' preferences, skin health, sleep/wake status, ability to move in bed, and the frequency, severity and type of residents' actual incontinence.
25178397	Sleeping difficulties in childhood have been associated with an increased risk of depression in adult life, but existing studies have not accounted for comorbid maternal sleeping difficulties and depression. This study aimed to determine the association between childhood sleeping difficulties and depression in adulthood after adjusting for the potential confounding influences of maternal depression and sleeping difficulties. Data from the British Cohort Study 1970, a prospective birth cohort with 30 years of follow-up (1975-2005) were used. At 5 years of age, 7437 parents of participants recorded information on whether their child had sleeping difficulties, the frequency of bed-wetting, nightmares, maternal depression and sleep difficulties. At 34 years of age, participants reported whether or not they had received medical treatment for depression in the past year. Parental reports of severe sleeping difficulties at 5 years were associated with an increased risk of depression at age 34 years [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.2, 3.2] whereas moderate sleeping difficulties were not (OR = 1.1, 95% CI = 0.9, 1.3). In conclusion, severe sleeping problems in childhood may be associated with increased susceptibility to depression in adult life.
25178332	The obstructive sleep apnea syndrome is the most common sleep disorder. It covers a multitude of symptoms associated with apnea. Next to polysomnography, otorhinolaryngological clinical examination plays an important role in establishing the diagnosis, in evaluating any oropharyngeal and hypopharyngeal modification.In this research, we intend to demonstrate the histopathological examination importance in establishing the tonsillar hypertrophy degree. This is made in direct correlation with its volume, and the sleep apnea degree. In this context, we have conducted a retrospective study between 2007-2012 on a group of 69 patients diagnosed by polysomnography with Obstructive Sleep Apnea (OSA). In the research, otorhinolaryngological examination was supplemented with histopathological examination of the parts collected after the surgery.	It has been demonstrated that the size, volume of the tonsil can be directly correlated with the severity of sleep apnea. The term "tonsil hypertrophy" is a histopathological one, with or without macroscopic implications. A specificity of tonsil enlargement without the narrowing of the oropharyngeal isthmus was demonstrated. This was in all groups of obstructive apnea, even in snoring patients with normal apnea-hypopnea index values, with a non-significant statistical correlation.	The use of multiple indices in the classification of OSA severity is an important advantage. Therefore, it can be proved that there is no singular structure to induce the disorder, but the cause is rather a combination of several elements. The polysomnographic examination remains the golden standard for assessing in patients with OSA.	
25175972	This chapter summarizes the current knowledge about the role of adenosine in the sleep-wake regulation with a focus on adenosine in the brain, regulation of adenosine levels, adenosine receptors, and manipulations of the adenosine system by the use of pharmacological and molecular biological tools. Adenosine is neither stored nor released as a classical neurotransmitter and is thought to be formed inside cells or on their surface, mostly by breakdown of adenine nucleotides. The extracellular level of adenosine increases in the cortex and basal forebrain (BF) during prolonged wakefulness and decreases during the sleep-recovery period. Therefore, adenosine is proposed to act as a homeostatic regulator of sleep. The endogenous somnogen prostaglandin (PG) D2 increases the extracellular level of adenosine under the subarachnoid space of the BF and promotes physiological sleep. There are four adenosine receptor subtypes: adenosine A1 receptor (R, A1R), A2AR, A2BR, and A3R. Both the A1R and the A2AR have been reported to be involved in sleep induction. The A2AR plays an important role in the somnogenic effects of PGD2. Activation of A2AR by its agonist infused into the brain potently increases sleep and the arousal effect of caffeine, an A1R and A2AR antagonist, was shown to be dependent on the A2AR. On the other hand, inhibition of wake-promoting neurons via the A1R also mediates the sleep-inducing effects of adenosine, whereas activation of A1R in the lateral preoptic area induces wakefulness. These findings indicate that A2AR plays a predominant role in sleep induction, whereas A1R regulates the sleep-wake cycle in a site-dependent manner. 
25175755	Morningness-eveningness or circadian typology can be viewed as an interesting aspect of individual differences. Morningness-eveningness is a preference for a given time of day for physical or mental performance, but also reflects aspects of affect. Here, we used seven different measures to assess differences in morningness-eveningness between Germany, Slovakia and India. The hypothesis was that Indians should be earliest chronotypes, followed by Slovakia and then Germany, because of higher temperatures in India, and the fact that Slovakia is located farther east compared to Germany. We applied the Composite Scale of Morningness (CSM), the Circadian Energy Scale (CIRENS), the CAEN Chronotype Questionnaire (CCQ), and habitual sleep-wake variables to calculate sleep duration, midpoint of sleep and social jetlag. Sample sizes were N = 300 (Germany), N = 482 (Slovakia) and N = 409 (India). Country had the strongest influence on morningness-eveningness. Germans were latest chronotypes and differed in all seven measures from Indians but differed from Slovakians only in the energy level at the evening and midpoint of sleep. Slovakians and Indians differed in all measures but the energy level (CIRENS). Women scored higher on the CSM, lower on CIRENS, lower on the morningness-eveningness (ME) scale, but higher on distinctness (DI) scale. Women slept longer and had an earlier midpoint of sleep. 
25174823	Rates of sleep disorders and associated adjustment were examined in patients with implantable cardioverter defibrillators (ICDs; n = 42; Mage = 61.57, SD = 12.60). One night of ambulatory polysomnography, 14 days of sleep diaries, and questionnaires (mood, sleepiness, fatigue, device acceptance) were administered. Controlling for ischemia, MANCOVA examined adjustment by sleep diagnosis. Apnea was most common (28.6%), followed by Insomnia (16.7%) and Comorbid Insomnia/Apnea (11.9%). Patients with insomnia reported poorer mood, greater sleepiness, and lower device acceptance than good sleepers; they also demonstrated poorer mood and less ICD device acceptance than patients with sleep apnea. Patients with comorbid insomnia/apnea also exhibited poorer mood and less ICD device acceptance than good sleepers; however, comorbid patients did not significantly differ from insomnia or apnea patients on any measure. Those with disordered sleep (regardless of type) reported greater fatigue than good sleepers. Assessment (and treatment) of difficulties with sleep, mood, fatigue, and device acceptance may be important for the comprehensive clinical management of ICD patients. Further research appears warranted. 
25174344	The ileal orthotopic neobladder (IONB) is often used in patients undergoing radical cystectomy. The IONB allows to void avoiding the disadvantages of the external urinary diversion.In IONB patients the quality of life (QoL) appears compromised by the need to urinate voluntarily. The patients need to wake up at night interrupting the sleep-wake rhythm with consequences on social and emotional life.At present the QoL in IONB patients is evaluated by generic questionnaires. These are useful when IONB patients are compared with patients with different urinary diversions but they are less effective when only IONB patients are evaluated. To address this problem a specific questionnaire-the IONB-PRO-was developed.A) Based on a conceptual framework, narrative-based interviews were conducted on 35 IONB patients. A basic pool of 43 items was produced and organized throughout two clinical and four QoL dimensions. An additional 15 IONB patients were interviewed for face validity testing.B) Psychometric testing was conducted on 145 IONB patients. Both classic test strategy and Rasch analysis were applied. Psychometric properties of the resulting scales were comparatively tested against other QoL-validated scales.	The IONB-PRO questionnaire includes two sections: one on the QoL and a second section on the capability of the patient to manage the IONB. For evaluation of the QoL, three versions were delivered: 1) a basic 23-item QoL version (3 domains 23-items; alpha 0.86÷ 9.69), 2) a short-form 12-item QoL scale (alpha = 0.947), and 3) a short-form 15-item Rasch QoL scale (alpha = 0.967). Correlations of the long version scales with the corresponding dimensions of the EORTC-QLQ C30 and the EORTC-BLM30 were significant. The short forms exhibited significant correlations with the global health dimension of the EORTC-QLQ and with the urinary subscales of the EORTC-BLM30. The effect size was approximately 1.00 between patients at the 1-year follow-up period and those with 3, 5, and > 5-year follow-up periods for all scales. No relevant differences were observed between the 12-item short-form and the Rasch scale.	The IONB-PRO long and short-forms demonstrated a high level of internal consistency and reliability with an excellent discriminanting validity.	

25174211	The face and associated cranial, oral and dental structures are among the most complicated areas of the body, contributing to an array of common orofacial disorders that include temporomandibular disorders (TMD), orofacial pain disorders and orofacial sleep disorders. This paper presents a broad, inclusive approach to diagnosis and management of TMD that reflects both conceptual models of human systems in understanding chronic illnesses as well as systematic reviews of treatment for successful management.
25173805	Along with the increase in life expectancy over the last century comes the increased risk for development of age-related disorders, including metabolic and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. These chronic disorders share two main characteristics: 1) neuronal loss in motor, sensory or cognitive systems, leading to cognitive and motor decline; and 2) a strong correlation between metabolic changes and neurodegeneration. In order to treat them, a better understanding of their complexity is required: it is necessary to interpret the neuronal damage in light of the metabolic changes, and to find the disrupted link between the peripheral organs governing energy metabolism and the CNS. This review is an attempt to present ghrelin as part of molecular regulatory interface between energy metabolism, neuroendocrine and neurodegenerative processes. Ghrelin takes part in lipid and glucose metabolism, in higher brain functions such as sleep-wake state, learning and memory consolidation; it influences mitochondrial respiration and shows neuroprotective effect. All these make ghrelin an attractive target for development of biomarkers or therapeutics for prevention or treatment of disorders, in which cell protection and recruitment of new neurons or synapses are needed. 
25172521	The circadian clock drives a number of metabolic processes including energy intake, storage and utilization coupled with the sleep/wake cycles. Globally, the increasing prevalence of type 2 diabetes (T2DM) has become a significant international public health concern. In view of the heavy societal burden caused by diabetes, and further, to reduce its growing incidence, it is clearly essential to understand the causes of this disease and to devise more effective strategies for its treatment. Although many factors cause T2DM, this article centers on the role of circadian regulation of metabolism. The correlation between the increased occurrence of T2DM and the ubiquity of modern social pressures such as 24/7 lifestyles as well as nocturnal lighting conditions point strongly to the hypothesis that malfunctioning of circadian controls may be involved in the etiology of the illness. Nocturnal light exposure, unusual timing of food, irregular sleep/wake schedules and traveling between different time zones are some of the factors responsible for improper entrainment of the clock. Recent reports have proposed that strengthening of circadian clock functioning and proper timing of food intake could stabilize glucose homeostasis. This strategy thus represents a chronotherapeutic option for non-pharmaceutical intervention in treating T2DM patients. 
25172271	This document reviews the literature on local brain manipulation of general anesthesia in animals, focusing on behavioral and electrographic effects related to hypnosis or loss of consciousness. Local inactivation or lesion of wake-active areas, such as locus coeruleus, dorsal raphe, pedunculopontine tegmental nucleus, perifornical area, tuberomammillary nucleus, ventral tegmental area and basal forebrain, enhanced general anesthesia. Anesthesia enhancement was shown as a delayed emergence (recovery of righting reflex) from anesthesia or a decrease in the minimal alveolar concentration that induced loss of righting. Local activation of various wake-active areas, including pontis oralis and centromedial thalamus, promoted behavioral or electrographic arousal during maintained anesthesia and facilitated emergence. Lesion of the sleep-active ventrolateral preoptic area resulted in increased wakefulness and decreased isoflurane sensitivity, but only for 6 days after lesion. Inactivation of any structure within limbic circuits involving the medial septum, hippocampus, nucleus accumbens, ventral pallidum, and ventral tegmental area, amygdala, entorhinal and piriform cortex delayed emergence from anesthesia, and often reduced anesthetic-induced behavioral excitation. In summary, the concept that anesthesia works on the sleep-wake system has received strong support from studies that inactivated/lesioned or activated wake-active areas, and weak support from studies that lesioned sleep-active areas. In addition to the conventional wake-sleep areas, limbic structures such as the medial septum, hippocampus and prefrontal cortex are also involved in the behavioral response to general anesthesia. We suggest that hypnosis during general anesthesia may result from disrupting the wake-active neuronal activities in multiple areas and suppressing an atropine-resistant cortical activation associated with movements. 
25172117	To compare distributions of body mass index (BMI) between individuals with different habitual sleep patterns.We performed cross-sectional analyses of 40,197 Swedish adults (64% women), who reported sleep duration and quality, weight, height, and possible confounding factors in 1997. Using quantile regression, we estimated associations between sleep patterns and selected percentiles of the distribution of BMI.	While the medians were similar, larger adjusted values of BMI were estimated in the upper part of the distribution among men and women with short sleep (≤5 h) compared with medium-length sleep (6-8 h). For example, in men, the 90th percentile of BMI was 0.80 kg/m(2) (95% confidence interval: 0.17-1.43 kg/m(2)) higher among short sleepers. In women, long sleepers (≥9 h) also showed larger values in the upper part of the BMI distribution; the 90th percentile was 1.23 kg/m(2) (0.42-2.04 kg/m(2)) higher than in medium-length sleepers. In male long sleepers, smaller values were estimated in the lower part of the BMI distribution; the 10th percentile was 0.84 kg/m(2) lower (0.35-1.32 kg/m(2)) than in medium-length sleepers. The 90th percentile of BMI in women with poor-quality compared with good-quality sleep was larger by 0.82 kg/m(2) (0.47-1.16 kg/m(2)); the 10th percentile was smaller by 0.17 kg/m(2) (0.02-0.32 kg/m(2)).	Short, long or poor-quality sleepers showed larger, or smaller, values at the tails of the BMI distribution, but similar medians. Hence, unfavorable sleep patterns and BMI were associated only in a subset of this study population.	
25172116	Patients with neuromuscular diseases improve their sleep when treated with noninvasive ventilation (NIV), but their sleep architecture during NIV may still be disturbed by side effects of NIV or inadequacy of the ventilator setting. Little is known about subjective sleep quality during NIV. The aims of this study were to evaluate subjective sleep quality of stable neuromuscular patients under long-term NIV by using Pittsburgh questionnaire (PSQI), and to assess its possible determinants.Fifty stable neuromuscular patients under long-term NIV were administered PSQI and underwent polysomnography. Arterial blood gases, forced vital capacity, and respiratory muscular strength were measured.	Thirty-three patients had global PSQI ≥ 5 and were classified as bad sleepers. Good and poor sleepers differed in age (P = 0.005), base excess (BE) (P = 0.02), NIV inspiratory pressure (P = 0.04), %N1 (P = 0.0006), and %N3 sleep stage (P = 0.02). Percent N3 duration and Arousal/Awakening Index were correlated with rate of patient-ventilator asynchronies (r = -0.41 and 0.37, respectively, P < 0.05) and with NIV inspiratory pressure (r = -0.44 and 0.36, P < 0.01 and <0.05, respectively). At the final multivariate regression model, only BE and %N3 independently predicted global PSQI (r(2) = 0.326, P < 0.001).	Subjective sleep quality is often poor in neuromuscular patients under long-term NIV. Amount of slow wave sleep and chronic hypoventilation resulting in increased BE are independent predictors of subjective sleep quality. Since inadequate NIV setting or application can influence sleep structure and alveolar ventilation, great care should be paid to the setting and the correct application of NIV to ensure a better subjective sleep quality.	
25171195	Apnea of prematurity is a common condition that is usually treated with caffeine, an adenosine receptor blocker that has powerful influences on the central nervous system. However, little is known about the long-term effects of caffeine on sleep in the developing brain.We hypothesized that neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep.	A total of 201 ex-preterm children aged 5-12 years who participated as neonates in a double-blind, randomized, controlled clinical trial of caffeine versus placebo underwent actigraphy, polysomnography, and parental sleep questionnaires. Coprimary outcomes were total sleep time on actigraphy and apnea-hypopnea index on polysomnography.	There were no significant differences in primary outcomes between the caffeine group and the placebo (adjusted mean difference of -6.7 [95% confidence interval (CI) = -15.3 to 2.0 min]; P = 0.13 for actigraphic total sleep time; and adjusted rate ratio [caffeine/placebo] for apnea-hypopnea index of 0.89 [95% CI = 0.55-1.43]; P = 0.63). Polysomnographic total recording time and total sleep time were longer in the caffeine group, but there was no difference in sleep efficiency between groups. The percentage of children with obstructive sleep apnea (8.2% of caffeine group versus 11.0% of placebo; P = 0.22) or elevated periodic limb movements of sleep (17.5% in caffeine group versus 11% in placebo group) was high, but did not differ significantly between groups.	Therapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood. Ex-preterm infants, regardless of caffeine status, are at risk for obstructive sleep apnea and periodic limb movements in later childhood.	
25169712	Few epidemiological studies of systemic lupus erythematosus (SLE) have been conducted in Australia, and current management practice and levels of unmet need in this country are not well characterised.To perform a systematic literature review to identify Australia-specific information on SLE, particularly areas of unmet need.	MEDLINE, EMBASE and the Cochrane Library were searched (1 January 1990 to 29 November 2013). All articles on prevalence, disease characteristics, management and outcomes of SLE in Australia were included.	There is limited published information on SLE in Australia. Of 24 articles included, 18 described results from observational studies, three were narrative reviews, one was a clinical update, and two were medical education articles. In remote regions, SLE was reported to be more prevalent in Aboriginal Australians than non-Aboriginal Australians; information in urban populations is lacking. Asian Australians may be more affected by SLE than non-Asian Australians. Pregnancy outcomes may also be adversely affected. Many Australians with SLE may experience high levels of unmet need, including delayed diagnosis, ongoing symptoms, flares, depression/anxiety, sleeping difficulty and decreased quality of life. Published guidance on the SLE management in Australia is limited and dated.	Published information on SLE in Australia is limited, but suggests that ethnicity may affect the prevalence and disease characteristics and that many Australians with SLE have unmet needs. Improvements in diagnosis, treatment and management are needed to alleviate these needs. Up-to-date guidance on the management of SLE would benefit healthcare professionals and patients.	
25169245	The aim of this study was to evaluate whether sleep restriction (SR) could affect the mechanisms and pathways' essentials for cancer cells in tongue cancer induced by 4-nitroquinoline 1-oxide in Wistar rats.The animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to sleep restriction for 21 days using the modified multiple platform method, which consisted of placing 5 rats in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways.	Although no histopathologic abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplastic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53, and for bcl-2. Following 12 weeks of 4NQO administration, we found significant differences between SR and control groups in p53, bax, and bcl-2 immunoexpression.	Our results reveal that sleep restriction exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.	
25168926	Although workers with poor sleep quality are reported to have problems with work performance, few studies have assessed the association between dietary factors and sleep quality using validated indexes. Here, we examined this association using information acquired from validated questionnaires.A total of 3,129 female workers aged 34 to 65 years were analyzed. Dietary intake was assessed using a self-administered diet history questionnaire (DHQ), and subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The relationship between the intake of several food groups and nutrients and sleep quality was examined using multivariable logistic regression models. The effect of eating habits on sleep quality was also examined.	Poor sleep quality was associated with low intake of vegetables (p for trend 0.002) and fish (p for trend 0.04) and high intake of confectionary (p for trend 0.004) and noodles (p for trend 0.03) after adjustment for potential confounding factors (age, body mass index, physical activity, depression score, employment status, alcohol intake and smoking status). Poor sleep quality was also significantly and positively associated with consumption of energy drinks and sugar-sweetened beverages, skipping breakfast, and eating irregularly. In addition, poor sleep quality was significantly associated with high carbohydrate intake (p for trend 0.03).	A low intake of vegetables and fish, high intake of confectionary and noodles and unhealthy eating habits were independently associated with poor sleep quality. Poor sleep quality was also associated with high carbohydrate intake in free-living Japanese middle-aged female workers.	
25168255	Narcolepsy is a chronic disorder of the sleep-wake cycle with pathological shifts between sleep stages. These abrupt shifts are induced by a sleep-regulating flip-flop mechanism which is destabilized in narcolepsy without obvious alterations in EEG oscillations. Here, we focus on the question whether the pathology of narcolepsy is reflected in EEG microstate patterns. 30 channel awake and NREM sleep EEGs of 12 narcoleptic patients and 32 healthy subjects were analyzed. Fitting back the dominant amplitude topography maps into the EEG led to a temporal sequence of maps. Mean microstate duration, ratio total time (RTT), global explained variance (GEV) and transition probability of each map were compared between both groups. Nine patients reached N1, 5 N2 and only 4 N3. All healthy subjects reached at least N2, 19 also N3. Four dominant maps could be found during wakefulness and all NREM- sleep stages in healthy subjects. During N3, narcolepsy patients showed an additional fifth map. The mean microstate duration was significantly shorter in narcoleptic patients than controls, most prominent in deep sleep. Single maps' GEV and RTT were also altered in narcolepsy. Being aware of the limitation of our low sample size, narcolepsy patients showed wake-like features during sleep as reflected in shorter microstate durations. These microstructural EEG alterations might reflect the intrusion of brain states characteristic of wakefulness into sleep and an instability of the sleep-regulating flip-flop mechanism resulting not only in pathological switches between REM- and NREM-sleep but also within NREM sleep itself, which may lead to a microstructural fragmentation of the EEG. 

25167073	Sleep is increasingly important in public health because sleep problems are associated with multiple negative health and quality-of-life outcomes, especially among those with chronic conditions. While evidence-based self-management programs have been widely studied, little is known about their specific impacts on sleep. Using data from the National Study of Chronic Disease Self-Management Program (n = 1168), improvements in sleep problems were observed for all subgroups except men. More sleep problem reductions were observed among younger participants compared with their older counterparts. This study confirmed the value of self-management programs for ameliorating sleep problems across diverse participant groups. 
25167071	The purpose of this study was to determine racial/ethnic differences in midlife women's sleep-related symptoms, relationships between their physical activity and sleep-related symptoms, and specific factors associated with their sleep-related symptoms in each racial/ethnic group. This was a secondary analysis of the data from 542 midlife women in the United States. The data were analyzed using descriptive statistics, χ tests, analysis of variance, hierarchical multiple linear regression analyses, and logistic regression analyses. The findings indicated that physical activities could improve midlife women's sleep-related symptoms, but the types of physical activities and racially/ethnically different factors associated with sleep-related symptoms need to be considered. 
25167070	More than 50% of community-dwelling adults have sleep complaints. Because aging is associated with decline in physical function, coexistent sleep difficulties may exacerbate functional decline. This pilot study explored the relationships between sleep, age, chronic disease burden, and physical function among 50 community-dwelling older adults. Findings revealed significant relationships between total sleep time and preclinical disability (r = -0.33, P ≤ .05) and mobility difficulty (r = -0.36, P ≤ .05). A regression analysis showed that total sleep time was significantly associated with mobility difficulty and preclinical disability, even after controlling for chronic disease burden. These findings suggest that total sleep time may be a catalyst for functional decline. 
25167069	Prolonged and heavy use of alcohol is associated with persistent sleep disturbances. Objective and subjective measures of sleep quantity and quality were collected on 164 individuals undergoing detoxification. A high prevalence of sleep disturbance was found in this sample. Sleep quality improved by week 4 but continued to be altered, signaling a target area for recovery management. This study supports the high prevalence of sleep disturbance in individuals undergoing alcohol treatment. Health promotion strategies in an addiction recovery model should address quality-of-life enhancements for individuals and their families including optimizing sleep quality and duration through sustained recovery. 
25167068	Sensory stimuli/inactivity may affect sleep. Sleep problems are associated with multiple health problems. We assessed TV habits in the Adventist Health Study-2 at baseline and sleep problems in the Biopsychosocial Religion and Health Study 1 to 4 years later. After exclusions, 3914 subjects split equally into TV watchers less than 2 hours per day or 2 or more hours per day. Watching TV 2 or more hours per day predicted problems falling asleep, middle of the night awakening, and waking early with inability to sleep again in multiple logistic regression. Excess TV watching disturbed sleep induction and quality, though the relationship may be bidirectional. TV habits should be considered in individuals with sleep problems. 
25166937	Altered sleep and wakefulness affect individuals' mood, memory, and psychomotor performance and thus directly impact their quality of life. Tools to analyze the quality of these factors should be available for clinical evaluation. This study aimed to translate into Brazilian Portuguese and culturally adapt the Patient-Reported Outcomes Measurement Information System (PROMIS), specifically the sleep and wake disturbances domains. The translation and cultural adaptation processes followed the guidelines proposed by the Functional Assessment of Chronic Illness Therapy (FACIT) organization. The methodology included translation, reconciliation, back-translation, review by PROMIS, review by independent reviewers, pretest, and incorporation of the results into the final version. The Portuguese version of the sleep and wake disturbances domains presents semantic, idiomatic, cultural, and conceptual equivalence with the items in the source language. 

25163993	Fragestellung: Es wurde überprüft, in wieweit sich eine Verbesserung des Körperkontakts positiv auf Regulationsstörungen im Säuglingsalter auswirkt. Zwei Interventionen wurden untersucht: 1. Elternberatung bezüglich Körperkontakt; 2. praktisches Üben von Körperkontakt in Verbindung mit Exposition. Beide Verfahren wurden durch eine videounterstützte Elternanleitung ergänzt. Methodik: Je Gruppe 20 Säuglinge mit Regulationsstörung. Vor und nach der Intervention Auswertung von Körper- und Blickkontakt über Videorating sowie Tagebuch bzgl. Schreien, Schlafen, Füttern, Unruhe, wach – ruhig oder spielt. Ergebnisse: a) Beide Interventionen führten zu einer Verbesserung des Körperkontakts, die jedoch nur in der Gruppe mit praktischem Üben auch noch nach 3 Monaten stabil war. b) Fasst man alle 40 teilnehmenden Säuglinge zusammen, so zeigen sich signifikante Veränderungen bezüglich der Regulationsbereiche «Unruhe/Quengeln», «Schlafen», «wach, ruhig oder spielt» sowie ein marginal signifikanter Effekt bezüglich des Schreiens. c) Für beide Verfahren zeigte sich: Diejenigen Kinder, deren Körperkontakt sich deutlich verbessert hatte, verbesserten sich auch bezüglich der Regulationsproblematik am deutlichsten. d) Das konkrete Üben des Körperkontakts mit Exposition ist bezüglich «Unruhe/Quengeln» und «Blickkontakt» der reinen Beratung überlegen. Schlussfolgerungen: Der Körperkontakt lässt sich über gezielte therapeutische Maßnahmen verbessern. Ein videounterstütztes Elterntraining, das mit Maßnahmen zur Verbesserung des Körperkontakts verbunden ist, wirkt sich positiv auf die Regulationsproblematik aus.This study concerns the influence of an improvement of body contact on regulatory disorders in infancy. Two interventions were examined: 1. parent counseling on the subject of body contact; 2. practical training of body contact in connection with exposure. Both methods were supplemented by a video-based parent training.	20 infants with regulatory disorder were assigned to each treatment. Body and eye contact were examined by means of video ratings before and after treatment. In addition, we measured the daily amount of crying, sleeping, feeding, being fussy, and quiet play by means of an infant behavior diary.	Both interventions resulted in an improvement of body contact, though only in the group with practical training was this improvement stable after 3 months. Taking all 40 participating infants together, we found significant improvements for "fussiness," "sleep duration," "awake, quiet or playing," and a marginal significant intervention effect for the duration of crying. Both interventions showed that children who had markedly improved in body contact also improved with regard to the regulation problem. Finally, the practical training of body contact was superior to pure counseling respective to the fussiness of the infants and to their gaze contact.	Body contact can be improved through specific therapeutic interventions. Video-based parent training in combination with interventions aiming at an improvement of body contact have a positive effect on the regulation problem.	
25162477	The study was designed to investigate the association between sleep disturbances and common mental disorders (CMDs) among Peruvian college students. A total of 2538 undergraduate students completed a self-administered questionnaire to gather information about sleep characteristics, sociodemographic, and lifestyle data. Evening chronotype, sleep quality, and daytime sleepiness were assessed using the Horne and Ostberg morningness-eveningness questionnaire, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale, respectivelty. Presence of CMDs was evaluated using the General Health Questionnaire. Logistic regression procedures were used to examine the associations of sleep disturbances with CMDs while accounting for possible confounding factors. Overall, 32.9% of the participants had prevalent CMDs (39.3% among females and 24.4% among males). In multivariable-adjusted logistic models, those with evening chronotype (odds ratios (OR) = 1.43; 95% CI 1.00-2.05), poor sleep quality (OR = 4.50; 95% CI 3.69-5.49), and excessive daytime sleepiness (OR = 1.68; 95% CI 1.41-2.01) were at a relative increased odds of CMDs compared with those without sleep disturbances. In conclusion, we found strong associations between sleep disturbances and CMDs among Peruvian college students. Early education and preventative interventions designed to improve sleep habits may effectively alter the possibility of developing CMDs among young adults.
25162023	Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats.
25161123	Neuropeptide S (NPS) is an endogenous peptide that exerts wakefulness promoting, analgesic, and anxiolytic effects when administered exogenously. However, it remains to be determined if endogenous NPS tone is involved in the control of the diurnal sleep-wake cycle, or spontanous behavior. In this study, we examined the effects of the NPS receptor antagonist [D-Cys((t)Bu)(5)]NPS (2 and 20 nmol, icv) on physiological sleep and spontaneous locomotor behavior. The higher dose of [D-Cys((t)Bu)(5)]NPS decreased the amount of time spent in wakefulness [control 782.5 ± 25.5 min, treatment 751.7 ± 28.1 min; p<0.05] and increased the time spent in NREMS [control 572.6 ± 17.2 min, treatment 600.2 ± 26.1 min; p<0.05]. There was no statistically significant difference in time spent in REMS. There were no behavioral changes including abnormal gross motor behavior in response to [D-Cys((t)Bu)(5)]NPS administration. Collectively these data suggest an involvement of the endogenous NPS/NPS receptor system in physiological sleep architecture.
25160887	Delayed sleep phase disorder is the most common of the circadian rhythm sleep disorders. Its treatment involves exploiting the intrinsic biological properties of the circadian pacemaker to advance biological rhythms, most notably the sleep-wake cycle, to a time which affords the individual an appropriate sleep opportunity compatible with normal societal functioning. This review highlights several new studies published in the last 18 months concerning sleep and circadian physiology relevant to the disorder and its management.In addition to new information regarding the epidemiology and associations of the disorder, the pathophysiological importance of light exposure across the entire day, with special relevance to the phase-delaying effects of artificial evening light, is being unravelled. Furthermore, disorder-specific differences in period length and sleep homeostasis are being considered as pathophysiological contributors to delayed sleep phase disorder. The molecular effects of chronic sleep deprivation and circadian misalignment are currently being explored as potential mechanistic markers of the deleterious health consequences associated with these states.	Advances in our understanding of the dynamics of circadian physiology, sleep-wake regulation and the deleterious effects of misalignment and sleep deprivation, are spurring on efforts to find optimal treatment paradigms for patients presenting to sleep clinics with delayed sleep phase disorder.	
25158922	In patients with cirrhosis, sleep disturbances are assumed to result from hepatic encephalopathy (HE). The effects of obstructive sleep apnea (OSA) on cognition, sleep parameters, or driving in patients with cirrhosis are unclear.We performed a cross-sectional and prospective study of 118 subjects. Subjects were assigned to 1 of 4 groups: those with OSA and cirrhosis (without hepatic encephalopathy or ascites, n = 34), those with cirrhosis only (n = 30), those with OSA only (n = 29), and those without OSA or cirrhosis (controls, n = 25). None of the OSA patients were receiving continuous positive airway pressure (CPAP) therapy. Subjects underwent cognitive testing (paper-pencil tests for psychomotor speed and attention, as well as executive function tests), sleep assessment (daytime sleepiness and night-time sleep quality), and a monotonous driving simulation (worsening lane deviations over time indicated poor performance). We also tested patients with OSA, with cirrhosis (n = 10) and without cirrhosis (n = 7), before and after CPAP therapy.	Daytime sleepiness and sleep quality were worse in subjects in the OSA groups (with or without cirrhosis) than subjects with cirrhosis alone or controls. Of subjects with only OSA, 36% had impaired psychomotor speed and attention, compared with more than 60% of subjects in both cirrhosis groups. In contrast, executive function was uniformly worse in subjects with OSA, with or without cirrhosis, than groups without OSA. Simulator performance (lane deviations) worsened over time in both OSA groups. CPAP therapy significantly increased executive function and sleep quality, and reduced simulator lane deviations and sleepiness, in OSA subjects with and without cirrhosis. After CPAP therapy, performance on the paper-pencil test improved significantly only in subjects with OSA without cirrhosis.	OSA should be considered in evaluating sleep impairment in patients with cirrhosis. In patients with cirrhosis and OSA, psychomotor speed and attention issues likely are related to cirrhosis, whereas executive function and simulator performance are affected by OSA. CPAP therapy improves executive function and simulator performance in patients with OSA, regardless of cirrhosis.	
25158581	Chronobiological treatments are non-pharmacological treatments that influence the circadian rhythms and the physiology of sleep. In these treatments, the sleep-wake cycle and exposure to environmental stimuli affecting the biological rhythms are controlled. The aim is to produce a therapeutic effect in the treatment of psychiatric disorders. Chronobiological treatments include manipulations of the sleep-wake cycle, like sleep deprivation and advanced sleep-wake rhythm, and scheduled exposures to light and darkness. The clinical use of chronobiological treatments in Finland has been minimal and limited to the treatment of mood disorders, especially depressive disorders.
25157012	Chronic sleep loss and associated sleepiness and daytime impairments in adolescence are a serious threat to the academic success, health, and safety of our nation's youth and an important public health issue. Understanding the extent and potential short- and long-term repercussions of sleep restriction, as well as the unhealthy sleep practices and environmental factors that contribute to sleep loss in adolescents, is key in setting public policies to mitigate these effects and in counseling patients and families in the clinical setting. This report reviews the current literature on sleep patterns in adolescents, factors contributing to chronic sleep loss (ie, electronic media use, caffeine consumption), and health-related consequences, such as depression, increased obesity risk, and higher rates of drowsy driving accidents. The report also discusses the potential role of later school start times as a means of reducing adolescent sleepiness. 
25156773	Allergic rhinitis and associated symptomatic nasal obstruction negatively affect sleep through a variety of mechanisms and may contribute to persistent symptoms and poor adherence with medical device therapy for sleep apnea. A history of sinonasal symptoms, particularly those that occur at night or in the supine position, is the cornerstone of the medical evaluation. Further research into the relationship between allergic rhinitis and sleep disturbance would benefit from improved anatomic and pathophysiologic phenotyping as well as more advanced outcome measures such as spectral electroencephalogram analysis or other polysomnography variables beyond the apnea-hypopnea index. 
25156772	Sleep disturbances are common in pregnancy and may be influenced by a multitude of factors. Pregnancy physiology may predispose to sleep disruption but may also result in worsening of some underlying sleep disorders, and the de novo development of others. Apart from sleep disordered breathing, the impact of sleep disorders on pregnancy, fetal, and neonatal outcomes is poorly understood. In this article, we review the literature and discuss available data pertaining to the most common sleep disorders in perinatal women. These include restless legs syndrome, insomnia, circadian pattern disturbances, narcolepsy, and sleep-disordered breathing. 
25156766	Restrictive lung disease leads to ventilatory defects and diffusion impairments. These changes may contribute to abnormal nocturnal pathophysiology, including sleep architecture disruption and impaired ventilation and oxygenation. Patients with restrictive lung disease may suffer significant daytime fatigue and dysfunction. Hypercarbia and hypoxemia during sleep may impact progression of lung disease and related symptoms. Little is known about the impact of treatment of sleep disruption on sleep quality and overall prognosis in restrictive lung disease. This review discusses the pathophysiology of sleep and comorbid sleep disorders in restrictive lung diseases including interstitial lung disease, neuromuscular disease, and obesity hypoventilation syndrome. 
25156765	Sleep disturbances are frequently observed in cystic fibrosis (CF). The resultant sleep fragmentation, short sleep duration, and gas-exchange abnormalities are postulated to contribute to the neurocognitive, cardiovascular, and metabolic abnormalities associated with CF. There are no outcomes data to establish the optimal procedure for screening and treating CF patients for sleep-related respiratory abnormalities. Therapy with supplemental oxygen and bilevel ventilation are widely considered to be effective in the short term, but there are few evidence-based data to support long-term improvements in morbidity and mortality. 
25156749	Sleep patterns face important changes during adolescence. This can have implications for the immune system, which is regulated by the sleep-wake cycle; however, most studies relating sleep and immune system have been conducted on adults.To study the relationships between sleep duration, immune cell counts, and cytokines in European adolescents participating in the HELENA Cross-Sectional Study.	Adolescents (12.5-17.5 years; n = 933; 53.9% girls) were grouped according to self-reported sleep duration into <8, 8-8.9 and ≥9 h/night. Blood samples were collected in the morning after an overnight fast to analyze counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, the lymphocyte subsets CD3(+), CD4(+), CD8(+), CD45RA(+), CD45RO(+), CD3(-)CD16(+)56(+) and CD19(+), and concentrations of cortisol, CRP, IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α and IFN-γ. Pro-/anti-inflammatory and Th1/Th2 cytokine ratios were calculated. Immune parameters were correlated to sleep duration and compared between the three groups.	Sleep duration was negatively associated with cortisol levels and WBC, neutrophil, monocyte, CD4(+) and CD4(+)CD45RO(+) counts; in girls it is also negatively associated with IL-5 and IL-6 levels. The 8-8.9 h/night group presented the highest IL-4 values and the lowest pro-/anti-inflammatory and Th1/Th2 cytokine ratios.	A sleep duration of 8-8.9 h/night was associated with a healthier immune profile in our adolescents.	
25156482	Knowledge on the significance of childhood psychotic symptoms and experiences (PE) is still limited. This study aimed to investigate the prevalence and clinical significance of PE in preadolescent children from the general population by use of in-depth psychopathological interviews and comprehensive diagnostic assessments.We investigated 1,632 children from the general population-based Copenhagen Child Cohort 2000. PE were measured by semistructured interviews using the K-SADS-PL-items on psychotic and affective symptoms, each symptom scored as not present versus likely or definitely present. The Development and Well-Being Assessment (DAWBA) was used independently to diagnose DSM-IV-mental disorders. Puberty development and sleep disturbance were self-reported. The associations between PE (any lifetime hallucination and/or delusion) and various mental problems and disorders were examined by multivariable binomial regression analyses, adjusting for gender and onset of puberty.	The weighted life time prevalence of PE at age 11-12 years was 10.9% (CI 9.1-12.7). The majority of children with PE (n = 172) either had a diagnosable DSM-IV-mental disorder (31.4%) or self-reported mental health difficulties in absence of a diagnosis (31.4%). The risk of delusions increased with onset of puberty. The risk of PE increased with emotional and neurodevelopmental disorders, subthreshold depressive symptoms, sleep problems and lack of sleep, regardless of whether PE were expressed as hallucinations and/or delusions. The highest correlations were seen for emotional and multiple disorders.	Psychotic experiences are particularly prevalent in the context of affective dysregulation and sleep disturbance, increase with onset of puberty and represent a trans-diagnostic marker of psychopathology.	
25156468	Recent research in bipolar disorder (BD) points to the relevance and persistence of cognitive deficits even in euthymia. Up to now, the mechanisms behind why some bipolar patients (BP) do not reach their former level of cognitive performance and psychosocial functioning while others remit completely, are not understood. In this study we aimed to identify a "cognitive deficit" vs. "non-deficit" subgroup within BD by using an extensive neuropsychological test battery. The test performance of 70 euthymic outpatients (BD-I and II, recruited as a sample of convenience from our bipolar disorder programme) was compared to 70 matched, healthy controls (HC). Furthermore, we investigated the association between demographic/clinical variables and the cognitive performance of BP. As expected, our sample of euthymic BP performed significantly worse than HC in psychomotor speed, divided attention, working memory, verbal memory, word fluency and problem solving. However, 41.4% of the patients did not have any neurocognitive deficits at all, and whether or not a patient belonged to the non-deficit group was not influenced by disease severity. Instead, our results demonstrate that patients suffering from persistent sleep disturbances and sub-threshold depressive symptomatology show more severe cognitive dysfunctions. In addition, antipsychotic treatment and comorbid anxiety disorder were associated with cognitive deficits. In sum, these results suggest that a major part of cognitive impairment is due to current symptomatology, especially sleep disorder and sub-syndromal depression. Rigorous treatment of these symptoms thus might well improve cognitive deficits and, as a consequence, overall functioning in BD. 
25155226	Sleep dysfunction is a highly prevalent condition that has long been implicated in accelerating disease states characterized by having an inflammatory component such as systemic lupus erythematosus, HIV, and multiple sclerosis. Inflammatory bowel disease (IBD) is a chronic, debilitating disease that is characterized by waxing and waning symptoms, which are a direct result of increased circulating inflammatory cytokines. Recent studies have demonstrated sleep dysfunction and the disruption of the circadian rhythm to result in an upregulation of inflammatory cytokines. Not only does this pose a potential trigger for disease flares but also an increased risk of malignancy in this subset of patients. This begs to question whether or not there is a therapeutic role of sleep cycle and circadian rhythm optimization in the prevention of IBD flares. Further research is needed to clarify the role of sleep dysfunction and alterations of the circadian rhythm in modifying disease activity and also in reducing the risk of malignancy in patients suffering from IBD. 
25155183	Sleep disturbances are a prevalent and disabling problem for patients with cancer. Sleep disturbances are present throughout the cancer trajectory, especially during oncological treatment. Previously sleep disturbances have primarily been quantified with subjective rating scales. Actigraphy is an easy to use, non-invasive method for objective measurement of sleep. We systematically reviewed the literature for studies using actigraphy to measure sleeping habits of patients with cancer, undergoing oncological treatment. Our study furthermore reviewed studies with interventions designed to reduce sleep disturbances in the patient population. 19 studies were included in the final review of which 13 had a descriptive study design and six included some kind of intervention. The studies were primarily performed in patients with breast cancer undergoing chemotherapy. We found that sleep disturbances are prevalent, and persistent in patients with cancer. The sleep disturbances seem to be aggravated by chemotherapy treatment and accumulate as the treatment continues. Sleep disturbances need further attention among clinicians working with patients with cancer. 
25152963	There is a paucity of pediatric data addressing the complex relationship between primary headaches and sleep disturbances. Our study objective was to explore headache-related factors that predict sleep disturbance and to compare sleep complaints with other forms of headache-related disability among youth with migraines.A prospective cohort study was conducted in patients 10-18 years old with migraine or probable migraine and without daily sleep complaints. The patients completed a 90-day internet-based headache diary. On headache days, patients rated headache intensity, answered Pediatric Migraine Disability Assessment-based questions modified for daily scoring, and reported sleep disturbances that resulted as a direct effect of proximate headaches.	Fifty-two patients generated 4680 diary entries, 984 patients (21%) involved headaches. Headache intensity (P = 0.009) and timing of headache onset (P < 0.001) were predictive of sleep disturbances. Three Pediatric Migraine Disability Assessment-based items were also associated with sleep disturbances: partial school-day absence (P = 0.04), recreational activities prevented (P < 0.001), and decreased functioning during recreational activities (P < 0.001). Sleep disturbances correlated positively and significantly with daily headache disability scores (rpb = 0.35; P < 0.01).	We conclude that specific headache factors predict sleep disturbances among youth with primary headaches.	
25151622	Sleep-wake (S-W) disturbances are frequently associated with alcohol use disorders (AUD), occurring during periods of active drinking, withdrawal, and abstinence. These S-W disturbances can persist after months or even years of abstinence, suggesting that chronic alcohol consumption may have enduring negative effects on both homeostatic and circadian sleep processes. It is now generally accepted that S-W disturbances in alcohol-dependent individuals are a significant cause of relapse in drinking. Although significant progress has been made in identifying the socio-economic burden and health risks of alcohol addiction, the underlying neurobiological mechanisms that lead to S-W disorders in AUD are poorly understood. Marked progress has been made in understanding the basic neurobiological mechanisms of how different sleep stages are normally regulated. This review article in seeking to explain the neurobiological mechanisms underlying S-W disturbances associated with AUD, describes an evidence-based, easily testable, novel hypothesis that chronic alcohol consumption induces neuroadaptive changes in the cholinergic cell compartment of the pedunculopontine tegmentum (CCC-PPT). These changes include increases in N-methyl-d-aspartate (NMDA) and kainate receptor sensitivity and a decrease in gamma-aminobutyric acid (GABAB)-receptor sensitivity in the CCC-PPT. Together these changes are the primary pathophysiological mechanisms that underlie S-W disturbances in AUD. This review is targeted for both basic neuroscientists in alcohol addiction research and clinicians who are in search of new and more effective therapeutic interventions to treat and/or eliminate sleep disorders associated with AUD. 
25150770	Non-motor complications of Parkinson's disease (PD), specifically cognitive impairment, sleep disturbances, and fatigue, are recognized as important contributors to poor patient outcomes and quality of life. How sleep problems and fatigue interrelate and impact cognitive function, however, has not systematically been investigated across the stages of PD. The aim of our study was to investigate the relationships among cognitive impairment, night-time sleep problems, daytime sleepiness, and fatigue across all severities of PD.We examined these non-motor problems using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in a study of 1319 PD patients drawn from three large cohort studies: the Parkinson's Progressive Markers Initiative, the Rush University PD Cognitive-Behavioral-Imaging study, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Clinimetric testing program study, which spanned the gamut of disease, from early to advanced PD. Generalized linear mixed models with logit linking functions and covariates including study cohort, age, PD duration, and presence/absence of PD medications were used to examine relationships between these three non-motor symptoms and cognitive impairment.	Of these three frequent, and often inter-twined, non-motor complications, greater daytime sleepiness and fatigue were associated with worse cognitive impairment across the full spectrum of PD (F[16,1158] = 2.40 and F[16,1158] = 3.45 respectively, p's < 0.0005), but an association with night-time sleep was not detected (p = 0.83).	Given this association of daytime sleepiness and fatigue with cognitive impairment, clinical monitoring for these problems should be considered across all points in the PD spectrum, from early to more advanced disease.	
25149132	The aim of treatment of depression is remission of symptoms and functioning. Although there is a relationship between remission of symptoms and remission of functioning, it is not known how individual residual symptoms are related to functioning. Here we report a post-hoc analysis of two studies which treated depressed patients with duloxetine in an open fashion for 10-12 weeks. We evaluated the association of individual residual symptoms and functional impairment in patients who remitted or partially remitted after acute treatment. Logistic regression was used to investigate residual symptoms associated with functional impairment at endpoint. Our results suggest that in partial remitters, the only residual symptom associated with a reduction in the risk of having impaired function was the resolution of painful physical symptoms (PPS). In patients who remitted, the presence of residual core mood symptoms (CMS), particularly in patients without any anxiety, predicted impaired functioning. The resolution of PPS in the presence of residual CMS was associated with less risk of impaired functioning. Our results contribute to understand better the role of specific residual symptoms on functional impairment. To achieve normal functioning, intervention on specific residual symptoms is recommended. 
25148759	To establish clinically relevant classifications of health outcome scores for four Neuro-QOL measures (lower extremity function, upper extremity function, fatigue, and sleep disturbance).We employed a modified educational standard-setting methodology to identify cut-scores for symptom severity. Clinical vignettes were developed to represent graduated levels of symptom severity. A clinician panel and a panel of persons with multiple sclerosis (PwMS) were recruited, and, in separate, 1-day meetings, the panelists identified adjacent vignettes they judged to represent the threshold between two levels of severity for a given domain (e.g., threshold between a vignette that indicated "no problems" with sleep and the adjacent one that represented "mild problems" with sleep). Working independently, each panel (PwMS and clinicians) reached consensus on its recommended thresholds for each of the four targeted measures. Cut-scores were defined as the mean location for each pair of threshold vignettes.	PwMS and clinician panels derived identical thresholds for severity levels of lower extremity function and sleep disturbance, but slightly different ones for upper extremity function and fatigue. In every case of divergence, PwMS set higher thresholds for more severe classifications of symptoms (by 0.5 SDs) than did clinicians.	The modified bookmarking method is effective for defining thresholds for symptom severity based on self-reported outcome scores and consensus judgments. Derived cut-scores and severity levels provide an interpretative context for Neuro-QOL scores. Future studies should explore whether these findings can be replicated and evaluate the validity of the classifications compared to external criteria.	
25147309	Implications for practice and research: Quality of life (QOL) in long-term survivors of gynaecological cancer is similar to that of women without a cancer history. Demographical and clinical variables do not predict QOL in gynaecological cancer survivors. Physical and mental QOL in gynaecological cancer survivors is most strongly related to psychosocial factors, such as insecure attachment style and current state of anxiety. Further research is needed on how attachment style may affect coping with cancer and ultimately, QOL.
25146413	This multi-site randomized trial evaluates the quality of life (QOL) benefits of an imagery-based group intervention titled 'Envision the Rhythms of Life'(ERL).Breast cancer survivors >6 weeks post-treatment were randomized to attend five weekly 4-h group sessions at a community center with therapist present (live delivery (LD), n = 48), therapist streamed via telemedicine (telemedicine delivery (TD), n = 23), or to a waitlist control (WL) group (n = 47). Weekly individual phone calls to encourage at-home practice began at session one and continued until the 3-month follow-up. Seven self-report measures of QOL were examined at baseline, 1-month and 3-month post-treatments including health-related and breast cancer-specific QOL, fatigue, cognitive function, spirituality, distress, and sleep.	The Bonferroni method was used to correct for multiple comparisons, and alpha was adjusted to 0.01. Linear multilevel modeling analyses revealed less fatigue, cognitive dysfunction, and sleep disturbance for LD and TD compared with WL across the follow-up (p's < 0.01). Changes in fatigue, cognitive dysfunction, sleep disturbance, and health-related and breast cancer-related QOL were clinically significant. There were no differences between LD and TD.	Both the live and telemedicine delivered ERL intervention resulted in improvements in multiple QOL domains for breast cancer survivors compared with WL. Further, there were no significant differences between LD and TD, suggesting telemedicine delivered ERL intervention may represent an effective and viable option for cancer survivors in remote areas.	
25145751	Chronic use of benzodiazepines and z-drugs (BZD/Zs), the most commonly used symptomatic treatment for sleep problems, is discouraged because of the unproven long-term effectiveness. In this study, we evaluated 1-year evolution of subjective sleep quality of chronic BZD/Z users compared with nonusers.All cognitively competent residents from ten Belgian nursing homes were screened and compiled in a group of chronic BZD/Z users or nonusers, based on the medication chart. We collected demographic, functional and psychometric characteristics (depressive symptoms with the 8-item Geriatric Depression Scale), sleep parameters (with the Pittsburgh Sleep Quality Index-PSQI) and medication use. We analysed evolution of sleep quality with nonparametric statistics. Associations with worsening of sleep quality were analysed with linear regression.	We collected data of 131 BZD/Z users and 95 nonusers. The mean age in both groups was 85 years and 77 % was female. Over a period of 1 year, the PSQI score evolved from 5.2 to 5.8 (p = 0.035) in the BZD/Z users, and from 4.3 to 4.7 (p = 0.078) in the nonusers. Though the mean deterioration in 1 year did not differ significantly between both groups, the BZD/Z users had a significantly worse sleep quality compared with nonusers at both time points. Depressive symptoms were significantly associated with worsening sleep quality (β = -0.243, p < 0.001).	Sleep quality in chronic BZD/Z users significantly decreased over 1 year and was significantly worse than in nonusers at the end of this period. This study suggests that using BZD/Zs chronically does not maintain or improve sleep quality. Depressive symptoms are an important factor in the deterioration of sleep quality.	
25142770	Sleep duration and sleep quality play important roles in the development of hypertension (HT) in middle-aged subjects, with controversial data in elderly. In this study, we investigated the link between HT and self-reported sleep in non-insomniac elderly subjects.We examined 500 participants without insomnia complaints aged 72 ± 1 years. An extensive instrumental evaluation was carried out, including 24-h blood pressure (BP) monitoring and an assessment of nocturnal BP dipping. Sleep duration and quality were evaluated by the Pittsburgh Sleep Quality Index (PSQI). The subjects were stratified into three groups according to sleep duration: short (< 6 h), normal (> 6h to < 8 h), and long (> 8 h) sleepers. A PSQI < 5 defined good sleepers (GS, n = 252), and a PSQI > 5 (n = 248) defined poor sleepers (PS).	PS represented 50% of the subjects, more frequently females. Compared to GS, PS did not differ in terms of HT, BP, baroreflex sensitivity (BRS), and BP dipping. Short, normal, and long sleepers accounted for 28%, 42%, and 30% of subjects, with HT, BP values, BRS, and gender not differing between groups. No relationship was found between nocturnal BP values and self-reported sleep measures. Logistic regression analysis indicated that neither sleep duration nor sleep quality predicts the prevalence of HT, the body mass index being the only factor affecting this association.	In a sample of non-insomniac elderly subjects, neither sleep duration nor sleep quality affected the prevalence of HT. These data argue against a relationship between self-reported sleep duration and quality and HT in elderly without insomnia.	
25142763	To report at a population level the prevalence of restless legs syndrome, insomnia, and the risk of obstructive sleep apnea in multiple sclerosis patients. Sleep patterns and associations with fatigue and daytime sleepiness were identified.A cross-sectional study was performed using a written survey that was mailed to 11,400 individuals from the Northern California Chapter of the National Multiple Sclerosis (MS) Society Database who self-identified as having MS. The survey included individual questions relating to demographics as well as several standard validated questionnaires related to primary sleep disorders, sleepiness, fatigue severity, and sleep patterns.	Among the 11,400 surveys mailed out, 2,810 (24.6%) were returned. Of these, 2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%) screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia, and 866 (36.8%) for restless legs syndrome. In contrast, only 4%, 11%, and 12% of the cohort reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia, and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents reported an abnormal level of fatigue based on the Fatigue Severity Scale. Both abnormal fatigue and sleepiness scores were associated with screening positive for obstructive sleep apnea, insomnia, and restless legs syndrome.	A significant percentage of MS subjects in our sample screened positive for one or more sleep disorders. The vast majority of these sleep disorders were undiagnosed. Greater attention to sleep problems in this population is warranted, especially in view of fatigue being the most common and disabling symptom of MS.	
25142762	The Psychomotor Vigilance Task (PVT) is one of the leading assays of sustained vigilant attention in sleep research and highly sensitive to the effects of sleep loss. Even though PVT is widely used in sleep deprivation studies, little is known about PVT performance in patients suffering from sleep-wake disorders. We aimed to quantify the impact of sleep-wake disorders on PVT outcome measures and examine whether PVT can distinguish between healthy controls and patients with sleep-wake disorders and whether PVT can distinguish between three different disorders that express excessive daytime sleepiness.We compared PVT data of 143 patients and 67 age- and gender-matched healthy controls. Patients were diagnosed with one of the following sleep-wake disorders: narcolepsy with cataplexy (n = 20), insufficient sleep syndrome (ISS, n = 67) and hypersomnia (HS, n = 56). Several PVT outcomes were analyzed: reciprocal mean reaction time, response variability, number of lapses, number of false reaction time, slowest and fastest 10% of reaction time, and duration of lapses.	PVT performance was generally better in healthy controls than in patients with any of the sleep-wake disorders analyzed. Patients with narcolepsy and HS performed worse on PVT than subjects with ISS. In controls, but not in patients, older subjects had slower reactions times and higher response variability in PVT.	PVT performance shows different patterns in patients with different sleep-wake disorders and control subjects and may add useful information to the diagnostic work-up of sleep-wake disorders.	
25142761	Patients with irritable bowel syndrome (IBS) often report sleep disturbances. Previously, we have shown that self-reported sleep difficulties predicted exacerbations of next-day IBS symptoms, mood disturbance, and fatigue. The purpose of this study was to explore whether objectively measured sleep using actigraphy, as well as self-report, predicts next-day symptoms in women with IBS and to explore whether or not symptoms also predict self-report and objective sleep.Women aged 18-45 years with IBS were community-recruited (n = 24, mean age = 32 ± 8 years). Participants completed sleep and IBS symptom diaries for one menstrual cycle and wore Actiwatch-64 actigraphs for 7 days at home. Statistical analyses used generalized estimating equation (GEE) models.	Poorer self-reported sleep quality significantly (p < 0.05) predicted higher next-day abdominal pain, anxiety, and fatigue, but was not significant for gastrointestinal (GI) symptoms or depressed mood. Actigraphic sleep efficiency (SEF) significantly predicted worsening next-day anxiety and fatigue, but not abdominal pain, GI symptoms, or depressed mood. On temporally reversed analyses, none of the symptoms significantly predicted subsequent sleep, except that GI symptoms significantly predicted higher actigraphic sleep efficiency.	This small exploratory study supports previous findings that self-reported sleep disturbance predicted exacerbation of next-day symptoms in women with IBS and extends this relationship using an objective sleep measure. The study adds further evidence that sleep quality predicts subsequent IBS symptoms, but not the converse. The findings from this small study support the importance of additional longitudinal research to further understand the relationships between sleep and IBS.	
25142760	Vulnerability to stress-related sleep disturbances and maladaptive sleep beliefs has been proposed to be predisposing factors for insomnia. Yet previous studies addressing these factors have been cross-sectional in nature and could not be used to infer the time sequences of the association. The current study used a six-year follow-up to examine the predisposing roles of these two factors and their interactions with major life stressors in the development of insomnia.One hundred seventeen college students recruited for a survey in 2006 participated in this follow-up survey in 2012. In 2006, they completed a packet of questionnaires including the Dysfunctional Beliefs and Attitudes about Sleep Questionnaire, 10-item version (DBAS-10), the Ford Insomnia Response to Stress Test (FIRST), and the Pittsburgh Sleep Quality Index (PSQI); in 2012 they completed the Insomnia Severity Index (ISI) and the modified Life Experiences Survey (LES).	Fourteen of the participants were found to suffer from insomnia as measured by the ISI. Logistic regression showed that scores on both DBAS-10 and FIRST could predict insomnia at follow-up. When the interaction of DBAS-10 and LES and that of FIRST and LES were added, both DBAS-10 and FIRST remained significant predictors, while the interaction of FIRST and LES showed a near-significant trend in predicting insomnia.	The results showed that both vulnerability to stress-related sleep disturbances and maladaptive sleep beliefs are predisposing factors for insomnia. The hypothesized interaction effect between sleep vulnerability and major life stressors was found to be marginal. The maladaptive sleep beliefs, on the other hand, showed a predisposing effect independent from the influences of negative life events.	
25142574	To determine whether sleep disturbances are found in the valproic acid model of autism spectrum disorders (ASD).Comparative study for sleep behavior, sleep architecture, electroencephalogram (EEG) spectral analysis, and glutamic acid decarboxylase (GAD) 65/67 protein expression in juvenile rats exposed to valproic acid (VPA), sodium salt, or saline in utero.	N/A.	Juvenile (postnatal day 32) male and female Sprague-Dawley rats.	In utero exposure to either saline or 400 mg/kg VPA administered intraperitoneally to the dams on gestational day 12.5. On postnatal days 22-24, all rats were implanted with transmitters to record EEG and electromyogram (EMG) activity.	During the light phase, when nocturnal animals are typically quiescent, the VPA-exposed animals spent significantly more time in wake (∼35 min) and significantly less time in non-rapid eye movement (NREM) sleep (∼26 min) compared to the saline controls. Furthermore, spectral analysis of the EEG revelled that VPA-exposed animals exhibited increased high-frequency activity during wake and rapid eye movement (REM) sleep and reduced theta power across all vigilance states. Interestingly, the gamma-aminobutyric acid (GABA)-ergic system, which modulates the induction and maintenance of sleep states, was also disrupted, with reduced levels of both GAD 65 and GAD67 in the cortical tissue of VPA-exposed animals compared to saline controls.	To date, the current animal models of ASD have been underutilized in the investigation of associated sleep disturbances. The VPA animal model recapitulates aspects of sleep disruptions reported clinically, providing a tool to investigate cellular and molecular dysregulation contributing to sleep disruptions in ASD.	
25142380	Fragmented sleep is a common and troubling symptom in ageing and Alzheimer's disease; however, its neurobiological basis in many patients is unknown. In rodents, lesions of the hypothalamic ventrolateral preoptic nucleus cause fragmented sleep. We previously proposed that the intermediate nucleus in the human hypothalamus, which has a similar location and neurotransmitter profile, is the homologue of the ventrolateral preoptic nucleus, but physiological data in humans were lacking. We hypothesized that if the intermediate nucleus is important for human sleep, then intermediate nucleus cell loss may contribute to fragmentation and loss of sleep in ageing and Alzheimer's disease. We studied 45 older adults (mean age at death 89.2 years; 71% female; 12 with Alzheimer's disease) from the Rush Memory and Aging Project, a community-based study of ageing and dementia, who had at least 1 week of wrist actigraphy proximate to death. Upon death a median of 15.5 months later, we used immunohistochemistry and stereology to quantify the number of galanin-immunoreactive intermediate nucleus neurons in each individual, and related this to ante-mortem sleep fragmentation. Individuals with Alzheimer's disease had fewer galaninergic intermediate nucleus neurons than those without (estimate -2872, standard error = 829, P = 0.001). Individuals with more galanin-immunoreactive intermediate nucleus neurons had less fragmented sleep, after adjusting for age and sex, and this association was strongest in those for whom the lag between actigraphy and death was <1 year (estimate -0.0013, standard error = 0.0005, P = 0.023). This association did not differ between individuals with and without Alzheimer's disease, and similar associations were not seen for two other cell populations near the intermediate nucleus. These data are consistent with the intermediate nucleus being the human homologue of the ventrolateral preoptic nucleus. Moreover, they demonstrate that a paucity of galanin-immunoreactive intermediate nucleus neurons is accompanied by sleep fragmentation in older adults with and without Alzheimer's disease.

25141012	To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit.Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later.	Outpatient.	Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, <6.5 h sleep/night.	Non-pharmacological sleep extension.	Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids.	Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 vs. 388.1±48.6 min/night; mean±SD; P<0.001 screening vs. randomization; actigraphy: 344.3 ±41.9 vs. 358.6±48.2 min/night; P<0.001) sleep quality improved (9.1±3.2 vs. 8.2±3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9±4.6 vs. 8.3±4.5 ESS score; P = 0.06), insulin resistance decreased (0.327±0.038 vs. 0.351±0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% vs. 11%; P = 0.007), and metabolic syndrome (42% vs. 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit.	Relatively small sample size.	Improvements in biochemical and behavioral parameters between screening and randomization changed the "true" study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the "Hawthorne effect", according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research.	

25137243	Sleep disturbances are common among women in midlife; prevalence increases among perimenopausal/postmenopausal women with vasomotor symptoms. Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the United States for moderate to severe vasomotor symptoms associated with menopause. In two pivotal phase 3 studies evaluating its efficacy and safety, improvements in sleep disturbances were also prospectively evaluated.Postmenopausal women with moderate to severe vasomotor symptoms were randomly assigned to paroxetine 7.5 mg (n = 591) or placebo (n = 593) once daily for 12 weeks (both studies) or 24 weeks (24-wk study). Predefined assessments on weeks 4, 12, and 24 included number of nighttime awakenings attributed to vasomotor symptoms, sleep-onset latency, sleep duration, and sleep-related adverse events. The two studies' data for weeks 1 to 12 were pooled.	At baseline, participants reported a mean of 3.6 awakenings/night attributed to vasomotor symptoms. Nighttime awakenings attributed to vasomotor symptoms were significantly reduced within 4 weeks of initiating paroxetine 7.5 mg treatment (39% reduction vs 28% for placebo; P = 0.0049), and reductions were sustained through 12 or 24 weeks of treatment. Paroxetine 7.5 mg treatment also significantly increased nighttime sleep duration (week 4, +31 vs +16 min for placebo; P = 0.0075), but no significant between-group differences in sleep-onset latency or sleep-related adverse events such as sedation were observed.	In postmenopausal women treated for menopausal vasomotor symptoms, paroxetine 7.5 mg significantly reduces the number of nighttime awakenings attributed to vasomotor symptoms and increases sleep duration without differentially affecting sleep-onset latency or sedation.	
25135784	Substance use disorders (SUD) are common and individuals who suffer from them are prone to relapse. One of the most common consequences of the use of and withdrawal from substances of abuse is sleep disturbance. Substances of abuse affect sleep physiology, including the neurotransmitter systems that regulate the sleep-wake system. Emerging research now highlights an interactive effect between sleep disorders and substance use. New findings in alcohol and sleep research have utilized sophisticated research designs and expanded the scope of EEG and circadian rhythm analyses. Research on marijuana and sleep has progressed with findings on the effects of marijuana withdrawal on objective and subjective measures of sleep. Treatment studies have focused primarily on sleep in alcohol use disorders. Therapies for insomnia in cannabis disorders are needed. Future research is poised to further address mechanisms of sleep disturbance in alcoholics and the effect of medical marijuana on sleep and daytime functioning. 
25135782	Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders. 
25135598	Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline.
25134878	Autism spectrum disorder (ASD) is defined by differences in social communication and restricted, repetitive patterns of behavior, interests, or activities. Skills and challenges can change depending on environmental stimuli, supports, and stressors. Quality of life can be improved by the use of accommodations, assistive technologies, therapies to improve adaptive function or communication, caregiver training, acceptance, access, and inclusion. This article focuses on the identification of ASD in adults, referrals for services, the recognition of associated conditions, strategies and accommodations to facilitate effective primary care services, and ethical issues related to caring for autistic adults. 
25134876	Sleep issues are common in people with psychiatric disorders, and the interaction is complex. Sleep disorders, particularly insomnia, can precede and predispose to psychiatric disorders, can be comorbid with and exacerbate psychiatric disorders, and can occur as part of psychiatric disorders. Sleep disorders can mimic psychiatric disorders or result from medication given for psychiatric disorders. Impairment of sleep and of mental health may be different manifestations of the same underlying neurobiological processes. For the primary care physician, key tools include recognition of potential sleep effects of psychiatric medications and familiarity with treatment approaches for insomnia in depression and anxiety. 
25134869	Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered. 
25133898	The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-α) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep. 
25133844	Sleep disturbance and heavy drinking increase risk of negative consequences in college students. Limited research exists on how they act synergistically, and the overall nature of sleep and sleep-related impairment in college student drinkers is poorly understood. A latent profile analysis was conducted on the sleep characteristics and daytime sleep-related consequences of college student drinkers who were at-risk based on Alcohol Use Disorders Identification Test-Consumption scores.Participants (N = 312, mean age = 18.90 (0.97) years) consumed a mean (SD) of 20.93 (13.04) drinks per week. Scores on the 10 items of the Sleep/Wake Behavior Problems Scale (SWPS) were the class indicators.	Four classes best described the sleep and sleep-related consequences of at-risk college drinkers. Classes represented different gradients and types of sleep patterns and sleep-related impairment; nearly half the sample reported late bedtimes and daytime consequences of insufficient sleep. Subsequent validation analyses indicated that these classes were directly correspondent with severity of alcohol consumption, alcohol-related consequences illicit substance use, and perceived health.	These findings indicate the presence of significant heterogeneity in college drinkers' sleep patterns and experiences of sleep-related impairment. Class differences significantly impact the level of alcohol and drug use and the consequences members experience. Greater alcohol use and sleep/wake problems are associated with increased risk for negative consequences for certain classes. These results suggest that college drinking interventions could benefit from the incorporation of sleep-related content and the value in adding brief alcohol assessments and interventions to other college health treatments.	
25133841	The current study examines associations between five factor personality traits and average sleep duration, sleep deficiency, and sleep problems.The participants were from two population-based samples from Australia (n = 1,104, age range 31-41) and Finland (n = 1,623, age range 30-45). Self-reports of sleep behavior, sleep problems (Jenkin's scale), and five factor model personality traits (NEO-FFI) were collected. Associations between personality traits and sleep were analyzed with linear regressions.	The results showed that higher extraversion, agreeableness, and conscientiousness were, in general, associated with better sleep, whereas higher neuroticism was associated with sleeping less well. Openness was not associated with sleep. Most of the associations were replicable between the samples from the two countries, but personality traits explained only small part of the variance in sleep behavior.	Increasing the knowledge on personality and sleep may benefit more personalized treatment of sleep disorders and help in personnel selection to jobs in which it is critical to stay alert. However, longitudinal research is needed to confirm the current findings.	
25133838	Psychosocial stress has been linked with an unhealthy lifestyle but the relation's direction remains unclear. Does stress induce sleeping problems, comfort food consumption, and lower physical activity, or do these unhealthy lifestyle factors enhance stress? This study examined the bidirectional stress-lifestyle relation in children.The relation between stress and lifestyle was examined over 2 years in 312 Belgian children 5-12 years old as part of the Children's Body Composition and Stress study. Stress-related aspects were measured by questionnaires concerning negative events, negative emotions, and behavioral problems. The following lifestyle factors were assessed: physical activity (by accelerometers), sleep duration, food consumption (sweet food, fatty food, snacks, fruits and vegetables), and eating behavior (emotional, external, restrained). Bidirectional relations were examined with cross-lagged analyses.	Certain stress aspects increased physical activity, sweet food consumption, emotional eating, restrained eating, and external eating (βs = .140-.319). All relations were moderated by sex and age: Dietary effects were mainly in the oldest children and girls; stress increased physical activity in the youngest, whereas it tended to decrease physical activity in the oldest. One reversed direction effect was found: Maladaptive eating behaviors increased anxiety feelings.	Relations were mainly unidirectional: Stress influenced children's lifestyle. Stress stimulated eating in the absence of hunger, which could facilitate overweight. Consequently, families should realize that stress may influence children's diet, and problem-solving coping skills should be acquired. In contrast to recent findings, stress might also stimulate physical activity in the youngest as positive stress coping style.	
25133792	The aim of the present study was to evaluate the development of the circadian rhythm of the salivary cortisol in premature infants and its correlation with the onset of the sleep-activity behavior pattern during the first 3 weeks of life under controlled light:dark conditions. Furthermore, we investigated the influence of acoustic stimulation by audiotaped lullabies or the maternal voice on the cortisol values and long-term sleep-activity patterns. The study was a block-randomized, prospective clinical trial with a study population of 62 preterm neonates (30<37 gestational age). We compared two study groups who listened either to music or to the maternal voice (music: N=20; maternal voice: N=20) with a matched control group (N=22). The acoustic stimulation took place every evening between 20:00 and 21:00 h for 30 min over a period of 2 weeks. The cortisol values and activity-rest behavior of the neonates were determined during the first 3 weeks of life on the 1st, 7th and 14th day. Actigraphic monitoring was used to record the activity pattern continuously over 24 h and a validated algorithm for neonates was used to estimate sleep and wakefulness. The saliva samples were obtained 10 min before and 10 min after the acoustic interventions for the study groups. Additionally, saliva samples were obtained from the control group seven times over a 24-h period (20:00, 21:00, 01:00, 05:00, 08:00, 13:00 and 17:00 h). The cortisol data were analyzed by fast Fourier transformation to assess periodic characteristics and frequencies. Hierarchical linear modeling was further performed for the statistical analysis.The cortisol rhythm analysis indicated a circadian rhythm pattern for only one premature infant, all others of the neonates showed no circadian or ultradian rhythm in cortisol. Cortisol level of the premature neonates was significantly higher during the first day of the study period at night-time (median: 17.1 nmol/L, IQR=9.7-24.4 nmol/L) than on days 7 (median: 9.6 nmol/L, IQR=4.7-14.6 nmol/L; Tukey-HSD, z=4.12, p<0.001) and 14 (IQR=5.8-13.7 nmol/L; Tukey-HSD, z=2.89, p<0.05). No significant effect of acoustic stimulation was observed on the cortisol concentration and sleep-wake behavior. The activity-sleep rhythm of preterm neonates was dominated by ultradian rhythm patterns with a prominent period length of 4 h (30.5%). Activity frequencies of neonates were also significantly higher overnight on the first study day (mean: 329±185.1 U) than of night seven (mean: 260.2±132.4 U; Tukey-HSD, z=2.50, p<0.05). Quiet-activity patterns increased, whereas high-activity patterns decreased during the observation period. Average sleep time increased significantly during the study time from day 1 to day 7 (Tukey-HSD, z=2.51, p<0.05). In conclusion, premature infants showed higher cortisol levels - without a circadian rhythmicity - and higher activity frequencies in the first days after birth which may reflect an adaptation process of neonates after birth. Cortisol concentrations and the activity patterns were not influenced by music interventions.	
25133759	Older adults have high rates of sleep disturbance, die by suicide at disproportionately higher rates compared with other age groups, and tend to visit their physician in the weeks preceding suicide death. To our knowledge, to date, no study has examined disturbed sleep as an independent risk factor for late-life suicide.To examine the relative independent risk for suicide associated with poor subjective sleep quality in a population-based study of older adults during a 10-year observation period.	A longitudinal case-control cohort study of late-life suicide among a multisite, population-based community sample of older adults participating in the Established Populations for Epidemiologic Studies of the Elderly. Of 14 456 community older adults sampled, 400 control subjects were matched (on age, sex, and study site) to 20 suicide decedents.	Primary measures included the Sleep Quality Index, the Center for Epidemiologic Studies-Depression Scale, and vital statistics.	Hierarchical logistic regressions revealed that poor sleep quality at baseline was significantly associated with increased risk for suicide (odds ratio [OR], 1.39; 95% CI, 1.14-1.69; P < .001) by 10 follow-up years. In addition, 2 sleep items were individually associated with elevated risk for suicide at 10-year follow-up: difficulty falling asleep (OR, 2.24; 95% CI, 1.27-3.93; P < .01) and nonrestorative sleep (OR, 2.17; 95% CI, 1.28-3.67; P < .01). Controlling for depressive symptoms, baseline self-reported sleep quality was associated with increased risk for death by suicide (OR, 1.30; 95% CI, 1.04-1.63; P < .05).	Our results indicate that poor subjective sleep quality is associated with increased risk for death by suicide 10 years later, even after adjustment for depressive symptoms. Disturbed sleep appears to confer considerable risk, independent of depressed mood, for the most severe suicidal behaviors and may warrant inclusion in suicide risk assessment frameworks to enhance detection of risk and intervention opportunity in late life.	

25132610	Few reports on sleep patterns of patients with spinal muscular atrophy type 1 (SMA1) have been published and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of infants with SMA1, compared with age- and sex-matched controls.Twelve SMA1 patients (six males, mean age 5.9 months) and 10 controls (five males, mean age 4.8 months) underwent full polysomnography to evaluate their sleep architecture and microstructure by means of the cyclic alternating pattern (CAP).	Compared with control children, SMA1 patients showed increased sleep latency and apnea/hypopnea index. CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes and of A2 and A3 indexes (number/h), indicating a dysfunction of the arousal system in these patients.	The results indicate the presence of an abnormality of sleep microstructure in SMA1 patients, characterized by a reduction of A2 and A3 CAP subtypes. We hypothesize that SMA1 patients have reduced arousability during non-rapid eye movement sleep, which could be interpreted as additional evidence of central nervous system involvement in this disease.	
25132206	Cancer-related fatigue (CRF) is one of the most common, persistent, and disabling symptoms associated with cancer and its treatment. Evidence-based treatments that are acceptable to patients are critically needed. This study examined the efficacy of mindfulness-based stress reduction (MBSR) for CRF and related symptoms.A sample of 35 cancer survivors with clinically significant CRF was randomly assigned to a 7-week MBSR-based intervention or wait-list control group. The intervention group received training in mindfulness meditation, yoga, and self-regulatory responses to stress. Fatigue interference (primary outcome) and a variety of secondary outcomes (e.g., fatigue severity, vitality, disability, depression, anxiety, and sleep disturbance) were assessed at baseline, post-intervention, and 1-month follow-up. Bonferroni correction was employed to account for multiple comparisons. Controls received the intervention after the 1-month follow-up. Participants in both groups were followed for 6 months after completing their respective MBSR courses to assess maintenance of effects.	Compared to controls, the MBSR group reported large post-intervention reductions as assessed by effect sizes (d) in the primary outcome, fatigue interference (d = -1.43, p < 0.001), along with fatigue severity (d = -1.55, p < 0.001), vitality (d = 1.29, p < 0.001), depression (d = -1.30, p < 0.001), and sleep disturbance (d = -0.74, p = 0.001). Results were maintained or strengthened at 1-month follow-up, the point at which significant improvements in disability (d = -1.22, p < 0.002) and anxiety (d = -0.98, p = 0.002) occurred. Improvements in all outcomes were maintained 6 months after completing the course. MBSR adherence was high, with 90% attendance across groups and high rates of participant-reported home practice of mindfulness.	Mindfulness-based stress reduction is a promising treatment for CRF and associated symptoms.	
25130760	Changes in sleep patterns often occur in older adults. Previous studies have documented associations between sleep duration, sleep quality, and obesity risk in older individuals, yet few studies have examined these trends in lower-income countries. The present cross-sectional study uses nationally representative datasets from six countries to examine these relationships.Two hypotheses related to obesity risk and sleep patterns were tested using data from the first wave of the World Health Organization's Study on global AGEing and adult health (SAGE). This longitudinal study draws on samples of older adults (>50 years old) in six middle-income countries (China, Ghana, India, Mexico, Russian Federation, and South Africa). Self-report data were used to measure sleep duration, sleep quality, lifestyle and sociodemographic information, while anthropometric measurements were collected to assess body mass index (BMI) and waist circumference (WC). Multiple linear regressions were used to examine the relationship between sleep patterns and obesity risk while controlling for lifestyle factors.	Shorter sleep durations in both men and women were significantly associated with higher BMI and WC measures (P < 0.05). Low sleep quality did not significantly contribute to increased obesity risk. Surprisingly, high sleep quality was significantly associated with increased male BMI and WC in China and India (P < 0.01).	This study documented an association between short sleep duration and increased obesity risk, which is important given the global increase of obesity-related diseases.	
25129884	Sleep disorders are common among patients hospitalized in coronary care unit (CCU). This study aimed to investigate the effect of Rosa damascene aromatherapy on sleep quality of patients hospitalized in CCU.In this randomized controlled trial, 60 patients who met the inclusion criteria were conveniently sampled and randomly allocated to the experimental and control groups. Patients in the control group received routine care. In the experimental group, patients received routine care and Rosa damascene aromatherapy for three subsequent nights. In the both groups the sleep quality was assessed using the Pittsburgh Sleep Quality Index.	After the study, the mean scores of five domains of Pittsburg Sleep Quality Index as well as the mean of total score of the index in the experimental group were significantly lower than the control group.	Rosa damascene aromatherapy can significantly improve the sleep quality of patients hospitalized in CCUs.	
25128183	To evaluate the course and predictors of neuropsychiatric symptoms (NPS) and cognition in patients with de novo Parkinson disease (PD).Cross-sectional study of the cohort of de novo, untreated (at enrollment) patients with PD and healthy controls (HCs) from the Parkinson's Progression Markers Initiative. Participants have serial assessments of global cognition and symptoms of depression, anxiety, psychosis, impulse control disorders (ICDs), sleep and wakefulness, apathy, and fatigue. Available data up to 24 months of follow-up were included.	The available sample size was as follows: baseline (PD = 423, HCs = 196), 12 months (PD = 261, HCs = 145), and 24 months (PD = 96, HCs = 83). Patients with PD experienced more depression, fatigue, apathy, and anxiety than HCs at all time points, and apathy (p = 0.001) and psychosis (p = 0.003) increased over time in patients with PD. Approximately two-thirds of patients with PD who screened positive for depression at any given visit were not taking an antidepressant. The Montreal Cognitive Assessment score decreased significantly over time in patients with PD (p < 0.001), but the change was comparable to that in HCs. At the 24-month visit, 44% of patients had been on dopamine replacement therapy (DRT) for at least 1 year, and this group reported more incident ICDs (p = 0.009) and excessive daytime sleepiness (p = 0.03).	Multiple NPS are more common in de novo, untreated patients with PD compared with the general population, but they also remain relatively stable in early disease, while global cognition slightly deteriorates. In contrast, initiation of DRT is associated with increasing frequency of several other NPS.	
25127232	Sleep deprivation and fatigue are common subjective complaints among astronauts. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members. We aimed to characterise representative sleep patterns of astronauts on both short-duration and long-duration spaceflight missions.For this observational study, we recruited crew members assigned to Space Transportation System shuttle flights with in-flight experiments between July 12, 2001, and July 21, 2011, or assigned to International Space Station (ISS) expeditions between Sept 18, 2006, and March 16, 2011. We assessed sleep-wake timing objectively via wrist actigraphy, and subjective sleep characteristics and hypnotic drug use via daily logs, in-flight and during Earth-based data-collection intervals: for 2 weeks scheduled about 3 months before launch, 11 days before launch until launch day, and for 7 days upon return to Earth.	We collected data from 64 astronauts on 80 space shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS missions (3248 in-flight days), with ground-based data from all astronauts (4014 days). Crew members attempted and obtained significantly less sleep per night as estimated by actigraphy during space shuttle missions (7·35 h [SD 0·47] attempted, 5·96 h [0·56] obtained), in the 11 days before spaceflight (7·35 h [0·51], 6·04 h [0·72]), and about 3 months before spaceflight (7·40 h [0·59], 6·29 h [0·67]) compared with the first week post-mission (8·01 h [0·78], 6·74 h [0·91]; p<0·0001 for both measures). Crew members on ISS missions obtained significantly less sleep during spaceflight (6·09 h [0·67]), in the 11 days before spaceflight (5·86 h [0·94]), and during the 2-week interval scheduled about 3 months before spaceflight (6·41 h [SD 0·65]) compared with in the first week post-mission (6·95 h [1·04]; p<0·0001). 61 (78%) of 78 shuttle-mission crew members reported taking a dose of sleep-promoting drug on 500 (52%) of 963 nights; 12 (75%) of 16 ISS crew members reported using sleep-promoting drugs.	Sleep deficiency in astronauts was prevalent not only during space shuttle and ISS missions, but also throughout a 3 month preflight training interval. Despite chronic sleep curtailment, use of sleep-promoting drugs was pervasive during spaceflight. Because chronic sleep loss leads to performance decrements, our findings emphasise the need for development of effective countermeasures to promote sleep.	The National Aeronautics and Space Administration.	
25127157	Sleep and exercise influence each other through complex, bilateral interactions that involve multiple physiological and psychological pathways. Physical activity is usually considered as beneficial in aiding sleep although this link may be subject to multiple moderating factors such as sex, age, fitness level, sleep quality and the characteristics of the exercise (intensity, duration, time of day, environment). It is therefore vital to improve knowledge in fundamental physiology in order to understand the benefits of exercise on the quantity and quality of sleep in healthy subjects and patients. Conversely, sleep disturbances could also impair a person's cognitive performance or their capacity for exercise and increase the risk of exercise-induced injuries either during extreme and/or prolonged exercise or during team sports. This review aims to describe the reciprocal fundamental physiological effects linking sleep and exercise in order to improve the pertinent use of exercise in sleep medicine and prevent sleep disorders in sportsmen. 
25126870	To determine the prevalence of sleep disorders in a population of Nigerian women during pregnancy and to evaluate the frequency of these sleep disorders according to the three trimesters of pregnancy.A prospective cross-sectional design. Participants' were interviewed at the antenatal clinic with a questionnaire to evaluate their sleep during and before pregnancy and to appraise disturbance in their sleep according to the trimester.	Two hundred and three pregnant women participated in the survey and were evaluated at one of three points in pregnancy: 1st trimester (n=57), 2nd trimester (n=71) and 3rd trimester (n=75). Overall, the prevalence of sleep disorder in the population surveyed was 35.5% (72/203), more women experienced sleep disturbances in the first (42.1%) and third (40%) trimester of pregnancy compared to the second (25.3%). In terms of types of sleep disorders; 96(47.3%) reported insomnia, 32(15.8%) sleep breathing disorders, 86(42.4%) excessive daytime sleepiness, 172(84.7%) mild sleepiness and 64(31.5%) significant specific awakenings. The most common reason for specific awakening was frequent urination (78.6%). These sleep disorders were more common in the third trimester of pregnancy but only insomnia and specific awakenings showed statistical significance, p=0.007 and 0.031 respectively. Logistic regression model showed that nulliparity, increased BMI and previous adverse obstetric events had significant independent associations with sleep disorders.	Sleep disorders are common in pregnancy, notably in the first and third trimesters.	
25126042	To review systematically medical-legal cases of sleep-related violence (SRV) and sexual behavior in sleep (SBS).We searched Pubmed and PsychINFO (from 1980 to 2012) with pre-specified terms. We also searched reference lists of relevant articles.	Case reports in which a sleep disorder was purported as the defense during a criminal trial and in which information about the forensic evaluation of the defendant was provided.	Information about legal issues, defendant and victim characteristics, circumstantial factors, and forensic evaluation was extracted from each case. A qualitative-comparative assessment of cases was performed.	Eighteen cases (9 SRV and 9 SBS) were included. The charge was murder or attempted murder in all SRV cases, while in SBS cases the charge ranged from sexual touching to rape. The defense was based on sleepwalking in 11 of 18 cases. The trial outcome was in favor of the defendant in 14 of 18 cases. Defendants were relatively young males in all cases. Victims were usually adult relatives of the defendants in SRV cases and unrelated young girls or adolescents in SBS cases. In most cases the criminal events occurred 1-2 hours after the defendant's sleep onset, and both proximity and other potential triggering factors were reported. The forensic evaluations widely differed from case to case.	SRV and SBS medical-legal cases did not show apparent differences, except for the severity of the charges and the victim characteristics. An international multidisciplinary consensus for the forensic evaluation of SRV and SBS should be developed as an urgent priority.	
25126032	A majority of patients diagnosed with obstructive sleep apnea are position dependent whereby they are at least twice as severe when sleeping supine (POSA). This study evaluated the accuracy and efficacy of a neck-worn device designed to limit supine sleep. The study included nightly measurements of snoring, sleep/wake, time supine, and the frequency and duration of feedback to monitor compliance.Thirty patients between ages 18 and 75 years, BMI ≤ 35 with an overall apnea-hypopnea index (AHI) ≥ 5 and an overall AHI ≥ 1.5 times the non-supine AHI, and an Epworth score ≥ 5 were prospectively studied. Subjective reports and polysomnography were used to assess efficacy resulting from 4 weeks of in-home supine-avoidance therapy and to measure device accuracy. From 363 polysomnography reports, 209 provided sufficient positional data to estimate one site's prevalence of positional OSA.	In 83% of participants exhibiting > 50% reduction in overall AHI, the mean and median reductions were 69% and 79%. Significant reductions in the overall and supine AHI, apnea index, percent time SpO2 < 90%, and snoring contributed to significant improvements in stage N1 and N2 sleep, reductions in cortical arousals and awakenings, and improved depression scores. Supine position was under-detected by > 5% in 3% of cases. Sleep efficiency by neck actigraphy was within 10% of polysomnography in 87% of the studies when position feedback was delivered. The prevalence of POSA was consistently > 70% when the overall AHI was < 60.	The neck position therapy device is accurate and effective in restricting supine sleep, improving AHI, sleep architecture and continuity, and monitoring treatment outcomes.	

25124772	Neurons producing melanin-concentrating hormone (MCH) or hypocretin/orexin (Hcrt) have been implicated in the sleep/wake cycle and feeding behavior. Sleep and feeding habits vary greatly among mammalian species, depending in part of the prey/predatory status of animals. However, the distribution of both peptides has been described in only a limited number of species. In this work, we describe the distribution of MCH neurons in the brain of the domestic pig. Using in situ hybridization and immunohistochemistry, their cell bodies are shown to be located in the posterior lateral hypothalamic area (LHA), as expected. They form a dense cluster ventro-lateral to the fornix while only scattered cells are present dorsal to this tract. By comparison, Hcrt cell bodies are located mainly dorsal to the fornix. Therefore, the two populations of neurons display complementary distributions in the posterior LHA. MCH projections are, as indicated by MCH-positive axons, very abundant in all cortical fields ventral to the rhinal sulcus, as well as in the lateral, basolateral and basomedial amygdala. In contrast, most of the isocortex is sparsely innervated. To conclude, the distribution of MCH cell bodies and projections shows some very specific features in the pig brain, that are clearly different of that described in the rat, mouse or human. In contrast, the Hcrt pattern seems more similar to that in these species, i.e. more conserved. These results suggest that the LHA anatomic organization shows some very significant interspecies differences, which may be related to the different behavioral repertoires of animals with regard to feeding and sleep/wake cycles. 
25124550	This nationwide population-based study investigated the risk of Parkinson's disease (PD) after zolpidem use in patients with sleep disturbance using the National Health Insurance Research Database (NHIRD) in Taiwan.In total, 59,548 adult patients newly diagnosed with sleep disturbance and who used zolpidem were recruited as the study cohort, along with 42,171 subjects who did not use zolpidem as a comparison cohort from 2002 to 2009. Each patient was monitored for 5 years, and those who subsequently had PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the study and comparison cohorts after adjusting for possible confounding risk factors.	The patients who received zolpidem had a higher cumulative rate of PD than those who did not receive zolpidem during the 5-year follow-up period (1.2% vs. 0.5%, P < 0.001). The adjusted hazard ratios were 1.10 (95% CI, 0.88-1.37), 1.41 (95% CI, 1.17-1.72), and 1.27 (95% CI, 1.05-1.55) for zolpidem use with 28-90, 91-365, and more than 365 cumulative defined daily doses (cDDDs), respectively, compared to those who did not use zolpidem.	Among the patients with sleep disturbance, zolpidem use increased the risk of PD after 5 years of follow-up. Further mechanistic research of zolpidem effect in PD is needed.	
25124303	Abstinence from chronic cocaine use is associated with abnormal sleep architecture. As sleep abnormalities are associated with clinical outcome in alcohol dependence, we hypothesized a similar relationship in cocaine dependence.We report data from a cocaine self-administration study (N=12) and the placebo arm of a randomized clinical trial (N=20). Self-administration participants underwent three cocaine self-administration sessions during a three-week inpatient stay. Treatment participants underwent two weeks of inpatient followed by six weeks of outpatient treatment including once-weekly cognitive behavioral therapy. Measurements included polysomnography from early and late in abstinence during the inpatient stays. Clinical outcomes included amount of cocaine self-administered, urine tests, and self-reported use and withdrawal symptoms.	Change in slow-wave sleep from early to late abstinence (ΔSWS; p=0.05), late abstinence rapid eye movement sleep (REM; p=0.002), and late abstinence total sleep time (p=0.02) were negatively correlated with the amount of cocaine self-administered. Early abstinence REM was positively correlated with withdrawal symptoms (p=0.02). Late abstinence REM was positively correlated with percent negative urines and maximum consecutive number of days abstinent (both p<0.001). ΔSWS was positively correlated with percent negative urines (p=0.03) and participants with increased SWS had greater percent negative urines (p=0.008) and maximum consecutive number of days abstinent (p=0.009).	Correlations between sleep deficits and amount of cocaine self-administered, clinical outcomes, and severity of withdrawal symptoms underscore the relevance of sleep in clinical outcomes in the treatment of cocaine dependence.	

25122112	Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid (GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese boy with a severe early onset phenotype due to a previously unreported mutation. Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course was complicated by the development of subdural hemorrhage probably as a result of rocking the child to sleep for erratic sleep-wake cycles. This case illustrates the need to recognize that trivial or unintentional shaking of such children, especially in the presence of cerebral atrophy, can lead to subdural hemorrhage. 
25119837	Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 ± 66.45 vs 170.81 ± 42.73 pg/mL) and ESS scores (7.45 ± 4.36 vs 3.84 ± 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD. 
25119831	Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms including gastrointestinal manifestations of nonspecific nature. Celiac disease and nongluten sensitivity frequently evolve in adults with gastrointestinal and extraintestinal symptoms similar to those found among patients with fibromyalgia. The objective of the present study was to evaluate the presence of celiac-type symptoms among patients with fibromyalgia in comparison with healthy subjects and with those experienced by adult celiac patients and subjects with gluten sensitivity. A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001). Regarding the existing data in the literature, the prevalence of fatigue, depression, cognitive symptoms and cutaneous lesions predominated among patients with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher among patients with fibromyalgia compared to gluten-sensitive patients and was similar among patients with fibromyalgia and celiac disease patient. The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiac disease or nonceliac gluten intolerance.
25119700	In all, 39 % of people living in Swiss nursing homes suffer from dementia. Detailed data about type and course of symptoms displayed by these patients in their terminal phase are lacking.This descriptive, retrospective study analysed 65 nursing documents from deceased people with dementia in four nursing homes in the canton of Zurich, Switzerland.	Difficulties with mobility (81 %), pain (71 %) and sleep disturbance (63 %) were the most frequent of the 10 identified symptoms. Towards the end of life, difficulties with mobility, sleep disturbance, agitation and other neuropsychiatric symptoms, such as episodes of depression, decreased (decrescent pattern), while pain, feeding problems, breathing abnormalities, apathy and anxiety increased (crescent pattern). Courses of pain were documented in 17 % of the nursing records. In addition, 76 % of the residents had been visited on a daily basis by next of kin in their last 7 days, compared with only one third of residents previously. Furthermore, daily communication between healthcare professionals and next of kin tripled during this period.	The documented prevalence of a high and increasing level of pain towards the end of life, combined with the lack of documented courses of pain, shows potential for improvement in pain relief and pain identification for patients with dementia in their terminal phase. The increasing number of visits by next of kin and the increasingly intensive contact between healthcare professionals and next of kin in the last 7 days are a strong indicator that the end of life can be predicted relatively well by the involved participants and appropriate reactions follow.	
25118620	Sleep and behavioral monitoring of young mice is necessary for understating the progress of symptoms in congenital and acquired diseases associated with sleep and movement disorders. In the current study, we have developed a non-invasive sleep monitoring system that identifies wake and sleep patterns of newborn mice using a simple piezoelectric transducer (PZT). Using this system, we have succeeded in detecting age-dependent occurrences and changes in sleep fragmentation of orexin/ataxin-3 narcoleptic mice (a narcoleptic mouse model with postnatal hypocretin/orexin cell death) across the disease onset. We also detected REM sleep/cataplexy patterns (i.e., immobility with clear heartbeat [IMHB] signals due to the flaccid posture) by the PZT system, and found that sudden onset of REM sleep-like episodes specifically occur in narcoleptic, but not in wild type mice, suggesting that these episodes are likely cataplexy. In contrast, gradual onset of IMHB likely reflects occurrence of REM sleep. In summary, we have shown that the PZT system is useful as a non-invasive sleep and behavior monitoring system to analyze the developmental aspects of sleep and movement disorders in mice models. 
25117857	Restorative sleep is an important factor for well-being, performance and quality of life. The basic diagnostic procedure of a sleep disorder is to take a comprehensive sleep history. Sleep disorders can and must be distinguished from the physiological changes of sleep in the elderly. Insomnia (difficulty in sleeping), daytime sleepiness (hypersomnia), sleep-related breathing disorders (SRBD) and movement disorders during sleep are also common in the elderly. They must be detected because they are treatable and can dominate the clinical picture of geriatric syndromes. Nursing home residents and dementia patients are in particular need of attention as their sleep is often adversely affected by the living environment and the daily institutional routine. 
25117823	Poor sleep quality, a novel risk factor of cardiovascular diseases (CVD), is highly prevalent in patients with chronic kidney disease (CKD). The association between poor sleep quality and cardiovascular damage in patients with CKD is unclear. This study is aimed to assess the prevalence and related risk factors of sleep disturbance and determine the relationship between sleep quality and cardiovascular damage in Chinese patients with pre-dialysis CKD.A total of 427 pre-dialysis CKD patients (mean age = 39 ± 15 years, 260 male/167 female) were recruited in this study. The demographics and clinical correlates were collected. The sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI), whereas the cardiovascular damage indicators (the Early/late diastolic peak flow velocity (E/A) ratio and left ventricular mass index (LVMI)) were determined by an echocardiographic examination.	Of the CKD patients, 77.8% were poor sleepers as defined by a PSQI score > 5. Median estimated glomerular filtration rate (eGFR) was 69.4(15.8-110.9) ml/min/1.73 m(2). Logistic regression analysis revealed that left ventricular hypertrophy (LVH) was independently associated with the PSQI score (OR = 1.092, 95% CI = 1.011-1.179, p = 0.025), after adjustment for age, sex and clinical systolic blood pressure, diastolic blood pressure, Phosphate, Intact parathyroid hormone (iPTH), Hemoglobin and eGFR. The linear regression analysis showed that the E/A ratios were independently associated with the PSQI score (β = -0.115, P = 0.028) after adjustment for a series of potential confounding factors.	Poor sleep quality, which is commonly found in pre-dialysis CKD patients, is an independent factor associated with cardiovascular damage in CKD patients. Our finding implies that the association between poor sleep and CVD might be mediated by cardiac remodeling.	
25117535	The energy allocation (EA) model defines behavioral strategies that optimize the temporal utilization of energy to maximize reproductive success. This model proposes that all species of the animal kingdom share a universal sleep function that shunts waking energy utilization toward sleep-dependent biological investment. For endotherms, REM sleep evolved to enhance energy appropriation for somatic and CNS-related processes by eliminating thermoregulatory defenses and skeletal muscle tone. Alternating REM with NREM sleep conserves energy by decreasing the need for core body temperature defense. Three EA phenotypes are proposed: sleep-wake cycling, torpor, and continuous (or predominant) wakefulness. Each phenotype carries inherent costs and benefits. Sleep-wake cycling downregulates specific biological processes in waking and upregulates them in sleep, thereby decreasing energy demands imposed by wakefulness, reducing cellular infrastructure requirements, and resulting in overall energy conservation. Torpor achieves the greatest energy savings, but critical biological operations are compromised. Continuous wakefulness maximizes niche exploitation, but endures the greatest energy demands. The EA model advances a new construct for understanding sleep-wake organization in ontogenetic and phylogenetic domains. 
25115947	We examined income-to-needs ratio, perceived economic well-being, and education and their relations with European and African American women's sleep (n = 219). Sleep was examined through actigraphy and self-reports. Income-to-needs ratio was related to sleep minutes. Perceived economic well-being and education were associated with subjective sleep problems. Perceived stress mediated relations between both income-to-needs ratio and economic well-being and subjective sleep problems. Chaos emerged as a mediator linking income-to-needs ratio and subjective sleep problems. African American women had fewer sleep minutes and lower sleep efficiency than European Americans, and more robust relations between economic well-being and stress was observed for European Americans. Findings highlight the importance of economic adversity for women's sleep and explicate some pathways of risk.
25115475	aircraft noise has been associated with several health effects. Because of the great success of low-cost flights, small airports have been turned into international airports thus exposing nearby residents to an increase in noise levels and potential disturbances and health disorders.to estimate the exposure levels and evaluate the health impact of aircraft noise on residents nearby six airports in Italy (Rome: Ciampino; Milan: Linate and Malpensa; Pisa; Turin; Venice) focusing on hypertension, acute myocardial infarction (AMI), annoyance and sleep disturbances.	residents in the local Municipalities considered at 31.12.2010 were included in the study and their addresses were geocoded. Aircraft noise exposure in 2011 was defined using the Integrated Noise Model linked to each participant's address. Lden (<55, 55-60, 61-65, 65-70 dB), Lnight, Leq (day and night) were calculated. Available exposure-response relationships were used to estimate the number of additional cases of hypertension, AMI, annoyance and sleep disturbances in the local population.	73,272 persons exposed to aircraft noise levels >55dB were considered: 55,915 (76.3%) were exposed to 55-60 dB; 16,562 (22.6%) to 60-65 dB; 795 (1.2%) to 65-70 dB. Exposure to aircraft noise levels above 55 dB was estimated to be responsible each year of 4,607 (95%CI 0-9,923) additional cases of hypertension; 3.4 (95%CI 0-10.7) cases of AMI; 9,789 (95%CI 6,895-11,962) cases of annoyance; 5,084 (95%CI 1,894-10,509) cases of sleep disturbances.	a significant impact of airport noise on the health of residents nearby six Italian airports was estimated. Epidemiological evaluation and noise mitigation measures should be introduced to protect the health of residents.	
25113417	To assess how change in sleep duration is related to subsequent obesity.In this 10-year follow-up, 4903 non-pregnant participants answered a questionnaire on sleeping habits, obesity, and lifestyle factors (questions identical to baseline questionnaire). Habitual normal sleepers were defined as sleeping 6-9 h/night at both baseline and follow-up, whereas women sleeping <6 h/night or ≥9 h/night at both occasions were defined as habitual short sleepers and habitual long sleepers, respectively. Logistic regression was used to analyze associations between changes in sleep duration, general obesity (body mass index ≥30 kg/m(2)), weight gain (≥10 kg) and also, central obesity (waist circumference ≥88 cm), and increase in waist circumference (≥10 cm) at follow-up.	Among younger women (aged <40 years) both habitual short sleepers and habitual long sleepers had a higher prevalence of general (short: 31.3%, P < 0.0001; long: 38.1%, P = 0.01) and central obesity (short: 60.5%, P = 0.01; long: 82.4%, P = 0.01) compared with habitual normal sleepers (general obesity: 8.9%; central obesity: 35.9%) at follow-up. Younger women who were short sleepers at baseline but normal sleepers at the follow-up had a higher prevalence of both general (19.3%, P = 0.01) and central obesity (45.4%, P = 0.07) compared with habitual normal sleepers at follow-up. In adjusted analyses, both habitual short [adjusted odds ratio (aOR), 6.78; 95% confidence interval (CI), 2.71-17.0] and long (aOR, 4.64; 95% CI, 1.09-19.8) sleep durations were risk factors for general obesity in younger women. In younger women habitual long sleep duration was a risk factor also for central obesity (aOR, 6.05; 95% CI, 1.19-30.7) whereas habitual short sleep duration was not (aOR, 1.93; 95% CI, 0.87-4.81). Similar results were seen also for weight gain and increased waist circumference as dependent variables. In addition, decreased sleep duration from normal to short duration was a risk factor for both weight gain (aOR, 1.85; 95% CI, 1.14-3.02) and increased waist circumference (aOR, 1.84; 95% CI, 1.20-2.81). There were no associations between changes in sleep duration and any of the measures of obesity at the follow-up in women aged >40 years at baseline.	In younger women, both habitual short and long sleep duration was a risk factor for obesity, whereas no such relationship was seen in older women.	
25113164	Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality.To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst off work, or both, in workers undertaking shift work in their present job and to assess their cost-effectiveness.	We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews.	We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while off work, alertness and sleepiness, or fatigue at work.	Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate.	We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined caffeine plus naps to decrease sleepiness or to increase alertness.Melatonin (1 to 10 mg) after the night shift may increase sleep length during daytime sleep (mean difference (MD) 24 minutes, 95% confidence interval (CI) 9.8 to 38.9; seven trials, 263 participants, low quality evidence) and night-time sleep (MD 17 minutes, 95% CI 3.71 to 30.22; three trials, 234 participants, low quality evidence) compared to placebo. We did not find a dose-response effect. Melatonin may lead to similar sleep latency times as placebo (MD 0.37minutes, 95% CI - 1.55 to 2.29; five trials, 74 participants, low quality evidence).Hypnotic medication, zopiclone, did not result in significantly longer daytime sleep length compared to placebo in one low quality trial and we could not use the data from the study on lormetazepam.Armodafinil taken before the night shift probably reduces sleepiness by one point on the Karolinska Sleepiness Scale (KSS) (MD -0.99, 95% CI -1.32 to -0.67; range 1 to 10; two trials, 572 participants, moderate quality evidence) and increases alertness by 50 ms in a simple reaction time test (MD -50.0, 95% CI -85.5 to -15.5) at three months' follow-up in shift work sleep disorder patients. Modafinil probably has similar effects on sleepiness (KSS) (MD -0.90, 95% CI -1.45 to -0.35; one trial, 183 participants, moderate quality evidence) and alertness in the psychomotor vigilance test in the same patient group. Post-marketing, severe skin reactions have been reported. Adverse effects reported by trial participants were headache, nausea and a rise in blood pressure. There were no trials in non-patient shift workers.Based on one trial, caffeine plus pre-shift naps taken before the night shift decreased sleepiness (KSS) (MD -0.63, 95% CI -1.09 to -0.17).We judged most trials to have a low risk of bias even though the randomisation method and allocation concealment were often not described.	There is low quality evidence that melatonin improves sleep length after a night shift but not other sleep quality parameters. Both modafinil and armodafinil increase alertness and reduce sleepiness to some extent in employees who suffer from shift work sleep disorder but they are associated with adverse events. Caffeine plus naps reduces sleepiness during the night shift, but the quality of evidence is low. Based on one low quality trial, hypnotics did not improve sleep length and quality after a night shift.We need more and better quality trials on the beneficial and adverse effects and costs of all pharmacological agents that induce sleep or promote alertness in shift workers both with and without a diagnosis of shift work sleep disorder. We also need systematic reviews of their adverse effects.	
25112718	Histamine (HA) regulates the sleep-wake cycle, synaptic plasticity and memory in adult mammals. Dopaminergic specification in the embryonic ventral midbrain (VM) coincides with increased HA brain levels. To study the effect of HA receptor stimulation on dopamine neuron generation, we administered HA to dopamine progenitors, both in vitro and in vivo.Cultured embryonic day 12 (E12) VM neural stem/progenitor cells expressed transcripts for HA receptors H1R, H2R and H3R. These undifferentiated progenitors increased intracellular calcium upon HA addition. In HA-treated cultures, dopamine neurons significantly decreased after activation of H1R. We performed intrauterine injections in the developing VM to investigate HA effects in vivo. HA administration to E12 rat embryos notably reduced VM Tyrosine Hydroxylase (TH) staining 2 days later, without affecting GABA neurons in the midbrain, or serotonin neurons in the mid-hindbrain boundary. qRT-PCR and Western blot analyses confirmed that several markers important for the generation and maintenance of dopaminergic lineage such as TH, Lmx1a and Lmx1b were significantly diminished. To identify the cell type susceptible to HA action, we injected embryos of different developmental stages, and found that neural progenitors (E10 and E12) were responsive, whereas differentiated dopaminergic neurons (E14 and E16) were not susceptible to HA actions. Proliferation was significantly diminished, whereas neuronal death was not increased in the VM after HA administration. We injected H1R or H2R antagonists to identify the receptor responsible for the detrimental effect of HA on dopaminergic lineage and found that activation of H1R was required.	These results reveal a novel action of HA affecting dopaminergic lineage during VM development.	
25110283	Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention. 
25109588	Cynomolgus monkeys are widely used as models of diseases and in pre-clinical studies to assess the impact of new pharmacotherapies on brain function and behaviour. However, the time course of electroencephalographic delta activity during sleep, which represents the main marker of sleep intensity associated with recovery during sleep, has never been described in this non-human primate. In this study, telemetry implants were used to record one spontaneous 24-h sleep-wake cycle in four freely-moving Cynomolgus monkeys, and to quantify the time course of electroencephalographic activity during sleep using spectral analysis. Animals presented a diurnal activity pattern interrupted by short naps. During the dark period, most of the time was spent in sleep with non-rapid eye movement sleep/rapid eye movement sleep alternations and sleep consolidation profiles intermediate between rodents and humans. Deep non-rapid eye movement sleep showed a typical predominance at the beginning of the night with decreased propensity in the course of the night, which was accompanied by a progressive increase in rapid eye movement sleep duration. Spectral profiles showed characteristic changes between vigilance states as reported in other mammalian species. Importantly, delta activity also followed the expected time course of variation, showing a build-up with wakefulness duration and dissipation across the night. Thus, Cynomolgus monkeys present typical characteristics of sleep architecture and spectral structure as those observed in other mammalian species including humans, validating the use of telemetry in this non-human primate model for translational sleep studies. 
25108342	The aim of this study was to suggest a new cutoff score for the Turkish version of Epworth Sleepiness Scale (ESS) in the patients with obstructive sleep apnea. In this study, the data of 483 patients who were admitted to our clinic with the complaints of daytime sleepiness and witnessed sleep apnea were reviewed retrospectively. The correlation between ESS and polysomnography (PSG) findings were assessed, and cutoff score of the Turkish version of the ESS was investigated. The mean apnea-hypopnea index (AHI) was 27.71 ± 26.69 eV/h, the mean ESS score was 8.42 ± 4.88. According to AHI, a statistically significant difference between ESS scores was detected (p = 0.001; p < 0.01). According to AHI (AHI ≥ 5, AHI ≥ 15 and AHI ≥ 30) the best cutoff score for ESS score was found as 8. The answers that were given to the ESS questions differ according to their sociocultural and economic condition. These results indicate that a score of 8 or higher on the ESS would seem a more appropriate cutoff score to suspect clinically relevant sleepiness in the Turkish population.
25108310	Neocortical layer VI is critically involved in thalamocortical activity changes during the sleep/wake cycle. It receives dense projections from thalamic nuclei sensitive to the wake-promoting neuropeptides orexins, and its deepest part, layer VIb, is the only cortical lamina reactive to orexins. This convergence of wake-promoting inputs prompted us to investigate how layer VIb can modulate cortical arousal, using patch-clamp recordings and optogenetics in rat brain slices. We found that the majority of layer VIb neurons were excited by nicotinic agonists and orexin through the activation of nicotinic receptors containing α4-α5-β2 subunits and OX2 receptor, respectively. Specific effects of orexin on layer VIb neurons were potentiated by low nicotine concentrations and we used this paradigm to explore their intracortical projections. Co-application of nicotine and orexin increased the frequency of excitatory post-synaptic currents in the ipsilateral cortex, with maximal effect in infragranular layers and minimal effect in layer IV, as well as in the contralateral cortex. The ability of layer VIb to relay thalamocortical inputs was tested using photostimulation of channelrhodopsin-expressing fibers from the orexin-sensitive rhomboid nucleus in the parietal cortex. Photostimulation induced robust excitatory currents in layer VIa neurons that were not pre-synaptically modulated by orexin, but exhibited a delayed, orexin-dependent, component. Activation of layer VIb by orexin enhanced the reliability and spike-timing precision of layer VIa responses to rhomboid inputs. These results indicate that layer VIb acts as an orexin-gated excitatory feedforward loop that potentiates thalamocortical arousal. 
25107635	Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26-12.98). These results require replication in larger prospective studies with longer follow-up.In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.	

25105558	Good sleep is critical for optimising recovery and athletic performance. Yet, few studies have investigated how athletes sleep before and during competition. The aim of this study was to determine whether such sleep is poorer than that before a usual training day. Twenty-one male endurance cyclists' (age: 19.9 ± 1.7 years) sleep/wake behaviour was assessed using wrist activity monitors for 11 nights, including a six-night baseline training phase, three nights before competition and two nights during competition. Cyclists had less sleep on the night before competition (6.5 ± 0.9 h) and during the first night of competition (6.8 ± 0.8 h) than at baseline (7.4 ± 0.6 h). Cyclists also went to bed and woke up earlier during competition than at baseline. Competition schedules and competition itself can disrupt the sleep/wake behaviour of athletes during competition. Future investigations should examine sleep during three stages of competition (i.e. before, during and after competition). This will help coaches develop a greater understanding of how sleep changes during different phases of competition and enable them to plan post-competition training programmes to ensure appropriate rest and recovery is obtained.
25105288	To examine the longitudinal relationships between Posttraumatic Stress Disorder (PTSD) and sleep problems among adolescent survivors in the Wenchuan earthquake, China.350 adolescent survivors were randomly selected from several primary and secondary schools in the counties of Wenchuan and Maoxian, the two areas most severely affected by the Wenchuan earthquake. Participants completed Revised Child PTSD Symptom Scale and Sleep Problems Subscale of Self-generated Child Behavior Problems Questionnaire at one year (T1), one-and-a-half years (T2), two years (T3) after the earthquake, respectively.	There was a bidirectional relationship between intrusive symptom clusters of PTSD and sleep problems from T1 to T2, and this relationship became non-significant from T2 to T3. There was a one-way predictive relationship of avoidance symptom clusters of PTSD onto sleep problems from T1 to T3. The hyperarousal symptom clusters of PTSD had effects on sleep problems from T1 to T2 but not from T2 to T3, while sleep problems have no significant effect on hyperarousal symptom clusters of PTSD from T1 to T3. In addition, the relationships between three symptom clusters of PTSD and sleep problems weakened with time change.	From 1 year to 1.5 years after the earthquake, all the three symptom clusters of PTSD could be important predictive factors for the development and maintenance of sleep problems, while sleep problems could only be risk factors for the intrusive symptom clusters of PTSD. From 1.5 years to 2 years, only the avoidance symptom clusters of PTSD were risk factors for sleep problems, and sleep problems had no significant effects on any symptom clusters of PTSD. Overall, the relationship between PTSD and sleep problems weakened with time change.	
25104243	Reductions in central serotonin activity with aging might be involved in sleep-related disorders in later life. Although the beneficial effects of aerobic exercise on sleep are not new, sleep represents a complex recurring state of unconsciousness involving many lines of transmitters which remains only partly clear despite intense ongoing research. It is known that serotonin released into diencephalon and cerebrum might play a key inhibitory role to help promote sleep, likely through an active inhibition of supraspinal neural networks. Several lines of evidence support the stimulatory effects of exercise on higher serotonergic pathways. Hence, exercise has proved to elicit acute elevations in forebrain serotonin concentrations, an effect that waned upon cessation of exercise. While adequate exercise training might lead to adaptations in higher serotonergic networks (desensitization of forebrain receptors), excessive training has been linked to serious brain serotonergic maladaptations accompanied by insomnia. Dietary supplementation of tryptophan (the only serotonin precursor) is known to stimulate serotonergic activity and promote sleep, whereas acute tryptophan depletion causes deleterious effects on sleep. Regarding sleep-wake regulation, exercise has proved to accelerate resynchronization of the biological clock to new light-dark cycles following imposition of phase shifts in laboratory animals. Noteworthy, the effect of increased serotonergic transmission on wake state appears to be biphasic, i.e. promote wake and thereafter drowsiness. Therefore, it might be possible that acute aerobic exercise would act on sleep by increasing activity of ascending brain serotonergic projections, though additional work is warranted to better understand the implication of serotonin in the exercise-sleep axis. 
25102810	This study investigated the mediating roles of sleep and depression on the relationships between stress, fat intake, and fruit and vegetable intake among low-income overweight and obese pregnant women by trimesters. Participants (N = 213) completed a self-administered survey including stress (exogenous variable), depression, sleep (mediators), fat intake, and fruit and vegetable intake (endogenous variables). Path analysis was performed to compare mediation effects among pregnant women in each trimester. Consistently across three trimesters, stress was related to depression but not sleep duration, night time sleep disturbance, sleep quality, sleep latency or fat intake. Sleep duration was not associated with depression. Depending on trimester, night time sleep disturbance, sleep quality, and sleep latency were related to depression; night time sleep disturbance and depression affected fat intake; stress influenced fruit and vegetable intake. Sleep duration, sleep disturbance, sleep quality, sleep latency and depression did not mediate the relationships between stress, fat intake, and fruit and vegetable intake in the second and third trimesters. However, depression mediated the relationship between stress and fat intake in the first trimester. Stress management interventions may help low-income overweight and obese pregnant women decrease depressive symptoms and therefore contribute to overall nutritional health.
25102425	"Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.
25100272	The current study investigated the short-term effect of illegitimate tasks on sleep quality, assessed by actigraphy. Seventy-six employees of different service jobs participated in a 2-week data collection. Data were analysed by way of multilevel analyses. As predicted, illegitimate tasks were positively related to sleep fragmentation and sleep-onset latency, but not to sleep efficiency and not to sleep duration. Time pressure, social stressors at work and at home, and the value of the dependent variable from the previous day were controlled. Results confirm the predictive power of illegitimate tasks for a variable that can be considered crucial in the development of long-term outcomes of daily experiences.
25096622	Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition. 
25093413	Despite their high prevalence, sleep disorders often remain unrecognized and untreated because of barriers to assessment and management. The aims of the present study were to examine associations of complaints of sleep disturbances with cardiovascular disease, related risk factors, and inflammation in the community and to determine the contribution of sleep disturbances to self-perceived physical health.The sample consists of n = 10.000 participants, aged 35 to 74 years of a population based community sample in Germany. Cross-sectional associations of complaints of sleep disturbances with cardiovascular risk factors and disease, biomarkers of inflammation, depression, anxiety, and physical health status were analyzed.	19% of our sample endorsed clinically significant sleep disturbances. In the unadjusted analyses severity of sleep disturbances increased with female sex, low socioeconomic status, living without a partnership, cardiovascular disease, depression, anxiety, poor physical health, increased levels of C-reactive protein and fibrinogen. After multivariate adjustment robust associations with coronary heart disease, myocardial infarction and dyslipidemia remained. Complaints of sleep disturbances were strong and independent contributors to self-perceived poor physical health beyond depression, anxiety and medical disease burden.	Given the high prevalence of complaints of sleep disturbances and their strong impact on health status, increased efforts should be undertaken for their identification and treatment.	

25092604	In January 2014, the US Food and Drug Administration approved tasimelteon (Hetlioz™), a melatonin-receptor agonist for the treatment of non-24-hour sleep-wake disorder. This article provides an overview of the mechanism of action, pharmacokinetic properties, as well as the clinical efficacy, safety, and tolerability of tasimelteon. Relevant information was identified through a comprehensive literature search of several databases using the key words tasimelteon, Non-24-hour Sleep-Wake disorder, Non-24, and melatonin. Further information was obtained from the tasimelteon package insert, fda.gov, clinicaltrials.gov, briefing materials provided by Vanda Pharmaceuticals, and posters from scientific meetings. 
25092525	Human and animal studies indicate that reward function is modulated by the circadian clock that governs our daily sleep/wake rhythm. For example, a robust circadian rhythm exists in positive affect, which is lower in the morning hours and peaks in the afternoon. A handful of functional neuroimaging studies suggest that systematic diurnal variation exists in brain activity related to other functions, but no published human studies have examined daily variation in the neural processing of reward. In the present study, we attempt to advance this literature by using functional neuroimaging methods to examine time-of-day changes in the responsivity of the reward circuit. Using a within-person design and a functional magnetic resonance imaging (fMRI) monetary reward task, we compared morning and afternoon reward-related brain activation in a sample of healthy young adults within 24h. Region of interest analyses focused on the striatum, and we hypothesized greater reward activation in the afternoon, concordant with the circadian peak in positive affect. Results were consistent with our hypothesis. In addition, we counterbalanced the order of morning and afternoon scans in order to explore the short-term stability of the neural response. Whole-brain analyses showed a markedly higher reactivity to reward throughout the brain in the first scan relative to the second scan, consistent with habituation to the monetary reward stimuli. However, these effects did not appear to explain the time-of-day findings. In summary, we report the first preliminary evidence of circadian variation in the neural processing of reward. These findings have both methodological and theoretical implications. 
25091534	Several child-report measures of sleep functioning have been developed but very few studies have examined the external validity of child self-reported sleep in relation to daytime functioning. This study examined child-reported sleep in relation to teacher-rated psychopathology symptoms and also tested the hypothesis that child-reported sleep would be associated with poorer child- and teacher-reported functioning after controlling for demographics and psychopathology symptoms that are known to be associated with adjustment.Participants were 175 children (81 boys, 94 girls) in 1st-6th grades (ages 6-13) and their teachers. Children completed the Sleep Self-Report. Teachers completed a measure of attention-deficit/hyperactivity disorder (ADHD), oppositional/conduct, and anxiety/depression symptoms. Children and teachers completed multiple measures of academic, behavioral, and social/peer functioning.	Child-reported sleep was significantly associated with teacher-rated inattentive and internalizing symptoms, even after controlling for child demographics, hyperactivity-impulsivity, and conduct problems. Multilevel modeling analyses further indicated that, after controlling for child demographics and psychopathology symptoms, child-reported sleep problems were significantly associated with poorer child- and teacher-reported academic, behavioral, and social functioning (including increased reactive aggression, peer rejection, loneliness, and lower friendship satisfaction and self-worth).	Findings provide initial support for the external validity of children's self-reported sleep functioning. Results of this study suggest that it may be clinically useful to screen for sleep problems by assessing for children's own perceptions of their sleep. Future studies should include both child- and parent-reported sleep functioning to further examine the utility of children's ratings of sleep functioning.	
25091533	The study aimed to analyze (i) the prevalence of sleep disorders in pre-school children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC), (ii) the possible association with motor, cognitive and behavioral problems, and (iii) the possible differences with typically developing children matched for age and gender.One-hundred children with CP (age range: 3-5 years, mean: 3.8 years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Preschool and Primary Scale of Intelligence, and the Child Behaviour Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. Further 100 healthy children matched for age and sex were assessed using the SDSC.	An abnormal total sleep score was found in 13% of children with CP while 35% had an abnormal score on at least one SDSC factor. SDSC total score was significantly associated with pathological internalizing scores on CBCL and active epilepsy on multivariate analysis. CP group reported higher significant median scores on SDSC total, parasomnias, and difficulty in initiating and maintaining sleep factors.	In pre-school children sleep disorders are more common in children with CP than in healthy control group and are often associated with epilepsy and behavioral problems.	
25091288	The increased prevalence of malocclusions represents a secular trend attributed to the interaction of genetic and environmental factors. The analysis of factors related to the causes of these changes is essential for planning public health policies aimed at preventing and clinically intercepting malocclusion. This study investigated the sucking habits, nocturnal mouth breathing, as well as the relation of these factors with malocclusion.This is a longitudinal study in which 80 mother-child pairs were monitored from the beginning of pregnancy to the 30th month after childbirth. Home visits for interviews with the mothers were made on the 12th, 18th and 30th months of age. Finger sucking, pacifier sucking, bottle feeding, breastfeeding and nocturnal mouth breathing, were the variables studies. On the 30th month, clinical examinations were performed for overjet, overbite and posterior crossbite. A previously calibrated single examiner (Kappa coefficient = 0.92) was responsible for all examinations. Data were analyzed using the chi-squared or Fisher's exact tests, at a significance level of 5%.	Bottle feeding was the most prevalent habit at 12, 18 and 30 months (87.5%; 90% and 96.25%, respectively). Breastfeeding was 40%, 25% and 12.50% at 12, 18 and 30 months, respectively. Nearly 70% of the children in this study had some sort of malocclusion. Pacifier sucking habit at 12, 18 and 30 months of age was associated with overjet and open bite; and at 30 months, an association with overbite was also observed. Finger sucking habit and breastfeeding at 12, 18 and 30 months were also associated with overjet and open bite. The posterior crossbite was associated with bottle feeding at 12 and 30 months, and nocturnal mouth breathers at 12 and 18 months.	Sucking habits, low rates of breastfeeding, and nocturnal mouth breathing were risk factors for malocclusion.	
25091131	Chronic pain disorders can exert major negative effects on virtually every aspect of an individual's life. It is not surprising then that many chronic pain sufferers find themselves at a point of emotional fragility where they experience thoughts of ending their life. Suicidal behavior encompasses a spectrum of experience, from "life weariness" or passive suicidal ideation, to more active suicidal intent and suicide completion. A range of risk factors for suicidal behavior in the general population have been identified, and these apply equally to the chronic pain population: a family history of mental illness, past history of suicide attempts, and the presence of comorbid depression. With regard specifically to chronic pain patients, elevated suicide risk is also associated with severe or recurrent headache, ambiguous diagnoses (psychogenic pain, abdominal pain), and medicolegal issues related to the pain. A number of suggestions for clinicians managing chronic pain patients with regards to managing suicide risk are given. 


25088326	Review infant sleep research with a focus on understanding the elements related to infant safety and infant and maternal well-being during nighttime care.This review summarizes current research and addresses the controversies and conflicting outcomes reported in infant nighttime care. This review addresses current literature on infant sleep patterns, as well as factors that influence infant sleep and are consequences of different care routines. Conversation points are provided to help nurse practitioners (NPs) address safety and practice concerns.	Shared information can help parents provide a safe and healthy environment for infants and help to facilitate communication ties between the healthcare providers and the families.	NPs need to help parents understand infant sleep patterns norms, what is current knowledge about infant nightwakings and parental presence, as well as about approaches to altering infant sleep patterns. Integrating this knowledge with parent preferences that are influenced by cultural practices and individual differences is crucial in helping parents develop a strong sense of competence and comfort with their choices and behaviors.	
25087458	Sleep deprivation (SD) can influence cognition, memory, and sleep/wake homeostasis and can cause impairments in many physiological processes. Because the homeostatic control of the sleep/wake cycle is closely associated with the hypothalamus, the current study was undertaken to examine proteomic changes occurring in hypothalamic astrocytes following chronic partial SD. After chronic partial SD for 7 days, astrocytes were prepared from rat hypothalamus using a Percoll gradient method, and their proteome profiles were determined by LC-MS/MS. Comparisons of the proteome profiles of hypothalamic astrocytes revealed that chronic partial SD increased (≥1.5-fold) 89 proteins and decreased (≤0.7-fold) 50 proteins; these changes in protein expression were validated by western blot or immunohistochemistry. DAVID and IPA analyses of these proteins suggested that SD may influence gliotransmission and astrocyte activation. PPP2R1A, RTN4, VAMP-2, LGI-1, and SLC17A7 were identified and validated as the main targets of SD in astrocytes. Our results suggest that SD may modulate gliotransmission in the hypothalamus, thereby disturbing sleep/wake homeostasis and increasing susceptibility to neurological disease; however, further studies are required to confirm whether the proteome changes are specific to SD.
25085886	Diurnal release of the orexin neuropeptides orexin-A (Ox-A, hypocretin-1) and orexin-B (Ox-B, hypocretin-2) stabilises arousal, regulates energy homeostasis and contributes to cognition and learning. However, whether cellular correlates of brain plasticity are regulated through orexins, and whether they do so in a time-of-day-dependent manner, has never been assessed. Immunohistochemically we found sparse but widespread innervation of hippocampal subfields through Ox-A- and Ox-B-containing fibres in young adult rats. The actions of Ox-A were studied on NMDA receptor (NMDAR)-mediated excitatory synaptic transmission in acute hippocampal slices prepared around the trough (Zeitgeber time (ZT) 4-8, corresponding to 4-8 h into the resting phase) and peak (ZT 23) of intracerebroventricular orexin levels. At ZT 4-8, exogenous Ox-A (100 nm in bath) inhibited NMDA receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) at mossy fibre (MF)-CA3 (to 55.6 ± 6.8% of control, P = 0.0003) and at Schaffer collateral-CA1 synapses (70.8 ± 6.3%, P = 0.013), whereas it remained ineffective at non-MF excitatory synapses in CA3. Ox-A actions were mediated postsynaptically and blocked by the orexin-2 receptor (OX2R) antagonist JNJ10397049 (1 μm), but not by orexin-1 receptor inhibition (SB334867, 1 μm) or by adrenergic and cholinergic antagonists. At ZT 23, inhibitory effects of exogenous Ox-A were absent (97.6 ± 2.9%, P = 0.42), but reinstated (87.2 ± 3.3%, P = 0.002) when endogenous orexin signalling was attenuated for 5 h through i.p. injections of almorexant (100 mg kg(-1)), a dual orexin receptor antagonist. In conclusion, endogenous orexins modulate hippocampal NMDAR function in a time-of-day-dependent manner, suggesting that they may influence cellular plasticity and consequent variations in memory performance across the sleep-wake cycle.
25085527	To investigate the prevalence of low back pain among Finnish firefighters and to examine whether sleep disturbances predict membership of low back pain trajectories.In this prospective study, 360 actively working firefighters responded to a questionnaire in 1996, 1999 and 2009. The outcome variables were radiating and local low back pain during the preceding year. Using logistic regression modeling, the likelihood of membership of pain trajectories was predicted by sleep disturbances at baseline.	During the 13-year follow-up, the prevalence of radiating low back pain increased from 16 to 29 % (p < 0.0001) and that of local low back pain from 28 to 40 % (p < 0.001). The following trajectories were identified: "pain free," "recovering," "new pain," "fluctuating" and "chronic." More than one-fifth of the participants belonged to the new pain trajectory as regards both pain types, 6 % of the participants belonged to the chronic radiating and 12 % to the chronic local low back pain trajectory. Those with sleep disturbances at baseline had a 2.4-fold risk (adjusted OR 2.4; 95 % CI 1.2-4.7) of belonging to the new pain or chronic radiating pain cluster compared to pain-free participants.	This is the first prospective study to show that low back symptoms are common and persistent among firefighters and that sleep disturbances strongly predict membership of a radiating pain trajectory. Occupational health and safety personnel, as well as the firefighters themselves, should recognize sleep problems early enough in order to prevent back pain and its development into chronic pain.	
25085207	Childhood maltreatment represents an important public health concern, as it is often associated with a host of negative outcomes across development. In recent years, researchers have begun to examine the link between negative health-related behaviors and history of childhood maltreatment. The current study considers the relationship between history of childhood maltreatment and sleep disturbances in adolescence. Further, the role of psychological distress is considered as an explanatory link between childhood maltreatment and adolescent sleep disturbances. The current study is a secondary analysis using a subsample (N=73) of child welfare-involved youth who participated in the initial and 2-year time-point of the Maltreatment and Adolescent Pathways (MAP) Longitudinal Study on the variables of interest. Youth reported on lifetime maltreatment experiences, psychological distress, and sleep disturbances, in addition to the other measures administered as part of the larger MAP study protocol. More severe childhood maltreatment was related to increased sleep disturbances during adolescence, and psychological distress was a significant mediator of the childhood maltreatment-adolescent sleep disturbance association. The results demonstrate that a history of childhood maltreatment represents a risk factor for sleep disturbances in adolescence. The findings highlight the importance of inquiring about health-related behaviors in child welfare youth and the need to promote psychological well-being within this population. 

25084361	Sleep is essential for the maintenance of the brain and the body, yet many features of sleep are poorly understood and mathematical models are an important tool for probing proposed biological mechanisms. The most well-known mathematical model of sleep regulation, the two-process model, models the sleep-wake cycle by two oscillators: a circadian oscillator and a homeostatic oscillator. An alternative, more recent, model considers the mutual inhibition of sleep promoting neurons and the ascending arousal system regulated by homeostatic and circadian processes. Here we show there are fundamental similarities between these two models. The implications are illustrated with two important sleep-wake phenomena. Firstly, we show that in the two-process model, transitions between different numbers of daily sleep episodes can be classified as grazing bifurcations. This provides the theoretical underpinning for numerical results showing that the sleep patterns of many mammals can be explained by the mutual inhibition model. Secondly, we show that when sleep deprivation disrupts the sleep-wake cycle, ostensibly different measures of sleepiness in the two models are closely related. The demonstration of the mathematical similarities of the two models is valuable because not only does it allow some features of the two-process model to be interpreted physiologically but it also means that knowledge gained from study of the two-process model can be used to inform understanding of the behaviour of the mutual inhibition model. This is important because the mutual inhibition model and its extensions are increasingly being used as a tool to understand a diverse range of sleep-wake phenomena such as the design of optimal shift-patterns, yet the values it uses for parameters associated with the circadian and homeostatic processes are very different from those that have been experimentally measured in the context of the two-process model. 
25084113	Melanin concentrating hormone (MCH), a neuropeptide produced mainly in neurons localized to the lateral hypothalamic area (LHA), has been implicated in the regulation of food intake, energy balance, sleep state, and the cardiovascular system. Hypothalamic MCH neurons also have multisynaptic connections with diaphragmatic motoneurons and project to many central chemoreceptor sites. However, there are few studies of MCH involvement in central respiratory control. To test the hypothesis that MCH plays a role in the central chemoreflex, we induced a down regulation of MCH in the central nervous system by knocking down the MCH precursor (pMCH) mRNA in the LHA using a pool of small interfering RNA (siRNA), and measured the resultant changes in breathing, metabolic rate, body weight, and blood glucose levels in conscious rats. The injections of pMCH-siRNA into the LHA successfully produced a ∼ 62% reduction of pMCH mRNA expression in the LHA and a ∼ 43% decrease of MCH levels in the cerebrospinal fluid relative to scrambled-siRNA treatment (P = 0.006 and P = 0.02 respectively). Compared to the pretreatment baseline and the scrambled-siRNA treated control rats, knockdown of MCH resulted in: 1) an enhanced hypercapnic chemoreflex (∼ 42 & 47% respectively; P < 0.05) only in wakefulness; 2) a decrease in body weight and basal glucose levels; and 3) an unchanged metabolic rate. Our results indicate that MCH participates not only in the regulation of glucose and sleep-wake homeostasis but also the vigilance-state dependent regulation of the central hypercapnic chemoreflex and respiratory control.
25083851	Sleep disorders are common in multiple sclerosis (MS). The aim of this study was to assess the subjective and objective sleep disturbances in patients with MS and to investigate their relationships with fatigue and excessive daytime sleepiness. All participants completed standardized questionnaires and underwent nocturnal polysomnography. English literature regarding MS and sleep disorders was systematically reviewed through PubMed searches. Eleven patients with MS with fatigue, 10 patients with MS without fatigue, and 11 controls were included in the study. According to the Pittsburg sleep quality index, 61.9% of the patients with MS were poor sleepers and based on the Epworth sleepiness scale, 38.1% of the patients with MS met the criteria of excessive daytime sleepiness. Additionally, patients with MS had more disturbed sleep with higher total arousal index (P < 0.01) and periodic limb movement arousal index (P < 0.001) than controls. None of the patients or controls had an apnea/hypopnea index greater than five. One patient had restless legs syndrome and four had rapid eye movement sleep behavior disorder. Our study shows that sleep disorders and excessive daytime sleepiness are frequent in MS.
25083019	Traditionally, sleep studies in mammals are performed using electroencephalogram/electromyogram (EEG/EMG) recordings to determine sleep-wake state. In laboratory animals, this requires surgery and recovery time and causes discomfort to the animal. In this study, we evaluated the performance of an alternative, noninvasive approach utilizing piezoelectric films to determine sleep and wakefulness in mice by simultaneous EEG/EMG recordings. The piezoelectric films detect the animal's movements with high sensitivity and the regularity of the piezo output signal, related to the regular breathing movements characteristic of sleep, serves to automatically determine sleep. Although the system is commercially available (Signal Solutions LLC, Lexington, KY), this is the first statistical validation of various aspects of sleep.EEG/EMG and piezo signals were recorded simultaneously during 48 h.	Mouse sleep laboratory.	Nine male and nine female CFW outbred mice.	EEG/EMG surgery.	The results showed a high correspondence between EEG/EMG-determined and piezo-determined total sleep time and the distribution of sleep over a 48-h baseline recording with 18 mice. Moreover, the piezo system was capable of assessing sleep quality (i.e., sleep consolidation) and interesting observations at transitions to and from rapid eye movement sleep were made that could be exploited in the future to also distinguish the two sleep states.	The piezo system proved to be a reliable alternative to electroencephalogram/electromyogram recording in the mouse and will be useful for first-pass, large-scale sleep screens for genetic or pharmacological studies.	Mang GM, Nicod J, Emmenegger Y, Donohue KD, O'Hara BF, Franken P. Evaluation of a piezoelectric system as an alternative to electroencephalogram/electromyogram recordings in mouse sleep studies.	
25083014	Upon awakening from sleep, a fully awake brain state is not reestablished immediately, but the origin and physiological properties of the distinct brain state during the first min after awakening are unclear. To investigate whether neuronal firing immediately upon arousal is different from the remaining part of the waking episode, we recorded and analyzed the dynamics of cortical neuronal activity in the first 15 min after spontaneous awakenings in freely moving rats and mice.Intracortical recordings of the local field potential and neuronal activity in freely-moving mice and rats.	Basic sleep research laboratory.	WKY adult male rats, C57BL/6 adult male mice.	N/A.	In both species the average population spiking activity upon arousal was initially low, though substantial variability in the dynamics of firing activity was apparent between individual neurons. A distinct population of neurons was found that was virtually silent in the first min upon awakening. The overall lower population spiking initially after awakening was associated with the occurrence of brief periods of generalized neuronal silence (OFF periods), whose frequency peaked immediately after awakening and then progressively declined. OFF periods incidence upon awakening was independent of ongoing locomotor activity but was sensitive to immediate preceding sleep/wake history. Notably, in both rats and mice if sleep before a waking episode was enriched in rapid eye movement sleep, the incidence of OFF periods was initially higher as compared to those waking episodes preceded mainly by nonrapid eye movement sleep.	We speculate that an intrusion of sleep-like patterns of cortical neuronal activity into the wake state immediately after awakening may account for some of the changes in the behavior and cognitive function typical of what is referred to as sleep inertia.	Vyazovskiy VV, Cui N, Rodriguez AV, Funk C, Cirelli C, Tononi G. The dynamics of cortical neuronal activity in the first minutes after spontaneous awakening in rats and mice.	
25083008	To examine recent national trends in outpatient visits for sleep related difficulties in the United States and prescriptions for sleep medications.Trend analysis.	Data from the National Ambulatory Medical Care Survey from 1999 to 2010.	Patients age 20 y or older.	The number of office visits with insomnia as the stated reason for visit increased from 4.9 million visits in 1999 to 5.5 million visits in 2010 (13% increase), whereas the number with any sleep disturbance ranged from 6,394,000 visits in 1999 to 8,237,000 visits in 2010 (29% increase). The number of office visits for which a diagnosis of sleep apnea was recorded increased from 1.1 million visits in 1999 to 5.8 million visits in 2010 (442% increase), whereas the number of office visits for which any sleep related diagnosis was recorded ranged from 3.3 million visits in 1999 to 12.1 million visits in 2010 (266% increase). The number of prescriptions for any sleep medication ranged from 5.3 in 1999 to 20.8 million in 2010 (293% increase). Strong increases in the percentage of office visits resulting in a prescription for nonbenzodiazepine sleep medications (∼350%), benzodiazepine receptor agonists (∼430%), and any sleep medication (∼200%) were noted.	Striking increases in the number and percentage of office visits for sleep related problems and in the number and percentage of office visits accompanied by a prescription for a sleep medication occurred from 1999-2010.	Ford ES, Wheaton AG, Cunningham TJ, Giles WH, Chapman DP, Croft JB. Trends in outpatient visits for insomnia, sleep apnea, and prescriptions for sleep medications among US adults: findings from the National Ambulatory Medical Care Survey 1999-2010.	

25082509	The Karolinska Sleepiness Scale and Samn-Perelli fatigue ratings, and psychomotor vigilance task performance are proposed as measures for monitoring commercial pilot fatigue. In laboratory studies, they are sensitive to sleep/wake history and circadian phase. The present analyses examined whether they reliably reflect sleep/wake history and circadian phase during transmeridian flight operations. Data were combined from four studies (237 pilots, 730 out-and-back flights between 13 city pairs, 1-3-day layovers). Sleep was monitored (wrist actigraphy, logbooks) before, during and after trips. On duty days, sleepiness, fatigue and mean response speed were measured pre-flight and at the top of the descent. Mixed-model analysis of variance examined associations between these measures and sleep/wake history, after controlling for operational factors. Circadian phase was approximated by local (domicile) time in the city where each trip began and ended. More sleep in the 24 h prior to duty was associated with lower pre-flight sleepiness and fatigue and faster response speed. Sleepiness and fatigue were greater before flights departing during the domicile night and early morning. At the top of the descent, pilots felt less sleepy and fatigued after more in-flight sleep and less time awake. Flights arriving in the early-mid-morning (domicile time) had greater sleepiness and fatigue and slower response speeds than flights arriving later. Subjective ratings showed expected associations with sleep/wake history and circadian phase. The response speed showed expected circadian variation but was not associated with sleep/wake history at the top of the descent. This may reflect moderate levels of fatigue at this time and/or atypically fast responses among pilots.
25080875	The purpose of this study is to determine whether there are some differences in the treatment responses to a multidisciplinary fibromyalgia (FM) treatment related with the baseline body mass index (BMI) of the participants. Inclusion criteria consisted of female sex, a diagnosis of FM (American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Baseline BMI was determined, and patients were randomly assigned to one of the two treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were pain intensity, functionality, catastrophizing, psychological distress, health-related quality of life, and sleep disturbances. One hundred thirty patients participated in the study. No statistical significant differences regarding pre-treatment outcomes were found among the different BMI subgroups, and between the two experimental conditions for each BMI category. General linear model analysis showed a significant interaction group treatment × time in pain intensity (p < .01), functionality (p < .0001), catastrophizing (p < .01), psychological distress (p < .0001), sleep index problems (p < .0001), and health-related quality of life (p < .05). No significant interactions were found in BMI × time, and in BMI × group treatment × time. There are not differences among normal weight, overweight and obese patients with FM regarding their response to a multidisciplinary treatment programme for FM which combines pharmacological treatment, education, physical therapy and cognitive behavioural therapy.
25079937	To investigate the prevalence and the correlates of sleep disturbance and depressive symptoms among Chinese adolescents and to examine the association between the two problems.Cross-sectional survey.	A total of 3186 school students in grades 7-12 were sampled from the schools in Guangdong. A stratified-cluster random-sampling strategy was used to select the schools.	A self-administered questionnaire was used. The Pittsburgh Sleep Quality index (PSQI) was used to assess the occurrence of sleep disturbance, and the Center for Epidemiology Scale for Depression (CES-D) was used to identify whether individuals had depressive symptoms.	The mean PSQI global score was 8.7 (±2.4) points, and 39.6% of the total sample had sleep disturbance. The mean CES-D score of students was 15.2 (±9.4) points, and 6.4% of the students had depressive symptoms. Additionally, girls and older adolescents were more likely to suffer from sleep disturbance, and the students who had depressive symptoms were 2.47 (95% CI 1.61 to 3.79) times more likely to suffer from sleep disturbance. Factors that were correlated with sleep disturbance and depressive symptoms were having a poor relationship with teachers, feeling lonely, suicide ideation and having run away from home.	Sleep disturbance was determined to be more prevalent among Chinese adolescents with depressive symptoms. Sleep disturbance and depressive symptoms were associated with each other, while school factors, family factors and psychosocial adjustment were comprehensively correlated with both.	
25079334	Recent investigation has demonstrated that approximately 75% of patients with medically refractory chronic rhinosinusitis (CRS) report abnormal sleep quality, with strong correlation between worse sleep quality and more severe CRS disease severity. It remains unknown whether the treatment effect of endoscopic sinus surgery (ESS) for CRS results in appreciable sleep quality improvements.Adult patients (aged ≥18 years) with a current diagnosis of recalcitrant chronic rhinosinusitis (CRS), who voluntarily elected ESS as the next treatment modality (n = 301), were prospectively evaluated within 4 academic, tertiary care centers using treatment outcome instruments: the Rhinosinusitis Disability Index, the 22-item Sinonasal Outcome Test, the 2-item Patient Health Questionnaire, and the Pittsburgh Sleep Quality Index (PSQI) both before and after ESS.	Seventy-two percent (72%) of patients with CRS were found to have poor sleep (PSQI > 5) at baseline with a mean (standard deviation) global PSQI score of 9.4 (4.6). Surgery improved overall mean global PSQI scores (by 2.2 points), and all 7 subdomain scores of the PSQI. Similarly, the odds of good sleep quality (PSQI ≤ 5) in patients treated with sinus surgery increased significantly (odds ratio [OR] 5.94; 95% confidence interval [CI], 3.06 to 11.53; p < 0.001). Stepwise multivariate linear regression found that acetylsalicylic acid (ASA) intolerance (β [standard error], -1.94 [0.93]; 95% CI, -3.77 to -0.11; p = 0.038), history of prior sinus surgery (β [standard error], 1.10 (0.54); 95% CI, 0.03 to 2.16; p = 0.044), and frontal sinusotomy (β [standard error], -1.03 [0.62]; 95% CI, -2.26 to 0.20; p = 0.099) were found to significantly associate with improvement in PSQI sleep scores.	Among patients with CRS, reduced sleep quality, poor disease-specific quality of life, and greater disease severity were improved following ESS.	
25078964	The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity. 
25078876	Diabetes mellitus (DM) and heart failure (HF) are often comorbid. Sleep disturbances, poor physical functioning, and high levels of daytime symptoms are prevalent and contribute to poor quality of life in both populations. However, little is known about the independent and additive effects of comorbid DM on sleep, physical function, and daytime symptoms among patients with HF.The aim of this study was to investigate the extent to which comorbid DM confers independent and additive effects on sleep disturbance, physical functioning, and symptoms among patients with stable HF.	This secondary analysis was conducted on a sample of 173 stable class II to IV HF patients. Self-report and polysomnography were used to measure sleep quality, objective sleep characteristics, and sleep-disordered breathing. Physical function measures included wrist actigraphy, the 6-minute walk test (6MWT), and the Medical Outcomes Study 36-item Short Form physical component summary score. Fatigue, sleepiness, and depression were also measured. Univariate analyses and hierarchical regression models were computed.	The sample included 173 (n = 119/68% HF and n = 54/32% HF plus DM) patients (mean [SD] age, 60.4 [16.1] years). In analyses adjusted for age, gender, body mass index, and New York Heart Association classification, the HF patients with DM had longer sleep latency and spent a greater percentage of time awake after sleep onset than the HF patients who did not have DM (all P < 0.05). There were no statistically significant differences in Respiratory Disturbance Index or self-reported sleep quality. Sleep duration was low in both groups. The patients with DM had shorter 6MWT distance, lower ratio of daytime to nighttime activity, as well as lower general health and self-reported physical function. Hierarchical regression models revealed that age and DM were the only significant correlates of the sleep variables, whereas age, gender, New York Heart Association class, and DM were all associated with 6MWT distance.	Comorbid DM contributes independent and additive effects on sleep disturbances and poor physical functioning in patients with stable HF.	
25078716	There are no previous epidemiologic studies on concurrent headache and sleep problems (HSP). This cross-sectional study aimed to determine the prevalence of HSP in Denmark, broadly characterize those with HSP, and examine associations between HSP and socioeconomic/lifestyle factors.A total of 129,150 randomly selected individuals were invited to participate in the Danish National Health Survey 2010. Respondents were asked about headache, sleep problems, depression and anxiety in the last two weeks, health-related lifestyle and quality of life (SF-12). Socioeconomic data were retrieved from national registers. Prevalence proportions were adjusted for stratified sampling and non-response. Regression analyses examined associations between HSP and socioeconomic/lifestyle factors.	Of 68,518 respondents, 16.3% reported only headache, 21.1% only sleep problems, and 18.1% HSP with 2.6% being severely affected. Prevalence was higher among women and the middle-aged. Severe HSP was associated with low socioeconomic position, non-Western ethnicity, unhealthy lifestyle, high stress and anxiety/depression. Those with HSP had substantially reduced quality of life; more so than those having only headache or only sleep problems.	HSP is a highly prevalent condition. Lifestyle modification, stress reduction, and screening for concurrent depression and anxiety may play important roles in management. The high prevalence of HSP suggests a common pathophysiological mechanism.	
25078069	The mandible movement (MM) signal provides information on mandible activity. It can be read visually to assess sleep-wake state and respiratory events. This study aimed to assess (1) the training of independent scorers to recognize the signal specificities; (2) intrascorer reproducibility and (3) interscorer variability. MM was collected in the mid-sagittal plane of the face of 40 patients. The typical MM was extracted and classified into seven distinct pattern classes: active wakefulness (AW), quiet wakefulness or quiet sleep (QW/S), sleep snoring (SS), sleep obstructive events (OAH), sleep mixed apnea (MA), respiratory related arousal (RERA) and sleep central events (CAH). Four scorers were trained; their diagnostic capacities were assessed on two reading sessions. The intra- and interscorer agreements were assessed using Cohen's κ. Intrascorer reproducibility for the two sessions ranged from 0.68 [95% confidence interval (CI): 0.59-0.77] to 0.88 (95% CI: 0.82-0.94), while the between-scorer agreement amounted to 0.68 (95% CI: 0.65-0.71) and 0.74 (95% CI: 0.72-0.77), respectively. The overall accuracy of the scorers was 75.2% (range: 72.4-80.7%). CAH MMs were the most difficult to discern (overall accuracy 65.6%). For the two sessions, the recognition rate of abnormal respiratory events (OAH, CAH, MA and RERA) was excellent: the interscorer mean agreement was 90.7% (Cohen's κ: 0.83; 95% CI: 0.79-0.88). The discrimination of OAH, CAH, MA characteristics was good, with an interscorer agreement of 80.8% (Cohen's κ: 0.65; 95% CI: 0.62-0.68). Visual analysis of isolated MMs can successfully diagnose sleep-wake state, normal and abnormal respiration and recognize the presence of respiratory effort. 
25077452	Although fatigue, sleep disturbance, depression, and anxiety are associated with pain in breast cancer patients, it is unknown whether acupuncture can decrease these comorbid symptoms in cancer patients with pain. The objective of this study was to evaluate the effect of electroacupuncture (EA) on fatigue, sleep, and psychological distress in breast cancer survivors who experience joint pain related to aromatase inhibitors (AIs).The authors performed a randomized controlled trial of an 8-week course of EA compared with a waitlist control (WLC) group and a sham acupuncture (SA) group in postmenopausal women with breast cancer who self-reported joint pain attributable to AIs. Fatigue, sleep disturbance, anxiety, and depression were measured using the Brief Fatigue Inventory (BFI), the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). The effects of EA and SA versus WLC on these outcomes were evaluated using mixed-effects models.	Of the 67 randomly assigned patients, baseline pain interference was associated with fatigue (Pearson correlation coefficient [r]=0.75; P < .001), sleep disturbance (r=0.38; P=.0026), and depression (r=0.58; P < .001). Compared with the WLC condition, EA produced significant improvements in fatigue (P=.0095), anxiety (P=.044), and depression (P=.015) and a nonsignificant improvement in sleep disturbance (P=.058) during the 12-week intervention and follow-up period. In contrast, SA did not produce significant reductions in fatigue or anxiety symptoms but did produce a significant improvement in depression compared with the WLC condition (P=.0088).	Compared with usual care, EA produced significant improvements in fatigue, anxiety, and depression; whereas SA improved only depression in women experiencing AI-related arthralgia.	
25073541	Weight, physical activity, and sleep are modifiable lifestyle factors that impact cognitive functioning in noncancer populations but have yet to be examined in cancer survivors. The aim of the study was to assess the relationship of obesity, physical activity, and sleep, with cognitive functioning among breast cancer survivors.Participants were 136 early-stage postmenopausal breast cancer survivors who completed an assessment of neuropsychological testing, height, weight, physical activity, and sleep. Linear regression models examined the associations of the seven neuropsychological domains with obesity, physical activity, and sleep. Logistic regression models examined odd of impairment in each domain. All models controlled for breast cancer treatment variables and relevant demographic and clinical variables.	Obese participants had significantly worse performance (β = -5.04, standard error (SE) = 2.53) and were almost three times more likely to be impaired (odds ratio (OR) = 2.87; 95% CI: 1.02-8.10) on the Information processing domain. The highest tertile of physical activity was significantly related to better performance on the executive functioning domain (β = 5.13, SE = 2.42) and attention domain (β = 4.26, SE = 2.07). The middle tertile of physical activity was significantly related to better performance (β = 9.00, SE = 3.09) and decreased odds of impairment (OR = 0.89, 95% CI: 0.07-0.91) on the visual-spatial domain. More hours of sleep per night was significantly associated with better performance (β = 2.69, SE = 0.98) and decreased odds of impairment (OR = 0.52; 95% CI: 0.33-0.82) on the verbal functioning domain.	These findings suggest that obesity, physical activity, and sleep are related to cognitive functioning among breast cancer survivors and have potential to be intervention targets to improve cognitive functioning.	
25072880	Studies in Polar Base stations, where personnel have no access to sunlight during winter, have reported circadian misalignment, free-running of the sleep-wake rhythm, and sleep problems. Here we tested light as a countermeasure to circadian misalignment in personnel of the Concordia Polar Base station during the polar winter. We hypothesized that entrainment of the circadian pacemaker to a 24-h light-dark schedule would not occur in all crew members (n = 10) exposed to 100-300 lux of standard fluorescent white (SW) light during the daytime, and that chronic non-time restricted daytime exposure to melanopsin-optimized blue-enriched white (BE) light would establish an a stable circadian phase, in participants, together with increased cognitive performance and mood levels. The lighting schedule consisted of an alternation between SW lighting (2 weeks), followed by a BE lighting (2 weeks) for a total of 9 weeks. Rest-activity cycles assessed by actigraphy showed a stable rest-activity pattern under both SW and BE light. No difference was found between light conditions on the intra-daily stability, variability and amplitude of activity, as assessed by non-parametric circadian analysis. As hypothesized, a significant delay of about 30 minutes in the onset of melatonin secretion occurred with SW, but not with BE light. BE light significantly enhanced well being and alertness compared to SW light. We propose that the superior efficacy of blue-enriched white light versus standard white light involves melanopsin-based mechanisms in the activation of the non-visual functions studied, and that their responses do not dampen with time (over 9-weeks). This work could lead to practical applications of light exposure in working environment where background light intensity is chronically low to moderate (polar base stations, power plants, space missions, etc.), and may help design lighting strategies to maintain health, productivity, and personnel safety. 
25072285	The aim of this study was to investigate the rate, longitudinal improvement, and risk factors of sleep disturbance after 4 common orthopaedic traumatic conditions.The functional status of 1095 patients was prospectively assessed using validated questionnaires for patients with acute proximal humerus (n = 111), distal radius (n = 440), tibial plateau (n = 109), and ankle fractures (n = 435). Patient reported sleep difficulty was compared with the overall functional and emotional status of each patient at 3, 6, and 12 months after treatment.	Sleep difficulty at 3-month follow-up was reported in 41% of patients with proximal humerus fracture, 25% of patients with distal radius fracture, 36% of patients with tibial plateau, and 19% of patients with ankle fracture. By 12-month follow-up, less than 20% of patients with all fracture types reported sleep difficulty. At 12-month follow-up, the SF-36 Mental Health category for patients with distal radius fractures (P = 0.001) and the Short Musculoskeletal Function Assessment Emotional category for patients with tibial plateau fractures (P = 0.024) and ankle fractures (P ≤ 0.001) were independent predictors of poor sleep, whereas the respective functional status categories were not.	At 12-month follow-up, poor sleep was independently associated with poor emotional status but not associated with poor functional status. The mental health status of patients with sleep difficulty in the latter stages of fracture healing should be carefully assessed to provide the highest level of care. The results of this study should allow orthopaedic trauma surgeons to counsel patients regarding expectations of difficulty sleeping after acute fractures.	Prognostic level II. See Instructions for authors for a complete description of levels of evidence.	
25071478	In humans, sleep and wakefulness and the associated cognitive processes are regulated through interactions between sleep homeostasis and the circadian system. Chronic disruption of sleep and circadian rhythmicity is common in our society and there is a need for a better understanding of the brain mechanisms regulating sleep, wakefulness and associated cognitive processes. This review summarizes recent investigations which provide first neural correlates of the combined influence of sleep homeostasis and circadian rhythmicity on cognitive brain activity. Markers of interindividual variations in sleep-wake regulation, such as chronotype and polymorphisms in sleep and clock genes, are associated with changes in cognitive brain responses in subcortical and cortical areas in response to manipulations of the sleep-wake cycle. This review also includes recent data showing that cognitive brain activity is regulated by light, which is a powerful modulator of cognition and alertness and also directly impacts sleep and circadian rhythmicity. The effect of light varied with age, psychiatric status, PERIOD3 genotype and changes in sleep homeostasis and circadian phase. These data provide new insights into the contribution of demographic characteristics, the sleep-wake cycle, circadian rhythmicity and light to brain functioning. 
25070645	Although sleep problems are associated with negative outcomes among adolescents, studies have not focused on sleep disorder symptoms among adolescents living in impoverished neighborhoods and how sleep problems may be related to two factors common in those environments: hopelessness and exposure to violence. This study used data from the longitudinal Mobile Youth Survey (MYS; N = 11,838, 49% female, 93% African-American) to examine trajectories of sleep problems by age (10-18 years) among impoverished adolescents as a function of gender, feelings of hopelessness, and exposure to violence. The results indicate that sleep problems associated with traumatic stress decline with age, with four notable distinctions. First, the steepest decline occurs during the early adolescent years. Second, the rate of decline is steeper for males than for females. Third, exposure to violence impedes the rate of decline for all adolescents, but more dramatically for females than for males. Fourth, the rate of decline is smallest for adolescents with feelings of hopelessness who also had been exposed to violence. To explore the generalizability of these results to other types of sleep disorders, we analyzed cross-sectional data collected from a subsample of 14- and 15-year-old MYS participants (N = 263, 49% female, 100% African-American) who completed a sleep symptoms questionnaire. Four results from the cross-sectional analysis extend the findings of the longitudinal analysis. First, the cross-sectional results showed that symptoms of apnea, insomnia, nightmares, and restless legs syndrome or periodic limb movement disorder (RLS/PLMD), as well as daytime sleepiness, increase as a function of hopelessness. Second, symptoms of insomnia, RLS, and nightmares, as well as daytime sleepiness, increase as function of exposure to violence. Third, symptoms of insomnia and RLS/PLMD are greater under conditions of combined hopelessness and exposure to violence than for either condition alone. Fourth, symptoms of RLS/PLMD are worst for females who have been exposed to violence and experience hopelessness. Overall, the findings suggest that hopelessness and exposure to violence have negative independent and multiplicative effects on adolescent sleep, particularly for females. Understanding the causal factors associated with inadequate sleep in impoverished adolescents is important for three reasons. First, sleep is an important aspect of adolescent development. Second, inadequate sleep has severe consequences for adolescent morbidity, mortality, and overall quality of life. Third, impoverished adolescents are at the most severe risk for poor outcomes, and improvement in their sleep may produce large gains.
25070475	Reports of studies evaluating rufinamide as an add-on therapy in children and adolescents with refractory epilepsy are restricted to a few publications. Prospective multicenter studies including children and adults have yielded important information about several types of epilepsies and syndromes. We evaluated the use of rufinamide in a single pediatric center with a large cohort and long-term follow-up period.We retrospectively included patients taking rufinamide from November 2008 to March 2013. Response was defined by a seizure reduction of ≥50% compared to baseline.	Three hundred patients with a median age of 9.1 years (range 0.4-29.6 years) were reviewed. Median follow-up was 9 months (range 1-37 months). Epilepsy etiology was classified as genetic (23.7%), structural/metabolic (41%), and unknown cause (35.3%). Overall, rufinamide treatment led to a median seizure frequency reduction of 59.2% from responders to baseline. Seizure reduction was greater in patients with genetic etiology compared to structural/metabolic (66.2% vs. 45.5% responders, p = 0.005). Rufinamide was discontinued in 110 (36.7%) of 300 patients: 63 (21%) due to unsatisfactory response, 47 (15.7%) due to side effects, and in 18 (6%) of those due to both. Most common adverse effects were sleepiness, vomiting, mood changes, nausea, and loss of appetite. Median time to loss of efficacy was 11.6 months (range 3-28 months).	Rufinamide provides satisfactory seizure reduction as an adjunctive treatment in refractory epilepsy. Results need to be interpreted in the setting of data acquisition, including inherent biases of retrospective studies. Patients with a known genetic etiology may have better responses than patients with structural/metabolic etiology.	
25069791	In the present study, the relationships between cortisol, cognitive function, depressive behavior, and sleep quality in chronic kidney disease (CKD) and hemodialysis (HD) patients was investigated. Patients underwent history taking, physical examination, biochemical analysis, 24-h urine collection (for CKD patients only), measurement of dialysis adequacy (for HD patients only), evaluation of cognitive function, depressive behavior and sleep quality. Among study participants 58 had creatinine clearance ≥60 mL/min/1.73 m(2) (Group 1), 41 had creatinine clearance between 30 and 59 mL/min/1.73 m(2) (Group 2), 25 had creatinine clearance between 15 and 29 mL/min/1.73 m(2) (Group 3) and 12 had creatinine clearance <15 mL/min/1.73 m(2) (Group 4). 38 patients were regular HD patients (Group 5). The cortisol levels in Group 1, 2, 3, 4 and 5 patients were 472.3 ± 138.4, 490.2 ± 214.3, 541.6 ± 172.8, 569.9 ± 101.0 and 637.8 ± 153.7 nmol/L, respectively (P < 0.0001 for trend). In both non-dialysis patient group and dialysis patients linear regression analysis showed that cortisol was independently related with Beck depression inventory (BDI) score (P: 0.013 and 0.001, respectively) but not with cognitive function and sleep quality. In conclusion serum cortisol levels were independently associated with depressive behavior both in CKD and HD patients but not with cognitive function and sleep quality.

25065908	Actimetry has been used to estimate the sleep-wake cycle instead of the rest-activity rhythm. Although algorithms for assessing sleep from actimetry data exist, it is useful to analyze the rest-activity rhythm using nonparametric methods. This would then allow rest-activity rhythm stability, fragmentation and amplitude to be quantified. In addition, sleep and wakefulness efficiency can be quantified separately. These variables have been used in studies analyzing the effect of age, diseases and their respective treatments on human circadian rhythmicity. In this study, we carried out a comprehensive analysis of the main results from published articles and devised a functional model of interaction among the several components involved in generating the sleep-wake cycle. The nonparametric variables render it possible to infer the main characteristics of circadian rhythms, such as synchronization with a zeitgeber, and its amplitude and robustness. 
25064378	Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the ventrolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over more than one location, and the best predictor might be symptoms. These are issues that need to undergo careful study on a syndromic, anatomic and physiological bases. This novel model opens up new avenues for understanding central nervous system sleep disorders, providing testable hypotheses regarding diagnosis and treatment. 
25063397	Most animals conduct daily activities exclusively either during the day or at night. Here, hormones such as melatonin and corticosterone, greatly influence the synchronization or regulation of physiological and behavioral cycles needed for daily activity. How then do species that exhibit more flexible daily activity patterns, responses to ecological, environmental or life-history processes, regulate daily hormone profiles important to daily performance? This study examined the consequences of (1) nocturnal activity on diel profiles of melatonin and corticosterone and (2) the effects of experimentally increased acute melatonin levels on physiological and metabolic performance in the cane toad (Rhinella marinus). Unlike inactive captive toads that had a distinct nocturnal melatonin profile, nocturnally active toads sampled under field and captive conditions, exhibited decreased nocturnal melatonin profiles with no evidence for any phase shift. Nocturnal corticosterone levels were significantly higher in field active toads than captive toads. In toads with experimentally increased melatonin levels, plasma lactate and glucose responses following recovery post exercise were significantly different from control toads. However, exogenously increased melatonin did not affect resting metabolism in toads. These results suggest that toads could adjust daily hormone profiles to match nocturnal activity requirements, thereby avoiding performance costs induced by high nocturnal melatonin levels. The ability of toads to exhibit plasticity in daily hormone cycles, could have broad implications for how they and other animals utilize behavioral flexibility to optimize daily activities in response to natural and increasingly human mediated environmental variation. 
25062968	The objective of the study was to explore the effects of olanzapine-fluoxetine combination (OFC) treatment of major depressive disorders on the quality of life in the acute treatment period. Methods were prospective and observational design. One hundred and three patients of major depressive disorders were observed. One group of 53 patients received OFC treatment (OFC group); the other group of 50 patients received the treatment of duloxetine (duloxetine group). Two groups were needed to be observed 8 weeks. Observed indicators were Hamilton Depression Rating Scale for Depression (HAMD-24) and four factor scores: the slow, sleep disorders, anxiety/somatization, and hopelessness, Clinical Global Impression-Severity of Illness (CGI-S), WHO quality of life scale (WHOQOL-BREF), and sub-rate measurements. HAMD-24 and four factor scores observation time were assessed before and after treatment; 1, 2, 4, 8 weeks, WHOQOL-BREF score, and sub-time measurements were assessed before treatment and 8 weeks after treatment. HAMD-24 scores of OFC patients in the first week were significantly lower than those of the duloxetine group. The sleep factor scores of OFC patients were significantly lower than those of the duloxetine group in 4 and 8 weeks. By the end of 8 weeks, OFC group was rated significantly lower than the duloxetine group in the physical area. In the acute treatment period, OFC treatment effected faster than the single duloxetine in patients with major depressive disorders. OFC effected within 1 week and was better than the single duloxetine in improving the sleep and physical conditions.
25062775	Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERα(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen.
25061767	Sleep has a critical role in promoting health. Research over the past decade has documented that sleep disturbance has a powerful influence on the risk of infectious disease, the occurrence and progression of several major medical illnesses including cardiovascular disease and cancer, and the incidence of depression. Increasingly, the field has focused on identifying the biological mechanisms underlying these effects. This review highlights the impact of sleep on adaptive and innate immunity, with consideration of the dynamics of sleep disturbance, sleep restriction, and insomnia on (a) antiviral immune responses with consequences for vaccine responses and infectious disease risk and (b) proinflammatory immune responses with implications for cardiovascular disease, cancer, and depression. This review also discusses the neuroendocrine and autonomic neural underpinnings linking sleep disturbance and immunity and the reciprocal links between sleep and inflammatory biology. Finally, interventions are discussed as effective strategies to improve sleep, and potential opportunities are identified to promote sleep health for therapeutic control of chronic infectious, inflammatory, and neuropsychiatric diseases. 
25061630	Critical to helping patients break the stranglehold of these 3 comorbidities is an understanding of how they interact with one other. 
25061250	Employee control over work times has been associated with favorable psychosocial and health-related outcomes, but the evidence regarding sleep quality remains inconclusive. We examined cross-sectional and prospective associations between work time control and sleep disturbances in a large working population, taking into account total hours worked.The data were from a full-panel longitudinal cohort study of Finnish public sector employees who responded to questions on work time control and sleep disturbances in years 2000-2001, 2004-2005, 2008-2009, and 2012. The analysis of cross-sectional associations was based on 129,286 person measurements from 68,089 participants (77% women) aged 17-73 years (mean 43.1). Data from 16,503 participants were used in the longitudinal analysis. Log-binomial regression analysis with the generalized estimating equations method was used.	Consistently in both cross-sectional and longitudinal models, less control over work time was associated with greater sleep disturbances in the total population and among those working normal 40-hour weeks. Among participants working more than 40 hours a week, work time that was both very high (cross-sectional prevalence ratio compared to intermediate work time control [PR] 1.32, 95% confidence interval [CI] 1.05-1.65) and very low (PR 1.23, 95% CI 1.08-1.39) was associated with sleep disturbances, after adjustment for potential confounding factors.	These data suggest that having few opportunities to influence the duration and positioning of work time may increase the risk of sleep disturbances among employees. For persons working long hours, very high levels of control over working times were also associated with increased risk of sleep disturbances.	Salo P, Ala-Mursula L, Rod NH, Tucker P, Pentti J, Kivimäki M, Vahtera J. Work time control and sleep disturbances: prospective cohort study of Finnish public sector employees.	
25061246	To investigate the longitudinal relationship between subjective and objective sleep disturbance and depressive symptoms.Longitudinal.	Three US clinical centers.	Nine hundred fifty-two community-dwelling older women (70 y or older).	At baseline, subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and objective sleep measures were assessed with wrist actigraphy. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS) at baseline and approximately 5 y later. The analysis was restricted to women with few (GDS 0-2) depressive symptoms at baseline.	There was an independent association between greater PSQI score (per standard deviation increase, indicating worse subjective sleep quality) at baseline and greater odds of worsening depressive symptoms (≥ 2-point increase in GDS) (Multivariate Odds Ratio [MOR] 1.19, confidence interval [CI] 1.01-1.40, P = 0.036). Higher scores specifically on the sleep quality (MOR 1.41, CI 1.13-1.77, P < 0.003) and sleep latency (MOR 1.21, CI 1.03-1.41, P = 0.018) PSQI subscales were also associated with greater odds for worsening depressive symptoms. Objective assessments revealed an association between baseline prolonged wake after sleep onset (WASO ≥ 60 min) and worsening depressive symptoms at follow-up (MOR 1.36, CI 1.01-1.84, P = 0.046). There were no associations between other objectively assessed sleep measures and worsening depressive symptoms.	In older women with few or no depressive symptoms at baseline, those with more subjectively reported sleep disturbance and more objectively assessed fragmentation of sleep at baseline had greater odds of worsening depressive symptoms 5 y later. Future studies investigating this relationship in more detail are indicated.	Maglione JE, Ancoli-Israel S, Peters KW, Paudel ML, Yaffe K, Ensrud KE, Stone KL, Study of Osteoporotic Fractures Research Group. Subjective and objective sleep disturbance and longitudinal risk of depression in a cohort of older women.	
25061245	To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults.Community-based longitudinal brain and cognitive aging study using a convenience sample.	Participants were studied in a research laboratory.	Relatively healthy adults aged 55 y and older at study commencement.	N/A.	Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance.	In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers.	Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance.	
25061135	Comorbid diabetes and depression are a major clinical challenge as the outcomes of each condition are worsened by the other. This article is based on the presentations and discussions during an international meeting on diabetes and depression convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the National Institute of Mental Health and the Dialogue on Diabetes and Depression. While the psychological burden of diabetes may contribute to depression in some cases, this explanation does not sufficiently explain the relationship between these two conditions. Shared biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, autonomic dysfunction, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors, are important to consider in understanding the link between depression and diabetes. Both individual psychological and pharmacological depression treatments are effective in people with diabetes, but the current range of treatment options is limited and has shown mixed effects on glycemic outcomes. More research is needed to understand what factors contribute to individual differences in vulnerability, treatment response, and resilience to depression and metabolic disorders across the life course and how best to provide care for people with comorbid diabetes and depression in different health care settings. Training programs are needed to create a cross-disciplinary workforce that can work in different models of care for comorbid conditions. 
25061122	To understand the effects of Whipple's disease (WD) of the brain on sleep function.Clinical and polysomnographic studies of two patients with severe disruption of sleep due to WD: a 48-year-old female with primary WD of the brain and a 41-year-old male with secondary WD of the brain.	The patient with primary WD had hypersomnolence with severe obstructive sleep apnoea, reduced sleep efficiency, frequent waking and sleep fragmentation. The patient with secondary WD was also hypersomnolent with oculomastictory myorhythmia. He was shown to have severe sleep initiation insomnia with poor sleep efficiency, severe obstructive sleep apnoea/hypopnoea and oculomasticatory myorhythmia at sleep-wake transitions.	WD of the brain may affect sleep biology in its primary and secondary forms leading to hypersomnolence from obstructive sleep apnoea, sleep fragmentation, reduced sleep efficiency, sleep initiation insomnia and intrusive oculomasticatory myorhythmia.	
25061120	Dementia is common in older people admitted to acute hospitals. There are concerns about the quality of care they receive. Behavioural and psychiatric symptoms of dementia (BPSD) seem to be particularly challenging for hospital staff. AIMS To define the prevalence of BPSD and explore their clinical associations.Longitudinal cohort study of 230 people with dementia, aged over 70, admitted to hospital for acute medical illness, and assessed for BPSD at admission and every 4 (± 1) days until discharge. Other measures included length of stay, care quality indicators, adverse events and mortality.	Participants were very impaired; 46% at Functional Assessment Staging Scale (FAST) stage 6d or above (doubly incontinent), 75% had BPSD, and 43% had some BPSD that were moderately/severely troubling to staff. Most common were aggression (57%), activity disturbance (44%), sleep disturbance (42%) and anxiety (35%).	We found that BPSD are very common in older people admitted to an acute hospital. Patients and staff would benefit from more specialist psychiatric support.	
25060968	Over the past decade, researchers have shifted focus from the manic and depressive episodes to the interepisode period in the study of sleep-wake disturbance in bipolar disorder. The objective of this systematic review was to compile and synthesize studies that employed sleep diary, actigraphy, polysomnography, and questionnaires to compare sleep-wake patterns in people with interepisode bipolar disorder or high-risk individuals vs. normal controls and/or people with primary insomnia. We searched key databases until June 2013. Our search identified 21 eligible studies, yielding 24 sleep-wake variables. A total of 531 people with interepisode bipolar disorder, 157 high-risk individuals, 678 normal controls and 67 adults with primary insomnia were evaluated. Using a random-effects model, our analyses suggest that adults with interepisode bipolar disorder appear worse than normal controls in most variables and comparable to adults with primary insomnia in certain aspects. Sleep onset latency, wake after sleep onset, and variability of sleep-wake variables were most consistently impaired in interepisode bipolar disorder. In comparison with controls, high-risk individuals were found to have higher variability in sleep efficiency and lower relative amplitude. The findings provide a foundation for the search for candidate endophenotypes and the development of novel interventions for bipolar disorder. 
25060106	The purpose of this study was to identify sleep disorder experience in older patients living in the community and acknowledging being depressed.For this study, 11 older patients with depression were purposively chosen. Data were collected through in-depth individual interviews from July 2013 to January 2014 and analyzed in terms of by Giorgi's phenomenological methodology.	The study results showed that sleep disorder experience in older patients with depression consisted of sixteen themes and five themes-clusters: 1) exposure of the causes of sleep disorders; 2) life is painful; 3) harassing themselves and their family; 4) difficulty in controlling themselves; 5) trying to deal with the sleep disorder to overcome the situation.	It is necessary to develop educational guidelines for patients with sleep disorders or nursing interventions that anyone can easily provide for elders in the communities. The first priority should be given to efforts to apply diverse methods to improve sleep hygiene and minimize the period of exposure to medication before starting medication for patients with sleep disorders.	
25059457	Converging evidence suggests that changes in plasma levels of amino acids are involved in Parkinson's disease (PD), but their roles in nonmotor symptoms (NMS) of PD remain unclear. The aim of this study was to evaluate the correlations between plasma amino acids and NMS of PD. Plasma levels of aspartate (Asp), glutamate (Glu), glycine (Gly) and γ-aminobutyric acid (GABA) were measured in 92 PD patients and 60 healthy controls. Four NMS, including depression, pain, sleep disturbances and autonomic dysfunction were assessed in enrolled subjects using the Hamilton Depression Scale, the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to evaluate the correlations between plasma levels of amino acids and NMS. PD patients exhibited significantly higher scores of NMS scales and lower plasma levels of amino acids compared to healthy controls. Within the PD group, plasma levels of Asp and Glu were negatively associated with the severity of depression and sleep disturbances. Moreover, decreased plasma level of GABA was correlated with more severe symptoms of sleep disturbances. After controlling for gender, disease duration, severity of motor symptoms and anti-parkinsonian medications, Glu but not Asp remained significantly associated with depression, along with Asp, GABA but not Glu remained negatively associated with sleep disturbances. The altered plasma levels of amino acids may be implicated in the pathogenesis of NMS of PD. 
25059029	Primary headaches account for 90% of all the forms of headache. The disease is characterized by high occurrence in the working-age population and by significant impact in countries with high economic and social development. These two epidemiological aspects carry significant economic costs that can be estimated calculating loss of working days due to illness and appreciable loss of labour productivity. In an occupational setting several circumstances are known to cause the onset of attacks in workers who already suffer from primary headache. In this sense, the following factors have an important role: interruption of the circadian sleep-wake rhythm, sleep deprivation, physical/mental distress, not ergonomic postures (mainly those involving the cervical-brachial district), prolonged use of display screen, acoustic discomfort. Among chemicals, in the current conditions of exposure, the olfactory characteristics seem of primary importance rather than the more "conventional" mechanism of toxicity. The main aim of this study is to provide useful information to occupational physicians on the management of workers suffering from primary headache, with regard either to the formulation of the judgement of suitability, or to their auxiliary role in the planning and organization of work. A second aim involves the identification of specific preventive measures in order to reduce the probability of occurrence of a headache attack. This also minimizes the risk of accidents and injuries and ensures workers' efficiency. After these considerations, we suggest guidelines for a flow chart (aimed to understand worker's suitability for his/her specific task). This guarantees not only safety and health of workers who suffer from the illness, but also safeguards any third worker from a possible consequence due to less working capacity and reduction of attention of employees working with a headache attack. In conclusion we also identify three critical factors: the diagnosis of the form of primary headache, the characteristics of the work and the effects due to pharmacological therapy. The study and characterization of these elements are a crucial step for a proper formulation of the judgement of suitability to work. We report a decision process for judgement formulation at the end of this article. It is organized with a hierarchical model, the first steps are the clinical examination and history, the last step, if necessary or advisable, is the neurological visit and a periodic verification of the adherence to treatment prescribed and the follow-up.
25058693	Most physiological processes in our body oscillate in a daily fashion. These include cerebral activity (sleep-wake cycles), metabolism and energy homeostasis, heart rate, blood pressure, body temperature, renal activity, and hormone as well as cytokine secretion. The daily rhythms in behaviour and physiology are not just acute responses to timing cues provided by the environment, but are driven by an endogenous circadian timing system. A central pacemaker in the suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, coordinates all overt rhythms in our body through neuronal and humoral outputs. The SCN consists of two tiny clusters of ~100,000 neurones in humans, each harbouring a self-sustained, cell-autonomous molecular oscillator. Research conducted during the past years has shown, however, that virtually all of our thirty-five trillion body cells possess their own clocks and that these are indistinguishable from those operative in SCN neurones. Here we give an overview on the molecular and cellular architecture of the mammalian circadian timing system and provide some thoughts on its medical and social impact. 
25057097	Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption. 

25056401	Fibromyalgia (FM) is associated with a number of comorbidities, including chronic widespread pain, fatigue and non-restorative sleep. Evidence has shown that FM is closely associated with overweight and obesity. The objective of the present study was to investigate the relationship between obesity and sleepiness in women with FM. A total of 100 adult female patients with a prior medical diagnosis of FM participated in the study. Body mass, height and waist circumference were measured, and body mass index (BMI) was calculated. The diet quality was evaluated by the Healthy Eating Index. Subjective analyses of daytime sleepiness [Epworth Sleepiness Scale (ESS)] and sleep quality (Pittsburgh Sleep Quality) were performed. An obesity rate of 41 % was found in all women (56.1 % were sleepy and 43.9 % were not, p = 0.04). Obese women showed a greater level of sleepiness when compared with non-obese (10.2 and 7.0, respectively, p = 0.004). Sleepy women showed a greater weight gain after the diagnosis of FM when compared with non-sleepy women (11.7 and 6.4 kg, respectively, p = 0.04). A positive and significant correlation between BMI and sleepiness (r = 0.35, p = 0.02) was also found. In multivariate logistic regression, moderate or severe sleepiness (ESS >12) was associated with obesity (odds ratio 3.44, 95 % CI 1.31-9.01, p = 0.04). These results demonstrate an important association between sleepiness and FM, suggesting that the occurrence of obesity may be involved with sleepiness in these patients.
25055982	Disturbed sleep and pain often co-exist and the relationship between the two conditions is complex and likely reciprocal. This 5-year prospective study examines whether disturbed sleep can predict the onset of multi-site pain, and whether non-disturbed sleep can predict the resolution of multi-site pain.The cohort (n = 1599) was stratified by the number of self-reported pain sites: no pain, pain from 1-2 sites and multi-site pain (≥3 pain sites). Sleep was categorized by self-reported sleep disturbance: sleep A (best sleep), sleep B and sleep C (worst sleep). In the no-pain and pain-from-1-2 sites strata, the association between sleep (A, B and C) and multi-site pain 5 years later was analysed. Further, the prognostic value of sleep for the resolution of multi-site pain at follow-up was calculated for the stratum with multi-site pain at baseline. In the analyses, gender, age, body mass index, smoking, physical activity and work-related exposures were treated as potential confounders.	For individuals with no pain at baseline, a significantly higher odds ratio for multi-site pain 5 years later was seen for the tertile reporting worst sleep [odds ratio (OR) 4.55; 95% confidence interval (CI) 1.28-16.12]. Non-disturbed (or less disturbed) sleep had a significant effect when predicting the resolution of multi-site pain (to no pain) (OR 3.96; 95% CI 1.69-9.31).	In conclusion, sleep could be relevant for predicting both the onset and the resolution of multi-site pain. It seems to be a significant factor to include in research on multi-site pain and when conducting or evaluating intervention programmes for pain.	
25055568	To evaluate the qualitative characteristics of a sleep in pregnant women in the 3rd term of the physiological pregnancy by a questionnaire survey.We have demonstrated questionnaire survey data of 400 pregnant women (mean age 27.5 +/- 8.2 years) in the 3rd term of pregnancy. Questioning conducted using the scale PSQI (PITTSBURGH SLEEP QUALITY INDEX--Pittsburgh Sleep Quality Assessment Questionnaire), EPWORTH SLEEPINESS SCALE (sleepiness questionnaire Epfort's) and screening questionnaire to identify obstructive sleep apnea.	We have determined that 78% of pregnant women to complain about sleep disorders, namely obstructive sleep disordered breathing, insomnia, "restless legs" syndrome, and combinations thereof. The frequency of sleep disorders increases as pregnancy progresses. Obstructive sleep disordered breathing increases with 10.12% in the 1st term to 31.7% in the 3rd term, insomnia--from 14.3% in the 1st term to 37.6% in the 3rd term. In pregnancy increases of sleep latency (from 14.3 to 44.9 minutes), and reduced the duration of a sleep (from 8.7 to 7.8 hours).	high frequency of sleep disorders in pregnancy requires early pathogenetic prevention of pathological conditions, both in the mother and in the fetus.	
25054634	Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep-wake cycle stabilization with PRM in the treatment of insomnia. 
25054079	Background: It is well known that the reinforcing properties of cocaine addiction are caused by the sharp increase of dopamine (DA) in the reward areas of the brain. However, other mechanisms have been speculated to contribute to the increase. Adenosine is one system that is associated with the sleep-wake cycle and is most important in regulating neuronal activity. Thus, more and more evidence is pointing to its involvement in regulating DA release. The current study set out to examine the role of adenosine in cocaine-induced DA release. Methods: Increasing doses of cocaine, caffeine, and their combination, as well as, 8-cyclopentyltheophylline (CPT), an adenosine A1 antagonist (alone and in combination with cocaine) were used to denote a response curve. A novel biosensor, the BRODERICK PROBE® was implanted in the nucleus accumbens to image the drug-induced surge of DA release in vivo, in the freely moving animal in real time. Results: Combinations of cocaine and caffeine were observed to block the increased release of DA moderately after administration of the low dose (2.5 mg/kg cocaine and 12.5 mg/kg caffeine) and dramatically after administration of the high dose (10 mg/kg cocaine and 50 mg/kg caffeine), suggesting neuroprotection. Similarly, CPT and cocaine showed a decreased DA surge when administered in combination. Thus, the low and high dose of a nonselective adenosine antagonist, caffeine, and a moderate dose of a selective adenosine antagonist, CPT, protected against the cocaine-induced DA release. Conclusions: These results show a significant interaction between adenosine and DA release and suggest therapeutic options for cocaine addiction and disorders associated with DA dysfunction.
25053747	The objective of the current article is to review the shared pathophysiological mechanisms which may underlie the clinical association between headaches and sleep disorders.The association between sleep and headache is well documented in terms of clinical phenotypes. Disrupted sleep-wake patterns appear to predispose individuals to headache attacks and increase the risk of chronification, while sleep is one of the longest established abortive strategies. In agreement, narcoleptic patients show an increased prevalence of migraine compared to the general population and specific familial sleep disorders have been identified to be comorbid with migraine with aura.	The pathophysiology and pharmacology of headache and sleep disorders involves an array of neural networks which likely underlie their shared clinical association. While it is difficult to differentiate between cause and effect, or simply a spurious relationship the striking brainstem, hypothalamic and thalamic convergence would suggest a bidirectional influence.	
25053606	Long-haul truck drivers in North America function in a work context marked by excess physical and psychological workload, erratic schedules, disrupted sleep patterns, extreme time pressures, and these factors' far-reaching consequences. These work-induced stressors are connected with excess risk for cardiometabolic disease, certain cancers, and musculoskeletal and sleep disorders, as well as highway crashes, which in turn exert enormous financial burdens on trucking and warehousing companies, governments and healthcare systems, along with working people within the sector. This article: 1) delineates the unique work environment of long-haul truckers, describing their work characteristics and duties; (2) discusses the health hazards of long-haul trucking that impact drivers, the general population, and trucking enterprises, examining how this work context induces, sustains, and exacerbates these hazards; and (3) proposes comprehensive, multi-level strategies with potential to protect and promote the health, safety, and well-being of truckers, while reducing adverse consequences for companies and highway safety. 
25050080	Evidence suggests a high prevalence of sleep-wake disturbances in patients with cancer, occurring at diagnosis, during treatment, and continuing to survivorship. Yet associations between sleep-wake disturbances and the impact on quality of life outcomes is less clear. The purpose of this narrative review of the literature is to evaluate sleep-wake disturbances in patients with cancer, to describe the influence of poor sleep on quality of life as an outcome, and to evaluate the evidence to recommend future interventions.This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. Four databases (CINAHL, MEDLINE, PsycINFO, and Embase) were searched using terms "cancer OR neoplasm", "sleep, sleep disturbance, sleep disorders or insomnia", and "quality of life"; the search included all years, English language, and peer-reviewed articles on research studies. Studies included measurements of sleep and quality of life in cancer patients at a minimum of two time points and demonstrated relationships between sleep and quality of life. Data were collected on date, patient demographics, cancer type and treatment, timeframe, design, measurement, variables, and results.	This narrative review demonstrates that sleep-wake disturbance is a major problem/symptom in patients with cancer. Of the 18 studies included, measurement of sleep-related variables included objective and subjective measures; however, direct measurement of the associations between sleep and quality of life was not common. Cognitive behavioral therapy for insomnia and mind-body interventions demonstrated feasibility when implemented into cancer care settings. In addition, the majority of interventions exhibited moderate effectiveness in improving sleep-wake disturbance and quality of life outcomes.	The studies predominantly reported that poor sleep negatively impacts quality of life. The intervention studies included nonpharmacologic interventions such as cognitive behavioral treatment and mind-body and exercise interventions with moderate-to-high levels of evidence for improvement in sleep measures and quality of life.	
25048010	The fundamental elucidation of how environmental influences provoke the initiation of disease as well as flares of inflammatory bowel disease (IBD) remains incomplete. The current understanding of these diseases suggests that ulcerative colitis (UC) and Crohn's disease (CD) result from poorly defined interactions between genetic and environmental factors which culminate in the pathologic effects and clinical manifestations of these diseases. The genetic variant appears not sufficient itself to lead to the development of the clinical disease, but likely must combine with the environmental factors. The intestinal microbiome is pivotal to IBD development. A greater understanding of the contribution of these factors to dysbiosis is critical, and we aspire to restoring a healthy microbiome to treat flares and ideally prevent the development of IBD and its complications. This article aims to place the environmental influences in the context of their potential contribution to the development of the pathophysiology of IBD. 
25047658	Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease.Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index and Beck Depression Inventory II screening measures as a cross-sectional survey. Scores greater than 5 (Pittsburgh Sleep Quality Index) and 16 (Beck Depression Inventory II) defined sleep disturbance and depression, respectively. Clinical and laboratory parameters were also assessed.	The mean Pittsburgh Sleep Quality Index score was 8.4 (SD ± 4.2) indicating a 71.2% prevalence of sleep disturbance. The mean Beck Depression Inventory II score was 8.0 (SD ± 8.9). Sixty five (20.6%) participants had a score indicating depression, and half of these (10.0%) had thoughts of suicide. Both Pittsburgh Sleep Quality Index and Beck Depression Inventory II scores were significantly correlated (p < .001). The number of days with mild/moderate pain (p = .001) and a history of headaches (p = .005) were independently associated with depression by multivariate regression analysis. Patients with sleep disturbance were older (p = .002), had higher body mass index (p = .011), had more days of pain (p = .003) and more frequent severe acute painful events (emergency room visits and hospitalizations) during the previous 12 months (p < .001).	More than 70 percent of adults with sickle cell disease had sleep disturbance, while 21 percent showed evidence of clinical depression. Sleep disturbance and depression were correlated, and were most common among those with more frequent pain. Providers caring for adults with sickle cell disease and frequent pain should consider screening for these common co-morbidities. Additional study is needed to confirm these findings and to determine if treatments for pain, depression or sleep disturbances will improve quality of life measures in this patient population.	
25045954	Toward identifying variables that may protect children against sleep problems otherwise associated with ethnic minority status and economic adversity, support coping was examined as a moderator. Participants were 235 children (113 boys, 122 girls; M age = 11.33 years, SD = 8.03 months), 64% European American and 36% African American. Children's sleep duration (minutes) and continuity (efficiency) were assessed through actigraphs worn for 1 week. Mothers reported on the family's monetary resources (income-to-needs ratio) and children reported on their support coping strategies. For children from lower income homes and African Americans, a higher level of support coping was a protective factor against fewer sleep minutes and reduced sleep efficiency, otherwise associated with economic adversity. Children from more economically advantaged homes had good sleep parameters regardless of their coping. The results build on the existing small body of work by demonstrating that children's support coping strategies have a protective role against sleep problems otherwise associated with ethnic minority status and economic adversity and present potential targets for intervention that may help reduce health disparities in an important health domain.
25042302	20 adults were randomly assigned to a massage therapy or a massage therapy plus a topical analgesic application group. Both groups received a weekly massage from a therapist and were taught self-massage (same procedure) to be done by each participant once daily over a four-week period.The massage plus topical analgesic group as compared to the massage group had greater improvement in hand function as measured by a digital hand exerciser following the first session and across the four-week period. That group also had a greater increase in perceived grip strength and a greater decrease in hand pain, depressed mood and sleep disturbances over the four-week period. Massage therapy has been effective for several pain syndromes including migraine headaches (Lawle and Cameron, 2006)), lower back pain (Hsieh et al., 2004), fibromyalgia (Kalichman, 2010), neck and shoulder pain (Kong et al., 2013), carpal tunnel syndrome (Elliott and Burkett, 2013), and pain related to upper limb arthritis (Field et al., 2013). The purpose of the current study was to determine whether applying a topical analgesic following massage might be more effective than massage alone in treating pain associated with hand arthritis.	
25042104	To investigate the role of nighttime vital sign assessment in predicting acute care transfers (ACT) from inpatient rehabilitation.Retrospective chart review.	Fifty patients unexpectedly discharged to acute care underwent chart review to determine details of each ACT.	Seven of 50 ACT possessed new vital sign abnormalities at the 11 pm vital sign assessment the night before ACT. None of these seven underwent ACT during the night shift the abnormalities were detected. Two of 50 ACT were transferred between 11 pm and 6:59 am; both demonstrating normal vital sign at the 11 pm assessment. During study period, an estimated 5,607 11 pm vital sign assessments were performed.	Nighttime vital sign assessments do not seem to be a good screening tool for clinical instability in the rehabilitation hospital.	Eliminating sleep disturbance is important to the rehabilitation inpatient as inadequate sleep hinders physical performance. Tailoring vital sign monitoring to fit patents' clinical presentation may benefit this population.	

25039493	Of elders with mild cognitive impairment, around half recover their cognitive function at some point in time. However, very little is known about the factors that influence their cognitive change towards recovery.This study evaluated the role of depression, instrumental activity of daily living and sleep quality as they affect cognition recovery among community-dwelling elders.	The study follows a longitudinal comparative research design using secondary data analysis. Community-dwelling elders with mild cognitive impairment were assessed twice with a 1-year interval to assess their levels of cognition. Adult participants were drawn from those who visited a community health centre, were aged 65 or over and who were assessed as having MCI.	Those with mild cognitive impairment when compared with the normal cognition group were more likely to be younger, have more education, living with their spouses and had better cognitive function at baseline assessment than other participants. Predictors for cognitive recovery among elders with mild cognitive impairment were age, depression and cognitive function at baseline assessment.	Participants included only those who visit a community health centre in an urban area of Korea, so the findings may not be applicable to other elders with less mobility or who live in rural areas.	With the understanding that cognitive function and depression predict the recovery of mild cognitive function, nurses might be able to identify and target those older adults who are likely to achieve recovery of cognitive function. Additionally, health policy options, as suggested by the study as having the potential to improve mild cognitive impairment recovery, could include public education strategies.	
25037839	This study aimed to evaluate (i) whether work, family, behavioral and sleep quality characteristics differ among individuals with different time in bed (TIB), and (ii) whether and how much the U-shaped associations between TIB and health can be explained by these characteristics.Participants were 3510 employees (2371 males and 1139 females) aged 20-65 years working in local government in Japan. They completed a questionnaire regarding work, family, and behavioral characteristics. Sleep quality and physical and mental functioning were evaluated using the Pittsburgh Sleep Quality Index and the Short Form 36.	High job demands, long work hours, and high work-family conflict were more prevalent among those with short TIB. Those with long TIB had daily drinking habits. Whereas those with short TIB had poor sleep, mainly due to poor subjective sleep quality and daytime dysfunction, those with long TIB had poor sleep, mainly due to long sleep latency, poor sleep efficiency and sleep disturbances. The U-shaped associations between TIB and poor physical and mental health, with the best health observed in those spending ~8 h in bed, weakened considerably after adjustment for sleep quality, followed by work and family characteristics. After adjusting for behavioral characteristics and long-standing illnesses, the associations hardly changed.	The U-shaped associations between TIB and health may be explained by U-shaped associations between TIB and poor sleep and psychosocial stress in work and family life.	
25037740	Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated. 
25037669	A nine-year-old female with a history of perinatal stroke, seizures, and type-I diabetes was seen for six weeks of Reiki to determine the effects of Reiki on relaxation, and in turn, the prevention of future seizures. The secondary and tertiary aims were to determine the effects of Reiki on sleep patterns and the stress levels of the mother. There was a decrease in stress in both the child and the mother, as measured by a modified Perceived Stress Scale and a Perceived Stress Scale, respectively. There was no change in the child's overall sense of well-being, as measured by a global questionnaire. There was a positive change in sleep patterns on 33.3% of the nights during which the study occurred, as reported on a sleep log kept by the mother. The child and the Reiki Master (a Reiki practitioner who has completed all three levels of Reiki certification training and trains and certifies individuals in the practice of Reiki as well as provides Reiki to individuals) experienced warmth and tingling sensations on the same area of the child during the Reiki sessions. The child relaxed within the first five to seven minutes of each session as reported by the Reiki Master. There were no reports of seizures during this study. Reiki may be a useful adjunct for children with increased stress levels and sleep disturbances secondary to their medical condition. Further research is warranted to evaluate the use of Reiki in children, particularly with a large sample size, and to evaluate the long-term use of Reiki and its effects on adequate sleep. 
25037297	Approximately 5% of older adults meet criteria for clinically significant insomnia disorders and 20% for sleep apnea syndromes. It is important to distinguish age-appropriate changes in sleep from clinically significant insomnia, with the latter having associated daytime impairments. Non-pharmacologic therapies, such as cognitive-behavioral therapy for insomnia, can be highly effective with sustained benefit. Pharmacologic therapies are also available, but may be associated with psychomotor effects. A high index of suspicion is crucial for effective diagnosis of sleep apnea because symptoms commonly noted in younger patients, such as obesity or loud snoring, may not be present in older patients. 
25037065	Universal screening at university health centers can facilitate early identification and treatment of behavioral health problems common among college students. This article describes the (a) process of implementing behavioral health screening at a university health center and (b) results of universal screening for depression, suicidal ideation, alcohol misuse, tobacco use, and sleep problems. We discuss the decision points involved in screening, including what to screen for, whom to screen, how to implement the screening measure, and how to deal with patients who screen positive. During the Spring and Fall 2010 academic semesters, 4,126 screening questionnaires were completed by students (62% female) accessing a university health center. Each semester, 9-13% of students screened positive for depression, 2.5-3% for suicidal ideation, and 33-38% for alcohol misuse, while 10% wanted help with smoking cessation and 12-13% with sleep problems. The results suggest that behavioral health screening in a university health center can help identify students with behavioral health concerns to increase access to care.
25036723	Sleep disturbances are common in patients with chronic lung diseases, but little is known about the prevalence in patients with bronchiectasis. A cross sectional study was conducted to investigate the prevalence and determinants associated with sleep disturbances, and the correlation between sleep disturbances and quality of life (QoL) in adults with steady-state bronchiectasis.One hundred and forty-four bronchiectasis patients and eighty healthy subjects were enrolled. Sleep disturbances, daytime sleepiness, and QoL were measured by utilizing the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and St. George Respiratory Questionnaire (SGRQ), respectively. Demographic, clinical indices, radiology, spirometry, bacteriology, anxiety and depression were also assessed.	Adults with steady-state bronchiectasis had a higher prevalence of sleep disturbances (PSQI>5) (57% vs. 29%, P<0.001), but not daytime sleepiness (ESS≥10) (32% vs. 30%, P = 0.76), compared with healthy subjects. In the multivariate model, determinants associated with sleep disturbances in bronchiectasis patients included depression (OR, 10.09; 95% CI, 3.46-29.37; P<0.001), nocturnal cough (OR, 1.89; 95% CI, 1.13-3.18; P = 0.016), aging (OR, 1.04; 95% CI, 1.01-1.07; P = 0.009) and increased 24-hour sputum volume (OR, 2.01; 95% CI, 1.22-3.33; P = 0.006). Patients with sleep disturbances had more significantly impaired QoL affecting all domains than those without. Only 6.2% of patients reported using a sleep medication at least weekly.	In adults with steady-state bronchiectasis, sleep disturbances are more common than in healthy subjects and are related to poorer QoL. Determinants associated with sleep disturbances include depression, aging, nighttime cough and increased sputum volume. Assessment and intervention of sleep disturbances are warranted and may improve QoL.	
25036609	Major depressive disorder (MDD) is a debilitating disease with symptoms like persistent depressed mood and sleep disturbances. The prefrontal cortex (PFC) has been implicated as an important structure in the neural circuitry of MDD, with pronounced abnormalities in blood flow and metabolic activity in PFC subregions, including the subgenual cingulate cortex (sgACC, or Brodmann area 25). In addition, deep brain stimulation in the sgACC has recently been shown to alleviate treatment-resistant depression. Depressed patients also show characteristic changes in sleep: insomnia, increased rapid-eye-movement (REM) sleep and shortened REM sleep latency. We hypothesized that sleep changes and depressive behavior may be a consequence of the abnormal PFC activity in MDD. The rat ventromedial PFC (vmPFC, prelimbic and infralimbic cortices) is considered to be the homolog of the human sgACC, so we examined the effect of excitotic lesions in the vmPFC on sleep-wake and depressive behavior. We also made lesions in the adjacent dorsal region (dmPFC) to compare the effect of this similar but distinct mPFC region. We found that both dmPFC and vmPFC lesions led to increased REM sleep, but only vmPFC-lesioned animals displayed increased sleep fragmentation, shortened REM latency and increased immobility in the forced swim test. Anatomic tracing suggests that the mPFC projects to the pontine REM-off neurons that interact with REM-on neurons in the dorsal pons. These results support our hypothesis that neuronal loss in the rat vmPFC resembles several characteristics of MDD and may be a critical area for modulating both mood and sleep. 
25035888	The review of the literature on sleep disorders in epilepsy over the last two decades is presented. Paroxysmal phenomena of epileptic origin, nonepileptic paroxysms, antiepileptic drugs, polypragmasia and comorbid depression may affect sleep in epilepsy.Shortening of sleep time may cause seizures, hallucinations and depression because sleep plays an important role in the regulation of excitatory and inhibitory processes in the brain both in healthy people and in patients with epilepsy. According to the literature data, drugs (short treatment courses of hypnotics) or nonpharmacological methods should be used for treatment insomnia inpatients with epilepsy.
25035883	The article reviews the literature on some nonmotor symptoms. Sections of the paper are devoted to depression, anxiety, apathy, cognitive dysfunction, psychotic signs, sleep disorders, pain, olfactory disorders.
25034185	The aim of this study was to investigate and describe frequency and characteristics of sleep disorders in a large cohort of community dwelling persons with several degrees and typologies of cognitive disorders. 236 patients (78 men and 158 women) were enrolled with different subtypes of dementia: Alzheimer's disease (AD), vascular dementia (VaD), mixed dementia, mild cognitive impairment (MCI), dementia with Lewy bodies (DLB), parkinson's disease dementia (PDD), and frontotemporal lobar degeneration (FTLD), respectively. The sleep disturbances evaluated were: insomnia, excessive daytime sleepiness (EDS), REM behavior disorder (RBD), restless legs syndrome (RLS), and nightmares. Every type of sleep disorder was present in each type of dementia but with significant differences. Insomnia is found to be more present and specific for AD; EDS was associated with the presence of dementia in the elderly with LBD or PDD; RLS and nightmares that were recognized mainly in FTD, LBD, and PDD patients scores; patients with MCI had a frequency of sleep disturbances of any type equal to that of patients with AD presenting mostly insomnia, nightmares or RLS more frequently; nightmares were more frequent among LBD and PDD patients. Frequency of RDB was more frequent in FTD, AD, and VaD. Our findings demonstrate that sleep disturbance was related to dementia. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. 

25033790	As the boundaries of harvesting wind energy expand to meet the ever-increasing societal energy demands, the number and size of wind turbines being constructed rises. As part of a larger project to monitor sound in an operating wind park in western New York State, a cross-sectional survey was conducted among individuals living in and around the wind park to characterize the perception, level of annoyance, and self-reported health effects of residents. We conducted the study in a 126 MW wind park consisting of 84 turbines spanning approximately 19 square miles of farmland. Short-term outdoor and indoor sound level measurements were also performed at each dwelling in which a questionnaire was administered. To our knowledge, this study is the first to collect sound measurements at individual residences. There was no apparent exposure-response relationship between an individual's level of annoyance and the short duration sound measurements collected at the time of the survey. There was a correlation between an individual's concern regarding health effects and the prevalence of sleep disturbance and stress among the study population. The siting process is unique to each community with varying degrees of success. Additional sound level measurements inside and outside homes in larger cohorts in concert with detailed questionnaires would be useful in verifying those exposure-response relationships found in studies using calculated sound level data. Additional research should include a detailed investigation of sleep patterns and possible disturbance in those living in and near operating wind turbine projects. 
25033784	Women sleep differently and report differently about sleep disturbances than men. However, it is unclear whether the sleep of women and men is affected differently by traffic noise exposure. We aimed to address gender specific noise effects by using objective and subjective exposure measures as well as objective and subjective outcome data. In a questionnaire survey conducted in 2008 including 733 women and 533 men from Basel, Switzerland, with follow-up 1 year later, we collected data on subjective sleep disturbances and annoyance to road traffic noise. Objective noise exposure data was obtained using validated propagation models. In a nested diary study with 119 participants, objective sleep efficiency and sleep duration was measured by means of actigraphic devices for 1551 nights. Data were analyzed using random intercept mixed-effects multilevel regression models adjusted for relevant confounding factors. Objectively measured sleep duration in highly exposed men (>55 dB) was reduced by 1.5 h (95% confidence interval [CI]: 2.3-0.8 h) compared with low exposed men (<30 dB). No noise effect on sleep duration was observed in women. The association of modeled noise exposure with self-reported sleep quality rating was also more pronounced in men (-0.8 unit, 95% CI: -1.4 to -0.2) than in women (-0.3 unit, 95% CI: -0.8 to 0.2). However, in highly annoyed women reduction in sleep quality and well-being rating tended to be stronger than in highly annoyed men. Our study provides some indications that noise exposure affects men's sleep differently than women's sleep, which may have distinct long-term health consequences. 
25032501	Sleep and wake are fundamental behavioral states whose molecular regulation remains mysterious. Brain states and body functions change dramatically between sleep and wake, are regulated by circadian and homeostatic processes, and depend on the nutritional and emotional condition of the animal. Sleep-wake transitions require the coordination of several brain regions and engage multiple neurochemical systems, including neuropeptides. Neuropeptides serve two main functions in sleep-wake regulation. First, they represent physiological states such as energy level or stress in response to environmental and internal stimuli. Second, neuropeptides excite or inhibit their target neurons to induce, stabilize, or switch between sleep-wake states. Thus, neuropeptides integrate physiological subsystems such as circadian time, previous neuron usage, energy homeostasis, and stress and growth status to generate appropriate sleep-wake behaviors. We review the roles of more than 20 neuropeptides in sleep and wake to lay the foundation for future studies uncovering the mechanisms that underlie the initiation, maintenance, and exit of sleep and wake states. 
25030802	Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic, has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse.The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys.	Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003-0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25-75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14-16 days) quetiapine treatment (25-250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥80 % cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study.	Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases in cocaine choice, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity.	These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse.	
25029874	Atrial fibrillation (AF) is the most common arrhythmia that affects the quality of life by causing deleterious health consequences, and impairing sleep quality. The severity of AF symptoms may range from very mild to the very intense which can be assessed by the European Heart Rhythm Association (EHRA) score. The aim of the study was to assess the prevalence of poor sleep quality in AF patients, in relation to the symptom severity based on the EHRA score.177 consecutive patients, hospitalized between 2011 and 2013 with non-valvular AF and no history of myocardial infarction, stroke or decompensation of heart failure within the last 6 months, were enrolled into the study. Sleep quality was assessed by the Pittsburg Sleep Quality Index (PSQI) in all patients at admission. Medical history and data concerning AF symptoms and severity by the EHRA score were gathered by a qualified physician.	Poor sleep quality was present in 49.7% of patients. Patients with poor sleep quality were more often females (66.6% vs. 35.8%; P = 0.007), were older (57.9 +/- 10.1 vs. 53.9 +/- 10.0 years; P = 0.005), and had higher systolic blood pressures (134.4 +/- 16.4 vs. 129.8 +/- 17.8 mmHg; P = 0.03). Poor sleep quality was present in 33.3% of the EHRA I group, 43.9% of the EHRA II group, 58.1% of the EHRA III group, and 61.5% of the EHRA IV group (p value for trend 0.01).	Poor sleep quality is highly prevalent in AF patients, affecting approximately half of them. It is related to the severity of symptoms, and prevalence rises with every degree of the EHRA score.	
25027730	This study aims to evaluate the sleep conditions in fibromyalgia syndrome and the influence of the temporomandibular disorders (TMDs) and fibromyalgia association in self-reported sleep quality.Forty female patients with fibromyalgia (FMS) were compared with 40 healthy women [control group (CG)]. Three questionnaires were used (i.e. RDC/TMD to diagnose TMD and to determine pain intensity and disability and Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) to assess sleep conditions). Statistical analyses were performed using the Wilcoxon-Mann-Whitney test to ordinal variables, Student's t-test to obtain the quantitative total scores of PSQI and chronic pain classification, Spearman's rho to determine the correlation between facial pain and quality sleep, and Fisher's exact test for other variables.	A moderate correlation between facial pain intensity and low sleep quality was found (rho = 0·56; P<0·0001); however, TMD and FMS association did not show worse sleep quality (P>0·05). Excessive daytime sleepiness was more prevalent in FMS (37·5%; P<0·0001) besides having the worst sleep quality (PSQI = 12·72) compared with CG (PSQI = 4·62).	Fibromyalgia patients experience intense facial pain in addition to poor sleep and high disabilities. TMD and FMS association do not appear to worsen this condition; however, facial pain intensity was correlated with low sleep quality.	
25027545	The aim of this study was to determine changes in overnight respiratory function and craniofacial and pharyngeal airway morphology following orthognathic surgery. The subjects were 40 patients in whom mandibular prognathism was corrected by orthognathic surgery: a one-jaw operation in 22 patients and a two-jaw operation in 18 patients. Morphological changes were studied using cone beam computed tomography immediately before surgery and at more than 6 months after surgery, and the apnoea-hypopnoea index (AHI) was measured with a portable polysomnography system. Pharyngeal airway volume was decreased significantly after surgery, especially in the one-jaw operation group. AHI was not changed significantly after surgery in either group, although AHI in one patient in the one-jaw operation group was increased to 19 events/h. There was no significant change in pharyngeal airway morphology in that patient, but he was obesity class 1 and was 54 years old. In conclusion, some patients who are obese, have a large amount of mandibular setback, and/or are of relatively advanced age may develop sleep-disordered breathing after mandibular setback; a two-jaw operation should therefore be considered in skeletal class III patients who have such risks because it decreases the amount of pharyngeal airway space reduction caused by mandibular setback surgery. 
25025716	With an estimated 70 million Americans suffering, sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many clinical research studies. Sleep is now also considered to be an important environmental and behavioral factor associated with the process of inflammation and the immune system. Increased sleepiness is considered part of the acute phase of response to tissue injury, and sleep loss activates inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α. Clinical studies in many immune-mediated diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis, have revealed an association of sleep disturbances with disease activity. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. The importance of sleep in inflammatory bowel disease has recently gained attention with some published studies demonstrating the association of sleep disturbances with disease activity, subclinical inflammation, and risk of disease relapse. A comprehensive review of sleep physiology and its association with the immune system is provided here. Experimental and clinical studies exploring this relationship in inflammatory bowel disease are reviewed, and the clinical implications of this relationship and future directions for research are also discussed.
25024659	Physical inactivity is linked to health outcomes such as obesity, diabetes, and psychiatric disorders. Sleep disturbance has been linked to the same adverse outcomes. We examine the influence of sleep on physical activity as a novel approach to understand these relationships. Specifically, our objective was to determine whether low sleep quality predicts low physical activity in posttraumatic stress disorder (PTSD), a disorder associated with sleep disturbance, physical inactivity, and poor health outcomes.We used data from the Mind Your Heart Study, a prospective cohort study of 736 outpatients recruited from two Department of Veterans Affairs (VA) medical centers. We assessed PTSD with the Clinician Administered PTSD Scale, sleep quality using an item from the Pittsburgh Sleep Quality Index, and physical activity by self-report at baseline and again one year later. Hierarchical multiple regression models and structural equation modeling were used to examine the relationships among PTSD, sleep, and physical activity.	Sleep quality but not PTSD status was prospectively associated with lower physical activity in a model adjusting for age, sex, apnea probability, depression, body mass index, and baseline physical activity (β = 0.129, SE = 0.072, p < 0.01). Structural equation modeling indicated that the results were consistent with sleep quality statistically mediating the relationship between PTSD status at baseline and physical activity one year later.	Worse sleep quality predicts lower physical activity in PTSD, providing possible evidence for a behavioral pathway from disturbed sleep to poor physical health outcomes.	
25024651	Elevated plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been associated with increased adverse health outcomes. The aim of this study was to investigate the association of sleep duration with risk of elevated hs-CRP levels in Taiwanese adults.We examined the association between sleep duration and hs-CRP in 353 healthy adults recruited from the physical examination center at a regional hospital in southern Taiwan. Elevated hs-CRP was defined as a plasma level ≥ 0.20 mg/dL. Short sleep duration was defined as ≤ 5.5 h per day. Multiple logistic regression analysis was used to assess the association of short duration of sleep with elevated hs-CRP levels.	In this study, short duration of sleep (odds ratio [OR] = 2.20; 95% confidence interval [CI]: 1.11-4.30), aged 70 years or older (OR = 4.58; 95% CI: 1.70-12.66), menopause (OR = 2.81; 95% CI: 1.52-5.3), higher heart rate (OR = 1.38; 95% CI: 1.10-1.75), higher body mass index (OR = 1.20; 95% CI: 1.09-1.34), higher white blood cell count (OR = 1.38; 95% CI: 1.14-1.66), and higher uric acid level (OR = 1.31; 95% CI: 1.06-1.63) were significantly associated with an increased risk of elevated hs-CRP levels.	In this study of healthy Taiwanese adults, short duration of sleep was significantly associated with elevated hs-CRP levels. Activation of pro-inflammatory pathways might represent a mechanism by which short sleep duration affects health.	
25024647	We report on a unique experiment designed to investigate the impact of prehistoric living conditions on sleep-wake behavior.A group of five healthy adults were assessed during life in a Stone Age-like settlement over two months.	The most notable finding was that nocturnal time in bed and estimated sleep time, as measured by actigraphy, markedly increased during the experimental period compared to the periods prior to and following the experiment. These increases were primarily driven by a phase-advance shift of sleep onset. Subjective assessments of health and functioning did not reveal any relevant changes across the study.	Our observations provide further evidence for the long-held belief that the absence of modern living conditions is associated with an earlier sleep phase and prolonged sleep duration.	A commentary on this article appears in this issue on page 723.	
25022986	To determine the role of health status and social support in the relationship between job stress and sleep disturbance, for both intermittent and chronic sleep disturbance.A total of 1946 mid-life adults completed three questionnaires spanning an 8-year time frame. Sleep disturbance was assessed at each time point, and participants were classified as experiencing intermittent, chronic or no sleep disturbance across this 8-year period. Independent variables included a range of job stress measures, social support, physical and mental health, and demographic characteristics.	After controlling for physical and mental health, perceived lack of job marketability increased risk of intermittent sleep disturbance (odds ratio (OR)=1.33, p=0.012). No other job stress measures were associated with either intermittent or chronic sleep disturbance after adjusting for years of education, social support, and employment status. Poorer mental and physical health status, although significantly increasing odds for intermittent sleep disturbance, represented a significantly greater increase in the odds for chronic sleep disturbance over and above intermittent disturbance (OR=0.96, p<0.001 for both SF-12 mental and physical health).	This population-based cohort study found little evidence that job stress had an independent effect on chronic or intermittent sleep disturbance independent of health, social support, and education. Risk profiles for intermittent and chronic sleep disturbance did not differ with regard to job stress; however, various demographic and social support factors were distinguishing factors. Health status, both physical and mental, also showed a significantly greater impact on chronic sleep disturbance than intermittent sleep disturbance. Karasek's model of job strain had little value in predicting sleep disturbance outcomes.	
25022743	To assess the effectiveness of a weighted-blanket intervention in treating severe sleep problems in children with autism spectrum disorder (ASD).This phase III trial was a randomized, placebo-controlled crossover design. Participants were aged between 5 years and 16 years 10 months, with a confirmed ASD diagnosis and severe sleep problems, refractory to community-based interventions. The interventions were either a commercially available weighted blanket or otherwise identical usual weight blanket (control), introduced at bedtime; each was used for a 2-week period before crossover to the other blanket. Primary outcome was total sleep time (TST) recorded by actigraphy over each 2-week period. Secondary outcomes included actigraphically recorded sleep-onset latency, sleep efficiency, assessments of child behavior, family functioning, and adverse events. Sleep was also measured by using parent-report diaries.	Seventy-three children were randomized and analysis conducted on 67 children who completed the study. Using objective measures, the weighted blanket, compared with the control blanket, did not increase TST as measured by actigraphy and adjusted for baseline TST. There were no group differences in any other objective or subjective measure of sleep, including behavioral outcomes. On subjective preference measures, parents and children favored the weighted blanket.	The use of a weighted blanket did not help children with ASD sleep for a longer period of time, fall asleep significantly faster, or wake less often. However, the weighted blanket was favored by children and parents, and blankets were well tolerated over this period.	
25022734	Sleep disturbance is common in patients with atopic dermatitis (AD). However, studies have largely been questionnaire-based, and the pathophysiology remains unclear. The aims of this study were to determine objective characteristics of sleep disturbance in children with AD and explore contributing factors and clinical predictors.Sleep parameters were measured by actigraphy and polysomnography in 72 patients with AD and 32 controls ages 1 to 18 years. Urinary 6-sulfatoxymelatonin levels, serum cytokines, and total and allergen-specific immunoglobulin E (IgE) levels were also measured.	The patients with AD had significantly reduced sleep efficiency, longer sleep onset latency, more sleep fragmentation, and less nonrapid eye movement sleep. Results from actigraphy correlated well with those from polysomnography. The AD disease severity was associated with sleep disturbance (r = 0.55-0.7), and a Scoring Atopic Dermatitis index of ≥48.7 predicted poor sleep efficiency with a sensitivity of 83.3% and a specificity of 75% (area under the curve = 0.81, P = .001). Lower nocturnal melatonin secretion was significantly associated with sleep disturbance in the patients with AD. Other correlates of sleep disturbance included pruritus, scratching movements, higher total serum IgE levels, and allergic sensitization to dust mite and staphylococcal enterotoxins.	Poor sleep efficiency is common in children with AD and can be predicted by the Scoring Atopic Dermatitis index. Melatonin and IgE might play a role in the sleep disturbance. Further studies are required to explore the mechanisms and clinical implications, and actigraphy could serve as a useful evaluating tool.	
25020156	Although marital separation and divorce are associated with many negative health outcomes, few studies examine the psychophysiological mechanisms that may give rise to these outcomes. This study examined changes in resting blood pressure (BP) as a function of sleep complaints in recently divorced adults.Recently separated adults (n = 138; 38 men) completed a self-report measure of sleep complaints and a resting blood pressure (BP) assessment in the laboratory at three occasions across 7.5 months.	Multilevel analyses revealed that although sleep complaints were not associated with concurrent BP, sleep complaints predicted significant increases in both systolic and diastolic BP at the subsequent laboratory visit. In addition, time since the separation from an ex-partner moderated the association between sleep complaints at baseline and resting systolic blood pressure (SBP) 3 months later. People who reported high sleep complaints 10 weeks or more after their separation demonstrated greater increases in SBP.	In recently separated adults, greater sleep complaints may index increased risk for future increases in BP. This work helps pinpoint one potential mechanistic pathway linking marital separation with an important, health-relevant biological outcome.	
25018625	Maintaining a stable and adequate sleeping pattern is associated with good health and disease prevention. As a restorative process, sleep is important for supporting immune function and aiding the body in healing and recovery. Aging is associated with characteristic changes to sleep quantity and quality, which make it more difficult to adjust sleep-wake rhythms to changing environmental conditions. Sleep disturbance and abnormal sleep-wake cycles are commonly reported in seriously ill older patients in the intensive care unit (ICU). A combination of intrinsic and extrinsic factors appears to contribute to these disruptions. Little is known regarding the effect that sleep disturbance has on health status in the oldest of old (80+), a group, who with diminishing physiological reserve and increasing prevalence of frailty, is at a greater risk of adverse health outcomes, such as cognitive decline and mortality. Here we review how sleep is altered in the ICU, with particular attention to older patients, especially those aged ≥80 years. Further work is required to understand what impact sleep disturbance has on frailty levels and poor outcomes in older critically ill patients. 
25018024	The co-effect of asthma and obstructive sleep apnea (OSA) on sleep quality among children remained unclear.To compare sleep quality and emotional/behavioral problems among asthmatic and non-asthmatic children with or without moderate to severe obstructive sleep apnea.	An AHI-range-matched BMI-range-matched cross-sectional design was used to examine polysomnographic evaluation and emotional/behavioral problems in 102 non-obese children aged between 6 and 12 years old, categorized as with or without asthma and sleep disordered breathing.	Asthmatic children in AHI ≤ 5/h group revealed a significantly longer sleep latency, a greater leg movement index (LMI), and a lower ratio of slow wave sleep compared with non-asthmatic AHI ≤ 5/h group. Compared with non-asthmatic AHI > 5/h group, asthmatic children displayed a higher ratio of REM sleep, sleep stage 1 and 2, a lower ratio of slow wave sleep, as well as a greater respiratory arousal index and LMI. There was no significant difference in emotional/behavior problems among groups.	Sleep disturbance exists in asthmatic children with or without moderate to severe obstructive sleep apnea. Non-obese asthmatic children had less slow wave sleep compared with non-asthmatic children. We might recommend that sleep quality could be noticed and evaluated in children with asthma.	
25017741	The aim of this study is to estimate the prevalence of nocturnal sleeping problems and its associated factors among university students in mainly low- and middle-income countries.A cross-sectional survey was conducted with 20,222 undergraduate university students (mean age, 20.8; SD = 2.8) from 27 universities in 26 countries across Asia, Africa and the Americas.	Overall, 10.4% reported severe or extreme nocturnal sleeping problems (male, 10.2%; female, 10.5%) in the past month. Noctural sleeping problems differed by country, from 32.9% in Indonesia to 3.0 % in Thailand among Asian countries, from 13.7% in Mauritius to 7.5% in South Africa, and from 11.8% in Jamaica to 6.1% in Columbia in the Americas. In multivariate logistic regression analysis, coming from a poor family background, staying off campus (on their own or with parents or guardians), stress (history of child sexual abuse), poor mental health (depression and PTSD symptoms), health risk behaviour (tobacco use, heavy internet use, gambling, skipping breakfast and having sustained an injury), lack of social support and poor academic performance were associated with nocturnal sleeping problems.	A significant prevalence of past-month nocturnal sleeping problems was found. Potential factors associated with the risk of reporting sleeping complaints were identified, which may assist in prevention strategies to promote a better quality of sleep.	
25017715	To review controlled clinical trials of traditional Chinese medicine (TCM) therapies for hot flushes and at least one other co-occurring symptom among sleep, cognitive function, mood, and pain.An experienced reference librarian performed an extensive search of PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for randomized, controlled trials reported in English between 2004 and July 2011. Of 1193 abstracts identified, 58 trials examined effectiveness of therapies for hot flushes and at least one additional co-occurring symptom.	Eleven trials (13 publications) examined TCM therapeutics of acupuncture, Chinese herbal medicine (CHM) or moxibustion. Acupuncture trials (eight) yielded mixed results; five trials significantly reduced hot flushes. Of those five trials, one also showed benefit for sleep and pain and two trials found benefit for mood symptoms. Of three CHM trials, three trials had significant findings: one for hot flushes and mood, one for hot flushes and pain, and one for hot flushes, sleep, mood symptoms and pain. Moxibustion and counseling (one trial) significantly reduced hot flushes, mood symptoms and pain. None of the trials reported any serious adverse events.	TCM therapeutics of acupuncture, CHM and moxibustion show promising results for the treatment of mood and pain symptoms co-occurring with hot flushes. Although the controlled clinical trials of TCM therapeutics reviewed here measured multiple symptom outcomes, few report treatment effects in ways that allow clinicians to consider symptom clusters when prescribing therapies. Future studies need to measure and report results for individual symptoms or group like symptoms together into subscales. Controlled clinical trials with larger numbers of participants are essential to allow evaluation of these therapies on hot flushes and multiple co-occurring symptoms.	
25017455	Sleep disturbance is a common experience in fibromyalgia (FM). The field lacks a sleep specific patient reported outcome (PRO) measure developed and validated in a FM population. The study objective is to gain an in-depth understanding of sleep in FM and to develop a PRO measure of it.Research involved the following stages: 1) A literature review conducted to identify key concepts associated with FM patient experience of sleep and PRO measures that have been used to assess this; 2) Qualitative interviews with therapeutic area experts; 3) Focus groups with FM patients who experienced sleep disturbance; 4) Development of a conceptual framework and the Fibromyalgia Sleep Diary (FMSD); and 5) Cognitive interviews with patients to explore content validity of the FMSD.	The literature review and expert interviews supported sleep disturbance being an important aspect of the FM patient experience, and underscored the need for a new FM specific sleep PRO measure. Results from the focus groups demonstrated that FM patients experience sleep disturbances that they attribute to their FM symptoms, such as pain and stiffness, confirming the importance of understanding more about sleep changes. Aspects of sleep raised by FM patients included poor sleep quality and insufficient quantity including difficulty with falling asleep, getting comfortable, and staying asleep; restlessness; light sleep; not feeling rested upon awakening; and difficulty starting the day. Cognitive interview results showed that the 8-item FMSD, developed to reflect the concepts identified above, was relevant to FM patients with content that was interpreted as intended.	The FMSD was developed in line with the recommendations of the FDA PRO guidance and ISPOR PRO Task Force. The qualitative evidence generated thus far strongly supports the content validity of the FMSD as a PRO measure of sleep disturbance in FM populations. Psychometric evaluation of the FMSD to demonstrate reliability, validity and sensitivity to change is recommended as a next step.	
25011661	Various studies have linked the occurrence of cardiovascular events and low ambient temperatures as well as the morning blood pressure surge (MBPS). We hypothesized that low ambient temperatures produce a higher sympathetic change during the last rapid eye movement (REM) sleep transition and that this may play an important role in cold-related cardiovascular events.All experiments were carried out on 12 healthy male adults, aged 24.00±0.74 years, who participated in two experimental conditions randomly (>1 day apart): warm (23 °C) and cold (16°C). Blood pressure (BP) was measured every 30 min for 24 h by autonomic ambulatory BP monitoring. The electroencephalograms, electrocardiograms, ambient temperature, near-body temperature, and physical activity were recorded by miniature polysomnography for 24 h.	The cold conditions resulted in: (i) higher MBPS than under warm conditions; (ii) significant and greater sympathetic index changes during the sleep-wake transition than during cover-to-uncover and supine-to-sit position tests; (iii) the non-REM-REM transition-related sympathetic elevation during the cold conditions being significantly higher in late sleep period than in early sleep period; (iv) at 1h prior to morning awakening, the value of total power of heart rate variability changes being significantly negatively correlated with the changes of near-body temperature; and (v) significantly higher arousal index and shorter average interval of REM periods than in warm conditions.	Cold exposure elevates the amplitude of MBPS and is associated with late sleep stage transition sympathetic activation, which might have important implications for cold-related cardiovascular events.	
25010602	Poor sleep quality is common in chronic obstructive pulmonary disease (COPD). It is associated with poor quality of life. Pulmonary rehabilitation (PR) improves quality of life, exercise capacity, and anxiety and depression. Its effect on sleep quality is uncertain.To determine whether PR improves sleep quality in COPD.	A prospective controlled 'before and after' study of sleep quality in COPD patients attending a community PR programme was conducted. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Lung function, disease-specific quality of life (COPD assessment test--CAT), exercise capacity (incremental shuttle walk test--ISWT), and anxiety and depression (Hospital Anxiety and Depression Scale--HADS) were measured. Change in sleep quality was compared with a COPD control group.	Twenty-eight participants completed PR. The control group comprised 24 patients. Prevalence of poor sleep quality (PSQI ≥5) was 78%. There were no differences between observation and control groups in sleep quality, age or severity. Quality of life was strongly correlated with quality of sleep (r=0.64, P<0.001). PR improved the quality of life (CAT change 3.0; 95% CI, 0.7-5.3), exercise capacity (ISWT change (metres) 81.0; 15.3-146.6), anxiety (HADS score ≥8: change 2.33; 0.45-4.22), and depression (HADS score ≥8: change 2.90; 1.92-3.88). PR did not improve sleep quality (PSQI mean change 0.79; -0.35 to 1.93).	PR did not improve sleep quality in COPD despite improving quality of life, exercise capacity, anxiety and depression. New strategies, independent of PR, are required to improve sleep quality in COPD.	
25010217	Depression in pediatric inflammatory bowel disease is increasingly recognized to be a heterogeneous condition with diverse underlying predisposing and precipitating factors. Although there is a growing awareness regarding the benefits of integrating behavioral health into medical care, the way psychiatric treatments can best target different aspects of depression and related dysfunction has not been systematically explored.This review discusses neurobiological risk factors for depression in inflammatory bowel disease including inflammation, associated anti-inflammatory treatment with corticosteroids, pain, and sleep disturbance, as well as psychosocial factors including reactions to illness, illness perception, and disease and environmental stressors with an emphasis on how these factors can influence treatment decisions. Empirically supported psychosocial and psychopharmacological interventions are discussed within this context.	Understanding the diverse pathways that can lead to depression in youths with inflammatory bowel disease can lead to the development of more targeted interventions and better integration of psychosocial care into the medical treatment of inflammatory bowel disease.	
25009494	Some individuals are able to successfully reach very old ages, reflecting higher adaptation against age-associated effects. Sleep is one of the processes deeply affected by aging; however few studies evaluating sleep in long-lived individuals (aged over 85) have been reported to date. The aim of this study was to characterize the sleep patterns and biochemical profile of oldest old individuals (N = 10, age 85-105 years old) and compare them to young adults (N = 15, age 20-30 years old) and older adults (N = 13, age 60-70 years old). All subjects underwent full-night polysomnography, 1-week of actigraphic recording and peripheral blood collection. Sleep electroencephalogram spectral analysis was also performed. The oldest old individuals showed lower sleep efficiency and REM sleep when compared to the older adults, while stage N3 percentage and delta power were similar across the groups. Oldest old individuals maintained strictly regular sleep-wake schedules and also presented higher HDL-cholesterol and lower triglyceride levels than older adults. The present study revealed novel data regarding specific sleep patterns and maintenance of slow wave sleep in the oldest old group. Taken together with the favorable lipid profile, these results contribute with evidence to the importance of sleep and lipid metabolism regulation in the maintenance of longevity in humans. 
25008095	Rotator cuff tears are a common cause of shoulder pain. There is an absence of information about symptomatic rotator cuffs from the patients' perspective; this limits the information clinicians can share with patients and the information that patients can access via sources such as the internet. This study describes the experiences of people with a symptomatic rotator cuff, their symptoms, the impact upon their daily lives and the coping strategies utilised by study participants.An interpretive phenomenological analysis approach was used. 20 participants of the UKUFF trial (The United Kingdom Rotator Cuff Surgery Trial) agreed to participate in in-depth semi-structured interviews about their experiences about living with a symptomatic rotator cuff tear. Interviews were digitally recorded and fully transcribed. Field notes, memos and a reflexive diary were used. Data was coded in accordance with interpretive phenomenological analysis. Peer review, code-recode audits and constant comparison of data, codes and categories occurred throughout.	The majority of patients described intense pain and severely disturbed sleep. Limited movement and reduced muscle strength were described by some participants. The predominantly adverse impact that a symptomatic rotator cuff tear had upon activities of daily living, leisure activities and occupation was described. The emotional and financial impact and impact upon caring roles were detailed. Coping strategies included attempting to carry on as normally as possible, accepting their condition, using their other arm, using analgesics, aids and adaptions.	Clinicians need to appreciate and understand the intensity and shocking nature of pain that may be experienced by participants with known rotator cuff tears and understand the detrimental impact tears can have upon all areas of patient's lives. Clinicians also need to be aware of the potential emotional impact caused by cuff tears and to ensure that patients needing help for conditions such as depression are speedily identified and provided with support, explanation and appropriate treatment.	
25005596	To study whether job strain, that is, psychological job demands and decision latitude, and sleep disturbances among persons with occasional neck/shoulder/arm pain (NSAP) are prognostic factors for having experienced at least one episode of troublesome NSAP, and to determine whether sleep disturbances modify the association between job strain and troublesome NSAP.Prospective cohort study.	Stockholm, Sweden.	A population-based cohort of individuals with occasional NSAP (n=6979) who answered surveys in 2006 and 2010.	Report of at least one episode of troublesome NSAP in 2010.	The ORs for troublesome NSAP at follow-up were in individuals exposed to passive jobs 1.2 (95% CI 0.9 to 1.4); to active jobs 1.3 (95% CI 1.1 to 1.5); to high strain 1.5 (95% CI 1.0 to 2.4); to mild sleep disturbances 1.4 (95% CI 1.3 to 1.6) and to severe sleep disturbances 2.2 (95% CI 1.6 to 3.0). High strain and active jobs were associated with having experienced at least one episode of troublesome NSAP during the previous 6 months in persons with sleep disturbances, but not in individuals without sleep disturbances.	Our results indicate that high strain, active jobs and sleep disturbances are prognostic factors that should be taken into account when implementing preventive measures to minimise the risk of troublesome NSAP among people of working age. We suggest that sleep disturbances may modify the association between high strain and troublesome NSAP.	
25003919	To determine the relation between the degrees of chronic pain and drowsiness levels.The study was conducted with 115 patients, who answered the questionnaire as diagnostic criteria in the survey. After evaluation based on the protocol of chronic pain registry RDC/TMD- Axis II, the Epworth Sleepiness Scale was applied to assess drowsiness levels.	Among the participating patients, there were more females (80%), and the type of pain more prevalent was chronic (70.4%). Concerning the grades of chronic pain, grade II predominated (38.3%), corresponding to high pain intensity and low disability. The ratio observed for levels of sleepiness was more prevalent for sleep debt average (38.3%).	The grades of chronic pain and the levels of sleepiness did not correlate with each other or with the gender of patients.	
25003859	Sleep disruption is an emergent military health issue, but remarkably little is known of its prevalence or comorbidities in the combat zone. This study was designed to quantify the prevalence and mental health correlates of sleep disruption among military personnel serving within a ground combat zone during Operation Enduring Freedom. This was a large, cross-sectional survey of active duty and reserve U.S. Navy personnel (N = 3,175). Self-reported sleep measures included total hours of sleep per day, total hours of sleep required to feel well-rested, difficulty falling asleep, and difficulty staying asleep. The survey also measured mental health symptoms, including post-traumatic stress symptoms, anxiety, and depression. Participants reported an average of 5.9 hours of sleep per day despite requiring on average 6.8 hours to feel well rested. More than half (56%) were classified as sleep deficient, and 67% reported 6 or fewer hours of sleep per day. Adjusted for covariates, individuals endorsing sleep disruption were at substantially elevated risk of meeting criteria for post-traumatic stress disorder, generalized anxiety disorder, and major depressive disorder. This study documents the prevalence of sleep disruption in a very large and difficult-to-access sample of military members serving in a combat zone, and details robust associations with mental health. 
25003651	A great body of research indicates that eveningness is associated with negative psychological outcomes, including depressive and anxiety symptoms, behavioral dyscontrol and different health impairing behaviors. Impaired subjective sleep quality, increased circadian misalignment and daytime sleepiness were also reported in evening-type individuals in comparison with morning-types. Although sleep problems were consistently reported to be associated with poor psychological functioning, the effects of sleep disruption on the relationship between eveningness preference and negative emotionality have scarcely been investigated. Here, based on questionnaire data of 756 individuals (25.5% males, age range = 18-43 years, mean = 25.3 ± 5.8 years), as well as of the evening-type (N = 211) and morning-type (N = 189) subgroups, we examined the relationship among sleep problems, eveningness and negative emotionality. Subjects completed the Hungarian Version of the Horne and Östberg Morningness-Eveningness Questionnaire (MEQ-14), The Athen Insomnia Scale (AIS) and the Epworth Sleepiness Scale (ESS). Moreover, a composite score of Negative Emotionality (NE) was computed based on the scores of the Short Beck Depression Inventory (BDI-9), the Perceived Stress Scale (PSS-4) and the General Health Questionnaire (GHQ-12). Morning and evening circadian misalignment was calculated based on the difference between preferred and real wake- and bedtimes. Two possible models were tested, hypothesizing that sleep problems (circadian misalignment, insomniac symptoms and daytime sleepiness) moderate or mediate the association between eveningness and negative emotionality. Eveningness preference was correlated with increased NE and increased AIS, ESS and circadian misalignment scores. Our results indicate that eveningness-preference is an independent risk factor for higher negative emotionality regardless of the effects of age, gender, circadian misalignment and sleep complaints. Nevertheless, while chronotype explained ∼6%, sleep problems (AIS and ESS) accounted for a much larger proportion (∼28%) of the variance of NE. We did not find a significant effect of interaction (moderation) between chronotype and sleep problems. In contrast, insomniac symptoms (AIS) emerged as a partial mediator between chronotype and NE. These findings argue against the assumption that indicators of mental health problems in evening-type individuals can be explained exclusively on the basis of disturbed sleep. Nevertheless, negative psychological outcomes seem to be partially attributable to increased severity of insomniac complaints in evening-types. 
25003649	We aimed to examine the reliability and validity of the Japanese version of the Children's ChronoType Questionnaire (CCTQ) in preschool children. The CCTQ consists of 16 items on sleep-wake parameters for scheduled and free days, a 10-item of the Morningness/Eveningness Scale (CCTQ-M/E), and a single item on chronotype. Out of 502 children aged 3-6 years living in Okayama Prefecture, we evaluated 346 (188 boys and 158 girls) between May and June 2012. Their parents filled out the questionnaires two times at an interval of two weeks. Cronbach's α of the CCTQ-M/E was 0.77. For test-retest reliability, Pearson's correlation coefficient of the CCTQ-M/E between the two observations was 0.898 (p<0.001). Kruskal-Wallis test with post-hoc tests was used to compare sleep-wake parameters measured with the CCTQ among the three groups of children, morning (M)-type, neither (N)-type and evening (E)-type, who were classified according to the CCTQ-M/E score. Sleep-wake parameters in timing were significantly different among the children with M-type, N-type and E-type (p<0.001). Post-hoc pairwise comparisons revealed that sleep-wake parameters in timing were significantly delayed from the M-type to the N-type children (p<0.001), from the M-type to the E-type children (p<0.001), and from the N-type to the E-type children (p<0.001), except that wake-up time and get-up time were not significantly different between the children with N-type and E-type on scheduled days when their start time was regularly fixed. Out of these 346 children, we evaluated 72 (35 boys and 37 girls) to see the correlations between subjectively and objectively measured sleep-wake parameters from June to October 2012. Spearman's correlation coefficients between sleep-wake parameters measured with the CCTQ and an actigraph were 0.512-0.836 on scheduled days (p<0.001) and 0.380-0.786 on free days (p<0.001). Based on these findings we conclude that the Japanese version of the CCTQ is a reliable and valid measure for assessing chronotypes in preschool children.
25002838	The question of how structurally and pharmacologically diverse general anesthetics disrupt consciousness has persisted since the nineteenth century. There has traditionally been a significant focus on "bottom-up" mechanisms of anesthetic action, in terms of sensory processing, arousal systems, and structural scales. However, recent evidence suggests that the neural mechanisms of anesthetic-induced unconsciousness may involve a "top-down" process, which parallels current perspectives on the neurobiology of conscious experience itself. This article considers various arguments for top-down mechanisms of anesthetic-induced unconsciousness, with a focus on sensory processing and sleep-wake networks. Furthermore, recent theoretical work is discussed to highlight the possibility that top-down explanations may be causally sufficient, even assuming critical bottom-up events. 
25002497	Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics approach. Here we have used untargeted and targeted liquid chromatography (LC)/MS metabolomics to examine the effect of acute sleep deprivation on plasma metabolite rhythms. Twelve healthy young male subjects remained in controlled laboratory conditions with respect to environmental light, sleep, meals, and posture during a 24-h wake/sleep cycle, followed by 24 h of wakefulness. Two-hourly plasma samples collected over the 48 h period were analyzed by LC/MS. Principal component analysis revealed a clear time of day variation with a significant cosine fit during the wake/sleep cycle and during 24 h of wakefulness in untargeted and targeted analysis. Of 171 metabolites quantified, daily rhythms were observed in the majority (n = 109), with 78 of these maintaining their rhythmicity during 24 h of wakefulness, most with reduced amplitude (n = 66). During sleep deprivation, 27 metabolites (tryptophan, serotonin, taurine, 8 acylcarnitines, 13 glycerophospholipids, and 3 sphingolipids) exhibited significantly increased levels compared with during sleep. The increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of acute sleep deprivation and deserve further study. This report, to our knowledge the first of metabolic profiling during sleep and sleep deprivation and characterization of 24 h rhythms under these conditions, offers a novel view of human sleep/wake regulation. 


24999989	Poor sleep quality has been observed in individuals with substance use disorders and is often a trigger for relapse. To date, little research has investigated sleep quality among individuals with prescription opioid (PO) dependence. The present study aimed to address this gap in the literature by examining subjective and objective sleep disturbances among PO dependent individuals.Subjects were 68 non-treatment seeking individuals (33 PO dependent, 35 healthy controls). Subjective sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). Subjects were admitted for an overnight inpatient hospital stay during which objective sleep data was collected using an actigraphy device. Self-report pain was measured with the Brief Pain Inventory.	Significant group differences in subjective sleep quality were revealed in the PSQI (p<0.01) and ISI (p<0.01). Poor sleep quality (i.e., PSQI total score>5) was identified in 80.6% of the PO group, as compared to 8.8% of the control group (p<.001). Significant group differences in sleep quality were identified in five of six actigraphy variables: total time asleep, sleep efficiency, latency of onset of sleep, total time awake and time mobile. Furthermore, significant associations between pain severity and sleep quality were observed.	Results indicate high rates of sleep impairment and poor sleep quality among PO dependent individuals. Pain severity was significantly correlated with sleep quality. Although preliminary, the findings highlight the importance of assessing and treating sleep disturbances, as well as pain, among patients with PO dependence.	
24998016	Depressive disorder is frequently accompanied by changes in psychomotor activity and disturbances of the sleep-wake cycle. The chronobiological effects of electroconvulsive therapy (ECT) in patients with treatment-resistant depression (TRD) are largely unknown. The objective of the current study was to measure the influence of ECT on patients' activity and sleep. 15 patients with unipolar TRD were treated with ECT. Activity levels were measured with wrist actigraphy before and after ECT. Remission rate (score on the 17-item Hamilton Depression Rating Scale lower than 8 points) was 40.0%. Remitters had increases of 56.0% on light activity, 49.8% on total activity, and 70.2% on circadian amplitude, while there was no significant change of these variables in subjects who did not experience remission. The circadian acrophase and actigraphic sleep-parameters were not significantly affected by treatment. 
24997846	Amplitude integrated electroencephalogaphy (aEEG) is becoming an important tool for the assessment of cerebral activity in preterm newborns. Describing the relationship between early aEEG patterns and intraventricular hemorrhage (IVH) can improve our knowledge of neurological injury in the preterm newborn. The aim of this prospective study was to identify early changes in the aEEG in premature newborns that could be associated to severe neurological lesion/death. Preterm newborns with a birth weight ≤1,500 g and/or 32 weeks of gestation were included. aEEG monitoring was performed during the first 72 h of life. A qualitative analysis of the aEEG recordings was performed, based on continuity, sleep-wake cycles (SWCs), inferior lower margin amplitude (LMA), and bandwidth (BW). Key outcomes were severe IVH and/or death. Ninety-two subjects were included (mean gestational age 28 weeks). In 28.6 % of subjects with HIV III/IHP, a low-voltage pattern was observed. A statistically significant relationship was found between low-voltage tracings and death and neurological lesion/death. Absent SWCs during the first 72 h were also related to death.Early aEEG patterns can be predictive of neurological outcome in the preterm newborn. Low-voltage tracing and absence of SWCs are associated with severe neurological lesions/death.	
24996194	Stimulation of the protease-activated receptor 1 (PAR1) in vitro, was shown to induce synaptic retrograde signaling through the endocannabinoid 2-arachidonoylglycerol (2-AG) synthesis and activation of the cannabinoid receptor type 1 (CB1R). The activation of PAR1 by the agonist S1820 in the lateral hypothalamus (LH) increases rapid eye movement sleep (REMS) and food intake in rats, and both effects are prevented by the CB1R inverse agonist AM251. In the present study, we implanted rats with electrodes and with cannulae aimed bilaterally to the LH. We administered tetrahydrolipstatin (THL), an inhibitor of the diacylglycerol lipase (DAGL), the enzyme responsible for 2-AG synthesis, to evaluate the sleep-wake cycle and food ingestion. THL in the LH readily prevented the increase in REMS and food intake induced by PAR1 stimulation, further supporting 2-AG as an upstream activator of PAR1. Our results demonstrate that the effect of PAR1 on REMS and food intake is blocked by the inhibition of DAGL, further suggesting that PAR1 stimulation in the lateral hypothalamus of rats induces an increase in sleep and food intake through 2-AG. 
24995450	This paper is based on Dr Morrison's presentation at the St Andrews Day Festival Symposium held at the Royal College of Physicians on 29 November 2014. In this case, as discussed at the Symposium, the patient has presented with 'tired all the time', one of the most common complaints seen by GPs and one which can be linked to a number of physical and psychological causes. Dr Morrison assesses whether Neurology is the most appropriate place for this patient.
24994918	Cognitive impairment is a common complaint among cancer survivors and may be a consequence of the tumors themselves or direct effects of cancer-related treatment (eg, chemotherapy, endocrine therapy, radiation). For some survivors, symptoms persist over the long term and, when more severe, can impact quality of life and function. This section of the NCCN Guidelines for Survivorship provides assessment, evaluation, and management recommendations for cognitive dysfunction in survivors. Nonpharmacologic interventions (eg, instruction in coping strategies; management of distress, pain, sleep disturbances, and fatigue; occupational therapy) are recommended, with pharmacologic interventions as a last line of therapy in survivors for whom other interventions have been insufficient. 
24993935	Sleep is an essential component for athlete recovery due to its physiological and psychological restorative effects, yet few studies have explored the habitual sleep/wake behaviour of elite athletes. The aims of the present study were to investigate the habitual sleep/wake behaviour of elite athletes, and to compare the differences in sleep between athletes from individual and team sports. A total of 124 (104 male, 20 female) elite athletes (mean ± s: age 22.2 ± 3.0 years) from five individual sports and four team sports participated in this study. Participants' sleep/wake behaviour was assessed using self-report sleep diaries and wrist activity monitors for a minimum of seven nights (range 7-28 nights) during a typical training phase. Mixed-effects analyses of variances were conducted to compare the differences in the sleep/wake behaviour of athletes from two sport types (i.e. individual and team). Overall, this sample of athletes went to bed at 22:59 ± 1.3, woke up at 07:15 ± 1.2 and obtained 6.8 ± 1.1 h of sleep per night. Athletes from individual sports went to bed earlier, woke up earlier and obtained less sleep (individual vs team; 6.5 vs 7.0 h) than athletes from team sports. These data indicate that athletes obtain well below the recommended 8 h of sleep per night, with shorter sleep durations existing among athletes from individual sports.
24993832	In light of the high prevalence of sleep disorders in patients suffering from posttraumatic stress disorder (PTSD), this study sought to compare the effect of prazosin and hydroxyzine on sleep quality in this patient group.A total of 100 patients suffering from PTSD were assessed (mean age = 35.51 years, SD = 6.41; 28% females). Next, they were randomly assigned to one of three treatment groups: prazosin (33 patients), hydroxyzine (34 patients) or placebo (33 patients). The trial lasted for 8 weeks. The patients' sleep quality was assessed using the Pittsburgh Sleep Quality Index. Items taken from the Mini International Neuropsychiatric Interview were used to operationalize PTSD.	Compared to controls, patients treated with prazosin and hydroxyzine reported improved sleep and less nightmares. Improvement was greatest in patients treated with prazosin compared to hydroxyzine and placebo. Improvement in sleep was associated with an amelioration of their PTSD symptoms.	Both prazosin and hydroxyzine can be used to treat psychopharmacological sleep disorders and nightmares in patients suffering from PTSD, also leading to reductions in PTSD symptoms.	
24993561	Sleep problems are prevalent among older adults, often persist untreated, and are predictive of health detriments. Given the limitations of conventional treatments, non-pharmacological treatments such as mindfulness-based interventions (MBIs) are gaining popularity for sleep ailments. However, nothing is yet known about the impact of MBIs on sleep in older adults with prodromal sleep disturbances. This article details the design and methodology of a 6-week parallel-group RCT calibrated to test the treatment effect of the Mindful Awareness Practices (MAPs) program versus sleep hygiene education for improving sleep quality, as the main outcome, in older adults with prodromal sleep disturbances. Older adults with current sleep disturbances will be recruited from the urban Los Angeles community. Participants will be randomized into two standardized treatment conditions, MAPs and sleep hygiene education. Each condition will consist of weekly 2-hour group-based classes over the course of the 6-week intervention. The primary objective of this study is to determine if mindfulness meditation practice as engaged through the MAPs program leads to improved sleep quality relative to sleep hygiene education in older adults with prodromal sleep disturbances. 
24993077	to describe the levels of mobility in older cancer patients receiving palliative care in Korea, and to examine the associations of their mobility with lifestyle factors (sleep disturbance, physical activity) and physical symptoms (pain, fatigue).In this cross-sectional descriptive study, 91 older cancer patients receiving palliative care were interviewed using a semi-structured survey questionnaire. Mobility was measured using the 6MWT. Physical activity behavior was measured using the classification of the ACSM. Sleep disturbance was assessed using the frequency sub-category of the SHQ. Both pain and fatigue were measured using a VAS.	The mean 6MWT distance was 220.38 m. Participants in their 60 s, 70 s, and 80 s walked, on average, 260.93 m, 205.31 m, and 157.05 m, respectively. Approximately 73% of the participants engaged in regular physical activity. Those engaged in regular physical activity were significantly more mobile than those who were not (t = 2.44; p = .017). Higher levels of mobility were correlated with lower levels of sleep disturbance (r = -.37), fatigue (r = -.23), and pain (r = -.27). Significant predictors for mobility included levels of sleep disturbance, medication status, age, number of family members and monthly income, accounting for 34.7% of the variance in mobility.	Korean cancer patients have relatively low levels of mobility. Cancer patients aged over 80 years are a vulnerable group at risk for impaired mobility. Older palliative care patients are more active than one might expect. Levels of mobility are inversely associated with pain, fatigue, and sleep-related symptoms.	
24992089	Delayed sleep phase syndrome (DSPS) comprises a persistent or recurrent pattern of sleep disturbances, sleep disruption that leads to insomnia and/or excessive daytime sleepiness, and impaired functioning in social, occupational, or other spheres. Aripiprazole (APZ), a second-generation antipsychotic, manifests a novel mechanism of action by serving as a partial agonist of both D2 and serotonergic 5-HT1A receptors and antagonist of 5-HT2A receptors. We have used APZ to treat DSPS. One reason it was effective may be that the insomnia induced by daytime APZ was effective in treating the patient's daytime sleepiness. Another reason may be APZ increases histamine release which controls sleep-wake cycles. Thus, APZ may be therapeutic for DSPS. 
24991933	Sleep-disturbed breathing (SDB) is common in patients with precapillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB in patients with PH, and NOT improves exercise capacity. We investigated the effect of NOT and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in patients with PH and SDB.In a randomized, placebo-controlled, double-blind, crossover trial, 23 patients with arterial (n = 16) or chronic thromboembolic PH (n = 7) and SDB defined as a mean nocturnal oxygen saturation < 90% or dips (> 3%) > 10/h with daytime Pao2 ≥ 7.3 kPa were studied. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo each during 1 week separated by a 1-week washout period. Three-lead ECG was recorded during overnight polysomnography at the end of each treatment period. Repolarization indices were averaged over three cardiac cycles at late evening and at early morning, and nocturnal arrhythmias were counted.	NOT was associated with a lower overnight (68 ± 10 beats/min vs 72 ± 9 beats/min, P = .010) and early morning heart rate compared with placebo. At late evening, the heart rate-adjusted PQ time was increased under acetazolamide compared with placebo (mean difference, 10 milliseconds; 95% CI, 0-20 milliseconds; P = .042). In the morning under NOT, the heart rate-adjusted QT (QTc) interval was decreased compared with placebo (mean difference, -25 milliseconds; 95% CI, -45 to -6 milliseconds; P = .007), and the interval between the peak and the end of the T wave on the ECG was shorter compared with acetazolamide (mean difference, -11 milliseconds; 95% CI, -21 to -1 milliseconds; P = .028). Arrhythmias were rare and similar with all treatments.	In patients with PH with SDB, NOT reduces nocturnal heart rate and QTc in the morning, thus, favorably modifying prognostic markers.	ClinicalTrials.gov; No.: NTC-01427192; URL: www.clinicaltrials.gov.	
24990308	Sleep problems are an under-emphasized cause of disability in Parkinson's disease (PD). Difficult sleep maintenance (light and fragmented sleep) and difficulties in initiating sleep are often the earliest and the most frequent symptoms observed in PD patients. In fluctuating patients, nocturnal akinesia, dystonia, painful cramps, and parasomnias may aggravate nocturnal problems. Treatment of sleep problems can be complex and challenging for the physicians. Dopaminergic treatment may improve some of the nocturnal symptoms in PD. In this paper, the effect of drugs and technique that ensure a more continuous delivery of dopaminergic drugs on sleep problems in PD is reviewed. 
24989251	Disrupted sleep may be a prodromal symptom or a predictor of depressive disorders. In this study we investigated the relationship between depression symptoms and disrupted sleep using a novel model of stress-mimicked sleep disorders in rats.SD rats were injected with corticosterone (10, 20 or 40 mg/kg, sc) or vehicle for 7 d. Their sleep-wake behavior was monitored through implanted EEG and EMG electrodes. Their depressive behaviors were assessed using forced swim test, open field test and sucrose preference test.	The corticosterone-treated rats showed significantly reduced sleep time, disinhibition of rapid-eye-movement (REM) sleep and altered power spectra during non-REM sleep. All depressive behavioral tests did not show significant difference across the groups. However, individual correlation analysis revealed statistically significance: the immobility time (despair) was negatively correlated with REM sleep latency, slow wave sleep (SWS) time ratio, SWS bouts and delta power density, and it was positively correlated with REM sleep bouts and beta power density. Meanwhile, sucrose preference (anhedonia) was positively correlated with total sleep time and light sleep bouts, and it was negatively correlated with the REM sleep time ratio.	In stress-mimicked rats, sleep disturbances are a predictor of depressive disorders, and certain symptoms of depression may be related to the disruption of several specific sleep parameters.	
24988965	To study the effect of melatonin (melaxen) on sleep disorders in patients with mild cranial-brain injury (CBI) in the early rehabilitation period.Sixty patients were randomized to equal groups treated or not treated with melaxen. Along with neurological and somatic examination, polysomnography and scales for measurement depression and quality of life ( ESS, BDI, EuroQol etc) were used.	Melatonin improved sleep (sleep latency, number of wakings per night etc) and decreased the severity of depression in the early rehabilitation period after mild CBI. Further research is needed to fully understand the effect of melatonin on sleep disorders in CBI, in particular in its later stages.	
24988606	Relaxin-3, a member of the relaxin peptide family, was discovered in 2001 as a homologue of relaxin--a well-known reproductive hormone. However, it is the brain which turned out to be a major expression site of this newly discovered peptide. Both its molecular structure and expression pattern were shown to be very conserved among vertebrates. Extensive research carried out since the discovery of relaxin-3 contributed to the significant progress in our knowledge regarding this neuropeptide. The endogenous relaxin-3 receptor (RXFP3) was identified and the anatomy of the yet uncharacterized mammalian brain system was described, with nucleus incertus as the main center of relaxin-3 expression. Not only its diffusive projections throughout the whole brain, which reach various brain structures such as the hippocampus, septum, intergeniculate leaflet or amygdala, but also functional studies of the relaxin-3/RXFP3 signaling system, allowed this brain network to be classified as one of the ascending nonspecific brain systems. Thus far, research depicts the connection of relaxin-3 with phenomena such as feeding behavior, spatial memory, sleep/wake cycle or modulation of pituitary gland hormone secretion. Responsiveness of relaxin-3 neurons to stress factors and the strong orexigenic effect exerted by this peptide suggest its participation in modulation of feeding by stress, in particular of the chronic type. The discovery of relaxin-3 opened a new research field which will contribute to our better understanding of the neurobiological basis of feeding disorders.
24988149	To determine the sensitivity, specificity and the positive and negative predictive value of taking a detailed sleep history for making the diagnosis of psychophysiological insomnia.Retrospective case file study.	We examined 767 patients referred to the Amsterdam Centre for Sleep and Wake Disorders, and who underwent polysomnography for the first time between 1 January and 31 December 2010. We compared the probable diagnosis made following history-taking with the final diagnosis made after polysomnography. In this we differentiated between organic and non-organic insomnia. The sensitivity, specificity, positive and negative predictive values of the sleep history were calculated.	In 24.8% of the 303 patients whose histories did not indicate organic insomnia, polysomnography showed there to be an organic cause. Primary causes were obstructive sleep apnoea (13.2%), upper airway resistance syndrome (5.4%), and periodic limb movement disorder (4.0%) or a combination of these. In the histories of 464 patients there were indications that the insomnia had an organic cause and in 325 of them this was confirmed by polysomnography. The sensitivity of detailed history taking to psychophysiological insomnia was 62.1%, the specificity 81.3%, the positive predictive value was 75.2% and the negative predictive value was 70.0%. In patients under the age of 40 with a score on the Epworth sleepiness scale < 10 (i.e. no hypersomnolence), a BMI < 25 kg/m2 and indications of psychophysiological insomnia, organic insomnia could not be demonstrated, with the exception of one parasomnia.	History-taking only meant that the organic cause was missed in a substantial percentage of patients with insomnia, in particular in older patients with hypersomnolence and a high BMI.	
24986287	To investigate the indications for conducting polysomnography studies and their outcomes.Retrospective analysis of pediatric polysomnography studies performed over a four-year period (2009-2012).	425 diagnostic studies and 100 non-invasive positive-pressure ventilation titration studies were conducted. Of these, 389 were performed in male children. Obstructive sleep apnea was the most common diagnosis; 49.6% (211 studies). Other diagnoses included central apnea, narcolepsy, and periodic limb movement disorder. Night time symptoms (snoring, frequent night awakenings, restless sleep) were present in 294 children, and 161 children had daytime symptoms (excessive daytime sleepiness, early morning fatigue, poor concentration at school). 13 studies (2.5%) were inadequate for analysis, reflecting the challenges of conducting studies in children.	Dedicated pediatric sleep laboratories with properly trained staff are important to minimize failure rates and diagnose these conditions accurately.	
24985316	To examine whether allostatic load (AL), a measure of cumulative physiologic dysregulation across biological systems, was associated with sleep apnea, insomnia, and other sleep disturbances.Data from the National Health and Nutrition Examination Survey 2005-2008 were used. AL was measured using nine biomarkers representing cardiovascular, inflammatory, and metabolic system functioning. A total of 3330 US adults aged 18 years and older were included in this study.	The prevalence of high AL (AL score  ≥3) was the highest among African Americans (26.3%), followed by Hispanic Americans (20.3%), whites (17.7%), and other racial/ethnic group (13.8%). After adjustment for sociodemographic and lifestyle factors, high AL was significantly associated with sleep apnea (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.40-2.63), snoring (OR, 2.20; 95% CI, 1.79-2.69), snorting/stop breathing (OR, 2.16; 95% CI, 1.46-3.21), prolonged sleep latency (OR, 1.42; 95% CI, 1.08-1.88), short sleep duration (<6 hours) (OR, 1.35; 95% CI, 1.00-1.82), and diagnosed sleep disorder (OR, 2.26; 95% CI, 1.66-3.08). There was no clear evidence that observed associations varied by sociodemographic characteristics.	This study suggests significant associations of high AL with sleep apnea, sleep apnea symptoms, insomnia component, short sleep duration, and diagnosed sleep disorder among US adults.	

24983754	Typologies of sleep problems have usually relied on identifying underlying causes or symptom clusters. In this study the value of using the patient's own reasons for sleep disturbance are explored. Using secondary data analysis of a nationally representative psychiatric survey the patterning of the various reasons respondents provided for self-reported sleep problems were examined. Over two thirds (69.3%) of respondents could identify a specific reason for their sleep problem with worry (37.9%) and illness (20.1%) representing the most commonly reported reasons. And while women reported more sleep problems for almost every reason compared with men, the patterning of reasons by age showed marked variability. Sleep problem symptoms such as difficulty getting to sleep or waking early also showed variability by different reasons as did the association with major correlates such as worry, depression, anxiety and poor health. While prevalence surveys of 'insomnia' or 'poor sleep' often assume the identification of an underlying homogeneous construct there may be grounds for recognising the existence of different sleep problem types particularly in the context of the patient's perceived reason for the problem. 
24982613	The hypothalamus is the central regulator of a broad range of homeostatic and instinctive physiological processes, such as the sleep-wake cycle, food intake, and sexually dimorphic behaviors. These behaviors can be modified by various environmental and physiological cues, although the molecular and cellular mechanisms that mediate these effects remain poorly understood. Recently, it has become clear that both the juvenile and adult hypothalamus exhibit ongoing neurogenesis, which serve to modify homeostatic neural circuitry. In this report, we share new findings on the contributions of sex-specific and dietary factors to regulating neurogenesis in the hypothalamic mediobasal hypothalamus, a recently identified neurogenic niche. We report that high fat diet (HFD) selectively activates neurogenesis in the median eminence (ME) of young adult female but not male mice, and that focal irradiation of the ME in HFD-fed mice reduces weight gain in females but not males. These results suggest that some physiological effects of high fat diet are mediated by the stimulation of ME neurogenesis in a sexually dimorphic manner. We discuss these results in the context of recent advances in understanding the cellular and molecular mechanisms that regulate neurogenesis in postnatal and adult hypothalamus. 
24980065	Previous studies have suggested a propensity towards morningness in teenagers and adults born preterm. We set out to study sleep in a subsample from The Helsinki Study of Very Low Birth Weight Adults cohort, with emphasis on sleep timing, duration, and quality. We compared young adults who were born prematurely at very low birth weight (VLBW; <1500 g) with controls born at term.We measured sleep by actigraphy in young adults aged 21-29 years. A total of 75 individuals (40 VLBW and 35 controls) provided adequate data. Group differences in sleep parameters were analyzed using t-test and linear regression models.	VLBW adults woke up on average 40 min earlier [95% confidence interval (CI), 9-70] and reported 40 min earlier get up time (95% CI, 8-71) than did the controls. The difference remained after adjustment for confounders. We found no group difference in sleep duration or measures of sleep quality.	Our findings of earlier rising in the VLBW group are suggestive of an advanced sleep phase in that group. These results reinforce previous suggestions that chronotype may be programmed early during life.	
24978952	Community pharmacies may potentially assist in screening for chronic conditions such as sleep disorders, which remain both under-diagnosed and untreated. We aimed to compare a subjective risk-assessment-only questionnaire (RAO) for common sleep disorder screening against the same risk-assessment questionnaire plus a nasal flow monitor as an objective marker of possible underlying obstructive sleep apnea (OSA) (RA+) in a community pharmacy setting. The primary outcome was the number of participants identified in RAO or RA+ group who were likely to have and consequently be diagnosed with OSA. Further outcomes included the number of participants identified as being at risk for, referred for, taking-up referral for, and then diagnosed with OSA, insomnia, and/or restless legs syndrome (RLS) in either group.In a cluster-randomized trial, participants were recruited through 23 community pharmacies. Using validated instruments, 325 (RAO = 152, RA+ = 173) participants were screened for OSA, insomnia, and RLS.	218 (67%) participants were at risk of OSA, insomnia or RLS and these participants were referred to their primary physician. The proportion of screened participants identified as being at risk of OSA was significantly higher in the RA+ group (36% in RAO vs. 66% in RA+, OR 3.4, 95% CI (1.8-6.5), p<0.001). A 12-month follow-up was completed in 125 RAO and 155 RA+ participants. Actual referral uptake was 34% RAO, 26% RA+, OR 4.4, 95% CI (1.4-19.2), p = 0.31. The OSA diagnosis rate was higher in the RA+ arm (p = 0.01). To yield a single additional confirmed OSA diagnosis, 16 people would need to be screened using the RA+ protocol.	These results demonstrate that utilising either screening method is feasible in identifying individuals in the community pharmacy setting who are likely to have OSA, insomnia and/or RLS. Secondly, adding an objective marker of OSA to a questionnaire-based prediction tool resulted in more confirmed OSA diagnoses.	ACTR.org.au ACTRN12608000628347.	
24978619	Sleep disturbance may cause physical and psychological problems. The relationship between sleep disturbance and the burden of caregiving among family caregivers (FCs) has not previously been investigated.The purposes of this study were to (1) assess subjective and objective information on the sleep patterns of FCs of advanced cancer patients and (2) identify the components of caregiving burden that are risk factors for sleep disturbance among these FCs.	A prospective, cross-sectional study of 176 FCs was conducted. Subjective and objective tools measuring sleep quality and caregiver burden were used. A hierarchical regression model was applied to identify the predictive factors for sleep disturbance among FCs.	Approximately 72.2% of FCs experienced sleep disturbance. The major sleep disturbance was frequent "wake after sleep onset" to provide patient care; a nap during the day was necessary. Correlations were strong between caregiver burden and sleep quality. The final regression model, which included subjective and objective burden, predicted 56.6% of the variance in sleep disturbance.	Sleep disturbance was common in FCs of advanced cancer patient, and our results demonstrated the relationship between sleep disturbance and caregiving burden.	Family caregivers with risk factors for sleep disturbance should be identified and be provided resources for sleep quality improvement.	
24978368	This review highlights recent advances in premotor and nonmotor features in Parkinson's disease, focusing on these issues in the context of prodromal and early-stage Parkinson's disease.Although Parkinson's disease patients experience a wide range of nonmotor symptoms throughout the disease course, studies demonstrate that nonmotor features are not solely a late manifestation. Indeed, disturbances of smell, sleep, mood, and gastrointestinal function may herald Parkinson's disease or related synucleinopathies and precede these neurodegenerative conditions by 5 or more years. In addition, other nonmotor symptoms such as cognitive impairment are now recognized in incident or de-novo Parkinson's disease cohorts. Many of these nonmotor features reflect disturbances in nondopaminergic systems and early involvement of peripheral and central nervous systems, including olfactory, enteric, and brainstem neurons as in Braak's proposed pathological staging of Parkinson's disease. Current research focuses on identifying potential biomarkers that may detect persons at risk for Parkinson's disease and permit early intervention with neuroprotective or disease-modifying therapeutics.	Recent studies provide new insights into the frequency, pathophysiology, and importance of nonmotor features in Parkinson's disease as well as the recognition that these nonmotor symptoms occur in premotor, early, and later phases of Parkinson's disease.	
24978159	Sleep problems are common in patients with heart failure (HF) and might be associated with patient outcomes.The aim of this study was to describe the course of sleep problems in HF patients over 1 year and the association between sleep problems and rehospitalization.	Data from 499 HF patients (mean age, 70 years) were used in this analysis. Sleep problems were assessed with the item "Was your sleep restless" from the Center for Epidemiological Studies Depression Scale during hospitalization for HF (baseline) and after 1 year.	A total of 43% of patients (n = 215) reported sleep problems at baseline, and 21% of patients (n = 105), after 1 year. Among the 215 patients with problems with sleep at baseline, 30% (n = 65) continued to have sleep problems over time. Among the 284 patients without sleep problems at baseline, 14% (n = 40) reported sleep problems after 1 year. After adjustments for potential cofounders, patients with continued sleep problems had an almost 2-fold increased risk for all-cause hospitalizations (hazard ratio, 2.1; P = .002) and cardiovascular hospitalizations (hazard ratio, 2.2; P = .004).	One-third of HF patients with sleep problems at discharge experienced persistent sleep problems at follow-up. Continued sleep problems were associated with all-cause and cardiovascular rehospitalizations.	
24978151	To systematically review published articles for the prevalence of menopausal symptoms in Asian women.A comprehensive and systematic literature search was performed using MEDLINE, EMBASE, PsycINFO, CINAHL, SCOPUS and Google scholar in June 2013 to retrieve all English-language studies that included information on the prevalence of menopausal symptoms in women living in Asian countries. Risk of bias of included studies was assessed using a risk-of-bias tool explicitly designed for the systematic review of prevalence studies.	Twenty-three independent studies met our inclusion criteria. Physical symptoms were the most prevalent symptoms compared to psychological, vasomotor and sexual symptoms. There was a wide variation in the prevalence of all symptoms across the menopausal stages due to the differences in modes of recruitment, study design, sampling procedures, the time frame over which symptoms were assessed and use of different diagnostic or screening tools. A high level of bias was observed for both external and internal validity for most studies.	Although there is a wide variation in the reported prevalence of menopausal symptoms, physical symptoms predominate, followed by psychological symptoms, vasomotor symptoms and sexual symptoms. Further studies of representative samples are necessary to understand whether the variations in prevalence reporting are a function of methodological issues or due to ethnic, cultural or other socioeconomic differences.	
24977966	Sleep disorders are frequent and disturbing, mostly chronic conditions. Despite the fact practice of sleep medicine is a young field. Sleep disorders were reduced to insomnia and even insomnia was not well studied until 1960ies. This article maps amazing development of sleep disorders treatment from the beginning till current date. The text covers both scientific and clinical perspectives on most frequent sleep related disorders including insomnias, hypersomnias, parasomnias, sleep related movement and breathing disorders, restless legs syndrome and circadian rhythm sleep disorders.
24975344	Neurofibromatosis type 1 (NF1) is frequently associated with neurological disorders unrelated to neurofibromas, including sleep disorders.This article reviews the prevalence of sleep disorders in patients with NF1, compares rates to data reported in the literature, and analyses the relationship between cognitive disorder and attention deficit hyperactivity disorder (ADHD) in these patients.	Comparative retrospective study reviewing data collected between January 2010 and January 2012 from patients diagnosed with NF1 in a tertiary hospital.	We included 95 paediatric patients with NF1 who completed the Bruni Sleep Disturbance Scale in Children. The overall prevalence of sleep disorders was 6.3%, which was lower than in the general paediatric population. Patients with NF1 and ADHD had a higher prevalence of sleep onset and maintenance disorders (18% vs 6.3%), sleep-wake transition disorders (12.5% vs 6.3%), and daytime sleepiness (12.5% vs 7.9%); differences were not statistically significant. A statistically significant difference was found in the subdomain of nocturnal hyperhidrosis (21.9% vs 6.3%, P < 0.05). Patients with NF1 and IQ<85 showed higher prevalence rates of daytime sleepiness (20% vs 6.7%) and of sleep hyperhidrosis (11% vs 0%).	The prevalence of sleep disorders in our cohort of patients with NF1 was no higher than in the general paediatric population, although some of these disorders are more common in cases with cognitive disorders or ADHD.	
24974199	Sleep disturbance and psychopathology are common during adolescence and are highly prevalent in individuals diagnosed with autism spectrum disorder (ASD). The aim of this study was to investigate relationships between sleep disturbance, psychopathology symptoms, and daytime functioning in adolescents with high-functioning autism spectrum disorder (HFASD) compared to typically developing (TD) adolescents.Twenty-seven adolescents with HFASD and 27 age- and sex-matched TD adolescents completed questionnaires related to sleep, psychopathology and daytime functioning. Participants also completed a 7-day sleep/wake diary. A subsample of HFASD adolescents (55%) and all the TD adolescents wore an actigraphy monitor concurrently with the sleep diary.	Adolescents with HFASD had significantly higher scores for depressed mood, anxiety and pre-sleep arousal compared with TD adolescents and poorer daytime functioning. There were more significant correlations between sleep variables and psychopathology variables, and sleep variables and daytime functioning, in the HFASD group than in the TD group. Standard regression found that sleep variables significantly accounted for 57% of the variance in daytime functioning symptoms of insufficient sleep in the HFASD group, while psychopathology variables accounted for 63% of the variance in daytime functioning.	Both sleep disturbance and psychopathology are more prevalent in adolescents with HFASD and are major contributors to poor daytime functioning in these individuals.	
24974198	The relationship between epilepsy and sleep is bidirectional as seizures disrupt sleep and coexisting sleep disorders have detrimental effects on seizure control and quality of life for both the children and their families. Previous research has reported on sleep disturbance in children with epilepsy primarily by subjective parental reports. Actigraphy may provide a more accurate objective evaluation of sleep, but the validity of this sleep measure for children with epilepsy has not yet been assessed. The primary objective of this study was to validate the use of actigraphy as a tool in studying sleep patterns in children with epilepsy.This was a prospective study comparing sleep and wake epochs recorded for 24 h simultaneously by actigraphy and by continuous video-electroencephalography (VEEG) monitoring in 27 patients aged 2-18 years with medically refractory epilepsy.	Strong correlations were found between actigraphy and VEEG sleep variables including night sleep period (r = 0.99), night sleep time (r = 0.96), duration of night wake time (r = 0.93) and number of significant wakings during the night (r = 0.81).	The study results validate that actigraphy is a reliable and objective clinical and research tool for evaluating sleep and wakefulness in children with epilepsy.	
24973469	To analyze the interventions aimed at the practice of sleep hygiene, as well as their applicability and effectiveness in the clinical scenario, so that they may be used by pediatricians and family physicians for parental advice.A search of the PubMed database was performed using the following descriptors: sleep hygiene OR sleep education AND children or school-aged. In the LILACS and SciELO databases, the descriptors in Portuguese were: higiene E sono, educação E sono, educação E sono E crianças, e higiene E sono E infância, with no limitations of the publication period.	In total, ten articles were reviewed, in which the main objectives were to analyze the effectiveness of behavioral approaches and sleep hygiene techniques on children's sleep quality and parents' quality of life. The techniques used were one or more of the following: positive routines; controlled comforting and gradual extinction or sleep remodeling; as well as written diaries to monitor children's sleep patterns. All of the approaches yielded positive results.	Although behavioral approaches to pediatric sleep hygiene are easy to apply and adhere to, there have been very few studies evaluating the effectiveness of the available techniques. This review demonstrated that these methods are effective in providing sleep hygiene for children, thus reflecting on parents' improved quality of life. It is of utmost importance that pediatricians and family physicians are aware of such methods in order to adequately advise patients and their families.	
24973419	The existence of a correlation and/or comorbidity between sleep disorders and headache, related to common anatomical structures and neurochemical processes, has important implications for the treatment of both conditions.The high prevalence of certain sleep disorders in children with migraine and the fact that sleep is disrupted in these patients highlight the importance of a specific therapy targeted to improve both conditions.	The treatment of sleep disorders like insomnia, sleep apnea, sleep bruxism and restless legs syndrome, either with behavioral or pharmacological approach, often leads to an improvement of migraine. Drugs like serotoninergic and dopaminergic compounds are commonly used for sleep disorders and for migraine prophylaxis and treatment: Insomnia, sleep-wake transition disorders and migraine have been related to the serotonergic system abnormality; on the other hand prodromal symptoms of migraine (yawning, drowsiness, irritability, mood changes, hyperactivity) support a direct role for the dopaminergic system that is also involved in sleep-related movement disorders.	Our review of the literature revealed that, beside pharmacological treatment, child education and lifestyle modification including sleep hygiene could play a significant role in overall success of the treatment. Therefore comorbid sleep conditions should be always screened in children with migraine in order to improve patient management and to choose the most appropriate treatment.	
24973244	Although general adult population studies show a U-shaped association between sleep duration and mortality, prolonged rather than short sleep duration was more consistently associated with higher mortality in older populations. Failing health or frailty is a possible mechanism. Thus, we examined the relationship among sleep duration, frailty status, and mortality in an elderly cohort.A total of 3427 community-living adults 65 years or older were examined for general health, mood, subjective sleep measures (insomnia, napping, sleep apnea, nighttime sleep duration, sleep medications), frailty, and 5-year mortality.	After 5 years, 12.9% of men and 4.5% of women had died. Mean nighttime sleep duration was 7.3 hours. Proportion of participants who slept 10 or more hours increased with increasing frailty. Age-adjusted hazard ratio (HR) for 5-year mortality of long nighttime sleep (≥ 10 hours) was 2.10 (95% confidence interval [CI] 1.33-3.33) in men, and 2.70 (95% CI 0.98-7.46) in women. The HR in men was attenuated (HR 1.75; 95% CI 1.09-2.81) after adjustment for frailty and other covariates, whereas that of women strengthened (HR 2.88; 95% CI 1.01-8.18). Mortality increased sharply with nighttime sleep of 10 hours or more. Nighttime sleep of 10 or more hours (HR 1.75, men; HR 2.88, women) and frailty (HR 2.43, men; HR 2.08, P = .08 in women) were independently associated with 5-year mortality after full adjustment for covariates.	Frailty and long nighttime sleep duration of 10 or more hours were independently associated with 5-year mortality in older adults.	
24973019	What are the differences between the occurrence of menopausal symptoms in German women, migrant Chinese women in Germany and Chinese women in their native country? Can these potential discrepancies be explained by sociocultural differences? What are the differences in menopausal symptoms in connection with the consumption of soya?Cross-sectional study 2005-2008. Survey of three groups of women aged between 45 and 60 years (native German women in Berlin, migrant Chinese women in several German cities, Chinese women in Beijing) with an evaluated set of questionnaires surveying socio-demographic data, use of hormone therapy, migration/acculturation, MRS II and other areas.	A total of 2,109 questionnaires were sent out and a 41 % response rate was achieved, although this varied greatly across the three individual study groups. The results of the MRS II factor analysis were almost identical for German women and migrant Chinese women, but there were some differences in content compared to the Chinese study group. Chinese women surveyed in Beijing reported severe symptoms significantly less frequently in all three symptom groups (factors) of MRS II than the German women and the migrant Chinese women, but the values from the German women and migrant Chinese women surveyed are relatively similar. In all three study groups there are no significant differences in the stated severity of the symptoms, regardless of whether soya is consumed frequently or less frequently.	The question whether the differences found are solely cultural or migration-related must be examined in further studies. The special experiences and situation in life of migrant women should be taken into particular account by attending physicians during the care and treatment of women in this phase of life.	
24971530	Disordered circadian rhythms are associated with various psychiatric conditions and metabolic diseases. We recently established a mouse model of a psychophysiological stress-induced chronic sleep disorder (CSD) characterized by reduced amplitude of circadian wheel-running activity and sleep-wake cycles, sleep fragmentation and hyperphagia. Here, we evaluate day-night fluctuations in plasma concentrations of free amino acids (FAA), appetite hormones and prolactin as well as the hepatic expression of circadian clock-related genes in mice with CSD (CSD mice). Nocturnal increases in wheel-running activity and circadian rhythms of plasma prolactin concentrations were significantly disrupted in CSD mice. Hyperphagia with a decreased leptin/ghrelin ratio was found in CSD mice. Day-night fluctuations in plasma FAA contents were severely disrupted without affecting total FAA levels in CSD mice. Nocturnal increases in branched-chain amino acids such as Ile, Leu, and Val were further augmented in CSD mice, while daytime increases in Gly, Ala, Ser, Thr, Lys, Arg, His, Tyr, Met, Cys, Glu, and Asn were significantly attenuated. Importantly, the circadian expression of hepatic clock genes was completely unaffected in CSD mice. These findings suggest that circadian clock gene expression does not always reflect disordered behavior and sleep rhythms and that plasma FFA profiles could serve as a potential biomarker of circadian rhythm disorders. 
24970263	Although visual impairment is a well-recognized consequence of cataract development, little is known about the ability of the melanopsin-based photosensitive retinal ganglion cells (pRGCs) to regulate sleep-wake timing in the presence of cataract. In this study, we replaced a cataractous natural crystalline lens with two different types of artificial intraocular lenses, a UV-blocking lens or a blue-filtering lens. We investigated the level of sleep disturbance before cataract surgery and any change in sleep due to improved light transmission following surgery and compared this in both types of intraocular lens.Quality of sleep in 961 patients undergoing cataract surgery was assessed by administering the validated self-reported Pittsburgh Sleep Quality Index (PSQI) questionnaire. The PSQI distinguishes good sleepers from poor sleepers by scoring seven different sleep components over the last month, which are combined to produce an overall score for sleep quality. Patients received either an ultraviolet-blocking (UVB) clear intraocular lens (IOL) or a blue-filtering (BF) IOL. Questionnaires were completed four times: 1 month preoperatively and again 1, 6 (UVB-IOL only), and 12 months postoperatively.	Half of the patients reported poor sleep in the presence of cataract in both the UVB-IOL (mean PSQI = 6.35; SD = 3.82) and BF-IOL (mean PSQI = 6.39; SD = 4.04) groups. Cataract removal improved overall sleep quality significantly 1 month postoperatively in the UVB-IOL (mean PSQI = 5.89; SD = 3.71) and BF-IOL (mean PSQI = 6.08; SD = 3.88) groups. Sleep latency also improved for the UVB-IOL (preoperative mean = 1.16; SD = 1.003) and BF-IOL (preoperative mean = 1.17; SD = 1.03) groups at 1 month (UVB-IOL group mean = 1.01; SD = 0.923 and BF-IOL group mean = 1.00; SD = 0.95), which was sustained at 6 months for the UVB-IOL group (mean = 1.02; SD = 0.93) and 12 months for both the UVB-IOL and BF-IOL groups (6 months: UVB-IOL group mean = 0.96; SD = 0.92 and for the BF-IOL group mean = 0.99; SD = 0.96).	Overall sleep quality and sleep latency improves after removal of cataract irrespective of the type of IOL implanted. These data show that implantation of BF-IOL does not have a negative impact on the sleep-wake cycle.	
24969450	To explore the effect of occupational stress and effort-reward imbalance on sleep quality of people's police.A cluster sampling survey of sleep quality and occupational stress correlated factors was conducted on 287 police from a city public security bureau by questionnaires in May, 2011; the relationship between sleep quality and occupational stress correlated factors was analyzed by one-way ANOVA and multivariate non-conditional logistic regression using effort-reward imbalance model (ERI) and demand-control-support model (DCS). And the subjects were divided into high tension group and low tension group using the 1.0 of ERI and DCS coefficients as the boundary.	The sleep quality score of shift work police was higher than day work police (11.95 ± 6.54 vs 9.52 ± 6.43, t = 2.77, P < 0.05).In ERI model, the sleep quality score in high tension group was higher than low tension group (14.50 ± 6.41 vs 8.60 ± 5.53, t = -5.32, P < 0.01), and in DCS model, the sleep quality score in high tension group was also higher than low tension group (13.71 ± 6.62 vs 9.46 ± 6.04, t = -3.71, P < 0.01).For the regression analysis of ERI model as an argument, sex (OR = 3.0, 95%CI:1.16-7.73) , age for 30-39 years (OR = 3.48, 95%CI:1.32-9.16) , intrinsic effort (OR = 2.30, 95%CI:1.10-4.81) and daily hassles (OR = 2.15, 95%CI:1.06-4.33) were risk factors of low sleep quality, and reward (OR = 0.26, 95%CI:0.12-0.52) was the protective factor.For the regression analysis of DCS model as an argument , age for 30-39 years (OR = 2.55, 95%CI:1.02-6.37) , depressive symptom (OR = 2.10, 95%CI:1.14-3.89) and daily hassles (OR = 3.25, 95%CI:1.70-6.19) were risk factors of low sleep quality.While the ERI model and the DCS model were analyzed simultaneously, sex (OR = 3.03, 95%CI:1.15-7.98) , age for 30-39 years (OR = 3.71, 95%CI:1.38-9.98) and daily hassles (OR = 2.09, 95%CI:1.01-4.30) were the risk factors of low sleep quality, and reward (OR = 0.22, 95%CI:0.10-0.48) was the protective factor.	Occupational stress and effort-reward imbalance affected the sleep quality to people's policeman.	
24969249	To explore the symptom experience, coping strategies, and children's descriptions of their quality of life (QOL) after treatment for a brain tumor.An interpretive descriptive qualitative study.	A pediatric hospital setting in Ontario, Canada.	12 children aged 9-18 years.	Content analysis of semistructured interviews was guided by interpretive description methodology.	Children described symptoms including feeling tired, pain, headaches, emotional problems, difficulty thinking and remembering, problems with sleep, physical problems, and weight changes. Symptoms interfered with physical activity, keeping up with school, maintaining appearances, and communication. Coping strategies included reconditioning, taking breaks, taking medication, challenging themselves, volunteering, maintaining friendships, laughing, and using aids.	Survivors experienced multiple symptoms that had an effect on their life, but overall, they described good QOL.	Caregivers need to understand the complexity of their patient's symptom experience and its impact on his or her daily life. Coping strategies can be identified to help mitigate potentially negative QOL outcomes.	

24969187	Sleep complaints are common in hemodialysis (HD) patients. Sleep quality (SQ) is a predictor of quality of life and mortality risk in HD. The aim of this study was to examine factors that may have a role in SQ. In this cross-sectional analytic study, 138 end-stage renal disease patients receiving maintenance HD for >3 months were included. The Pittsburgh Sleep Quality Index (PSQI) was used to measure individual's SQ. Patients with a global PSQI score >5 were assumed as poor sleepers. Eighty-eight patients (64%) were classified as poor sleepers. Poor sleepers were older and more likely had diabetes. They had significantly higher serum ferritin and calcium levels and lower serum parathyroid hormone level (all P-values <0.05). The global PSQI score was positively correlated with age, serum calcium level and presence of diabetes as the underlying cause of renal failure. In the multi-variable binary regression model, presence of diabetes (Odds Ratio (OR) = 3.67, P = 0.008) and body pain (OR = 1.182, P = 0.014) were the significant independent predictors for poor SQ. Poor SQ was common among our HD patients, especially among diabetic cases and, therefore, there is a need to pay more attention to the care of this subgroup with regard to the diagnosis and management of sleep complaints. 
24969183	Poor sleep quality is a common problem that can potentially predict mortality risk and quality of life in hemodialysis (HD) patients. Also, inflammation is a common feature in HD patients. To determine sleep quality and its correlation with serum C-reactive protein (CRP) level in these patients, we studied 132 chronic HD patients in two university-affiliated teaching hospitals in Sari, Iran during September 2010. Pittsburgh Sleep Quality Index was employed to assess the sleep quality of the patients in addition to CRP, albumin, cholesterol, phosphorus and hemoglobin levels. There were 104 (78.7%) patients who suffered from poor sleep quality. A significant correlation was found between serum CRP level and the patients' sleep quality (P <0.05). There was also a significant correlation between sleep quality and serum phosphorus and albumin levels and body mass index (P <0.05). Furthermore, a significant positive correlation existed between the different components of sleep quality and CRP (P <0.05). We conclude that there is a correlation between decreased sleep quality in HD patients and elevated CRP levels, which may have therapeutic implications. 
24968229	Sleep-disordered breathing (SDB) is associated with adverse outcomes in patients with chronic heart failure (CHF). Additionally, heart rate turbulence (HRT) reflects changes in the sinus cycle length of baroreceptor in response to hemodynamic fluctuations after ventricular premature beat. Recent studies have suggested that HRT as a marker of vagal activity has a predictive value of poor prognosis in CHF patients. However, little is known about the relationship between SDB and HRT in CHF patients.In this study, 75 patients with CHF were enrolled. We simultaneously performed Holter ECG during a 24-hr period and portable sleep monitoring at nighttime, and determined the respiratory disturbance index (RDI), HRT (turbulence onset (TO) and turbulence slope (TS)) during that 24-hr period. These patients were divided into two groups based on the presence of severe SDB: Group A (RDI≥30, n = 17) and Group B (RDI<30, n = 58). TS was significantly lower in Group A than in Group B across the 24-hr period (nighttime: 3.6±1.1 vs. 6.9±1.3; daytime: 3.7±0.8 vs. 7.0±1.1; all-day: 3.5±0.7 vs. 6.7±0.9% ms/RR, P<0.05, respectively). TO did not differ between the two groups. Furthermore, there was a significant negative correlation between all-day TS and RDI (R = -0.257, P = 0.027). Moreover, in the multiple regression analysis, RDI was an independent factor to determine all-day TS.	In patients with severe SDB, blunted TS was observed across 24 hours. These results suggest that SDB induce impairment of vagal activity across a 24-hour period and may be associated with poor prognosis in CHF patients.	
24965830	Self-perceived mental fatigue is a common presenting symptom in many neurological diseases. Discriminating objective fatigability from self-perceived mental fatigue might facilitate neuropsychological diagnosis and treatment programs. However clinically valid neuropsychological instruments suitable for assessment of fatigability are still lacking. The prime aim of the study was to investigate aspects of cognitive fatigability and to identify properties of neuropsychological tests suitable to assess fatigability in patients with persistent cognitive complaints after mild brain injury. Another aim was to investigate whether cognitive fatigability captured by neuropsychological measures is influenced by depression or sleep disturbances.Twenty-four patients with persistent cognitive symptoms after mild traumatic brain injury (mTBI), (aged 18-51 years) and 31 healthy controls (aged 20-49 years) underwent neuropsychological testing measuring three cognitive fatigability domains: Attention fatigability was assessed using the Ruff 2 & 7 Selective Attention Test, executive fatigability using the Color Word Test (Stroop), and psychomotor fatigability using the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). Subjective fatigue was measured using the Fatigue Severity Scale and a questionnaire of everyday consequences of fatigue. Depression was screened using the Hospital Anxiety and Depression Scale and sleep disturbances using the Pittsburgh Sleep Quality Index.	The patients reported significantly more mental fatigue and performed worse on tests of psychomotor and executive fatigability than the healthy controls. Furthermore, the cognitive fatigability measures were not influenced by depression or sleep disturbances, as was the case in self-reported fatigue.	Tests demanding executive or simultaneous processing of several neuropsychological functions seem most sensitive in order to capture cognitive fatigability. Clinical tests that can capture fatigability enable a deeper understanding of how fatigability might contribute to cognitive complaints and problems in maintaining daily activities.	
24965582	To examine the evidence for adjunctive non-pharmacological interventions in the treatment of mania in an acute inpatient setting.A selective review of original and review papers was conducted. The electronic databases PsycINFO and PubMed were searched using the following MeSH terms: mania, mania treatment and inpatient.	Four studies were identified in the search for non-psychopharmacological interventions for mania that commenced in an inpatient setting: Interpersonal and Social Rhythm Therapy (IPSRT), Group Cognitive Behavioural Therapy (G-CBT), sensory room, and dark room therapy. Only two of these were designed exclusively for patients with bipolar disorder and the other two included these patients in a heterogeneous group of acute psychiatric inpatients.	Sleep and circadian regulation (Social Rhythm Therapy) that focuses on the establishment and maintenance of regular daily rhythms, particularly in relation to sleep-wake times, meal times and socialization, provides a potentially useful model for managing mania in the inpatient setting. However, there is an urgent need for further research into the effective treatment of mania.	
24965304	Evidence indicates that men and African Americans may be more susceptible to weight gain resulting from sleep loss than women and whites, respectively. Increased daily caloric intake is a major behavioral mechanism that underlies the relation between sleep loss and weight gain.We sought to assess sex and race differences in caloric intake, macronutrient intake, and meal timing during sleep restriction.	Forty-four healthy adults aged 21-50 y (mean ± SD: 32.7 ± 8.7 y; n = 21 women, n = 16 whites) completed an in-laboratory protocol that included 2 consecutive baseline nights [10 or 12 h time in bed (TIB)/night; 2200-0800 or 2200-1000] followed by 5 consecutive sleep-restriction nights (4 h TIB/night; 0400-0800). Caloric intake and meal-timing data were collected during the 2 d after baseline sleep and the first 3 d after sleep restriction.	During sleep restriction, subjects increased daily caloric intake (P < 0.001) and fat intake (P = 0.024), including obtaining more calories from condiments, desserts, and salty snacks (Ps < 0.05) and consumed 532.6 ± 295.6 cal during late-night hours (2200-0359). Relative to women, men consumed more daily calories during baseline and sleep restriction, exhibited a greater increase in caloric intake during sleep restriction (d = 0.62), and consumed a higher percentage of daily calories during late-night hours (d = 0.78, Ps < 0.05). African Americans and whites did not significantly differ in daily caloric intake, increased caloric intake during sleep restriction, or meal timing. However, African Americans consumed more carbohydrates, less protein, and more caffeine-free soda and juice than whites did during the study (Ps < 0.05).	Men may be more susceptible to weight gain during sleep loss than women due to a larger increase in daily caloric intake, particularly during late-night hours. These findings are relevant to the promotion of public health awareness by highlighting nutritional risk factors and modifiable behaviors for weight gain related to sleep-wake timing.	
24964253	Traumatic brain injury (TBI) involves diffuse axonal injury and induces subtle but persistent changes in brain tissue and function and poses challenges for early detection of neurological injury. The present study uses an automated behavioral analysis system to assess alterations in rodent behavior in the subacute phase in a preclinical mouse model of TBI, controlled cortical impact (CCI) injury. In the first few weeks following CCI, mice demonstrated normal exploratory behaviors and other typical home-cage behaviors. However, beginning 4 weeks post-injury, CCI mice developed disruptions in sleep-wake patterns, including an increased number of awakenings from sleep. Such impaired sleep maintenance was accompanied by an increased latency to reach peak sleep in CCI mice. These sleep disruptions implicate involvement of the thalamocortical network, the activity of which must be tightly regulated to control sleep maintenance. After injury, there was an increase in reactive microglia in thalamic regions as well as delayed reactive astrocytosis that was evident in the thalamic reticular nucleus, which preceded the development of sleep disruptions. These data suggest that cortical injury may trigger inflammatory responses in deeper neuroanatomical structures, including the thalamic reticular nucleus. Such engagement of the thalamus may perturb the thalamocortical network that regulates sleep/awake patterns and contribute to sleep disruptions observed in this model as well as those documented in patients with TBI.
24964250	To investigate the independent and interactive associations of physical activity (PA) and screen time (ST) with depression, anxiety and sleep quality among Chinese college students.A cross-sectional study was conducted in Wuhan University, China from November to December 2011. The students reported their PA, ST and socio-economic characteristics using self-administered questionnaires. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). Depression and anxiety were assessed using the Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS), respectively. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the independent and interactive relationships of PA and ST with depression, anxiety and sleep quality.	A total of 1106 freshmen (471 females and 635 males) aged 18.9±0.9 years were included in the study. After adjustment for potential confounders, high PA and low ST were independently associated with significantly lower risks for poor sleep quality (OR: 0.48, 95% CI: 0.30-0.78) and depression (OR: 0.67, 95%CI: 0.44-0.89), respectively. An interactive inverse association was observed for combined effects of PA and low ST on depression (OR: 0.62, 95%CI: 0.40-0.92) and sleep quality (OR: 0.51, 95%CI: 0.27-0.91). No statistically significant associations were found between PA, ST and anxiety among the participants.	These findings suggest an independent and interactive relationship of high PA and low ST with significantly reduced prevalence of depressive problems and favorable sleep quality among Chinese college freshmen.	

24962165	This review examines the relationship between anxiety disorders and sleep related problems (SRPs) in school-aged youth. Following an overview of normative sleep patterns and maturational sleep changes, the review addresses issues related to sleep measurement. SRPs are reviewed in relation to executive functions (e.g. affect regulation) as is the shared role of neurological regions in the regulation of anxiety and sleep. Studies of the association between SRPs and anxiety in anxiety-disordered samples are reviewed with explicit consideration of the potential mechanisms underlying the sleep-anxiety relationship (e.g., arousal, sleep hygiene, parental accommodation). Specific cognitive-behavioral treatments for SRPs and anxiety are reviewed with regard to their impact on comorbid anxiety or SRPs. Methodological limitations are noted and recommendations for future research are proposed.
24962083	In childhood, severe psychomotor impairment (SPMI) is associated with profound sleep disturbances. With the help of newly developed and validated measures, we systematically assessed how much a child's sleep disturbance affects parental sleep and quality of life (QoL) in this specific patient group.Parents and their children with SPMI were enrolled from three outpatient centers and one in-patient center in Germany. We administered a set of questionnaires to the parents that addressed their child's sleep quality, the sleep disturbance-related parental burden, and the impact on both parental sleep and QoL. Additional questionnaires were used to gather data describing our sample group to allow for comparison with published norms.	Parents of 214 children, adolescents, and young adults with SPMI (114 males, 100 females; mean age 10y 5mo, SD 5y 6mo, range 0.1-25y) responded to the questionnaire set (response rate of 66%). We found severe impairment of parental health status and QoL. More than 50% of the parents suffered from a sleep disorder (e.g. prolonged sleep latency, shortened sleep duration). Sleep disturbances in children, adolescents, and young adults correlated strongly with parental sleep disturbances, parental impairment of physical and mental functioning, parental social functioning, and parental working ability.	Sleep-related difficulties have a significant sociomedical impact on the parents of children, adolescents, and young adults with complex neurological diseases. Typically, parents are severely affected in various aspects of daily living. There is a need for novel diagnostic and therapeutic approaches that match the complex sociomedical needs of these patients and their families.	
24961941	The aim of this study was to examine the impact of gout on quality of life (QOL) and study differences by gender and race.Ten race- and sex-stratified nominal groups were conducted, oversampling for African-Americans and women with gout. Patients presented, discussed, combined and rank-ordered their concerns.	A total of 62 patients with mean age 65.1 years, 60% men, 64% African-American, participated in 10 nominal groups: African-American men (n = 23; 3 groups); African-American women (n = 18; 3 groups); Caucasian men (n = 15; 3 groups); and Caucasian women (n = 6; 1 group). The most frequently cited high-ranked concerns among the ten nominal groups were: (1) effect of gout flare on daily activities (n = 10 groups); (2) work disability (n = 8 groups); (3) severe pain (n = 8 groups); (4) joint swelling and tenderness (n = 6 groups); (5) food restrictions (n = 6 groups); (6) medication related issues (n = 6 groups); (7) dependency on family and others (n = 5 groups); (8) emotional Impact (n = 5 groups); (9) interference with sexual function (n = 4 groups); (10) difficulty with shoes (n = 4 groups); and (11) sleep disruption (n = 4 groups). Compared with men, women ranked the following concerns high more often: problems with shoes (n = 4 versus n = 0 groups); dependency (n = 3 versus n = 2 groups); and joint/limb deformity (n = 2 versus n = 0 group). Compared with Caucasians, African-Americans ranked the following concerns high more often: dietary restrictions (n = 6 versus n = 0 groups); severe pain (n = 6 versus n = 2 groups); gout bringing the day to a "halt" (n = 2 versus n = 0 group); effect on emotional health (n = 4 versus n = 1 groups); and the need for canes/crutches during flares (n = 2 versus n = 0 group).	Gout has a significant impact on a patient's QOL. Important differences in the impact of gout by gender and race were noted.	
24958893	There is emerging evidence in the literature to suggest that disruption of the normal circadian rhythm (sleep-wake cycle signalling) is a potential risk factor to explain the increased incidence of metabolic syndrome. Over the last century, obesity, diabetes and other components of metabolic syndrome have been on the rise. On the other hand, the amount of sleep has decreased from an average of 6-8 h per night. Furthermore, the quality of sleep has declined with more individuals voluntarily decreasing their amount of sleep to work or enjoy leisure activities. Over the last decade, researchers have examined the relationship between disruption in human circadian system and the emergence of symptoms related to metabolic syndrome. Indeed, epidemiological studies suggest a relation between sleep duration and diabetes and obesity. Moreover, experimental animal and human studies suggest such a relation. These studies propose optimum sleep duration of 7-8 h per night to avoid circadian rhythm disruption and suggest that sleep disturbance, whether iatrogenic or disease-related, should be considered as a risk factor for metabolic syndrome, and be addressed. This field is in its infancy and further understanding of specific pathophysiological pathways of circadian desynchronisation will help in developing novel preventive and therapeutic strategies.
24958682	Cluster headache is an excruciating unilateral headache with autonomic symptoms whose periodic nocturnal activity, which interrupts sleep, has been attributed to a hypothalamic generator.We describe a patient with a longstanding episodic cluster headache who experienced, on two occasions, a period of nocturnal awakenings without pain or autonomic symptoms, lasting one week before the onset of a cluster bout. Awakenings occurred twice/night at the same hours of impending cluster attacks and had no apparent trigger, being unusual for this patient who had no previous sleep disturbances. Neurological examination and brain imaging were normal.	This case documents two new aspects of cluster headache. It suggests that repeated nocturnal awakenings can be a warning sign of an impending cluster period, a finding that may have therapeutic implications, and also that hypothalamic activation may begin several days before trigemino-autonomic symptoms, thus behaving as a true bout generator.	
24957753	We tested the hypothesis that sleep training would improve emotional, social and behavioural functioning in children with attention-deficit/hyperactivity disorder (ADHD) compared to children with ADHD without such intervention and to healthy controls.Forty children with ADHD were randomly assigned to intervention and control conditions. Parents of 20 children with ADHD were instructed and thoroughly supervised in improving their children's sleep schedules and sleep behaviour. Parents of the other 20 children with ADHD and parents of 20 healthy children received general information about sleep hygiene. At baseline and 12 weeks later, parents and children completed questionnaires related to children's sleep and psychological functioning.	Relative to the control groups, children in the intervention group improved sleep quantitatively and qualitatively (F values < 3.33, P values < 0.05). The intervention group children reported improvements in mood, emotions, and relationships (F values < 2.99, P values < 0.05). Parents reported that their children improved in physical and psychological wellbeing, mood, emotions, relationships, and social acceptance (F values < 3.02, P values < 0.05).	Training and monitoring parents of children with ADHD in regulating and supervising children's sleep schedules leads to positive changes in the emotions, behaviour and social lives of these children.	
24954442	The aim of this study was to have a linguistic validation of the Sleep Disturbance Scale for Children (SDSC) in Iranian children with Persian language.The study included a randomly selected sample of children, aged 6-15 years, from three primary and secondary schools located in Isfahan City, Iran. Following the forward-backward translation method, parents completed the SDSC as well as the Pediatric Quality of Life Inventory (PedsQL). Reliability (Cronbach's α) and convergent validity (item-subscale and subscale-total correlations) were assessed. The association of SDSC scores with PedsQL scores was evaluated for construct validity.	One hundred children were studied; mean age, 9.36±2.58 years, 68 girls. Scale Cronbach's α was 0.82, ranging from 0.40 for 'disorder of arousal' to 0.86 for 'sleep hyperhidrosis' subscales. Convergent validity was acceptable according to the corrected item-subscale correlations (r = 0.22-0.76) and corrected subscale-total correlations (r = 0.30-0.50). The SDSC total score as well as its subscales, except the 'disorder of arousal', were associated with the total PedsQL score and its factors (r = -0.20 to -0.64).	The overall psychometric properties of the Persian version of the SDSC seem to be appropriate in Iranian children.	
24953771	To test several circadian rhythm variables in a female population to identify the best tool to assess chronodisruption in obesity and metabolic syndrome (MetS) to define a score to be used for chronodisruption characterization in clinical practice.Anthropometric measurements and markers of circadian rhythms, such as sleep and feeding diary, Horne-Ostberg questionnaire, melatonin and cortisol measurements, and wrist temperature measurements, were determined. MetS variables were also analyzed. Study was conducted in 70 women. Data were subjected to factor analysis. Receiver operating characteristic curves were used as predictors of chronodisruption risk, and a score was calculated to classify the subjects of risk.	Factor analysis showed that the first-factor grouped variables were related to the skin temperature measurement. Second factor consisted of variables related to salivary cortisol levels and obesity-related measurements. Third factor included variables related to sleep-wake cycle. Fourth factor referred to peripheral temperature variables and included the classification of subjects according to the Horne-Ostberg questionnaire. To obtain a final punctuation we performed the weighted mean of the first four factors. The final range was from 27 to 57, mean value of 42. Punctuation was defined as the "chronodisruption score." Women displaying higher chronodisruption scores had higher MetS risk.	The study demonstrates that wrist temperature recordings, together with two questions of sleep onset and offset, and one morning salivary cortisol determination could be enough to characterize the chronobiology of obesity and MetS, a new chronodisruption score was developed.	
24952234	Pediatric epilepsy has been reported to be associated with both sleep problems and cognitive deficits. In turn, in healthy children, poorer sleep has been associated with deficits in cognitive functioning. We hypothesized that poor sleep in childhood epilepsy may contribute to cognitive deficits. Using actigraphy, we objectively measured the sleep of children with epilepsy alongside that of healthy controls. In contrast to previous reports, we did not find any differences in objectively measured sleep between children with epilepsy and healthy controls. However, significant deficits in cognitive functioning were demonstrated that were not explained by differences in sleep. 
24951161	The goal of this project was to evaluate the relationship between self-reported sleep habits, daytime sleepiness, and drug use variables in individuals with cocaine and methamphetamine (METH) use disorders. Participants with a cocaine or meth use disorder completed questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and a demographic/drug use form. Participants with a cocaine (N=51) or meth use disorder (N=85) were separated into those with either high or low sleep deficits. In participants with a cocaine use disorder, ANOVA revealed significantly higher ESS scores among those defined as "poor sleepers" (with a PSQI score >5) when compared to those defined as "good sleepers" (with a PSQI score ≤5). In addition, poor sleepers reported using cocaine for more days out of the past 30 when compared to good sleepers. Interestingly, good sleepers reported using more grams of cocaine/day compared to poor sleepers. In participants with a METH use disorder, ANOVA revealed significantly higher ESS scores among poor sleepers when compared to good sleepers. Finally, individuals with a METH use disorder that endorsed elevated daytime sleepiness also had significantly higher PSQI scores when compared to those with normal daytime sleepiness. The results indicate that drug use variables, such as recent and daily use, may affect sleep quality and daytime sleepiness in individuals with stimulant use disorders; however, further investigations (i.e. in cocaine and METH users that do not meet criteria for a cocaine or METH use disorder) must be conducted in order to provide more conclusive evidence of the impact these usage variables may have on these sleep characteristics. 
24951101	Review controlled clinical trials of isoflavones and amino acid preparation effects on hot flashes and at least one other symptom including mood, sleep, pain, and cognitive function that women report during the menopausal transition and early postmenopause.An experienced reference librarian searched PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for English-language randomized controlled trials between 2004 and July 2011. Seventeen trials of isoflavones and amino acid effects on hot flashes and one additional symptom were identified.	In five trials of soy isoflavone preparations, two (6g soy germ extract and 25 g soy protein in soy nuts) significantly decreased hot flashes, but no other symptoms. In the seven trials of other isoflavones, six significantly reduced hot flashes; in addition, red clover (80 mg) significantly reduced mood symptoms; Rexflavone (350 mg) for women with Kupperman Index>20 significantly reduced sleep symptoms; two trials had significant reductions for pain: isoflavone powder (90 mg) and red clover (80 mg). The only trial in this systematic review that significantly reduced cognitive symptoms was red clover (80 mg). In one trial, red clover isoflavone (80 mg/day) significantly relieved hot flashes, mood, pain, and cognitive symptoms. Amino acids yielded no significant results. Equol supplements of 30 mg/day for non-Equol producing women significantly reduced mood symptoms in one trial. The magnolia bark extract combination significantly reduced hot flashes, mood, and sleep symptoms.	Isoflavone trials yielded significant reductions on hot flashes and co-occurring symptoms during the menopausal transition and postmenopause, but studies require replication with larger sample sizes and attention to measurement of outcomes.	
24951013	Chronic widespread pain (CWP) is common and associated with prominent negative consequences. The aim of this study was to assess the prevalence of persistent CWP in an 11-year prospective cohort study in the general population, and to examine anxiety, depression, alcohol use, poor sleep, body mass index (BMI) and chronic disease, along with demographic, lifestyle and other health-related variables as possible predictors for the assumed CWP persistence.CWP was defined as having pain at three or more predefined sites (involving the trunk and upper and lower limbs) for at least three months in the last year. We used a Norwegian general population cohort of 28,367 individuals who responded to both the second (1995-1997) and the third (2006-2008) waves of the Nord-Trøndelag Health Study (HUNT2 and HUNT3, respectively). Data were analysed with logistic regression models.	CWP prevalence in HUNT2 was 17%. Of those reporting CWP in HUNT2, 53% still reported CWP at follow-up in HUNT3. Adjusted analyses revealed that depression and alcohol consumption were not substantially associated with the 11-year prospective CWP outcome. Poor sleep, obesity and chronic disease predicted persistent CWP, and being male and/or 60 years or older was protective.	This cohort study revealed that nearly half of the participants with baseline CWP resolved from CWP 11 years later. Among those whose CWP did not resolve, obesity, sleeping problems and chronic disease predicted CWP persistence, while aging and male sex was protective. Anxiety, mixed anxiety and depression, former smoking, and overweight were weakly associated, while depression, moderate exercise, and alcohol use were not associated with persistent CWP.	
24950219	Cannabinoid type 1 (CB1) receptors are expressed in the nervous and cardiovascular systems. In mice, CB1 receptor deficiency protects from metabolic consequences of a high-fat diet (HFD), increases sympathetic activity to brown fat, and entails sleep anomalies. We investigated whether sleep-wake and diet-dependent cardiorespiratory control is altered in mice lacking CB1 receptors. CB1 receptor knock-out (KO) and intact wild-type (WT) mice were fed standard diet or a HFD for 3 months, and implanted with a telemetric arterial pressure transducer and electrodes for sleep scoring. Sleep state was assessed together with arterial pressure and heart rate (home cage), or breathing (whole-body plethysmograph). Increases in arterial pressure and heart rate on passing from the light (rest) to the dark (activity) period in the KO were significantly enhanced compared with the WT. These increases were unaffected by cardiac (β1) or vascular (α1) adrenergic blockade. The breathing rhythm of the KO during sleep was also more irregular than that of the WT. A HFD increased heart rate, impaired cardiac vagal modulation, and blunted the central autonomic cardiac control during sleep. A HFD also decreased cardiac baroreflex sensitivity in the KO but not in the WT. In conclusion, we performed the first systematic study of cardiovascular function in CB1 receptor deficient mice during spontaneous wake-sleep behavior, and demonstrated that CB1 receptor KO alters cardiorespiratory control particularly in the presence of a HFD. The CB1 receptor signaling may thus play a role in physiological cardiorespiratory regulation and protect from some adverse cardiovascular consequences of a HFD. 
24950023	Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep-wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body. 
24948186	Quality of sleep is essential for physical and mental health and influences the perception of the patient's well-being during the day. In patients with chronic allergic diseases sleep disorders may increase the severity of the condition, complicate the management and impair their quality of life. When children are concerned, their parents are also affected by the problem. We evaluated the presence of disrupted sleep in parents of children with atopic disorders, and its relationship with clinical features and the presence of disturbed sleep in children.Parents of children suffering from allergic diseases were recruited from the Pediatric Allergy Units of Parma University. Evaluation of sleep in parents was based on the Pittsburg Sleep Quality Index (PSQI), while in children it was based on the Sleep Disturbance Scale for Children (SDSC).	Of the 102 parents invited, 92 filled in the questionnaire. Only the questionnaires with more than a 95% completion rate were considered for analysis. PSQI mean score in parents was 6.6 (SD 2.6); 75.6% of them had a PSQI ≥ 5, indicating that most parents had a sleep quality perceived as bad. The PSQI ≥ 5 was more common in parents of children with asthma and rhinitis. In children, SDSC mean score was 42.1 (SD: 9.4); 62.3% had a total score ≥ 39. The quality of sleep in parents and children was significantly correlated (p<0.001).	These findings make it apparent that an alteration of sleep in children can also affect the parents. Such effect further weighs the burden of respiratory allergy and needs to be considered in future studies.	
24947799	Patients with cancer frequently suffer from insomnia symptoms, and additionally, their family members also often experience these symptoms. The aim of this study was to investigate the prevalence of insomnia symptoms in both family members and patients with hematological malignancies. We conducted an observational cross-sectional study using a clinical self-reported questionnaire for sleep conditions, depressive symptoms (two-question method), and worries (five items that originated from the Brief Cancer Worry Inventory). One hundred twelve family members and 153 patients were investigated. A t test and Chi-square test were used to compare the prevalence of insomnia and depressive symptoms between family members and patients. Logistic regression was used to determine whether insomnia symptoms or worries related to patients' disease had an impact on depressive symptoms. The presence of insomnia symptoms in family members (87 %) was significantly higher than that in patients (60 %, p < 0.001). The prevalence of depressive mood and anhedonia in family members were 55 and 34 %, respectively, and these values were higher than those in patients (43 and 28 %, respectively). Insomnia symptoms and worries about present/prospective disease conditions were significantly associated with depressive mood (insomnia symptoms, odds ratios (OR) 4.3, confidence intervals (CI) 1.2-15.2, p = 0.025; worries, OR 4.4, CI 1.0-19.3, p = 0.048). Taken together, our results demonstrated that insomnia symptoms and depressive symptoms are highly prevalent in family members as well as in patients with hematological malignancies.
24947107	In French law (Code du Sport), the status of elite athlete is allowed for young athletes beginning at the age of 12 years. For these young athletes, the aim is to reach the highest level of performance in their sport without compromising academic performance. Training time is therefore often substantial and sleep patterns appear to play a key role in performance recovery. The aim of this study was to assess sleep patterns and their effects on academic performance in young elite athletes.Sleep patterns were assessed using questionnaires completed during a specific information-based intervention on sports medicine topics. The academic performance of young elite athletes was assessed by collecting their grades (transmitted by their teachers).	Sleep patterns were assessed for 137 young elite athletes (64 females, 73 males; mean age, 15.7 years) and academic performance for 109 of them. Daily sleep duration during school periods (8h22 ± 38 min) were shorter compared to holidays and week-ends (10h02 ± 1h16, P<0.0001). Fifty-six athletes (41 %) subjectively estimated their sleep quality as poor or just sufficient. Poor sleep quality was correlated with poor academic performance in this specific athlete population.	Sleep is the most important period for recovery from daily activity, but little information is available regarding the specific population of young elite athletes. The results reported herein suggest insufficiency (quantitatively and qualitatively) of sleep patterns in some of the young athletes, possibly leading to detrimental effects on athletic performance. Moreover, disturbed sleep patterns may also impact academic performance in young elite athletes.	Teachers, athletic trainers, physicians, and any other professionals working with young elite athletes should pay particular attention to this specific population regarding the possible negative repercussions of poor sleep patterns on academic and athletic performance.	
24946912	To explore the psychological mechanisms involved in the close association between maternal mood and self-reports of sleep quality during the perinatal period using appraisal theory of emotions.Repeated measures.	Antenatal clinics of a health center associated with the Northern Hospital in Melbourne, Australia.	122 pregnant women in their third trimester of gestation.	Participants completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale, and an appraisal questionnaire during the third trimester of gestation, within 7 to 10 days after childbirth, and at 10 to 12 weeks postpartum. Correlational and regression analyses were used to explore the associations between sleep reports and appraisals.	Self-reports of poor sleep quality, impaired daytime dysfunction due to poor sleep, and the global PSQI score were associated with a low perceived ability to cope practically and emotionally with motherhood-related issues as well as with negative expectations about the future.	Appraisal dimensions associated with self-reports of poor sleep quality are similar to those related to maternal distress identified by previous research. This finding contributes to a better understanding of the association between self-reports of sleep and maternal mood. Practical implications are discussed.	
24946074	The aim of this study was to demonstrate that two REM clusters, which emerge following bilateral pedunculopontine tegmental nucleus (PPT) lesions in rats, are two functionally distinct REM states. We performed the experiments in Wistar rats, chronically instrumented for sleep recording. Bilateral PPT lesions were produced by the microinfusion of 100 nl of 0.1M ibotenic acid (IBO). Following a recovery period of 2 weeks, we recorded their sleep for 6h. Bilateral PPT lesions were identified by NADPH - diaphorase histochemistry. We applied Fourier analysis to the signals acquired throughout the 6h recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We analyzed the topography of the sleep/wake states architecture and their transition structure, their all state-related EEG microstructures, and the sensorimotor (SMCx) and motor (MCx) cortex REM related cortico-muscular coherences (CMCs). Bilateral PPT lesion in rats increased the likelihood of the emergence of two distinct REM sleep states, specifically expressed within the MCx: REM1 and REM2. Bilateral PPT lesion did not change the sleep/wake states architecture of the SMCx, but pathologically increased the duration of REM1 within the MCx, alongside increasing Wake/REM1/Wake and NREM/REM2/NREM transitions within both cortices. In addition, the augmented total REM SMCx EEG beta amplitude and REM1 MCx EEG theta amplitude was the underlying EEG microstructure pathology. PPT lesion induced REM1 and REM2 are differential states with regard to total EMG power, topographically distinct EEG microstructures, and locomotor drives to nuchal musculature.
24945266	Lung cancer patients undergo various treatments leading to sleep problems, rest-activity circadian rhythms disruption, and reduced levels of physical activity. It is important to understand the relationships among these variables. Appropriate interventions can possibly be implemented to improve sleep quality in lung cancer patients.The objective of this study was to examine the relationships of circadian rhythms and physical activity with objective sleep parameters in 106 of Taiwanese lung cancer patients.	This study used a cross-sectional design. The instruments included an actigraph to measure the objective sleep parameters (total sleep time [TST], sleep efficiency, and sleep-onset latency [SOL]), rest-activity circadian rhythms (r24 [24-hour autocorrelation coefficient] and I < O [in-bed less than out-of-bed dichotomy index]), and physical activity frequency (UP activity mean). The daily physical activity amount in minutes was measured by the Bouchard 3-day physical activity record.	Patients performing light-intensity physical activity of 295 min/d or greater had better values for the TST, sleep efficiency, SOL, r24, and I < O than those performing less than 295 min/d (all P < .05). Significant predictors of the TST included age (β = -.31), I < O (β = .32), and UP activity mean (β = -.42). Predictors of the SOL included current treatment (β = .20), I < O (β = -.28), UP activity mean (β = .51), and 24-hour light-activity minutes (β = -.23).	Marked circadian rhythms and adequate light-intensity physical activity may improve sleep quality in lung cancer patients.	Adequate light-intensity physical activity can be an effective intervention to improve sleep quality in lung cancer patients.	
24944250	Our previous study demonstrated that physical exercise under dim lights (<10 lux) accelerated reentrainment of the sleep-wake cycle but not the circadian melatonin rhythm to an 8-h phase-advanced sleep schedule, indicating differential effects of physical exercise on the human circadian system. The present study examined the effects of bright light (>5,000 lux) on exercise-induced acceleration of reentrainment because timed bright lights are known to reset the circadian pacemaker. Fifteen male subjects spent 12 days in temporal isolation. The sleep schedule was advanced from habitual sleep times by 8 h for 4 days, which was followed by a free-run session. In the shift session, bright lights were given during the waking time. Subjects in the exercise group performed 2-h bicycle running twice a day. Subjects in the control kept quiet. As a result, the sleep-wake cycle was fully entrained by the shift schedule in both groups. Bright light may strengthen the resetting potency of the shift schedule. By contrast, the circadian melatonin rhythm was phase-advanced by 6.9 h on average in the exercise group but only by 2.0 h in the control. Thus physical exercise prevented otherwise unavoidable internal desynchronization. Polysomnographical analyses revealed that deterioration of sleep quality by shift schedule was protected by physical exercise under bright lights. These findings indicate differential regulation of sleep-wake cycle and circadian melatonin rhythm by physical exercise in humans. The melatonin rhythm is regulated primarily by bright lights, whereas the sleep-wake cycle is by nonphotic time cues, such as physical exercise and shift schedule. 
24943526	The objective of this study is to propose a Cloud Computing based platform for sleep behavior and chronic disease collaborative research. The platform consists of two main components: (1) a sensing bed sheet with textile sensors to automatically record patient's sleep behaviors and vital signs, and (2) a service-oriented cloud computing architecture (SOCCA) that provides a data repository and allows for sharing and analysis of collected data. Also, we describe our systematic approach to implementing the SOCCA. We believe that the new cloud-based platform can provide nurse and other health professional researchers located in differing geographic locations with a cost effective, flexible, secure and privacy-preserved research environment. 
24942599	The military population is particularly vulnerable to a multitude of sleep-related disorders owing to the type of work performed by active duty servicemembers (ADSMs). Inadequate sleep, due to insufficient quantity or quality, is increasingly recognized as a public health concern. Traditionally, ADSMs have been encouraged that they can adapt to insufficient sleep just as the body adapts to physical training, but there is a substantial body of scientific literature which argues that this is not possible. Additionally, the military work environment creates unique challenges with respect to treatment options for common sleep disorders like obstructive sleep apnea, restless legs syndrome, and parasomnias. This review highlights sleep disorders which are prevalent in the modern military force and discusses the impact of poor sleep on overall performance. Medical treatments and recommendations for unit leaders are also discussed.

24941511	Adolescents have unique sleep behaviors related to physiological and developmental differences. Research suggests that sleep debt related to these adolescent differences contributes to risk for accidents, behavioral changes, and other health concerns. In addition, the impact of pain related to trauma, surgery, and chronic illness can further alter the sleep patterns of this age group. Limited normative parameters describe the sleep of healthy adolescents. A comparative study of 26 adolescents from 12 through 18 years of age was designed to describe the sleep patterns of two groups of adolescents. Sleep parameters, including actual sleep time, sleep efficiency, nighttime awakenings, and other sleep patterns of adolescents following post-operative tonsillectomy and adenoidectomy (T & A), were compared with an age and gender-matched sample of healthy adolescents. All adolescents wore wrist-actigraphy and documented sleep information in a diary for three continuous days. Healthy adolescents had significantly less (p = 0.003) actual hours of night time sleep and significantly less (p = 0.039) sleep efficiency than adolescents in the post-operative sample during the three days. None of the adolescents in this study had sufficient actual hours of nighttime sleep. Findings support the need for nurses to assess adolescent sleep patterns and to educate teens and their families about the importance of adequate sleep. Further research is needed to establish sleep interventions that will improve the sleep hygiene of both healthy adolescents and those who experience sleep disruption due to painful conditions.
24941261	Sleep-related disorders (SRDs) are common in sickle cell disease, however, identification may be time-consuming. Simultaneous survey of multiple SRDs utilizing a simplified instrument would facilitate screening. A simplified questionnaire investigating SRDs [sleep-disordered breathing (SDB), restless legs syndrome (RLS), insomnia, parasomnias, and daytime effects of disrupted sleep] was administered to 2-18-year-old children with sickle cell disease. One hundred participants completed this 5-7 minute survey without difficulties: 54 awoke unrefreshed, 41 had short-term insomnia, 30 had sleep-maintenance insomnia, 21 had chronic sleep-onset insomnia, 54 had chronic habitual snoring and 11 met the criteria for RLS. Sleep-maintenance insomnia was associated with increased body mass index (BMI) (p = 0.001), and chronic sleep-onset insomnia was associated with higher hemoglobin (Hb) levels (p = 0.04). Survey-reported symptoms of SRDs were significantly higher than that reported in the general pediatric population. A fast and simplified SRD survey is feasible and suggests a high prevalence of SRDs in children with sickle cell disease.
24940169	Juvenile idiopathic arthritis is a chronic disease that may lead to various consequences for patients and caregivers, especially in relation to sleep quality. Sleep is an essential process for homeostasis of the organism. In general, caregivers of children with JIA are more susceptible to these sleep disorders and a lower quality of life. This impairment in sleep can potentially affect the health of caregiver. For this reason, it is very important to continue to evaluate the quality of sleep in caregivers and how to support these JIA children's caregivers more effectively. 
24940168	Sleep problems are common among children with chronic illnesses such as Juvenile Idiopathic Arthritis (or JIA). However, little is known about the frequency and severity of sleep disturbance(s) and the factors that are associated with sleep problems in children with JIA. The mechanism(s) of the relationships characterizing the development or exacerbation of sleep problems in children with JIA are still unknown, however studies have reported an association. The purpose of this study was to synthesize existing research related to sleep problems in children with JIA.The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the conduct and reporting of this review. An experienced librarian conducted searches in MEDLINE, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to January 2012, to identify potentially relevant citations. Two members independently selected, rated methodological quality using the QUIPS tool, and extracted data from included studies.	Ten studies were included and findings varied across studies; studies were mostly cross-sectional, or case-controlled designs, with only one cohort study available. Four studies found that children and adolescents diagnosed with JIA had significantly more sleep disturbances when compared to healthy controls. Pain was most often associated with sleep disturbances. The heterogeneous findings highlight the complex relationships between JIA and sleep, and low methodological quality of studies in the field.	This review supports an association between poor sleep and increased symptoms related to JIA, specifically the experience of pain. However, results need to be interpreted cautiously given the inconsistent findings regarding factors associated with sleep problems in JIA, the limited evidence available, and its low quality. Furthermore it is not yet determined if the poor sleep patterns predate the symptoms reported with JIA. More research is vital to understanding the factors that predict or perpetuate poor sleep in children and adolescents diagnosed with JIA.	
24939522	Standard polysomnography (PSG) typically utilizes 4-6 channels of electroencephalography (EEG), which is inadequate to evaluate focal epileptiform activity. Though technical capability has long existed for more extensive EEG recording, few sleep laboratories have utilized this technique. The objective of this study was to determine the utility of combining PSG with 18-channel EEG in select patients with paroxysmal nocturnal events or other symptoms concerning for sleep disorders, nocturnal seizures or both.Consecutive combined PSG-EEG studies (n=237) were performed between 10/1/2005 and 8/1/2009. Demographics, referral source, indications, and results were reviewed and analyzed.	Of the 237 consecutive combined PSG-EEG studies performed, 93% revealed the presence of a primary sleep disorder, 38% were shown to have abnormal EEGs, and 37% had both. Among the 221 subjects (93%) shown to have sleep disorders, the majority of these cases were obstructive sleep apnea (OSA) 89%, followed by periodic limp movements of sleep (PLMS) 22% and rapid eye movement behavior disorder (RBD) 6%. Significantly more patients with known epilepsy were diagnosed with OSA then were patients without a seizure history.	Combined PSG-EEG, utilizing 18-channel EEG, is an under-utilized technique which can assist in diagnosing paroxysmal nocturnal events, and differentiate between the presence of a primary sleep disorder, seizure activity, or both. Our study further illustrates the importance of considering sleep disorders in epilepsy patients.	
24938585	Rapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson's disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD.A total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD.	Among the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p=0.01). The RBD group reported more NMS of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall NMS (p=0.002).	In PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.	
24938137	The objective of this study was to determine the frequency, nature, and impact of sleep disorders in children and adolescents with Tourette syndrome and to raise awareness about their possible inclusion as a Tourette syndrome comorbidity.Using a prospective questionnaire, we interviewed 123 patients of age ≤21 years with a confirmed diagnosis of Tourette syndrome. Each completed questionnaire was then reviewed in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for categorization to a form of sleep disorder.	Of the 123 patients with Tourette syndrome, 75 (61%) had comorbid attention deficit hyperactivity disorder and 48 (39%) had Tourette without attention deficit hyperactivity disorder. The sleep problems observed included problems in the nature of sleep, abnormal behaviors during sleep, and impact of sleep disturbances on quality of life. Within these cohorts, 31 (65%) of the 48 Tourette-only patients and 48 (64%) of the 75 Tourette + attention deficit hyperactivity disorder patients could fit into some form of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, coded sleep disorders. Of the 48 Tourette + attention deficit hyperactivity disorder patients with sleep disorders, 36 (75%) had insomnia signs, which could be explained by the co-occurrence of attention deficit hyperactivity disorder and high stimulant use. However, 10 (32%) of the 31 Tourette-only patients with sleep disorders had insomnia irrespective of attention deficit hyperactivity disorder or medication use.	Sleep problems are common in children with Tourette syndrome irrespective of comorbid attention deficit hyperactivity disorder, justifying their inclusion as a comorbidity of Tourette syndrome.	

24936715	Several environmental exposures are associated with increased risk of coronary heart disease (CHD). Exposure to secondhand smoke may increase the risk by as much as 25% to 30%. Exposure to third hand smoke, residual components of tobacco smoke that remain in the environment after a cigarette is extinguished, also appears to increase risk. These residual components can remain in rooms and automobiles for up to 30 years and enter the body through the skin or via inhalation or ingestion. Exposure to particulate matter air pollution from automobile emissions, power plants, and other sources is yet another environmental risk factor for CHD, resulting in tens of thousands of deaths annually in the United States. Exposure to other environmental toxins, particularly bisphenol A and phthalates, also has been linked to CHD. There are sociodemographic risks for CHD, with numerous studies showing that lower socioeconomic status is associated with higher risk. Behavioral risk factors include poor diet, such as frequent consumption of fast food and processed meals; sleep disturbance; and psychological stress, particularly related to marital or work issues. Finally, although high alcohol consumption is associated with increased CHD risk, moderate alcohol consumption (ie, less than 1 to 2 drinks/day), particularly of wine and possibly beer, appears to reduce the risk.
24934076	The study examined the relationships among pain, pain coping, and sleep, and assessed factors (age, gender, frequency, and intensity of pain) that affect pain, coping, and sleep in children with sickle cell disease (SCD).Participants (66) were 39 children (M = 11.5 years) and 27 adolescents (M = 15.5 years) with SCD who completed an electronic visual analog scale (eVAS), Pain Coping Questionnaire, and Pittsburg Sleep Quality Index.	About two-thirds of the children reported pain the previous month. No significant differences were found between pain and age, gender, pain intensity, or frequency. Most children coped with pain by seeking information, problem solving, seeking social support, and positive self-statements. There were significant negative correlations in males between worse pain severity and behavioral distraction and internalizing or catastrophizing. The majority (91.2%) had mild to severe sleep disturbances, with 18.2% requiring sleeping medication three or more times a week. There were no significant differences between sleep and age, gender, pain intensity, or frequency.	Children with SCD experience pain that affects sleep patterns and the way they cope with pain. Nurses need to concurrently assess pain, coping, and sleep and promote sleep hygiene and positive coping strategies during pain episodes.	
24933083	To assess the relationship between sleep, time of exercise, and intensity of exercise in a large American sample.The 2013 National Sleep Foundation Sleep in America Poll was a cross-sectional study of 1000 adults stratified by age (23–60 years) and U.S. geographical region. Sleep outcomes included self-reported sleep quality, total sleep time, sleep latency, and waking unrefreshed. Exercise timing was characterized as morning (>8 h before bed), afternoon (4–8 h before bed), or evening (<4 h before bed). Exercise intensity was assessed with a modified version of the International Physical Activity Questionnaire.	After adjustment for confounders, evening moderate or vigorous exercisers did not differ in any of the reported sleep metrics compared to non-exercisers. Morning vigorous exercisers had the most favorable sleep outcomes, including greater likelihood of reporting good sleep quality (OR = 1.88, p < .001) and lower likelihood of waking unrefreshed (OR = 0.56, p = .03). Most individuals who performed vigorous evening exercise believed that their sleep was of equal or better quality (97%) and duration (98%) on days they exercised.	Evening exercise was not associated with worse sleep. These findings add to the growing body of evidence that sleep hygiene recommendations should not discourage evening exercise.	



24932153	Current emphasis on patient outcomes within sleep medicine, with a particular focus on quality improvement and contained costs, calls for sleep specialists to develop innovative models for long-term care and management of sleep disorders patients. Multidisciplinary sleep centers can facilitate highest-quality care that is timely and cost-effective. Effective resource use in a multidisciplinary sleep center can help minimize fragmentation of care, reduce effort duplication, and control costs. Proposed strategies to help achieve a balance between quality of care and cost-effectiveness include: (1) multidisciplinary specialty clinics, (2) optimized use of information technology, and (3) adoption of reliable performance measures.
24932152	We describe a case series of 4 patients with varying degrees of obstructive sleep apnea who incidentally had a history of nocturnal leg cramps. None of the patients had periodic limb movements during the study and denied symptoms consistent with restless legs syndrome. In 3 of the 4 patients, nocturnal leg cramps resolved with CPAP treatment for OSA, while the fourth patient noted near-resolution of cramping after starting CPAP. In patients presenting with muscle cramps, obstructive sleep apnea should be considered.
24932150	Depression is a commonly diagnosed comorbidity in sleep disorder clinics. However, screening instruments for major depressive episode (MDE) have not been validated in this setting. We aimed to validate the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory - Fast Screen (BDI-FS) with the Mini International Neuropsychiatric Interview (MINI) in patients with suspected obstructive sleep apnea (OSA).Cross-sectional study.	Academic center.	One hundred one new patients with a clinical suspicion of OSA, as assessed by a sleep physician.	MDE, generalized anxiety disorder (GAD), and panic disorder (PD) were assessed by (1) a diagnostic interview utilizing the MINI and (2) by two self-report questionnaires: HADS and BDI-FS. A receiver operating characteristic (ROC) analysis was undertaken to assess which HADS and BDI-FS threshold yielded the highest correlation for a diagnosis of MDE and/or GAD/PD as assessed with an interview conducted using the MINI.	A HADS-Depression score ≥ 8 gave optimal sensitivity (83.1%) and specificity (83.3%) with an area under the ROC curve (AUC) 0.851 for predicting the diagnosis of MDE. A HADS-Anxiety score ≥ 11 gave an optimal sensitivity (93.1%) and specificity (84.7%) with an AUC 0.911 for predicting the diagnosis of GAD/PD. A BDI-FS threshold ≥ 6 gave optimal sensitivity (86.7%) and specificity (82.9%) with an AUC 0.897 for MDE.	The HADS and BDI-FS are accurate screening instruments with high concurrent validity for identifying the probability of a patient having MDE and-in the case of HADS-GAD and PD disorder in a sleep disorders clinic.	
24932141	Despite several polysomnographic normative studies and multiple surveys of sleep disorders in the general population, few data have been collected on healthy sleepers. We aimed to survey the characteristics of healthy sleep.We prospectively investigated the sleep history of 100 subjects of a representative population sample who reported undisturbed sleep and in whom relevant sleep disorders were ruled out by a two-step screening procedure. Approximately four subjects had to be contacted for identifying 1 eligible subject who participated.	The median reported time in bed was from 23:00 (21:30-02:00) to 07:00 (05:30-11:00). The total sleep duration was 7.3 h (5-10 h), varying from 7.5 h in the age group ≤ 30 years to 7 h in subjects aged 40-60 years and to 8 h in subjects > 60 years (p = 0.002). The median sleep efficiency was high (93.3%, range: 55.6% to 100%). Fifty-one subjects reported occasional snoring. Forty-five subjects reported sporadic non-bothersome sleep-related movement disorders (25 sleep-related leg cramps, 22 lifetime bruxism, 5 restless legs syndrome), and 36 had a history of sporadic non-bothersome parasomnias (27 nightmares, 12 sleepwalking, 1 sleep paralysis).	In this population of healthy sleepers, snoring is the most common finding. Moreover, non-bothersome forms of recognizable sleep-related movement disorders and parasomnias are surprisingly common. These findings may suggest that diagnostic criteria of sleep disorders should not only be based on the presence of symptoms but also account for a minimum frequency or discomfort.	
24932139	This research examined the impact of daylight exposure on the health of office workers from the perspective of subjective well-being and sleep quality as well as actigraphy measures of light exposure, activity, and sleep-wake patterns.Participants (N = 49) included 27 workers working in windowless environments and 22 comparable workers in workplaces with significantly more daylight. Windowless environment is defined as one without any windows or one where workstations were far away from windows and without any exposure to daylight. Well-being of the office workers was measured by Short Form-36 (SF-36), while sleep quality was measured by Pittsburgh Sleep Quality Index (PSQI). In addition, a subset of participants (N = 21; 10 workers in windowless environments and 11 workers in workplaces with windows) had actigraphy recordings to measure light exposure, activity, and sleep-wake patterns.	Workers in windowless environments reported poorer scores than their counterparts on two SF-36 dimensions--role limitation due to physical problems and vitality--as well as poorer overall sleep quality from the global PSQI score and the sleep disturbances component of the PSQI. Compared to the group without windows, workers with windows at the workplace had more light exposure during the workweek, a trend toward more physical activity, and longer sleep duration as measured by actigraphy.	We suggest that architectural design of office environments should place more emphasis on sufficient daylight exposure of the workers in order to promote office workers' health and well-being.	
24931561	The study determined the prevalence of sleep disorders by ethnicity and sex, and related daytime functioning, working memory, and mental health among older adolescent to emerging adult college students. Participants were U.S.A. undergraduates (N = 1684), aged 17-25, recruited from 2010 to 2011. Participants completed online questionnaires for all variables. Overall, 36.0% of the sample screened positive for sleep disorders with insomnia, restless legs syndrome, and periodic limb movement disorder being the most prevalent. Women reported more insomnia and daytime impairment. African-Americans reported more early morning awakenings and less daytime impairment. Students with insomnia symptoms or restless legs syndrome tended to have lower working memory capacities. Students with nightmares or parasomnias had greater odds for mental disorders. In an older adolescent to emerging adult college student sample, sleep disorders may be a common source of sleep disturbance and impairment. Certain sleep disorders may be associated with lower working memory capacity and poor mental health.
24931546	Leg pain and discomfort are common complaints in any primary physician's clinic. Two common causes of pain or discomfort in legs are nocturnal leg cramps (NLC) and restless leg syndrome (RLS). NLC present as painful and sudden contractions mostly in part of the calf. Diagnosis of NLC is mainly clinical and sometimes involves investigations to rule out other mimics. RLS is a condition characterized by the discomfort or urge to move the lower limbs, which occurs at rest or in the evening/night. The similarity of RLS and leg cramps poses the issue of errors in diagnosing and differentiating the two. In this paper we review the pathopysiology of each entity and their diagnosis as well as treatment. The two conditions are then compared to appreciate the differences and similarities. Finally, suggestions are recommended for complete assessment. 
24930962	Chronic pain is associated with impairments in sleep; however, the relationship between prescription opioid status and sleep is unclear. The primary aim of this study was to examine differences in self-reported sleep quality between groups of patients who varied based on chronic pain and prescription opioid status.This is a cross-sectional study with retrospective review of patient medical records.	The study was performed in a single VA medical center located in the Pacific Northwest.	Participants with chronic pain and a current prescription for opioid medications (N=72), chronic pain and no opioid prescription (N=104), or who did not report current chronic pain or opioid prescription (N=91) were included.	All participants completed self-report questionnaires assessing demographic characteristics, sleep parameters, pain-related variables, and psychiatric symptoms. Data on prescription opioid use were extracted from patients' medical records.	In unadjusted analyses, patients with chronic pain who were prescribed opioids were more likely to have sleep apnea diagnoses in their medical record and reported more impairment on sleep global score and across four sleep parameter subscales (subjective sleep quality, sleep latency, sleep disturbance, and use of sleeping medications). In linear regression analyses controlling for demographic and clinical covariates, prescription opioid status was associated with sleep latency, and opioid dose was significantly associated with sleep latency and sleep global score.	Prescription opioid status and dose were associated with impairment in self-reported sleep. For patients with chronic pain, consideration should be given to use of nonpharmacological interventions to improve sleep.	
24930893	Binge alcohol drinking is among the most common pattern of alcohol consumption in our society. Binge alcohol consumption has serious negative consequence on mental and physical health. Although alcohol consumption is known to have profound impact on sleep, it is yet unknown as to how binge alcohol affects/alters sleep-wakefulness. The objective of this study was to examine the effect of acute binge alcohol administration on sleep-wakefulness.Male Sprague Dawley rats were used in the study. Under standard aseptic surgical conditions, rats (N = 7) were implanted with sleep-recording electrodes. After postoperative recovery and habituation, baseline sleep-wakefulness was recorded. Subsequently, rats were exposed to binge alcohol treatment as follows: One hour before light onset, a priming dose of 5 g/kg of alcohol was administered followed by 2 subsequent doses (adjusted based on the intoxication level of the rat) approximately 8 hours apart. Sleep-wakefulness was continuously recorded for 3 days post-binge.	Acute binge alcohol administration had no significant effect on sleep-wakefulness on post-binge Day 1. However, on post-binge Day 2, after blood alcohol concentration (BAC) was 0, sleep disruptions were observed manifested by a reversal of sleep-wakefulness as evident from insomnia-like symptoms (significant increase in wakefulness; significant reduction in nonrapid eye movement [NREM] sleep) during the normal sleep (light) period and excessive sleep (significant increase in NREM sleep) during the normal active (dark) period similar to excessive daytime sleepiness in humans. All sleep-wakefulness changes were normalized on Day 3 post-binge.	Alcohol hangover is defined as the presence of unpleasant symptoms that peak when BAC is 0. Our results suggest that the reversal of sleep-wakefulness accompanies alcohol hangover after binge alcohol administration.	
24930318	Cramps are painful sensations caused by intense involuntary contractions of skeletal muscles, mostly in the calves, usually lasting from a few seconds to several minutes. Although cramps are mostly idiopathic, theycan bea symptom of other forms of myalgia, restless legs syndrome or spasticity. Especially nocturnal cramps can cause considerable distress for patients requiring fast pain reduction and effective prophylaxis. Stretching the calf muscles helps preventing nocturnal cramps. Pharmacological treatment of leg cramps includes magnesium and quinine.
24929062	The hypothesis was that an orexin 2 receptor (OX2R) agonist would prevent sleep-related disordered breathing.In C57BL/6J (B6) mice, body plethysmography was performed with and without EEG monitoring of state (wakefulness, NREM and REM sleep). Outcome was apnea rate/h during sleep-wake states at baseline and with an intracerebroventricular administration of vehicle, 4 nMol of agonist OB(DL), and 4 nMol of an antagonist, TCS OX2 29.	A significant reduction (p=0.035, f=2.99) in apneas/hour occurred, especially with the agonist. Expressed as a function of the change from baseline, there was a significant difference among groups in Wake (p=0.03, f=3.8), NREM (p=0.003, f=6.98) and REM (p=0.03, f=3.92) with the agonist reducing the rate of apneas during sleep from 29.7±4.7 (M±SEM) to 7.3±2.4 during sleep (p=0.001). There was also a reduction in apneas during wakefulness. Administration of the antagonist did not increase event rate over baseline levels.	The B6 mouse is a preclinical model of wake-and sleep-disordered breathing, and the orexin receptor agonist at a dose of 4 nMol given intracerebroventricularly will reduce events in sleep and also wakefulness.	
24928941	In association with sleep-wake and fasting-feeding cycles, organisms experience dramatic oscillations in energetic demands and nutrient supply. It is therefore not surprising that various metabolic parameters, ranging from the activity status of molecular energy sensors to circulating nutrient levels, oscillate in time-of-day-dependent manners. It has become increasingly clear that rhythms in metabolic processes are not simply in response to daily environmental/behavioral influences, but are driven in part by cell autonomous circadian clocks. By synchronizing the cell with its environment, clocks modulate a host of metabolic processes in a temporally appropriate manner. The purpose of this article is to review current understanding of the interplay between circadian clocks and metabolism, in addition to the pathophysiologic consequences of disruption of this molecular mechanism, in terms of cardiometabolic disease development. 
24928125	To assess in a noninterventional setting the prevalence and severity of fatigue in patients with Parkinson disease (PD).This was a cross-sectional study conducted in Italian patients with PD. Objectives included the evaluation of the current prevalence and severity of fatigue in patients with PD measured using the 16-item Parkinson Fatigue Scale (PFS-16), distressing fatigue (defined as a PFS-16 mean score ≥3.3), and assessment of its clinical correlates.	A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean (±SD) score of 2.87 ± 0.99. Of these, 136 patients (33.8%) reported distressing fatigue (PFS-16 mean score ≥3.3). Patients with distressing fatigue were older (p = 0.044) and had a longer duration of PD (p < 0.0001) than those without distressing fatigue. The presence of distressing fatigue was associated with higher total Unified Parkinson's Disease Rating Scale (UPDRS) scores, poorer quality of life (39-item Parkinson's Disease Questionnaire [PDQ-39]), worse social and psychological behaviors, a higher severity of depressive symptoms, and a higher prevalence of sleep disorders (all p < 0.001). Logistic regression analyses revealed that higher total UPDRS scores, female sex, depression, sleep disorders, as well as higher UPDRS activities of daily living scores and PDQ-39 mobility scores increase the likelihood of distressing fatigue in patients with PD.	Approximately one-third of patients with PD have distressing fatigue, which is significantly associated with depression and sleep disorders. The fact that the presence of fatigue worsens patient quality of life supports the need to better diagnose and treat this debilitating symptom.	
24924956	The purpose of this mixed methods study was to describe the sleep and psychological characteristics of heavy-drinking college students, their perceptions of sleep and sleep/alcohol interactions, and their reactions to a proposed integrated sleep and alcohol Web-based intervention. Students (N = 24) completed standardized surveys and participated in semistructured focus group interviews. Participants reported a high degree of sleep disturbance, sleep obstacles, and sleep-related consequences, which were validated by both quantitative and qualitative investigations. Sleep disturbance and sleep-related impairment were associated with more frequent drinking and greater risks from drinking. Participants perceived that alcohol has positive and negative effects on sleep latency, continuity, and quality. They expressed overall enthusiasm for the intervention but had specific content and format preferences.
24924657	Short sleep duration and poor quality sleep are associated with coronary heart disease (CHD) mortality; however, the underlying pathophysiologic process remains unclear. Sleep apnea may confound the association because of its relationship with formation of thrombi, the vascular occlusive process in CHD. We tested whether sleep duration and quality were associated with prothrombotic biomarkers in adults with a low probability of apnea.We included adults aged 35-64 years recruited from the community and who had an apnea hypopnea index <15 after one night of screening (n=506). Sleep duration and maintenance were determined from 7 days of wrist actigraphy; daytime sleepiness was estimated using the Epworth Sleepiness Scale. Factor VIII (FVIII), von Willebrand factor (vWF), thrombin antithrombin (TAT) complexes, and plasminogen activator inhibitor-1 (PAI-1) were measured in fasting blood.	Sleep duration, maintenance, and daytime sleepiness were not associated with FVIII, vWf, or TAT. Sleep maintenance was modestly inversely associated with higher levels of log-transformed PAI-1 (β = -0.07, standard error (SE)=0.03 per 4.8%, p=0.04) following adjustment for demographic characteristics, cardiovascular risk factors, and body mass index (BMI).	Mild impairment in sleep was modestly associated with activation of coagulation; further study is needed to evaluate the role of fibrinolytic factors in sleep-mediated coronary thrombosis.	
24923407	A link between mild traumatic brain injury (mTBI) and neurodegenerative diseases, specifically Alzheimer's disease and chronic traumatic encephalopathy (CTE), has long been suspected. Shared clinical symptomology - most notably the prominent role of central auditory dysfunction and sleep-wake disturbances in both disease states - and similar findings on postmortem pathological examination has further reinforced suspected commonality between these seemingly disparate entities. However, conventional imaging techniques, including computed tomography and anatomic magnetic resonance, are unable to detect the symptomatic injuries in mTBI patients and therefore detection of neurodegenerative changes in vivo has previously not been reported. Recent research using diffusion tensor imaging, a novel imaging technique, and focused on patient-reported symptoms has for the first time demonstrated imaging findings in mTBI patients in vivo that are strikingly similar to Alzheimer's dementia and CTE. Moving forward, research will focus on identifying what renders certain patients with mTBI susceptible to developing full-fledged Alzheimer's disease and CTE later in life.
24922562	Because of increased levels of airborne particulate matter in Southwest Asia, deployed military personnel are at risk for developing acute and chronic lung diseases. Increased respiratory symptoms are reported, but limited data exist on reported lung diseases.To evaluate new respiratory complaints in military personnel returning from Southwest Asia to determine potential etiologies for symptoms.	Returning military personnel underwent a prospective standardized evaluation for deployment-related respiratory symptoms within 6 months of returning to their duty station.	Prospective standardized evaluation included full pulmonary function testing, high-resolution chest tomography, methacholine challenge testing, and fiberoptic bronchoscopy with bronchoalveolar lavage. Other procedures including lung biopsy were performed if clinically indicated. Fifty patients completed the study procedures. A large percentage (42%) remained undiagnosed, including 12% with normal testing and an isolated increase in lavage neutrophils or lymphocytes. Twenty (40%) patients demonstrated some evidence of airway hyperreactivity to include eight who met asthma criteria and two with findings secondary to gastroesophageal reflux. Four (8%) additional patients had isolated reduced diffusing capacity and the remaining six had other miscellaneous airway disorders. No patients were identified with diffuse parenchymal disease on the basis of computed tomography imaging. A significant number (66%) of this cohort had underlying mental health and sleep disorders.	Evaluation of new respiratory symptoms in military personnel after service in Southwest Asia should focus on airway hyperreactivity from exposures to higher levels of ambient particulate matter. These patients may be difficult to diagnose and require close follow-up.	
24919097	The aim of this study was to determine the effect of relaxation exercises on quality of sleep of the elderly people staying in a nursing home. Control group had 44 elderly persons and the intervention group had 20 elderly persons in a nursing home. Quality of sleep in the intervention group increased statistically (P = .000). The elderly people should be encouraged to perform relaxation exercises. 
24917453	Poor sleep quality is often reported among patients with COPD. Pulmonary rehabilitation (PR) is beneficial in improving exercise capacity and health-related quality of life (HRQOL). However, its benefit in terms of sleep quality in patients with COPD remains unclear. This study aimed to investigate the effects of PR on sleep quality of patients with COPD.Thirty-four subjects with COPD were studied. All subjects participated in a 12-week (2 sessions/week) hospital-based out-patient PR study. Baseline and post-PR status were evaluated by spirometry, a sleep questionnaire (Pittsburgh Sleep Quality Index [PSQI]), a disease-specific questionnaire of HRQOL (St George Respiratory Questionnaire [SGRQ]), cardiopulmonary exercise testing, respiratory muscle strength, and the Borg dyspnea scale.	Mean FEV1/FVC in the subjects was 0.49 ± 0.13, and the mean FEV1 was 1.06 ± 0.49 L/min (49.7 ± 18.0% of predicted). After PR, the PSQI score decreased from 9.41 ± 4.33 to 7.82 ± 3.90 (P < .001). The number of subjects with a PSQI score > 5 also decreased (85.3-64.7%, P = .006). There were significant improvements in HRQOL (SGRQ, P = .003), exercise capacity (peak oxygen uptake, P < .001; and work rate, P < .001), dyspnea score (P < .001), and respiratory muscle strength (inspiratory muscle strength, P = .005; and expiratory muscle strength, P = .004) after PR. There were no significant changes in pulmonary function test results (FEV1, P = .77; FVC, P = .90; FEV1/FVC, P = .90).	PR results in significant improvement in sleep quality, along with concurrent improvements in HRQOL and exercise capacity. PR is an effective nonpharmacologic treatment to improve sleep quality in patients with COPD and should be part of their clinical management.	
24916951	To improve mechanistic understanding, this pilot randomized controlled trial examined mediators of an exercise intervention effects on sleep in breast cancer survivors (BCS).Forty-six postmenopausal BCS (≤Stage II, off primary treatment) were randomized to a 3-month exercise intervention or control group. Intervention included 160 min/week of moderate intensity aerobic walking, twice weekly resistance training (resistance bands), and six discussion groups (to improve adherence). Blinded assessments at baseline and post-intervention included sleep disturbance (PSQI and PROMIS®), objective sleep quality (accelerometer), serum cytokines, accelerometer physical activity, cardiorespiratory fitness, body composition, fatigue, and psychosocial factors. Mediation was tested using Freedman-Schatzkin difference-in-coefficients tests.	When compared with control, the intervention group demonstrated a significant increase in PSQI sleep duration (i.e., fewer hours of sleep/night) (d = 0.73, p = .03). Medium to large but non-significant standardized effect sizes were noted for PSQI daytime somnolence (d = -0.63, p = .05) and accelerometer latency (d = -0.49, p = .14). No statistically significant mediators were detected for PSQI sleep duration score or accelerometer latency. Daytime somnolence was mediated by tumor necrosis factor-alpha (mediated 23% of intervention effect, p < .05), interleukin (IL)-6:IL-10 (16%, p < .01), IL-8:IL-10 (26%, p < .01), and fatigue (38%, p < .05). Mediating or enhancing relationships for several of the sleep outcomes were noted for accelerometer physical activity, PROMIS® fatigue, exercise social support, and/or physical activity enjoyment.	Inflammation and psychosocial factors may mediate or enhance sleep response to our exercise intervention. Further study is warranted to confirm our results and translate our findings into more effective interventions aimed at improving sleep quality in BCS.	
24916389	Circadian oscillators are autonomous molecular rhythms that reside in cells to align whole-organism physiology and behavior to the 24-h day. In flies, as in mammals, the oscillator operates in cells that coexpress CLOCK (CLK) and CYCLE (CYC). Recent work in Drosophila has shown that CLK is unique in its ability to generate heterologous oscillators, indicating that Clk gene expression defines the circadian cell fate. Here, using standard in vitro and in vivo techniques, we show that TWIN-OF-EYELESS (TOY; dPax6) regulates Clk expression in small ventrolateral neurons (s-LNvs) that coordinate sleep-wake cycles. Crucially, toy binds multiple sites at the Clk locus, is expressed independent of CLK-CYC in LNvs, regulates CLK protein levels under optimal photoperiodic conditions, and sets clock-speed during endogenous free-run. Furthermore, TOY is necessary for the onset of Clk expression in LNvs during embryogenesis. We propose that TOY contributes to a transcription complex that functions upstream of the oscillator to promote Clk expression in s-LNvs.
24916093	To translate and validate the Sleep Disturbance Scale for Children (SDSC), a promising questionnaire for use among children in epidemiological studies, in Chinese children.In total, 3525 children aged 5-16 years were randomly selected from five primary schools in Shenyang. Internal consistency, reliability and factor analyses were undertaken to assess the construct validity of the SDSC.	Internal consistency indicated adequate reliability (Cronbach's α=0.81). Factor analytic results indicated a six-factor solution (ie, six types of sleep disorder) based on parent-reported sleep disorder symptoms. The mean total score of the SDSC was 39.28±7.83 and 156 (4.43%) children were identified as suffering from parent-reported sleep disorder. The prevalence for each sleep type disorder ranged from 3.46% to 6.30% with the highest for sleep hyperhidrosis (SHY) and the lowest for disorders of initiating and maintaining sleep. Significant differences were found between boys and girls in the prevalence of sleep breathing disorders (6.51% vs. 3.72%), SHY (8.62% vs. 4.00%) and parent-reported sleep disorders (5.19% vs. 3.67%).	The SDSC is reliable and useful in screening for parent-reported sleep disorders in Chinese children. Compared with other countries, parent-reported sleep disorders among Chinese elementary school children were at a relatively low level of prevalence.	

24914026	Accurately diagnosing sleep-related events, and particularly distinguishing nocturnal frontal lobe seizures from other sleep disorders such as parasomnias, can be challenging. This article reviews the differential diagnosis of paroxysmal events from sleep, epileptic and non-epileptic, considers important diagnostic points in the history, and evaluates the role of investigations in this setting. 
24913201	To investigate the effect of chronic pelvic pain (CPP), a debilitating condition, on sleep quality.The present case-control study enrolled women older than 18 years attending the Gynecology Clinic of Çanakkale Onsekiz Mart University Hospital, Çanakkale, Turkey, with CPP between August 2011 and August 2012. The control group was selected from women attending the clinic for another complaint. Sleep quality was evaluated via the Pittsburgh Sleep Quality Index, and differences between the groups were compared by t and χ(2) tests.	During the study period, 157 women were enrolled. Seventy-two had CPP symptoms, and 85 attended the clinic for other complaints. Poor sleep quality was found in 80% (n = 58) of the women with CPP, and 55% (n = 47) of the control group (P < 0.05).	Women with CPP were found to have poor sleep quality. Sleep education should be recommended in psychiatry and neurology clinics to increase the awareness of sleeping problems among these women.	
24912736	Stress plays a major role at the onset and relapse of pathological gambling (PG), but at the same time it can also be the aftermath of gambling behavior, thus revealing a reciprocal relationship. Although the role of stress has been well-documented, there is a paucity of studies investigating the effect of an adjunctive stress management program on PG. In this 8-week parallel randomized waitlist controlled trial pathological gamblers, already in the gamblers anonymous (GA) group, were assigned randomly in two groups, with the intervention group (n = 22) receiving an additional stress management program (consisting of education on diet and exercise, stress coping methods, relaxation breathing -RB- and progressive muscle relaxation -PMR). Self-reported measures were used in order to evaluate stress, depression, anxiety, sleep quality/disturbances, life-satisfaction and daily routine. The statistical analyses for the between group differences concerning the main psychosocial study outcomes revealed a statistically significant amelioration of stress, depression, anxiety symptoms and an increase of life-satisfaction and a better daily routine in participants of the intervention group. We hope that these will encourage researchers and clinicians to adopt stress management in their future work. 
24912303	Insomnia disorder is one of the most prevalent conditions comorbid with diabetes and has been shown to have a possible role in the development of diabetes. Insomnia is characterized by a state of excessive physiological and cognitive arousal with alterations in autonomic and hypothalamic-pituitary-adrenal function. The chronic neuroendocrine activation in insomnia may predispose insomniacs to the development of metabolic disorders including glucose intolerance. In contrast, diabetic complications, in combination with the disruption of a sleep-wake homeostatic and circadian process, can be key factors precipitating insomnia symptoms and involve several subtypes of insomnia. Furthermore, inappropriate lifestyles are also likely responsible for the exacerbation of insomnia and diabetes. Thus, the pathogenesis of insomnia disorder and diabetes could mutually interact to develop each disease with a vicious cycle, accounting for the high comorbidity between the diseases.
24912295	It has been reported that patients with epilepsy often have insomnia and/or daytime sleepiness; the symptomatologic features differ in seizure types. Not only the administration of anti-epileptics, but also inappropriate sleep hygiene cause daytime sleepiness. In subjective assessment of sleepiness, we need to pay attention if it can correctly assess or not. The prevalence of obstructive sleep apnea in patients with epilepsy is approximately 10-30%. Sleep apnea deteriorates the seizure control because of worsen sleep condition by sleep apnea, especially in elderly patients. Some researchers report that continuous positive airway pressure was effective for seizure control. Patients with epilepsy occasionally have REM sleep behavior disorder as comorbidity. Examination using polysomnography is required for differential diagnosis.
24910903	Sleep quality disturbances are common in patients with systemic lupus erythematosus (SLE). We evaluated sleep quality and its contributors in women with SLE. Also we evaluated the effects of sleep quality disturbance on patients' health-related quality of life (HRQoL).Sleep quality was assessed in 77 women with SLE (age 36.5 ± 10.1 years) using the Pittsburgh Sleep Quality Index (PSQI). Disease activity and cumulative disease damage were assessed with standard indices. Patients completed the Hospital Anxiety and Depression Scale and LupusQoL. Univariate and multivariate analyses were performed to find contributors of poor sleep quality and association of sleep quality with HRQoL.	Poor sleep quality was present in 44 patients (57.1%). Poor sleepers were older (P = 0.015) and had higher body mass index (P = 0.027) and more severe anxiety (P < 0.001) and depression symptoms (P < 0.007) compared with good sleepers. In the logistic regression model, age (β = 1.16, P = 0.006), disease activity (β = 1.10, P = 0.050), and anxiety/depression composite score (β = 1.16, P = 0.008) were independent contributors of poor sleep quality. Poor sleepers had impaired HRQoL in almost all domains of the LupusQoL than good sleepers (P < 0.05).	Poor sleep quality is common in women with SLE and significantly impairs their HRQoL. Age, disease activity and psychological factors were determinants of sleep quality in our study. Studies with objective sleep measures as well as interventional studies are warranted in this regard.	

24910393	Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline that is a growing public health crisis with a prevalence projected to more than double in the next 20 years. Sleep is frequently impaired in individuals with AD. Further, recent studies have linked numerous age-related sleep disturbances such as poor sleep efficiency and sleep apnea, to future risk of cognitive impairment. Aggregation of amyloid-β (Aβ) into extracellular plaques in the brain is a key step in AD pathogenesis and likely begins 20 years before the onset of dementia. Aβ concentrations in both humans and mouse models show Aβ concentrations rise during wakefulness and fall during sleep, that is, an Aβ diurnal pattern. There is evidence in animal models that changes in sleep time alter Aβ deposition, suggesting that sleep may play a role in AD pathogenesis. A hypothetical model for the role of sleep and the Aβ diurnal pattern in AD pathogenesis is proposed. 
24909899	Sleep/wake disorders are frequently associated with anxiety and depression and to elevated levels of cortisol. Even though these alterations are increasingly sought in animal models, no study has investigated the specific effects of chronic corticosterone (CORT) administration on sleep. We characterized sleep/wake disorders in a neuroendocrine mouse model of anxiety/depression, based on chronic CORT administration in the drinking water (35 μg/ml for 4 weeks, "CORT model"). The CORT model was markedly affected during the dark phase by non-rapid eye movement sleep (NREM) increase without consistent alteration of rapid eye movement (REM) sleep. Total sleep duration (SD) and sleep efficiency (SE) increased concomitantly during both the 24h and the dark phase, due to the increase in the number of NREM sleep episodes without a change in their mean duration. Conversely, the total duration of wake decreased due to a decrease in the mean duration of wake episodes despite an increase in their number. These results reflect hypersomnia by intrusion of NREM sleep during the active period as well as a decrease in sleep/wake continuity. In addition, NREM sleep was lighter, with an increased electroencephalogram (EEG) theta activity. With regard to REM sleep, the number and the duration of episodes decreased, specifically during the first part of the light period. REM and NREM sleep changes correlated respectively with the anxiety and the anxiety/depressive-like phenotypes, supporting the notion that studying sleep could be of predictive value for altered emotional behavior. The chronic CORT model in mice that displays hallmark characteristics of anxiety and depression provides an insight into understanding the changes in overall sleep architecture that occur under pathological conditions.


24908494	Sleep disorders are highly prevalent in patients with fibromyalgia (FM). Many of the daytime symptoms, such as chronic pain and fatigue, may be related to the non-restorative sleep patterns associated with the disease. Pain influences the sleep process and sleep disturbances decrease the pain threshold in a reciprocal framework. Thus, understanding the link between sleep and FM has become an important research topic in basic science. Therefore, in the current review we connect these topics and provide some insights into the cyclic relationship between sleep and pain, which has been addressed mainly in animal models. Additionally, we highlight the urgent need for sleep studies in FM animal models, which might improve the knowledge base and accelerate advances in this field. 
24908150	Obesity and excess bodyweight are highly prevalent in individuals with bipolar disorders (BD) and are associated with adverse consequences. Multiple factors may explain increased bodyweight in BD including side effects of psychotropic medications, and reduced physical activity. Research in the general population demonstrates that sleep disturbances may also contribute to metabolic burden. We present a cross-sectional study of the associations between body mass index (BMI) and sleep parameters in patients with BD as compared with healthy controls (HC).Twenty-six French outpatients with remitted BD and 29 HC with a similar BMI completed a 21-day study of sleep parameters using objective (actigraphy) and subjective (PSQI: Pittsburgh Sleep Quality Index) assessments.	In BD cases, but not in HC, higher BMI was significantly correlated with lower sleep efficiency (P=0.009) and with several other sleep parameters: shorter total sleep time (P=0.01), longer sleep onset latency (P=0.05), higher fragmentation index (P=0.008), higher inter-day variability (P=0.05) and higher PSQI total score (P=0.004).	The findings suggest a link between a high BMI and several sleep disturbances in BD, including lower sleep efficiency. Physiological mechanisms in BD cases may include an exaggeration of phenomena observed in non-clinical populations. However, larger scale studies are required to clarify the links between metabolic and sleep-wake cycle disturbances in BD.	
24907966	Chronic obstructive pulmonary disease is a leading cause of morbidity and mortality worldwide. Sleep-induced hypoxemia is defined as "an SpO2 (oxyhemoglobin saturation) during sleep of < 90% for more than five minutes with a nadir of at least 85%" or "> 30% of total sleep time with an SpO2 of < 90%" in subject with a baseline awake SpO2 of ≥ 90%. Patients with moderate or severe COPD run a high risk of developing SIH mainly because of alveolar hypoventilation and ventilation-perfusion mismatch. Compared to their non-SIH brethren, SIH COPD patients have greater degrees of pulmonary hypertension and cor pulmonale, require more frequent hospitalizations, and sustain higher mortality rates. And the necessity of treatment of isolated SIH in COPD has been debated for years. In this mini review, the definition, reasons, prevalence, clinical significance and treatment approaches of SIH in COPD are summarized.
24907046	The study examined prevalence of self-reported use of medication recommended or prescribed by a doctor for depression, anxiety, stress, and sleep problems; and modelled baseline factors that predicted use over 3 years for each condition.Analyses were undertaken on the 2001 and 2004 surveys of mid-aged women in the Australian Longitudinal Study on Women's Health. Dependent variables were self-reported use in past 4 weeks of medications recommended or prescribed by a doctor for depression, anxiety, stress, or sleep problems in 2001 and 2004. Generalized Estimating Equations (GEE) were used to predict medication use for each condition over 3 years.	Prevalence of prescribed medication use (2001, 2004) for each condition was depression (7.2, 8.9 %), anxiety (7.4, 9.0 %), stress (4.8, 5.7 %), and sleep problems (8.7, 9.5 %). Multivariable analyses revealed that odds of medication use across 3 years in all four conditions were higher for women with poorer mental and physical health, using hormone replacement therapy (HRT), or having seen a counsellor; and increased over time for depression, anxiety, and stress models. Medication use for depression was also higher for overweight/obese women, ex-smokers, and unmarried. Medication use for anxiety was higher for unmarried and non-working/low occupational women. Medication use for stress was higher for non-working women. Additional predictors of medication for sleep were surgical menopause, and area of residence.	Self-reported use of prescribed medication for four mental health conditions is increased over time after controlling for mental and physical health and other variables. Research needs to explore decision-making processes influencing differential rates of psychoactive medication use and their relationship with health outcomes.	

24905488	Sleep disorders can affect the health of physicians and patient outcomes.To determine the prevalence of sleep disorders among French anaesthesiologists and intensivists working in a public hospital.	A cross-sectional survey.	Anaesthesiologists and intensivists working in French public hospitals.	Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) was used to assess the degree of excessive daytime sleepiness.	Among 1504 responders, 677 (45%) physicians reported sleep disorders. The independent factors associated with sleep disorders were reporting of sleep disorders [odds ratio (OR) 12.04, 95% CI (95% confidence interval) 8.89 to 16.46], sleep time less than 7 h (OR 8.86, 95% CI 6.50 to 12.20), work stress (OR 2.04, 95% CI 1.49 to 2.83), stress at home (OR 1.77, 95% CI 1.24 to 2.53), anxiolytic use (OR 3.69, 95% CI 2.23 to 6.25), psychotropic drug use (OR 3.91, 95% CI 1.51 to 11.52) and excessive daytime sleepiness (OR 1.81, 95% CI 1.34 to 2.45). Six hundred and seventy-six (44%) responders reported excessive daytime sleepiness during their professional activity. The independent factors associated with excessive daytime sleepiness were female sex (OR 1.86, 95% CI 1.49 to 2.34), tea consumption (OR 1.47, 95% CI 1.14 to 1.91), regular practice of nap (OR 1.68, 95% CI 1.34 to 2.09), stress at home (OR 1.31, 95% CI 1.02 to 1.68), more than four extended work shifts monthly (OR 1.25, 95% CI 1.01 to 1.56) and sleep disorders (OR 1.73, 95% CI 1.31 to 2.29). Reporting sleep disorder duration and a sleep time less than 7 h were the two major risk factors for sleep disorders. Female sex was the major risk factor for excessive daytime sleepiness.	French anaesthesiologists did not report more sleep disorders than the general population, but their alertness is impaired by a factor of two.	
24904294	We present a preliminary study of a thalamo-cortico-thalamic (TCT) implementation on SpiNNaker (Spiking Neural Network architecture), a brain inspired hardware platform designed to incorporate the inherent biological properties of parallelism, fault tolerance and energy efficiency. These attributes make SpiNNaker an ideal platform for simulating biologically plausible computational models. Our focus in this work is to design a TCT framework that can be simulated on SpiNNaker to mimic dynamical behavior similar to Electroencephalogram (EEG) time and power-spectra signatures in sleep-wake transition. The scale of the model is minimized for simplicity in this proof-of-concept study; thus the total number of spiking neurons is ≈1000 and represents a "mini-column" of the thalamocortical tissue. All data on model structure, synaptic layout and parameters is inspired from previous studies and abstracted at a level that is appropriate to the aims of the current study as well as computationally suitable for model simulation on a small 4-chip SpiNNaker system. The initial results from selective deletion of synaptic connectivity parameters in the model show similarity with EEG power spectra characteristics of sleep and wakefulness. These observations provide a positive perspective and a basis for future implementation of a very large scale biologically plausible model of thalamo-cortico-thalamic interactivity-the essential brain circuit that regulates the biological sleep-wake cycle and associated EEG rhythms. 
24903537	To examine an association between self-reported sleep quality determined by Pittsburgh sleep quality index (PSQI) and metabolic syndrome.This study was designed as cross-sectional study. Participants were 1481 adults aged 20 years and above from general population (549 males and 932 females). We assessed the global sleep quality by PSQI. PSQI consists of 7 elements, i.e. subjective sleep quality, sleep latency (prolonged sleep onset time), sleep duration, habitual sleep efficiency (proportion of hours slept to hours spent in bed), sleep disturbance (interruption of sleep), use of sleep medication and daytime dysfunction (trouble staying awake while engaging in social activity). Any participants with score of 6 or more are diagnosed to have sleep disorder. We also assessed the above 7 elements, which consisted of a four-grade system (i.e. 0, 1, 2, 3). Metabolic syndrome consisted of abdominal obesity, hypertension, impaired glucose tolerance and dyslipidemia. Diagnosis of metabolic syndrome was done when the participants have abdominal obesity and meet two or more other components. All analyses were adjusted by age, drinking habit, smoking habit, working hours, exercise habit and depression.	Fifty-two male participants (9.5%) and 133 female (14.3%) scored 6 or more points in global PSQI score. The global PSQI score, sleep latency score and sleep disturbance score of participants with metabolic syndrome were higher level than those without the condition (p < 0.001, p = 0.009, p = 0.025 for male and p < 0.001, p < 0.001, p = 0.002 for females, respectively). The odds ratio of metabolic syndrome among participants with PSQI score of 6 or more points were 2.37 (95% confidence interval: 1.23-4.58) for males and 2.71 (1.45-5.07) for females in contrast to those with 5 or less points. The odds ratio of metabolic syndrome with sleep latency score of 2 was 2.65 (1.14-6.15) for male and 3.82 (1.81-8.09) for females in contrast with those of 0. The odds ratio of metabolic syndrome with sleep disturbance score of 1 was 1.76 (1.09-2.86) for males and 2.43 (1.26-4.69) for females in contrast with those of 0.	Global PSQI score and its components (especially, sleep latency and sleep disturbance) were associated with metabolic syndrome.	
24901751	Measuring fluctuation of vigilance states in early preterm infants undergoing long term intensive care holds promise for monitoring their neurological well-being. There is currently, however, neither objective nor quantitative methods available for this purpose in a research or clinical environment. The aim of this proof-of-concept study was, therefore, to develop quantitative measures of the fluctuation in vigilance states or brain activity cycling (BAC) in early preterm infants. The proposed measures of BAC were summary statistics computed on a frequency domain representation of the proportional duration of spontaneous activity transients (SAT%) calculated from electroencephalograph (EEG) recordings. Eighteen combinations of three statistics and six frequency domain representations were compared to a visual interpretation of cycling in the SAT% signal. Three high performing measures (band energy/periodogram: R = 0.809, relative band energy/nonstationary frequency marginal: R = 0.711, g-statistic/nonstationary frequency marginal: R = 0.638) were then compared to a grading of sleep wake cycling based on the visual interpretation of the amplitude-integrated EEG trend. These measures of BAC are conceptually straightforward, correlate well with the visual scores of BAC and sleep wake cycling, are robust enough to cope with the technically compromised monitoring data available in intensive care units, and are recommended for further validation in prospective studies. 
24899814	Tryptophan (TRP) and its neuroactive metabolite, kynurenic acid (KYNA), are thought to play key roles in central fatigue, but the specifics are still unknown. To clarify their roles in the brain, we developed a rat model of central fatigue induced by chronic sleep disorder (CFSD) by disturbing the sleep-wake cycle. Results showed that while 5-hydroxytryptamine (5-HT) concentration did not differ between control and CFSD groups, levels of TRP and KYNA in the CFSD group were about 2 and 5 times higher in the hypothalamus, and 2 and 3.5 times higher in the hippocampus, respectively. Moreover, CFSD-induced fatigue led to abnormal running performance (via treadmill test) and social interaction (via social-interaction test). These results support a TRP-KYNA hypothesis in central fatigue in which increased TRP concentration in the brain and subsequently synthesized KYNA may produce an amplified effect on central fatigue, with enhanced concentrations being a possible mechanism by which social-interaction deficits are generated. 
24899766	Narcolepsy is associated with obesity though it is uncertain whether this is caused by changes in glucose and fat metabolism. Therefore, we performed a detailed analysis of systemic energy homeostasis in narcolepsy patients, and additionally, investigated whether it was affected by three months of sodium oxybate (SXB) treatment.Nine hypocretin deficient patients with narcolepsy-cataplexy, and nine healthy sex, age, and BMI matched controls were enrolled. A hyperinsulinemic-euglycemic clamp combined with stable isotopes ([6,6-(2)H2]-glucose and [(2)H5]- glycerol) was performed at baseline. In seven patients a second study was performed after three months of SXB treatment.	Glucose disposal rate (GDR) per unit serum insulin was significantly higher in narcolepsy patients compared to matched controls (1.6 ± 0.2 vs. 1.1 ± 0.3 μmol/kgFFM/min/mU×L; P = 0.024), whereas β-cell function was similar (P = 0.50). Basal steady state glycerol appearance rate tended to be lower in narcolepsy patients (5.2 ± 0.4 vs. 7.5 ± 1.3 μmol/kgFM/min; P = 0.058), suggesting a lower rate of lipolysis. SXB treatment induced a trend in reduction of the GDR (1.4 ± 0.1 vs. 1.1 ± 0.2 μmol/kgFFM/min/mU×L; P = 0.063) and a reduction in endogenous glucose production (0.24 ± 0.03 vs. 0.16 ± 0.03 μmol/kgFFM/min/mU×L: P = 0.028) per unit serum insulin. After SXB treatment lipolysis increased (4.9 ± 0.4 vs. 6.5 ± 0.6 μmol/kgFM/min; P = 0.018), and body weight decreased in narcolepsy patients (99.2 ± 6.0 vs. 94.0 ± 5.4 kg; P = 0.044).	We show that narcolepsy patients are more insulin sensitive and may have a lower rate of lipolysis than matched controls. SXB stimulated lipolysis in narcolepsy patients, possibly accounting for the weight loss after treatment. While sodium oxybate tended to decrease systemic insulin sensitivity, it increased hepatic insulin sensitivity, suggesting tissue-specific effects.	
24899757	To examine associations of objectively and subjectively measured sleep with subsequent cognitive decline.A population-based longitudinal study.	Six centers in the United States.	Participants were 2,822 cognitively intact community-dwelling older men (mean age 76.0 ± 5.3 y) followed over 3.4 ± 0.5 y.	None.	OBJECTIVELY MEASURED SLEEP PREDICTORS FROM WRIST ACTIGRAPHY: total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of long wake episodes (LWEP). Self-reported sleep predictors: sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), TST. Clinically significant cognitive decline: five-point decline on the Modified Mini-Mental State examination (3MS), change score for the Trails B test time in the worse decile. Associations of sleep predictors and cognitive decline were examined with logistic regression and linear mixed models. After multivariable adjustment, higher levels of WASO and LWEP and lower SE were associated with an 1.4 to 1.5-fold increase in odds of clinically significant decline (odds ratio 95% confidence interval) Trails B test: SE < 70% versus SE ≥ 70%: 1.53 (1.07, 2.18); WASO ≥ 90 min versus WASO < 90 min: 1.47 (1.09, 1.98); eight or more LWEP versus fewer than eight: 1.38 (1.02, 1.86). 3MS: eight or more LWEP versus fewer than eight: 1.36 (1.09, 1.71), with modest relationships to linear change in cognition over time. PSQI was related to decline in Trails B performance (3 sec/y per standard deviation increase).	Among older community-dwelling men, reduced sleep efficiency, greater nighttime wakefulness, greater number of long wake episodes, and poor self-reported sleep quality were associated with subsequent cognitive decline.	
24899755	To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome (RLS)-related sleep disturbance.Randomized, double-blinded, crossover trial.	Twenty-three US sleep centers.	Eighty-five individuals with moderate to severe idiopathic RLS and associated sleep disturbance.	Participants were randomized across 6 treatment sequences comprising three 4-week periods on pregabalin 300 mg/day (n = 75), pramipexole 0.5 mg/day (n = 76), or placebo (n = 73).	Polysomnography was conducted over 2 nights at the end of each period. Primary (wake after sleep onset [WASO], pregabalin vs placebo) and key secondary endpoints were analyzed for statistical significance, with descriptive statistics for other endpoints. Pregabalin improved sleep maintenance, demonstrated by reductions in WASO (-27.1 min vs placebo [P < 0.0001]; -26.9 vs pramipexole) and number of awakenings after sleep onset (-2.7 vs placebo; -7.9 vs pramipexole [P < 0.0001]) by polysomnography, and an increase in subjective total sleep time (30.8 min vs placebo [P < 0.0001]; 26.8 vs pramipexole). Pregabalin also increased slow wave sleep duration (20.9 min vs placebo; 32.1 vs pramipexole [P < 0.0001]). Reduction in periodic limb movement arousal index (PLMAI) with pregabalin was similar to pramipexole and greater than placebo (-3.7 PLMA/h [P < 0.0001]), although reduction in total PLM in sleep was less than for pramipexole.	This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole.	
24899547	Fatigue is one of the most prevalent and significant symptoms experienced by breast cancer patients. This study aimed to investigate potential population heterogeneity in fatigue symptoms of the patients using the innovative non-normal mixture modeling.A sample of 197 breast cancer patients completed the brief fatigue inventory and other measures on cancer symptoms. Non-normal factor mixture models were analyzed and compared using the normal, t, skew-normal, and skew-t distributions. Selection of the number of latent classes was based on the Bayesian information criterion (BIC). The identified classes were validated by comparing their demographic profiles, clinical characteristics, and cancer symptoms using a stepwise distal outcome approach.	The observed fatigue items displayed slight skewness but evident negative kurtosis. Factor mixture models using the normal distribution pointed to a 3-class solution. The t distribution mixture models showed the lowest BIC for the 2-class model. The restored class (52.5 %) exhibited moderate severity (item mean = 2.8-3.2) and low interference (item mean = 1.1-1.9). The exhausted class (47.5 %) displayed high levels of fatigue severity and interference (item mean = 5.8-6.6). Compared to the restored class, the exhausted class reported significantly higher perceived stress, anxiety, depression, pain, sleep disturbance, and lower quality of life.	The non-normal factor mixture models suggest two distinct subgroups of patients on their fatigue symptoms. The presence of the exhausted class with exacerbated symptoms calls for a proactive assessment of the symptoms and development of tailored interventions for this subgroup.	
24899350	All mammals show daily rhythms in their physiological activity, for example, sleep-wake cycles. This rhythmicity is endogenously generated by a system called the circadian clock, and is composed of reactions occurring in several neural/cellular layers of multicellular organisms. Inter-cellular and inter-organ communication is important for the synchronous action of circadian rhythmicity across the whole body. The heart of the circadian system lies in the rhythmic neuronal activity of the suprachiasmatic nuclei (SCN) in the brain. The oscillation emerges as cell-autonomous rhythmic gene expression observed in individual SCN neurons. Inter-neuronal communication synchronizes the circadian phase of each neuron within the SCN. The integrated rhythmic SCN activity works as a pacemaker for the circadian clocks of non-SCN cells, each of which also rhythmically express clock genes. The -24-h period length of the circadian rhythm is predominantly determined by reactions at the molecular level. Cell-autonomous circadian oscillation is driven by a negative feedback loop of transcription regulation, where CRY/PER heterodimers act as the transcriptional repressors of their own genes. One of the rate limiting steps of circadian cycling is a phosphorylation of CRY and PER proteins followed by proteasome-mediated degradation of those proteins. Pharmacological and genetic perturbation of the phosphorylation or degradation pathways alters the circadian period length. This review provides a hierarchical view of the circadian system, which is important to uncover the different effects of medical or social perturbations on circadian regulation of inter-cellular synchronization, or cell-autonomous oscillation.
24894508	Although short sleep is associated with an increased risk of morbidity as well as mortality and has been shown to vary by industry of employment and occupation, little is known about the relationship between work and sleep among Asian Americans.Using a nationally representative sample of US adults (n = 125,610) in the National Health Interview Survey from 2004-2011, we estimated prevalence ratios for self-reported short sleep duration (<7 hours) in Asians compared to Whites by industry of employment and occupation using adjusted Poisson regression models with robust variance.	Asians were more likely to report short sleep duration than Whites (33 vs. 28%, p < 0.001), and the Asian-White disparity was widest in finance/information and healthcare industries. Compared to Whites after adjustments, short sleep was also more prevalent among Asians employed in Public administration (PR = 1.35 [95% CI: 1.17,1.56]), Education (PR = 1.29 [95% CI: 1.08,1.53]), and Professional/Management (PR = 1.18 [95% CI: 1.03,1.36]). Short sleep, however, was lower among Asians in Accommodation/Food (PR = 0.81 [95% CI: 0.66, 0.99]) with no difference in Retail. In professional and support-service occupations, short sleep was higher among Asians, but was not different among laborers.	U.S. Asian-White disparities in short sleep varied by industries, suggesting a need to consider both race and occupational characteristics to identify high-risk individuals.	
24893889	Sleep is considered an important time of healing and restoration during illness. The primary aim of this study was to determine the prevalence of self-reported sleep disturbance in children admitted to a tertiary children's hospital with a variety of medical diagnoses.Parents of children admitted to the hospital, aged between 1 and 18 years, were asked to complete a sleep diary during one night of their child's hospital stay. Children older than 12 years were asked to complete a diary independently. Descriptive statistics were used to summarise the data.	Overall, 107 children were surveyed for one hospital inpatient night. The overall prevalence of poor sleep was 52.3%. The wide age range and variety of diagnosis limited further detailed analysis of specific causes of this problem. Poor sleep prior to admission was the strongest predictor of poor sleep in hospital suggesting that these children already had an underlying sleep problem. Unprompted awakenings were predominantly due to toileting (17.8%) or were spontaneous (17.8%). Factors specific to the hospital environment that woke children were nursing cares (25.2%), alarms (12.1%) and pain (12.1%).	Children admitted to hospital have a higher prevalence of poor sleep compared with healthy children in the community. Children were woken frequently by both external noise and attention provided by hospital staff. Education of hospital staff about the importance of sleep for children and factors that affect children's sleep may reduce the negative impact of hospitalisation on children's sleep.	
24893318	Non-image-forming (NIF) responses to light powerfully modulate human physiology. However, it remains scarcely understood how NIF responses to light modulate human sleep and its EEG hallmarks, and if there are differences across individuals. Here we investigated NIF responses to light on sleep in individuals genotyped for the PERIOD3 (PER3) variable-number tandem-repeat (VNTR) polymorphism. Eighteen healthy young men (20-28 years; mean ± SEM: 25.9 ± 1.2) homozygous for the PER3 polymorphism were matched by age, body-mass index, and ethnicity. The study protocol comprised a balanced cross-over design during the winter, during which participants were exposed to either light of 40 lx at 6,500 K (blue-enriched) or light at 2,500 K (non-blue enriched), during 2h in the evening. Compared to light at 2,500 K, light at 6,500 K induced a significant increase in all-night NREM sleep slow-wave activity (SWA: 1.0-4.5 Hz) in the occipital cortex for PER3(5/5) individuals, but not for PER3(4/4) volunteers. Dynamics of SWA across sleep cycles revealed increased occipital NREM sleep SWA for virtually all sleep episode only for PER3(5/5) individuals. Furthermore, they experienced light at 6,500 K as significantly brighter. Intriguingly, this subjective perception of brightness significantly predicted their increased occipital SWA throughout the sleep episode. Our data indicate that humans homozygous for the PER3(5/5) allele are more sensitive to NIF light effects, as indexed by specific changes in sleep EEG activity. Ultimately, individual differences in NIF light responses on sleep may depend on a clock gene polymorphism involved in sleep-wake regulation.
24892898	Disordered sleep is associated with a number of adverse health consequences and is an integral component of many psychiatric disorders. Rates of substance use disorders (SUDs) are markedly higher among individuals with post-traumatic stress disorder (PTSD), and this relationship may be partly mediated by disturbed sleep. Sleep disturbances (e.g. insomnia, daytime sleepiness, vivid nightmares) are hallmark features of PTSD and there is evidence that individuals with PTSD engage in substance use as a means of coping with these symptoms. However, prolonged substance use can lead to more severe sleep disturbances due to the development of tolerance and withdrawal. Behavioural or pharmacological treatment of disordered sleep is associated with improved daytime symptoms and psychosocial functioning among individuals who have developed PTSD. Initial research also suggests that improving sleep could be similarly beneficial in reducing coping oriented substance use and preventing relapse among those seeking treatment for SUDs. Together, these findings suggest that ameliorating sleep disturbance among at-risk individuals would be a viable target for the prevention and treatment of PTSD and associated SUDs, but prospective research is needed to examine this hypothesis. Enhanced understanding of the interrelation between sleep, PTSD, and SUDs may yield novel prevention and intervention approaches for these costly, prevalent and frequently co-occurring disorders.
24892893	Rates of obesity and sleep disturbances are substantial in adults. A number of cross-sectional, longitudinal, and experimental studies have found that insufficient sleep and possibly longer sleep are associated with obesity and related eating patterns. Methodological discrepancies and limitations in the literature create ambiguity about the nature and potential mechanisms underlying these relationships. Insomnia and circadian patterns in eating and sleeping have also been examined in relation to weight. Although these studies are not as extensive as those examining sleep duration, the extant literature suggests possible associations between obesity and both insomnia (particularly when combined with short sleep duration) and circadian eating behaviours. However, research has only just begun to examine the benefits of combining sleep interventions with obesity treatment. The goal of the current review is to summarize research examining behavioural sleep patterns and disorders in relation to obesity, to discuss methodological considerations, and to provide an overview of studies examining whether addressing sleep disturbances can augment weight loss treatment effects. We conclude that future studies are needed that take into account sleep duration, sleep disorder co-morbidity, and chronobiology to explore the impact of sleep interventions on weight loss.
24892892	There is increasing awareness of the role of sleep disturbance as an important factor in health and disease. Although sub-clinical sleep disturbances (insufficient sleep duration or inadequate sleep quality) may be difficult to assess with conceptual and/or methodological clarity, this review attempts to summarize and synthesize these findings. First, the concept of sleep disturbance in a public health context is introduced, to provide context and rationale. Second, operational definitions of 'cardiometabolic disease' and 'sleep disturbance' are offered, to address many unclear operationalizations. Third, the extant literature is summarized regarding short or long sleep duration and/or insufficient sleep, insomnia and insomnia symptoms, general (non-specific sleep disturbances), circadian rhythm abnormalities that result in sleep disturbances, and, briefly, sleep-disordered breathing. Fourth, the review highlights the social/behavioural context of sleep, including discussions of sleep and race/ethnicity, socio-economic position, and other social/environmental factors, in order to place these findings in a social-environmental context relevant to public health. Fifth, the review highlights the issue of sleep as a domain of health behaviour and addresses issues regarding development of healthy sleep interventions. Finally, a research agenda of future directions is proposed.
24892891	Circadian rhythms are near 24-h patterns of physiology and behaviour that are present independent of external cues including hormones, body temperature, mood, and sleep propensity. The term 'circadian misalignment' describes a variety of circumstances, such as inappropriately timed sleep and wake, misalignment of sleep/wake with feeding rhythms, or misaligned central and peripheral rhythms. The predominance of early research focused on misalignment of sleep to the biological night. However, discovery of clock genes and the presence of peripheral circadian oscillators have expanded the definitions of misalignment. Experimental studies conducted in animal models and humans have provided evidence of potential mechanisms that link misalignment to negative outcomes. These include dysregulation of feeding behaviours, changes in appetite stimulating hormones, glucose metabolism and mood. This review has two foci: (1) to describe how circadian misalignment has been defined and evaluated in laboratory and field experiments, and (2) to describe evidence linking different types of circadian misalignment to increased risk for physical (cardiovascular disease, diabetes, obesity, cancer) and psychiatric (depression, bipolar, schizophrenia, attention deficit) disorders. This review will describe the role of circadian misalignment as a risk factor for disease in the general population and in clinical populations, including circadian rhythm sleep disorders and psychiatric disorders.

24891007	Randomised, double-blind, placebo-controlled crossover trial of melatonin supplementation to people with complete tetraplegia.To investigate the effect that 3 mg melatonin supplementation has on objective and subjective sleep, quality of life and mood of people living with complete tetraplegia.	Austin Hospital Sleep Laboratory and participants' homes, Melbourne, Victoria, Australia.	Two week run-in followed by 3 week nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3 week administration of the opposite treatment. Four testing sessions were conducted; the last nights of the run-in, treatment and washout periods. Testing sessions involved recording full polysomnography, completing a questionnaire battery and collecting urine and blood samples. The questionnaires assessed mood, sleep symptoms and health-related quality of life, and the urine and plasma samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively. A sleep diary was completed throughout the study.	Eight participants (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in which seven concluded the protocol. Endogenous-circulating melatonin was significantly higher (P < or = 0.01) following melatonin (urine: 152.94 μg h(-1) (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 μg h(-1) (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly following melatonin specifically for duration of sleep per night and psychological wellbeing. Objective sleep showed a significant increase in light sleep with melatonin, with all other sleep parameters being unchanged.	These results suggest that increasing melatonin in people with complete tetraplegia is beneficial, especially for subjective sleep. Investigation of the pharmacokinetics of melatonin metabolism in this population is warranted.	This project is proudly supported by the Transport Accident Commission.	
24889836	To evaluate sleep-wake disturbances in sedentary community-dwelling elderly adults with functional limitations.Cross-sectional.	Lifestyle Interventions and Independence in Elder (LIFE) Study.	Community-dwelling persons (mean age 78.9) who spent fewer than 20 min/wk in the previous month engaged in regular physical activity and fewer than 125 min/wk of moderate physical activity, and had a Short Physical Performance Battery (SPPB) score of <10 (N = 1,635).	Mobility was evaluated according to 400-m walk time (slow gait speed defined as <0.8 m/s) and SPPB score (≤ 7 defined moderate to severe mobility impairment). Physical inactivity was defined according to sedentary time, as a percentage of accelerometry wear time with activity of <100 counts/min; participants in the top quartile of sedentary time were classified as having a high sedentary time. Sleep-wake disturbances were evaluated using the Insomnia Severity Index (ISI) (range 0-28; ≥ 8 defined insomnia), Epworth Sleepiness Scale (ESS) (range 0-24; ≥ 10 defined daytime drowsiness), Pittsburgh Sleep Quality Index (PSQI) (range 0-21; >5 defined poor sleep quality), and Berlin Questionnaire (high risk of sleep apnea).	Prevalence rates were 43.5% for slow gait speed and 44.7% for moderate to severe mobility impairment, with 77.0% of accelerometry wear time spent as sedentary time. Prevalence rates were 33.0% for insomnia, 18.1% for daytime drowsiness, 47.8% for poor sleep quality, and 32.9% for high risk of sleep apnea. Participants with insomnia had a mean ISI score of 12.1, those with daytime drowsiness had a mean ESS score of 12.5, and those with poor sleep quality had a mean PSQI score of 9.2. In adjusted models, measures of mobility and physical inactivity were generally not associated with sleep-wake disturbances, using continuous or categorical variables.	In a large sample of sedentary community-dwelling elderly adults with functional limitations, sleep-wake disturbances were prevalent but only mildly severe and were generally not associated with mobility impairment or physical inactivity.	
24889393	To assess the relationships between migraine, depression, anxiety, stress, and sleep problems. Psychiatric conditions and sleep disturbances are common in migraineurs. Depression, anxiety, stress, migraine, and sleep problems frequently coexist as comorbidities. Eighty-seven episodic migraineurs (62 females, 25 males; 32.8 ± 6.9) and 41 control subjects (25 females, 16 males; 31.5 ± 5.6) were prospectively enrolled for the study. The participants completed a sociodemographic data form and a migraine disability assessment scale (MIDAS), depression, anxiety, stress scale (DASS), and Pittsburg Sleep Quality Index (PSQI). In migraineurs, a significant positive correlation was found between PSQI total scores and MIDAS scores (migraine related disability for at least three consecutive months) (r = 0. 234, p = 0.04). Only 24.1 % of migraineus (n = 21) had minimal or no disability, 75.9 % of the patients (n = 66) had more than a little disability according to MIDAS scores. PSQI total scores were also correlated with pain intensity over a three month period (MIDAS B) (r = 0.221, p = 0.04). While PSQI scores were found significantly different between migraineurs and control subjects (5.5 ± 2.9 vs 4.5 ± 2.5; p = 0.04), the correlation of all the DASS subscale scores between the groups was not statistically significant. Our findings showed that episodic migraine was a risk factor on its own for sleep disturbances without comorbid depression, anxiety, and stress. Moreover, migraine-related disability and pain intensity in migraine attacks were related to poor sleep quality.
24887407	In our previous studies, we found that the Ile394Thr SNP in the melanopsin gene (OPN4) was functionally associated with the pupillary light reflex. This indicates the possibility that OPN4*Ile394Thr is associated with other non-image forming responses. The aim of this study was therefore to determine whether OPN4*Ile394Thr is associated with sleep/wake timing.A total of 348 healthy Japanese university students participated in this study. Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits, including bedtime, wake time and sleep duration, were assessed separately for weekdays and weekends. A total of 328 samples, including 223 samples with TT genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical analysis. No significant difference in age or male/female distribution was found among the three genotype groups.	There was no significant difference in circadian preference among the genotype groups. During weekdays, bedtime, wake time and midpoint of sleep for CC subjects were significantly later than those for TT and TC subjects. However, there was no difference between TT and TC subjects in any of their sleep habits. During weekends, bedtime of CC subjects was significantly later than those of TT and TC subjects, and the midpoint of sleep of CC subjects was significantly later than that of TC subjects.	Our findings demonstrated that OPN4*Ile394Thr is associated with sleep/wake timing. We also found that the sleep/wake timing of subjects with the CC genotype was later than that of subjects with the TT or TC genotype.	
24886638	Osteoarthritis (OA) is a common problem in older women that is associated with pain and disabilities. Although yoga is recommended as an exercise intervention to manage arthritis, there is limited evidence documenting its effectiveness, with little known about its long term benefits. This study's aims were to assess the feasibility and potential efficacy of a Hatha yoga exercise program in managing OA-related symptoms in older women with knee OA.Eligible participants (N=36; mean age 72 years) were randomly assigned to 8-week yoga program involving group and home-based sessions or wait-list control. The yoga intervention program was developed by a group of yoga experts (N=5). The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score that measures knee OA pain, stiffness, and function at 8 weeks. The secondary outcomes, physical function of the lower extremities, body mass index (BMI), quality of sleep (QOS), and quality of life (QOL), were measured using weight, height, the short physical performance battery (SPPB), the Pittsburgh Sleep Quality Index (PSQI), the Cantril Self-Anchoring Ladder, and the SF12v2 Health Survey. Data were collected at baseline, 4 weeks and 8 weeks, and 20 weeks.	The recruitment target was met, with study retention at 95%. Based on ANCOVAs, participants in the treatment group exhibited significantly greater improvement in WOMAC pain (adjusted means [SE]) (8.3 [.67], 5.8 [.67]; p=.01), stiffness (4.7 [.28], 3.4 [.28]; p=.002) and SPPB (repeated chair stands) (2.0 [.23], 2.8 [.23]; p=.03) at 8 weeks. Significant treatment and time effects were seen in WOMAC pain (7.0 [.46], 5.4 [.54]; p=.03), function (24.5 [1.8], 19.9 [1.6]; p=.01) and total scores (35.4 [2.3], 28.6 [2.1]; p=.01) from 4 to 20 weeks. Sleep disturbance was improved but the PSQI total score declined significantly at 20 weeks. Changes in BMI and QOL were not significant. No yoga related adverse events were observed.	A weekly yoga program with home practice is feasible, acceptable, and safe for older women with knee OA, and shows therapeutic benefits.	
24885282	Less sleep time and snoring have been associated with cardiovascular disease (CVD) risk in Western populations; however, few studies have evaluated the different aspects of sleep duration and snoring frequency in relation to CVD, and this association has not been examined in China. The present study aimed to address the relation between sleep duration, snoring frequency and risk of acute myocardial infarction (AMI) in China population.We conducted a hospital-based case-control study. Cases were first AMI (n = 2909). Controls were matched to cases on age and sex. 2947 controls who did not report previous angina or physical disability completed a questionnaire on sleep duration and snoring frequency. We used logistic regression to control for other risk factors.	We observed an inverse association between serious snoring frequency and AMI risk. After adjustment for all the risk factors, and the OR for everyday group and 3-5 times per week group was 1.45 (95% CI: 1.01 to 1.91) and 1.93 (95% CI: 1.52-2.46) compared to no snoring group. The OR for serious level group and moderate group was 1.77 (95% CI: 1.29 to 2.43) and 1.37 (95% CI: 1.10 to 1.69) compared to no snoring group. People having serious snoring increased 77% risk of AMI. 15.2% people in control group have ≤ 6 hours sleeping, compared with 17.4% in AMI group.	Snoring frequency, including as much as everyday and 3-5 times per week, was positively associated with AMI risk and less sleep duration was associated with risk of AMI. Less sleep time could increase AMI risk in China population.	
24885237	Intermittent hypoxia (IH) plays a critical role in sleep breathing disorder-associated hippocampus impairments, including neurocognitive deficits, irreversible memory and learning impairments. IH-induced neuronal injury in the hippocampus may result from reduced precursor cell proliferation and the relative numbers of postmitotic differentiated neurons. However, the mechanisms underlying IH-induced reactive oxygen species (ROS) generation effects on cell proliferation and neuronal differentiation remain largely unknown.ROS generation significantly increased after 1-4 days of IH without increased pheochromocytoma-12 (PC12) cell death, which resulted in increased protein phosphatase 2A (PP2A) mRNA and protein levels. After 3-4 days of IH, extracellular signal-regulated kinases 1/2 (ERK1/2) protein phosphorylation decreased, which could be reversed by superoxide dismutase (SOD), 1,10-phenanthroline (Phe), the PP2A phosphorylation inhibitors, okadaic acid (OKA) and cantharidin, and the ERK phosphorylation activator nicotine (p < 0.05). In particular, the significantly reduced cell proliferation and increased proportions of cells in the G0/G1 phase after 1-4 days of IH (p < 0.05), which resulted in decreased numbers of PC12 cells, could be reversed by treatment with SOD, Phe, PP2A inhibitors and an ERK activator. In addition, the numbers of nerve growth factor (NGF)-induced PC12 cells with neurite outgrowths after 3-4 days of IH were less than those after 4 days of RA, which was also reversed by SOD, Phe, PP2A inhibitors and an ERK activator.	Our results suggest that IH-induced ROS generation increases PP2A activation and subsequently downregulates ERK1/2 activation, which results in inhibition of PC12 cell proliferation through G0/G1 phase arrest and NGF-induced neuronal differentiation.	
24882899	To study whether positive multiple sleep latency tests (MSLTs, mean sleep latency [MSL] ≤ 8 minutes, ≥ 2 sleep onset REM sleep periods [SOREMPs]) and/or nocturnal SOREMP (REM sleep latency ≤ 15 minutes during nocturnal polysomonography [NPSG]) are stable traits and can reflect incipient narcolepsy.Cross-sectional and longitudinal investigation of the Wisconsin Sleep Cohort Study.	Adults (44% females, 30-81 years) underwent NPSG (n = 4,866 in 1,518 subjects), and clinical MSLT (n = 1,135), with 823 having a repeat NPSG-MSLT at 4-year intervals, totaling 1725 NPSG with MSLT studies. Data were analyzed using linear mixed-effects models, and the stability of positive MSLTs was explored using κ statistics.	Prevalence of a nocturnal SOREMP on a NPSG, of ≥ 2 SOREMPs on the MSLT, of MSL ≤ 8 minutes on the MSLT, and of a positive MSLT (MSL ≤ 8 minutes plus ≥ 2 SOREMPs) were 0.35%, 7.0%, 22%, and 3.4%, respectively. Correlates of a positive MSLT were shift work (OR = 7.8, P = 0.0001) and short sleep (OR = 1.51/h, P = 0.04). Test-retest for these parameters was poor, with κ < 0.2 (n.s.) after excluding shift workers and short sleepers. Excluding shift-work, short sleep, and subjects with negative MSLTs, we found one undiagnosed subject with possible cataplexy (≥ 1/month) and a NPSG SOREMPs; one subject previously diagnosed with narcolepsy without cataplexy with 2 NPSG SOREMPs and a positive MSLT, and two subjects with 2 independently positive MSLTs (66% human leukocyte antigen [HLA] positive). The proportions for narcolepsy with and without cataplexy were 0.07% (95% CI: 0.02-0.37%) and 0.20% (95% CI: 0.07-0.58%), respectively.	The diagnostic value of multiple sleep latency tests is strongly altered by shift work and to a lesser extent by chronic sleep deprivation. The prevalence of narcolepsy without cataplexy may be 3-fold higher than that of narcolepsy-cataplexy.	

24880241	Hypothermia is a physiological condition assuring brain protection against hypoxic-related damages. In this context, investigations carried out on the facultative hibernator Mesocricetus auratus proved to be very useful for establishing the type of neurosignaling role exerted by cerebral α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subtypes during hypoxic/reperfusion injuries of the entrance (EN), torpor (TORP), and arousal (AROU) hibernating states. From the evaluation of the major AMPARs (GluR1 and GluR2), together with their scaffold proteins synapse-associated protein 97 kDa (SAP97) and PICK1, it resulted that GluR1 and SAP97 were mostly upregulated during the hypotensive (EN and TORP) states of the brainstem, amygdala, and hypothalamus, sites which are implicated with cardiovascular, motor, and sleep-wake events. In addition, elevated expression densities of the pro-apoptotic factor Bcl-2-associated X protein (Bax) resulted to be correlated to marked amino-cupric-silver stain signals during both hibernating states. Conversely, an increase of the neuroprotective factor GluR2, together with PICK1 and the anti-apoptotic B cell lymphoma 2 (Bcl-2), appeared to be linked with reduced argyrophilic signals in most of the above areas of the hypertensive AROU state. These first indications highlight distinct protective/degenerative measures of the above factors constituting key on/off switches during the various hibernating states that may provide potential therapeutic bearings on sleeping disorders. 

24878948	This study sought to determine the prevalence of fibromyalgia syndrome and to identify whether fibromyalgia was associated with various clinical symptoms and laboratory parameters in hemodialysis patients. One hundred and forty-eight hemodialysis patients were examined for fibromyalgia symptoms according to the American College of Rheumatology criteria. Demographic characteristics, as well as causes of kidney failure, dialysis duration, and symptoms related to fibromyalgia were investigated. Of 148 patients, 18 (12.2%) were diagnosed with fibromyalgia. Patients with fibromyalgia had significantly poorer sleeping satisfaction than the control group (P = .02).The Beck Depression Inventory score was higher in 77.8% of the fibromyalgia patients than that in the control group (P = .006), but there was no significant difference in the anxiety score between the two groups (P = .86).In conclusion, there was a higher prevalence of fibromyalgia in hemodialysis patients than previously reported. Sleep disturbances and depression levels correlated with fibromyalgia. 
24878886	Sleep disorders are very common in elderly institutionalized people with dementia and acupressure recently has been associated with conventional medicine in their treatment.Exploring the effectiveness of acupressure for the treatment of insomnia and other sleep disturbances and we want to show that the acupressure treatment is feasible also in elderly resident patients.	We enrolled institutionalized patients suffering from Alzheimer's disease with mild cognitive impairment and insomnia. A daily acupressure on HT7 point (H7 Insomnia Control(®)) was performed for a 8-week period. We administered the following scales: the mini mental state examination, the global deterioration scale, the neuropsychiatric inventory, the state-trait-anxiety inventory, the activity daily living and the instrumental activity daily living, the global health quality of life, and the Pittsburgh sleep quality index.	After receiving the acupressure treatment, patients saw a significant decrease of sleep disorders. The number of hours of effective sleep was perceived as increased. Furthermore, the time necessary to fall asleep decreased significantly and also the quality of sleep increased. Additionally, also the quality of life was bettered. Sedative drugs have been reduced in all patients involved in the study.	Acupressure can be recommended as a complementary, effective, and non-intrusive method to reduce sleep disturbances in old resident patients affected by cognitive disorders. A limitation of the study is the small sample size. More studies are needed to further validate the results of our study.	
24878318	The traditional sleep scoring approach has been invented long before the recognition of strictly local nature of the sleep process. It considers sleep as a whole-organism behavior state, and, thus, it cannot be used for identification of sleep onset in a separate brain region. Therefore, this paper was aimed on testing whether the practically useful, simple and reliable yes-or-no criterion of sleep onset in a particular cortical region might be developed through applying principal component analysis to the electroencephalographic (EEG) spectra. The resting EEG was recorded with 2-hour intervals throughout 43-61-hour prolongation of wakefulness, and during 12 20-minute attempts to nap in the course of 24-hour wakefulness (15 and 18 adults, respectively). The EEG power spectra were averaged on 1-min intervals of each resting EEG record and on 1-min intervals of each napping attempt, respectively. Since we earlier demonstrated that scores on the first and second principal components of the EEG spectrum exhibit dramatic changes during the sleep onset period, a zero-crossing buildup of the first score and a zero-crossing decline of the second score were examined as possible yes-or-no markers of regional sleep onsets. The results suggest that, irrespective of electrode location, sleep onset criterion and duration of preceding wakefulness, a highly significant zero-crossing decline of the second principal component score always occurred within 1-minute interval of transition from wakefulness to sleep. Therefore, it was concluded that such zero-crossing decline can serve as a reliable, simple, and practically useful yes-or-no marker of drop off event in a given cortical area. 
24877599	The purpose of this secondary analysis study was to determine whether care recipients' nighttime sleep patterns, medical comorbidity, observed nocturnal agitation behaviors, and caregivers' perceptions of nocturnal agitation behaviors in care recipients with dementia are associated with caregiver burden. Sixty care recipient-caregiver dyads, comprising older adults with geriatrician-diagnosed dementia living at home with caregivers, participated. Caregivers' perceptions of the frequency of care recipients' nocturnal agitation behaviors were associated with caregiver burden; however, objective, real-time data on the frequency of nocturnal agitation behaviors were not associated with burden. Care recipients' increased minutes of wakefulness before falling asleep and severe cognitive impairment with musculoskeletal/integument and neurological comorbidities were associated with higher caregiver burden. These results suggest that targeted interventions to reduce sleep onset latency, medical comorbidity, and caregivers' perception of frequency of nocturnal behaviors may reduce caregiver burden.
27186832	Hearing sound that does not originate in the world outside the body is an experience every human has at one time or another in life. Circadian rhythm is common for all living organisms and nearly all physiological functions, especially sleep-wake cycles, exhibit circadian rhythmicity. A short survey conducted in the study center revealed that majority of the tinnitus subjects reported a difference in tinnitus severity across the day. So the current study focused on finding out the influence of circadian rhythm on tinnitus severity.Study was conducted on 20 tinnitus subjects irrespective of age, gender, hearing status and type of tinnitus. Kannada version of MEQ was given to all the subjects to classify them to various circadian types. A visual analog scale was also given to rate the severity of the tinnitus in the morning and evening.	The result of the current study states that, there was a significant difference in the tinnitus severity for moderate morning type individuals in the morning and evening and not for the intermediate group.	So we can conclude that, circadian rhythm has a strong association with the severity of the tinnitus.	

24874320	To objectify indications for treatment with pantogam in premature infants with perinatal hypoxic-ischemic injury of the CNS.We studied 71 children, with GA (gestation age) 24-36 weeks (32,9±2,9 weeks), with perinatal hypoxic-ischemic injury of the CNS, I-II grades, and hyperexitability syndrome. The main group (33 patients) received pantogam in dose 50 mg/kg/day at the adjusted age (AA) 36-40 weeks from the conception. The comparison group included 38 patients. EEG day sleep monitoring was performed before and at the end of treatment.	Shortening of sleep cycle was observed in 78,8% children of the main group and in 78,9% of the comparison group. Duration of transitional sleep over 1 min was 78,79% and 81,58%. At AA 44-46 weeks, the frequency of sleep disorders decreased to 45,45% (p=0,012) and 52,63% (p=0,05). Duration of transitional sleep over 1 min was 45,45% and 65,79%. Duration of the latent period of the 2nd stage of slow wave sleep was 6,4±2,57 and 12,5±7,18 min (p=0,0004).	The treatment reduced sleep disorders, changed the duration of transitional sleep stage and latent period of the 2nd stage of slow wave sleep.	
24873137	Histaminergic neurons are located exclusively in the posterior hypothalamus from where they project to virtually all brain areas and fulfill a major role in the maintenance of waking. H3-receptors are firstly autoreceptors damping the release and synthesis of histamine and the firing of histamine neurons. This action also extends to heteroreceptors on most other neurotransmitter systems, allowing a powerful control over multiple homeostatic functions. The particular properties and locations of H3-receptors provide quite favorable attributes to make this a most promising target for sleep-wake control and sleep disorders. This review summarizes the most recent data on the role of H3-receptor in physiological sleep-wake regulation and preclinical and clinical evidence supporting H3-receptor as brain target for therapy of sleep and vigilance disorders.

24872650	Sleep deprivation is a common problem on intensive care units (ICUs) influencing not only cognition, but also cellular functions. An appropriate sleep-wake cycle should therefore be maintained to improve patients' outcome. Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-sedated.The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam.	Monocentric, randomized, double-blinded trial.	A total of 66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n = 34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus dose (0.015 mg/kg). Differences between groups were evaluated using a standardized sleep diary and the bispectral index (BIS).	Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was considered to be statistically significant.	Sleep quality and the frequency of awakenings were significantly better in the propofol group (Pg). In the same group lower BIS values were recorded (median BIS propofol 74.05, flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration.	Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-sedated was superior to flunitrazepam regarding sleep quality and sleep structure.	

24867919	Sleep disruptions occur early and frequently in Parkinson's disease (PD). PD patients also show a slowing of resting state activity. Alpha-synuclein is causally linked to PD and accumulates in sleep-related brain regions. While sleep problems occur in over 75% of PD patients and severely impact the quality of life of patients and caregivers, their study is limited by a paucity of adequate animal models.The objective of this study was to determine whether overexpression of wildtype alpha-synuclein could lead to alterations in sleep patterns reminiscent of those observed in PD by measuring sleep/wake activity with rigorous quantitative methods in a well-characterized genetic mouse model.	At 10 months of age, mice expressing human wildtype alpha-synuclein under the Thy-1 promoter (Thy1-aSyn) and wildtype littermates underwent the subcutaneous implantation of a telemetry device (Data Sciences International) for the recording of electromyograms (EMG) and electroencephalograms (EEG) in freely moving animals. Surgeries and data collection were performed without knowledge of mouse genotype.	Thy1-aSyn mice showed increased non-rapid eye movement sleep during their quiescent phase, increased active wake during their active phase, and decreased rapid eye movement sleep over a 24-h period, as well as a shift in the density of their EEG power spectra toward lower frequencies with a significant decrease in gamma power during wakefulness.	Alpha-synuclein overexpression in mice produces sleep disruptions and altered oscillatory EEG activity reminiscent of PD, and this model provides a novel platform to assess mechanisms and therapeutic strategies for sleep dysfunction in PD.	
24867908	The aim of this study is to find prevalence and severity of restless legs syndrome (RLS) in patients with fibromyalgia syndrome (FMS) and detect effect of FMS and RLS coexistance on quality of sleep and life.In this study, presence and severity of RLS were detected in patients with FMS and Pitsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Fibromyalgia Impact Questionnaire (FIQ) scores of all patients were measured.	One hundred and fifteen female patients with median age 49 (39.0-57.0)[median (25-75{\%} interquartile range)] were included in the study. In 42.6% of patients RLS coexisting with FMS was found. RLS was classified as moderate in 42.9% of patients and as severe in 49.0% of patients. In patients with FMS ans RLS sleep quality, daytime sleepiness and quality of life were more severely impaired (PSQI scores were 9.0 ± 4.4 vs 7.8 ± 4.3, p=0.003; ESS scores were 5.0(3.0-7.5) vs 3.0(1.0-4.3), p=0.036 and FIQ scores were 68.1 ± 9.8 vs 59.4 ± 16.9, p=0.027) compared to patients with only FMS. Prevalence of RLS was found higher in FMS than normal population and quality of sleep and quality of life were worse in patients with RLS.	Presence of RLS should be investigated in every patient with FMS and treatment plans should also cover RLS in case of coexistance with FMS. Prospective cohort studies are needed for better explanation of FMS and RLS coexistance.	
24867878	Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevated pulmonary pressures that lead to right heart failure and premature mortality. Patients experience multiple symptoms including dyspnea, fatigue and chest pain, but little is known about sleep disturbance, PAH symptoms, psychological distress and health-related quality of life (HRQOL) in PAH.The purpose of this study was to describe the occurrence of sleep disturbance and compare PAH symptoms, psychological distress, and HRQOL across severity of sleep disturbance.	One hundred and ninety-one participants completed a socio-demographic and clinical data form, PAH Symptom Severity Scale, Profile of Mood States (POMS) short form and the Medical Outcomes Short Form-36 (SF-36). Descriptive statistics were used to describe sleep disturbances; analysis of variance models were used to quantify differences in PAH symptoms, psychological distress and HRQOL by sleep disturbance groups.	The majority of participants (n=162, 85%) were women with a mean age of 53 years. Sixty-five (34%) reported no sleep disturbance; 54 (28%) mild sleep disturbance; 41 (22%) moderate sleep disturbance; and 31 (16%) severe sleep disturbance. Those reporting higher sleep disturbance severity reported worse PAH symptoms, psychological distress, and HRQOL.	Sleep disturbance is a significant finding in PAH. Increasing levels of sleep disturbance are associated with worse PAH symptoms, psychological states, and health-related quality of life. Interventions that decrease sleep disturbances may improve symptoms and HRQOL.	
24866353	The severity of injury from vehicle crash is a result of a complex interaction of factors related to drivers' behavior, vehicle characteristics, road geometric and environmental conditions. Knowing to what extent each factor contributes to the severity of an injury is very important. The objective of the study was to assess factors that contribute to crash injury severity in Ethiopia. Data was collected from June 2012 to July 2013 on one of the main and busiest highway of Ethiopia, which extends from the capital Addis Ababa to Hawassa. During the study period a total of 819 road crashes was recorded and investigated by trained crash detectors. A generalized ordered logit/partial proportional odds model was used to examine factors that might influence the severity of crash injury. Model estimation result suggested that, alcohol use (Coef.=0.5565; p-value=0.017), falling asleep while driving (Coef.=1.3102; p-value=0.000), driving at night time in the absence of street light (Coef.=0.3920; p-value=0.033), rainfall (Coef.=0.9164; p-value=0.000) and being a minibus or vans (Coef.=0.5065; p-value=0.013) were found to be increased crash injury severity. On the other hand, speeding was identified to have varying coefficients for different injury levels, its highest effects on sever and fatal crashes. In this study risky driving behaviors (speeding, alcohol use and sleep/fatigue) were a powerful predictor of crash injury severity. Therefore, better driver licensing and road safety awareness campaign complimented with strict police enforcement can play a pivotal role to improve road safety. Further effort needed as well to monitor speed control strategies like; using the radar control and physical speed restraint measures (i.e., rumble strips). 
24865547	Restless legs syndrome (RLS) is characterized by unpleasant sensations, pain in the legs along with irresistible urges to move the legs when at rest. It is often accompanied by sleep disturbance. The purpose of this study was to assess the association of anxiety and sleepiness with sexual function in hemodialysis patients with and without RLS. Sociodemographic parameters, laboratory data of hemodialysis patients from three dialysis centers were collected prospectively. Anxiety, sleepiness, sexual function, and presence of RLS symptoms were assessed with standardized questionnaires as the RLS Diagnosis and Scale, Hamilton Anxiety Rating Scale, Epworth Sleepiness Scale (ESS), Arizona Sex Experiences Scale (ASEX). Univariate, regression tree method were used for statistical analysis. RLS was observed in 45.9% (n = 113) of hemodialysis patients (n = 246). The mean age of patients and duration of hemodialysis were 59.7 ± 14.0 and 4.9 ± 4.2 years, respectively. The correlation between Arizona Sexual Experiences Scale (ASEX) and sociodemographic features was significant (P < 0.0001). Patients with RLS had higher scores for anxiety (9.4 ± 7.8 with RLS and 6.8 ± 6.0 without), higher ESS (ESS, 6.6 ± 5.2 with RLS and 4.6 ± 4.0 without), and higher ASEX (24.6 ± 5.7 with RLS and 22.5 ± 6.8 without) than did those without RLS. The presence of RLS symptoms in hemodialysis patients was associated with sleepiness, anxiety, and sexual dysfunction. A regression tree method, which is a different statistical method, can help physicians estimate patients ASEX, RLS, ESS, and anxiety scores. 

24864160	Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression. 
24863509	The relationships among suicidal ideation, sleep, depression, anxiety, and effects on epilepsy require more research.The aim of this study was to estimate the prevalence of suicidal ideation in outpatients with epilepsy, and relate this to sleep quality, daytime sleepiness, depression, and anxiety.	Ninety-eight non-selected patients were evaluated. The subjects were classified as "suicidal ideators" or "non-ideators", based on their response to item 9 of the Beck Depression Inventory.	The prevalence of suicidal ideation was 13.3% (χ2=50.46, p<0.001). The differences between cases with or without suicidal ideation were statistically significant in relation to sleep quality (p=0.005) and symptoms of depression (p=0.001) and anxiety (p=0.002).	Our results revealed that depression and anxiety were associated with sleep quality, daytime sleepiness, and suicidal ideation and that depression and sleep disturbance were good predictors of suicide in subjects with epilepsy.	
24863387	Organisms experience dramatic fluctuations in demands and stresses over the course of the day. In order to maintain biological processes within physiological boundaries, mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors have an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 h period, but so too does responsiveness of target tissues to these signals or stimuli. Emerging evidence suggests that these daily endocrine oscillations do not occur solely in response to behavioural fluctuations associated with sleep-wake and feeding-fasting cycles, but are orchestrated by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks by genetic and/or environmental factors seems to precipitate numerous common disorders, including the metabolic syndrome and cancer. Collectively, these observations suggest that strategies designed to realign normal circadian rhythmicities hold potential for the treatment of various endocrine-related disorders. 
24860176	Noradrenergic neurotransmission in the brainstem is closely coupled to changes in muscle activity across the sleep-wake cycle, and noradrenaline is considered to be a key excitatory neuromodulator that reinforces the arousal-related stimulus on motoneurons to drive movement. However, it is unknown if α-1 noradrenoceptor activation increases motoneuron responsiveness to excitatory glutamate (AMPA) receptor-mediated inputs during natural behaviour. We studied the effects of noradrenaline on AMPA receptor-mediated motor activity at the motoneuron level in freely behaving rats, particularly during rapid eye movement (REM) sleep, a period during which both AMPA receptor-triggered muscle twitches and periods of muscle quiescence in which AMPA drive is silent are exhibited. Male rats were subjected to electromyography and electroencephalography recording to monitor sleep and waking behaviour. The implantation of a cannula into the trigeminal motor nucleus of the brainstem allowed us to perfuse noradrenergic and glutamatergic drugs by reverse microdialysis, and thus to use masseter muscle activity as an index of motoneuronal output. We found that endogenous excitation of both α-1 noradrenoceptor and AMPA receptors during waking are coupled to motor activity; however, REM sleep exhibits an absence of endogenous α-1 noradrenoceptor activity. Importantly, exogenous α-1 noradrenoceptor stimulation cannot reverse the muscle twitch suppression induced by AMPA receptor blockade and nor can it elevate muscle activity during quiet REM, a phase when endogenous AMPA receptor activity is subthreshold. We conclude that the presence of an endogenous glutamatergic drive is necessary for noradrenaline to trigger muscle activity at the level of the motoneuron in an animal behaving naturally. 
24860139	Dementia with Lewy bodies (DLB) is recognised as the second most common form of dementia in older people. Delirium is a condition of acute brain dysfunction for which a pre-existing diagnosis of dementia is a risk factor. Conversely delirium is associated with an increased risk of developing dementia. The reasons for this bidirectional relationship are not well understood. Our aim was to review possible similarities in the clinical presentation and pathophysiology between delirium and DLB, and explore possible links between these diagnoses. A systematic search using Medline, Embase and Psychinfo was performed. References were scanned for relevant articles, supplemented by articles identified from reference lists and those known to the authors. 94 articles were selected for inclusion in the review. Delirium and DLB share a number of clinical similarities, including global impairment of cognition, fluctuations in attention and perceptual abnormalities. Delirium is a frequent presenting feature of DLB. In terms of pathophysiological mechanisms, cholinergic dysfunction and genetics may provide a common link. Neuroimaging studies suggest a brain vulnerability in delirium which may also occur in dementia. The basal ganglia, which play a key role in DLB, have also been implicated in delirium. The role of Cerebrospinal fluid (CSF) and serum biomarkers for both diagnoses is an interesting area although some results are conflicting and further work in this area is needed. Delirium and DLB share a number of features and we hypothesise that delirium may, in some cases, represent early or 'prodromal' DLB. Further research is needed to test the novel hypothesis that delirium may be an early marker for future DLB, which would aid early diagnosis of DLB and identify those at high risk. 
24860070	Improvements in mobile telecommunication technologies have enabled clinicians to collect patient-reported outcome (PRO) data more frequently, but there is as yet limited evidence regarding the frequency with which PRO data can be collected via smartphone applications (apps) in breast cancer patients receiving chemotherapy.The primary objective of this study was to determine the feasibility of an app for sleep disturbance-related data collection from breast cancer patients receiving chemotherapy. A secondary objective was to identify the variables associated with better compliance in order to identify the optimal subgroups to include in future studies of smartphone-based interventions.	Between March 2013 and July 2013, patients who planned to receive neoadjuvant chemotherapy for breast cancer at Asan Medical Center who had access to a smartphone app were enrolled just before the start of their chemotherapy and asked to self-report their sleep patterns, anxiety severity, and mood status via a smartphone app on a daily basis during the 90-day study period. Push notifications were sent to participants daily at 9 am and 7 pm. Data regarding the patients' demographics, interval from enrollment to first self-report, baseline Beck's Depression Inventory (BDI) score, and health-related quality of life score (as assessed using the EuroQol Five Dimensional [EQ5D-3L] questionnaire) were collected to ascertain the factors associated with compliance with the self-reporting process.	A total of 30 participants (mean age 45 years, SD 6; range 35-65 years) were analyzed in this study. In total, 2700 daily push notifications were sent to these 30 participants over the 90-day study period via their smartphones, resulting in the collection of 1215 self-reporting sleep-disturbance data items (overall compliance rate=45.0%, 1215/2700). The median value of individual patient-level reporting rates was 41.1% (range 6.7-95.6%). The longitudinal day-level compliance curve fell to 50.0% at day 34 and reached a nadir of 13.3% at day 90. The cumulative longitudinal compliance curve exhibited a steady decrease by about 50% at day 70 and continued to fall to 45% on day 90. Women without any form of employment exhibited the higher compliance rate. There was no association between any of the other patient characteristics (ie, demographics, and BDI and EQ5D-3L scores) and compliance. The mean individual patient-level reporting rate was higher for the subgroup with a 1-day lag time, defined as starting to self-report on the day immediately after enrollment, than for those with a lag of 2 or more days (51.6%, SD 24.0 and 29.6%, SD 25.3, respectively; P=.03).	The 90-day longitudinal collection of daily self-reporting sleep-disturbance data via a smartphone app was found to be feasible. Further research should focus on how to sustain compliance with this self-reporting for a longer time and select subpopulations with higher rates of compliance for mobile health care.	
24858728	In his initial description of shaking palsy, James Parkinson first noted that sleep became disturbed with advancing paralysis agitans. More recent studies have confirmed that the majority of patients with Parkinson's disease (PD) suffer from some sleep disturbances. This can manifest as difficulty in falling or staying asleep, fractionated sleep, specific parasomnias, and daytime sleepiness. In this article, we will explore the pathophysiology of these varied sleep disorders. In most cases, however, the definitive etiology is debated, and phenotypes are often felt to be multifactorial. Some of these may be associated with dopaminergic dysfunction, some presumed to arise from varied non-dopaminergic PD pathology, and some from PD treatments. 
24858716	Evidence from observational studies on light at night (LAN) exposure, sleep duration, endogenous melatonin levels, and risk for breast cancer in women is conflicting. This led us to conduct a dose-response analysis of published observational data. Pertinent studies were identified by searching Medline, Web of Science, and EMBASE through April 2013. The dose-response relationship between sleep duration, urinary 6-sulphatoxymelatonin levels, and breast cancer was assessed using the restricted cubic spline model and by multivariate random-effects metaregression. A separate meta-analysis was also carried out to calculate the relative risks (RRs) with 95% confidence intervals (CIs) for breast cancer for the comparable categories or highest levels of exposure versus the lowest levels. Twelve case-control and four cohort studies were included in the analysis. High artificial LAN exposure is associated with an increased risk for breast cancer (RR=1.17, 95% CI: 1.11-1.23), but not ambient LAN exposure (RR=0.91, 95% CI: 0.78-1.07). The summary RR for breast cancer is 1.00 (95% CI: 0.995-1.01) for an increment of 1 h of sleep per night. No significant dose-response relationship between sleep duration and breast cancer was found either for the linearity test (Ptrend=0.725) or for the nonlinearity (Ptrend=0.091) test. An increasein of 15 ng/mg creatinine in urinary 6-sulphatoxymelatonin is associated with a 14% reduced risk for breast cancer (RR=0.86, 95% CI: 0.78-0.95), with a linear dose-response trend (Ptrend=0.003). There was no evidence of substantial heterogeneity or publication bias in the analysis. Our study adds to the evidence of LAN breast cancer theory. Further research in this area is warranted. 
24857255	The purpose of this review was to quantify the strength of evidence for a directional relationship between sleep disturbance and depression in adolescents. A literature search was conducted to identify research investigating the relationship between sleep disturbance and depression in adolescent samples (12-20 y). Twenty-three studies were identified; 13 explored associations between depression and sleep disturbance; seven examined the prospective role of sleep disturbance in the development of depression; and three investigated the role of adolescent depression in the development of subsequent sleep disturbance. Average weighted mean differences in sleep/depression-related outcome variables were calculated between adolescents with depression, and non-clinical adolescents, or those in remission. Adolescents with depression experienced significantly more wakefulness in bed (sleep onset latency, wake after sleep onset, number of awakenings and sleep efficiency), lighter sleep (more stage 1), and reported more subjective sleep disturbance. Overall effect sizes from longitudinal and treatment studies suggest sleep disturbance acts as a precursor to the development of depression. At follow-up, depressed adolescents had significantly longer sleep onset, more wake after sleep onset, and lower sleep efficiency compared to adolescents who were non-clinical, or had undergone remission. Little support was found for a predictive role of depressive symptoms in the development of sleep disturbance. Based on these findings we propose a model to understand the development of depression from initial sleep disturbance, provide recommendations for clinicians and recommendations for future research.
24854994	The purpose of this study was to examine the correlations among objective sleep variables, sleep-wake cycle parameters, and daily physical activity in hemodialysis patients and controls. Twenty-four hemodialysis patients (HD group) were compared with a control group consisting of 24 healthy participants matched for age, height, and weight. Sleep variables (total sleep time [TST], sleep efficiency [SE], sleep latency [SL], and waking after sleep onset [WASO]), sleep-wake cycle parameters (the sleep-wake cycle period and the peak of sleep-wake cycle variance), and daily physical activity (steps per day) for each participant were assessed by objective methods for two weeks. While there was no difference in TST between the two groups, the HD group showed a significantly increased SL (HD: 0:29±0:20 vs control: 0:16±0:13, p < 0.05) and WASO (HD: 2:21±1:00 vs control: 1:35±0:41, p<0.05) and decreased SE (HD: 67.1±13.6% vs control: 77.5±9.7%, p<0.01) compared to the control group. There was no significant difference in sleep-wake cycle period between the HD and control groups. However, the peak of sleep-wake cycle variance in the HD group (0.050±0.028) was significantly lower (t = 2.49, p<0.05) than in the control group (0.068±0.019). The number of daily steps taken in the HD group (4,774± 2,845 steps) was also significantly lower than in the control group (8,696± 3,047). The peak of sleep-wake cycle variance was significantly correlated with SE (r = 0.532, p<0.01), SL (r = -0.501, p<0.01), and WASO (r = -0.436, p<0.01), whereas the number of steps showed a weak correlation only with WASO (r = -0.308, p<0.05) among the objective sleep parameters. Our results suggest that sleep quality in HD patients may be more effectively improved by maintaining the regular 24-hour sleep-wake cycle rather than by increasing the amount of daily physical activity, indicating that intervention such as measures to prevent napping during hemodialysis sessions may prove effective in improving the quality of sleep in HD patients. 
24852799	Stress is considered to be an important cause of disrupted sleep and insomnia. However, controlled and experimental studies in rodents indicate that effects of stress on sleep-wake regulation are complex and may strongly depend on the nature of the stressor. While most stressors are associated with at least a brief period of arousal and wakefulness, the subsequent amount and architecture of recovery sleep can vary dramatically across conditions even though classical markers of acute stress such as corticosterone are virtually the same. Sleep after stress appears to be highly influenced by situational variables including whether the stressor was controllable and/or predictable, whether the individual had the possibility to learn and adapt, and by the relative resilience and vulnerability of the individual experiencing stress. There are multiple brain regions and neurochemical systems linking stress and sleep, and the specific balance and interactions between these systems may ultimately determine the alterations in sleep-wake architecture. Factors that appear to play an important role in stress-induced wakefulness and sleep changes include various monominergic neurotransmitters, hypocretins, corticotropin releasing factor, and prolactin. In addition to the brain regions directly involved in stress responses such as the hypothalamus, the locus coeruleus, and the amygdala, differential effects of stressor controllability on behavior and sleep may be mediated by the medial prefrontal cortex. These various brain regions interact and influence each other and in turn affect the activity of sleep-wake controlling centers in the brain. Also, these regions likely play significant roles in memory processes and participate in the way stressful memories may affect arousal and sleep. Finally, stress-induced changes in sleep-architecture may affect sleep-related neuronal plasticity processes and thereby contribute to cognitive dysfunction and psychiatric disorders. 
24852666	Our study aimed to examine the relationship between perceived sleep quality and depression using Pittsburgh Sleep Quality Index (PSQI) and Cole's model to materialize the concept of perceived sleep quality in the non-cognitively impaired elderly. Older adults aged 60+ were recruited from the baseline study of Suwon Project (SP) between 2009 and 2011 (n=2040). Perceived sleep quality was measured using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K), and depression was accessed using the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K). We excluded the cognitively impaired elderly using the Korean version-Mini Mental Status Examination (K-MMSE) score less than or equal to 17. In multivariable adjusted logistic regression related to PSQI-K components, poor perceived sleep quality, including poor subjective sleep quality (Odds ratio (OR)=1.27, 95% confidence interval (CI)=1.01-1.61), longer sleep latency (OR=1.32, 95% CI=1.13-1.55) and the frequent use of sleeping medication (OR=1.30, 95% CI=1.10-1.53) were significantly associated with depression after adjusting for age, sex, education, living status, current smoking and current alcohol drinking, the number of comorbidity and Beck Anxiety Inventory (BAI). PSQI-K global score also had greater odds of reporting depression (OR=1.12, 95% CI=1.07-1.16). These results suggested that poor perceived sleep quality was associated with a greater level of depression in the elderly. 
24851803	It has been acknowledged that poor quality of sleep significantly correlates with poor quality of life; evidence suggests that counselling has a positive impact not only on the cancer patient's quality of life, but also on family members and friends. The aim of this service evaluation was to determine if there was an improvement in clients' quality of life and sleep patterns following counselling as offered by a local cancer charity. A total of 60 matched pre- and post-counselling questionnaires were completed and subjected to statistical analysis. When considering quality of life, in the domains of Role Emotional, Mental Health and Mental Component Summary Score, it can be concluded that counselling has a positive effect on emotional health and mental wellbeing. The mean total number of hours sleep per night significantly increased from 6 hours sleep per night at baseline to 6.8 hours sleep per night at the completion of counselling (p=0.005) showing clients gained an extra 48 minutes sleep per night. The improved emotional and mental wellbeing alongside the extra 48 minutes sleep per night provides evidence that there is a positive outcome for those patients and families who use counselling services. Nurses and other members of the multidisciplinary team should be encouraged to discuss supportive therapies with patients and those affected by cancer at all stages of the cancer trajectory, regardless of social status, gender or cancer type. 
24850818	The Australian general practice workforce is ageing. This and a trend towards higher exit intentions and earlier retirement make it increasingly important to identify those work and personal factors affecting intention to leave, which are amenable to change.To assess the various work, occupational and individual health factors associated with early retirement intentions among Australian rural general practitioners (GPs) that may be amenable to intervention.	A cross-sectional study of GPs practising in rural Australia. Odds ratios of early retirement intentions across work, occupational and individual health factors were calculated.	There were 92 participants (response rate 56%), and 47% of responders intended to retire before 65. GPs with medium to high burnout levels had higher odds of intending to retire. Increased job satisfaction and work ability scores were associated with decreased retirement intentions, whereas increased physical and mental work ability demands were associated with an increase in retirement intentions. Absenteeism was not related to retirement intentions but presenteeism was. GPs reporting any work-related sleep problems were found to have a 3-fold increase in the odds of early retirement intentions. The odds of early retirement intentions also increased with higher psychological distress, worsening general health and longer working hours.	From a health policy reform perspective, the greatest impact on reducing early retirement intentions among ageing GPs could potentially be made by intervening in areas of working hours, burnout and work-related sleep issues, followed by job satisfaction, psychological distress, health, general workability and mental and physical work ability.	
24848704	This study investigated whether computer use is associated with health symptoms through sleep duration among 15-year olds in Finland, France and Denmark.We used data from the WHO cross-national Health Behaviour in School-aged Children study collected in Finland, France and Denmark in 2010, including data on 5,402 adolescents (mean age 15.61 (SD 0.37), girls 53%). Symptoms assessed included feeling low, irritability/bad temper, nervousness, headache, stomachache, backache, and feeling dizzy. We used structural equation modeling to explore the mediating effect of sleep duration on the association between computer use and symptom load.	Adolescents slept approximately 8 h a night and computer use was approximately 2 h a day. Computer use was associated with shorter sleep duration and higher symptom load. Sleep duration partly mediated the association between computer use and symptom load, but the indirect effects of sleep duration were quite modest in all countries.	Sleep duration may be a potential underlying mechanism behind the association between computer use and health symptoms.	
24847992	The optimal management of sleep problems is a significant challenge, particularly in patients with psychiatric illness, because disturbed sleep is a known risk factor for relapse. This study used the short Dysfunctional Beliefs and Attitudes Scale to assess beliefs about sleep in adults with acute psychiatric disorders (N=100) recruited from inpatient and outpatient clinics. The subjects showed highly dysfunctional beliefs and attitudes about sleep and held diverse opinions about, but had low confidence in, their own capacity for optimal sleep management. They did not report excessive daytime sleepiness. We conclude that individuals with acute psychiatric illness worry significantly about their sleep and hold more dysfunctional beliefs about sleep than people without psychiatric illness. The absence of excessive daytime sleepiness in this sample, although counterintuitive, is consistent with findings in other studies. Given that two thirds of the sample expressed interest in non-pharmacological strategies to better manage their sleep problems, cognitive reshaping therapies appear to have clinical potential as alternatives to hypnosedative medication once a comprehensive sleep workup has excluded a physical sleep disorder such as obstructive sleep apnea. Dysfunctional beliefs and high concern about sleep offer potential targets for psychotherapy.
24847727	To describe the frequency of reported sleeping, depression and pain problems, the severity of these problems and the degree of self-estimated difficulties in mental functions and activities in relation to the sleep disturbance and pain category group in patients on long-term sick-leave.Cross-sectional study.	A total of 1206 patients experiencing difficulty in resuming work.	Patient examinations by specialists in psychiatry, orthopaedic surgery and rehabilitation medicine. Validated questionnaires, including status regarding depression, sleep, pain and functioning were used.	The prevalence of sleep disturbance was 83%; 74% of the patients with moderate/severe sleep disturbance also had moderate/severe pain problems and 26% had no/mild pain problems. Fifty-seven percent of the patients with no/mild sleep disturbance and 83% of the patients with moderate/ severe sleep disturbance also had depression. The degree of difficulty in performing the 6 selected International Classification of Functioning, Disability and Health activities and mental functions was higher for the category with moderate/severe sleep problems, compared with those with no/mild sleep problems.	To optimize rehabilitation for patients on long-term sick-leave experiencing difficulties in returning to work, the results indicate a need also to focus attention on sleep problems and not only on pain and depression. This may entail the planning of measures to improve decision-making and concentration and alleviate lassitude, fatigability, sadness and pessimistic thoughts.	
24846773	Sleep disorders are frequent in Alzheimer's disease (AD), with a significant impact on patients and caregivers and a major risk factor for early institutionalization. Micro-architectural sleep alterations, nocturnal sleep fragmentation, decrease in nocturnal sleep duration, diurnal napping and even inversion of the sleep-wake cycle are the main disorders observed in patients with AD. Experimental and epidemiological evidence for a close reciprocal interaction between cognitive decline and sleep alterations is growing. Management of sleep disorders in AD is pre-eminently behavioral. Association of melatonin and bright light treatment seems to be promising as well. The presence of sleep complaints, especially excessive somnolence in demented patients, should draw attention to possible associated sleep pathologies such as sleep apnea syndrome or restless legs syndrome. 
24846338	EEG studies show that 5-HT is involved in regulation of sleep-wake state and modulates cortical oscillations. Vortioxetine is a 5-HT3 , 5-HT7 , and 5-HT1D receptor antagonist, 5-HT1B partial agonist, 5-HT1A agonist, and 5-HT transporter inhibitor. Preclinical (animal) and clinical studies with vortioxetine show positive impact on cognitive metrics involving cortical function. Here we assess vortioxetine's effect on cortical neuronal oscillations in actively awake rats.Telemetric EEG recordings were obtained with the following treatments (mg·kg(-1) , s.c.): vehicle, vortioxetine (0.1, 1.0, 3.0, 10), 5-HT1A agonist flesinoxan (2.5), 5-HT3 antagonist ondansetron (0.30), 5-HT7 antagonist SB-269970-A (10), escitalopram (2.0), duloxetine (10) and vortioxetine plus flesinoxan. Target occupancies were determined by ex vivo autoradiography.	Vortioxetine dose-dependently increased wakefulness. Flesinoxan, duloxetine, ondansetron, but not escitalopram or SB-269970-A increased wakefulness. Quantitative spectral analyses showed vortioxetine alone and with flesinoxan increased θ (4-8 Hz), α (8-12 Hz) and γ (30-50 Hz) power. Duloxetine had no effect on θ and γ, but decreased α power, while escitalopram produced no changes. Ondansetron and SB-269970 (≈31-35% occupancy) increased θ power. Flesinoxan (≈41% occupancy) increased θ and γ power.	Vortioxetine increased wakefulness and increased frontal cortical activity, most likely because of its 5-HT7 and 5-HT3 antagonism and 5-HT1A agonism. Vortioxetine differs from escitalopram and duloxetine by increasing cortical θ, α and γ oscillations. These preclinical findings suggest a role of vortioxetine in modulating cortical circuits known to be recruited during cognitive behaviours and warrant further investigation as to their clinical impact.	
24846000	To examine longitudinal bidirectional associations between two depressive symptom clusters-the cognitive-affective and somatic-vegetative clusters--and insulin resistance, a marker of prediabetes.Participants were 269 adults aged 50 to 70 years without diabetes enrolled in the Pittsburgh Healthy Heart Project, a prospective cohort study. At baseline and 6-year visits, participants completed the Beck Depression Inventory-II (BDI-II) and underwent a blood draw to quantify fasting insulin and glucose. We examined baseline BDI-II total, cognitive-affective, and somatic-vegetative scores as predictors of 6-year change in the homeostatic model of assessment (HOMA) score, an estimate of insulin resistance computed from fasting insulin and glucose. We also examined baseline HOMA score as a predictor of 6-year change in BDI-II total and subscale scores.	Regression analyses, adjusted for demographic factors and baseline HOMA score, revealed that the baseline BDI-II somatic-vegetative score (β = 0.14, p = .025), but not the cognitive-affective (β = 0.001, p = .98) or total (β = 0.10, p = .11) scores, predicted 6-year HOMA change. This result persisted in models controlling for anxiety symptoms and hostility. Several factors were examined as candidate mediators; however, only change in body mass index was a significant mediator (p = .042), accounting for 23% of the observed association. Baseline HOMA score did not predict 6-year change in BDI-II total or subscale scores (all p values >.56).	Among adults aged 50 to 70 years, the somatic-vegetative symptoms of depression (e.g., fatigue, sleep disturbance, and appetite changes) may worsen insulin resistance and increase diabetes risk, partly, by increasing body mass index.	
24845621	Evidence suggests that amyloid-beta (Aβ) depositions parallel sleep deficits in Alzheimer's disease (AD). However, it remains unknown whether impaired sleep and changes in plasma Aβ levels are related in amnestic mild cognitive impairment (aMCI) subjects, and whether both markers are further associated with cortical thinning in canonical AD regions. To jointly address this issue, we investigated relationships between changes in physiological sleep and plasma Aβ concentrations in 21 healthy old (HO) adults and 21 aMCI subjects, and further assessed whether these two factors were associated with cortical loss in each group. aMCI, but not HO subjects, showed significant relationships between disrupted slow-wave sleep (SWS) and increased plasma levels of Aβ42. We also found that shortened rapid-eye movement (REM) sleep in aMCI correlated with thinning of the posterior cingulate, precuneus, and postcentral gyrus; whereas higher levels of Aβ40 and Aβ42 accounted for grey matter (GM) loss of posterior cingulate and entorhinal cortex, respectively. These results support preliminary relationships between Aβ burden and altered sleep physiology observed in animal models of AD amyloidosis, and provide precise cortical correlates of these changes in older adults with aMCI. Taken together, these findings open new research avenues on the combined role of sleep, peripheral Aβ levels and cortical integrity in tracking the progression from normal aging to early neurodegeneration. 


24844879	Sleep problems, prevalent among older adults, are associated with poor outcomes and high health care costs. In 2008, rest and sleep became its own area of occupation in the American Occupational Therapy Association's Occupational Therapy Practice Framework. The current scoping review examined a broad context of sleep research to highlight efficacious interventions for older adults that fall within the occupational therapy scope of practice and present an agenda for research and practice. Four sleep intervention areas clearly aligned with the practice framework, including cognitive behavioral therapy for insomnia, physical activity, multicomponent interventions, and other interventions. Occupational therapy is primed to address sleep problems by targeting the context and environment, performance patterns, and limited engagement in evening activities that may contribute to poor sleep. Occupational therapy researchers and clinicians need to work collaboratively to establish the evidence base for occupation-centered sleep interventions to improve the health and quality of life of older adults.
24843683	'Morningness' and 'eveningness' represent the sleep-wake patterns of the circadian rhythm might also affect glycemic control in patients with type 2 diabetes. The aim of this study was to examine the relationship between the morningness-eveningness trait and metabolic parameters.The study participants comprised 101 Japanese male workers with type 2 diabetes treated in an outpatient clinic. Blood samples were obtained, and a morningness-eveningness questionnaire (MEQ), where a high score represents morningness; and the Pittsburg Sleep Quality Index (PSQI), where the higher the score the worse the sleep quality, were carried out.	MEQ correlated positively with age, and high-density lipoprotein cholesterol (HDL-C), and negatively with glycated hemoglobin (HbA1c) and PSQI. Multivariate regression analysis showed that MEQ was significantly associated with HbA1c and HDL-C. In addition, we classified the study patients into three groups: 'morning type', 'neither type' and 'evening type' according to the sum of the MEQ score, and analyzed the difference between morning type (n = 32) and evening type (n = 11). We found that HbA1c, low-density lipoprotein cholesterol and PSQI of the morning type group were significantly lower than those of the evening type group.	The present study suggests that 'eveningness' type male Japanese workers with type 2 diabetes suffer inadequate glycemic control.	
24843067	Sleep is important to child development, but there is limited understanding of individual developmental patterns of sleep, their underlying determinants, and how these influence health and well-being. This article explores the presence of various sleep patterns in children and their implications for health-related quality of life.Data were collected from the Longitudinal Study of Australian Children. Participants included 2926 young children followed from age 0 to 1 years to age 6 to 7 years. Data on sleep duration were collected every 2 years, and covariates (eg, child sleep problems, maternal education) were assessed at baseline. Growth mixture modeling was used to identify distinct longitudinal patterns of sleep duration and significant covariates. Linear regression examined whether the distinct sleep patterns were significantly associated with health-related quality of life.	The results identified 4 distinct sleep duration patterns: typical sleepers (40.6%), initially short sleepers (45.2%), poor sleepers (2.5%), and persistent short sleepers (11.6%). Factors such as child sleep problems, child irritability, maternal employment, household financial hardship, and household size distinguished between the trajectories. The results demonstrated that the trajectories had different implications for health-related quality of life. For instance, persistent short sleepers had poorer physical, emotional, and social health than typical sleepers.	The results provide a novel insight into the nature of child sleep and the implications of differing sleep patterns for health-related quality of life. The findings could inform the development of effective interventions to promote healthful sleep patterns in children.	
24842006	This is the first study determining correlates of suicide behavior in children with eating disorders using multiple sleep, psychological, and demographic variables. Mothers rated suicide ideation and attempts in 90 children ages 7-18 with bulimia nervosa or anorexia nervosa. Suicide ideation was more prevalent in children with bulimia nervosa (43%) than children with anorexia nervosa (20%). All children with bulimia nervosa who experienced ideation attempted suicide, whereas only 3% of children with anorexia nervosa attempted suicide. Correlates of ideation were externalizing behavior problems and sleep disturbances. Correlates of attempts were bulimia nervosa, self-induced vomiting, nightmares, and physical or sexual abuse. These problems should be assessed and targeted for intervention because of their association with suicide behavior. 
24841836	Although sleep disturbances are commonly reported among children exposed to violence, objective evidence of such disturbances is rare. This longitudinal, home-based study assessed the effects of a known community- or family-violence incident on both actigraphy-derived and subjectively reported sleep outcomes of an ethnically mixed, urban sample of children aged 8-16 years. We hypothesized that increased event severity (child physical assault, witnessed homicide) would be associated with lower sleep duration and poorer sleep quality both at baseline and at 3-month follow-up. Covariate-adjusted analyses based on a generalized estimating equations approach showed that children physically assaulted during the event showed lower sleep duration and sleep efficiency and greater wake after sleep onset than those not physically assaulted. Physically assaulted children were more likely to have a later bedtime than non-assaulted children, but this difference decreased at 3 months. Children witnessing a homicide showed greater wake after sleep onset at baseline and reported greater sleep problems than those witnessing a non-homicide event, but these differences decreased at 3 months. They were also somewhat more likely to have greater nightly variation in sleep duration. Collectively, results suggest that violence exposure influences children's sleep, but that specific dimensions of sleep may exhibit different susceptibility to different characteristics of violence, especially over time.
24841111	The objective of this study was to determine whether daytime sleepiness is independently associated with coronary heart disease (CHD) and stroke or whether the positive association is explained by short sleep duration, disturbed sleep, and circadian disruption, conditions that are associated with cardiometabolic risk factors for vascular events.Longitudinal analyses of data from the Nurses' Health Study II comprising 84,003 female registered nurses aged 37-54 at baseline were conducted in 2001 with follow-up until 2009. Multivariate Cox regression was used to explore the relationship between reported daytime sleepiness and the incidence of either CHD or stroke (n=500 cases).	Women who reported daytime sleepiness almost every day, compared with rarely/never, had an elevated adjusted risk of cardiovascular disease (CVD) (hazard ratio (HR)=1.58, 95% confidence interval (CI) 1.15-2.17). Controlling for sleep variables (sleep duration, snoring, shift work, and sleep adequacy) or potential metabolic biological mediators of disrupted sleep (diabetes, hypercholesterolemia, and hypertension) appreciably attenuated the relationship (HR=1.17, 95% CI 0.84-1.65; and HR=1.34, 95% CI 0.97-1.85, respectively). Controlling for both sleep variables and metabolic risk factors eliminated an independent association (HR=1.09, 95% CI 0.77-1.53). A similar pattern was observed for CHD and stroke individually.	Daytime sleepiness was not an independent risk factor for CVD in this cohort of women, but rather, was associated with sleep characteristics and metabolic abnormalities that are risk factors for CVD.	
24840814	The sensitivity of melatonin to light suppression is expected to be higher in children because children have large pupils and pure crystal lenses. However, melatonin suppression by light in children remains unclear.We investigated whether light-induced melatonin suppression in children is larger than that in adults.	Thirty-three healthy primary school children (mean age, 9.2 ± 1.5 y) and 29 healthy adults (mean age, 41.6 ± 4.7 y) participated in two experiments. In the first experiment, salivary melatonin concentrations in 13 children and 13 adults were measured at night under a dim light (<30 lux) and a moderately bright light (580 lux) in an experimental facility. Pupil diameters were also measured under dim light and bright light. In the second experiment, melatonin concentrations in 20 children and 16 adults were measured under dim light in the experimental facility and under room light at home (illuminance, 140.0 ± 82.7 lux).	In experiment 1, the melatonin concentration was significantly decreased by exposure to moderately bright light in both adults and children. Melatonin suppression was significantly larger in children (88.2%; n = 5) than in adults (46.3%; n = 6; P < .01), although the data for some participants were excluded because melatonin concentrations had not yet risen. In experiment 2, melatonin secretion was significantly suppressed by room light at home in children (n = 15; P < .05) but not in adults (n = 11).	We found that the percentage of melatonin suppression by light in children was almost twice that in adults, suggesting that melatonin is more sensitive to light in children than in adults at night.	
24836675	Previous studies showed enhanced attention and decreased inhibitory processes during early non-rapid eye movement sleep in primary insomnia patients, as measured by event-related potentials. The current study aims to examine information processing during sleep in non-insomniac individuals with high vulnerability (HV) to stress-related sleep disturbances.Twenty-seven non-insomniac individuals were recruited, 14 with low vulnerability and 13 with HV. After passing a screening interview and polysomnographic recording, subjects came to the sleep laboratory for 2 nights (a baseline night and a stress-inducing night) for event-related potentials recordings.	The HV group demonstrated shorter P2 latency during the first 5 min of stage 2 sleep and higher P900 amplitudes under the stress condition during slow-wave sleep, which indicates an increased level of inhibitory processes. In addition, they had shorter N1 latencies during slow-wave sleep that could indicate an elevated level of attention processing during deep sleep.	Unlike patients with chronic insomnia, individuals with high sleep vulnerability to stress show a compensatory process that may prevent external stimulation from interfering with their sleep. This may be one of the factors preventing their acute sleep disturbances from becoming chronic problems.	
24833792	Children with progressive, non-curable genetic, metabolic, or neurological conditions require specialised care to enhance their quality of life. Prevention and relief of physical symptoms for these children needs to begin at diagnosis, yet, little is known about their patterns of symptoms and functional abilities.To describe these children's symptoms, as well as how the children's condition affects them physically.	Cross-sectional, baseline results from an observational, longitudinal study, Charting the Territory, that followed 275 children and their families.	Seven tertiary care children's hospitals in Canada, 2 in the USA. Families were eligible based on the child's condition. A total of 275 children from 258 families participated.	The 3 most common symptoms in these children were pain, sleep problems, and feeding difficulties; on average, they had 3.2 symptoms of concern. There was a pattern of under-reporting of children's symptoms for clinicians compared with parents. Regardless of use of associated medications, pain, feeding and constipation symptoms were often frequent and distressing. Children with a G/J tube had a higher total number of symptoms, and respiratory problems, pain, feeding difficulties and constipation were more likely to occur. They also tended to have frequent and distressing symptoms, and to need extensive mobility modifications which, in turn, were associated with higher numbers of symptoms.	These children experience multiple symptoms that have been previously documented individually, but not collectively. Effective interventions are needed to reduce their symptom burden. Future longitudinal analyses will examine which disease-modifying interventions improve, or do not improve, symptom burden.	
24833726	Intraoperative recruitment manoeuvres (RMs) combined with PEEP reverse the decrease in functional residual capacity (FRC) associated with anaesthesia and improve intraoperative oxygenation. Whether these benefits persist after operation remains unknown. We tested the hypothesis that intraoperative RMs associated with PEEP improve postoperative spirometry including FRC and reduce the incidence of postoperative hypoxaemia in morbidly obese (MO) patients undergoing laparoscopic gastric bypass.After IRB approval and informed consent, 50 MO patients undergoing laparoscopic gastric bypass under volume-controlled ventilation (tidal volume 6 ml kg(-1) of IBW) were randomly ventilated with either 10 cm H₂O PEEP or with 10 cm H₂O PEEP and one RM carried out after induction of pneumoperitoneum, and another after exsufflation. Anaesthesia and analgesia were standardized. Spirometry was assessed before operation and 24 h after surgery. Postoperative oxygenation and the apnoea-hypopnoea index (AHI) were recorded during the first postoperative night.	Age, BMI, and STOP BANG score were similar in both groups. FRC decrease after surgery was minimal [0.15 (0.14) litre in control and 0.38 (0.19) litre in the RM group] and similar between the groups (P=0.35). FVC, FEV1, mean [Formula: see text], percentage of time spent with [Formula: see text] below 90%, and AHI did not differ significantly between the groups.	This study demonstrates that when added to a protective mechanical ventilation combining low tidal volume and high PEEP, two RMs do not improve postoperative lung function including FRC, arterial oxygenation, and the incidence of obstructive apnoea in MO patients after laparoscopic upper abdominal surgery.	EudraCT 2011-000999-33.	
24831251	To examine the speed and trajectory of changes in sleep/wake parameters during short-term treatment of insomnia with cognitive-behavioral therapy (CBT) alone versus CBT combined with medication; and to explore the relationship between early treatment response and post-treatment recovery status.Participants were 160 adults with insomnia (mean age, 50.3 years; 97 women, 63 men) who underwent a six-week course of CBT, singly or combined with 10 mg zolpidem nightly. The main dependent variables were sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency, and sleep quality, derived from sleep diaries completed daily by patients throughout the course of treatment.	Participants treated with CBT plus medication exhibited faster sleep improvements as evidenced by the first week of treatment compared to those receiving CBT alone. Optimal sleep improvement was reached on average after only one week for the combined treatment compared to two to three weeks for CBT alone. Early treatment response did not reliably predict post-treatment recovery status.	Adding medication to CBT produces faster sleep improvement than CBT alone. However, the magnitude of early treatment response is not predictive of final response after the six-week therapy. Additional research is needed to examine mechanisms involved in this early treatment augmentation effect and its impact on long-term outcome.	
24830553	In Drosophila, serotonin (5-HT) regulates aggression, mating behaviour and sleep/wake behaviour through different receptors. Currently, how these various receptors are themselves regulated is still not completely understood. The KCTD12-family of proteins, which have been shown to modify G-protein-coupled receptor (GPCR) signalling in mammals, are one possibility of auxiliary proteins modulating 5-HT receptor signalling. The KCTD12-family was found to be remarkably conserved and present in species from C. elegans to humans. The Drosophila KCTD12 homologue Kctd12-like (Ktl) was highly expressed in both the larval and adult CNS. By performing behavioural assays in male Drosophila, we now reveal that Ktl is required for proper male aggression and mating behaviour. Previously, it was shown that Ktl is in a complex with the Drosophila 5-HT receptor 5-HT7, and we observed that both Ktl and the 5-HT1A receptor are required in insulin-producing cells (IPCs) for proper adult male behaviour, as well as for hyperaggressive activity induced by the mammalian 5-HT1A receptor agonist 8-hydroxy-2-dipropylaminotetralin-hydrobromide. Finally, we show that Ktl expression in the IPCs is necessary to regulate locomotion and normal sleep/wake patterns in Drosophila, but not the 5-HT1A receptor. Similar to what was observed with mammalian KCTD12-family members that interact physically with a GPCR receptor to regulate desensitization, in Drosophila Ktl may function in GPCR 5-HT receptor pathways to regulate their signalling, which is required for proper adult male behaviour.
24829263	Few studies have examined the behavioral and clinical indicators of sleep difficulty among older African Americans diagnosed with arthritis. This study aimed to examine the association of sleep, pain, and comorbid indicators among this population.Using a cross-sectional design, 193 older African Americans (70.4 ± 9.11 years of age) completed a series of questions assessing health, pain, and sleep.	Findings showed that young old participants (β = -.28, p < .001) reported more difficulty sleeping and being awakened due to pain (β = -.17, p < .05) than the old old adults.	There is significant within-group variability, with young old adults being most affected by sleep difficulties.	While the relationship between pain and sleep may be intuitive for majority populations, the dynamics of this association may be useful in promoting sleep awareness and providing resources for caregivers and health care professionals to better meet the needs of this population.	
24828644	Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system. The activity of these cells was controlled by optogenetics by expressing channelrhodopsin2 (E123T/T159C) or archaerhodopsin-T in MCH neurons. Acute optogenetic activation of MCH neurons at 10 Hz induced transitions from non-REM (NREM) to REM sleep and increased REM sleep time in conjunction with decreased NREM sleep. Activation of MCH neurons while mice were in NREM sleep induced REM sleep, but activation during wakefulness was ineffective. Acute optogenetic silencing of MCH neurons using archaerhodopsin-T had no effect on any vigilance states. Temporally controlled ablation of MCH neurons by cell-specific expression of diphtheria toxin A increased wakefulness and decreased NREM sleep duration without affecting REM sleep. Together, these results indicate that acute activation of MCH neurons is sufficient, but not necessary, to trigger the transition from NREM to REM sleep and that MCH neurons also play a role in the initiation and maintenance of NREM sleep. 
24826835	Patients treated for nonfunctioning pituitary macroadenomas (NFMAs) have fatigue and alterations in sleep characteristics and sleep-wake rhythmicity frequently. As NFMAs often compress the optic chiasm, these complaints might be related to dysfunction of the adjacent suprachiasmatic nucleus (SCN). We aimed to explore whether indirect indices of SCN functioning are altered in the long term after surgery for NFMAs.We studied 17 NFMA patients in long-term remission after transsphenoidal surgery, receiving adequate and stable hormone replacement for hypopituitarism, and 17 control subjects matched for age, gender, and BMI. Indirect indices of SCN function were assessed from 24-h ambulatory recordings of skin and core body temperatures, blood pressure, and salivary melatonin levels. Altered melatonin secretion was defined as an absence of evening rise, considerable irregularity, or daytime values >3 pg/ml. We additionally studied eight patients treated for craniopharyngioma.	Distal-proximal skin temperature gradient did not differ between NFMAs and control subjects, but proximal skin temperature was decreased during daytime (P=0.006). Core body temperature and non-dipping of blood pressure did not differ, whereas melatonin secretion was often altered in NFMAs (OR 5.3, 95% CI 0.9-30.6). One or more abnormal parameters (≥2.0 SDS of control subjects) were observed during nighttime in 12 NFMA patients and during daytime in seven NFMA patients. Similar patterns were observed in craniopharyngioma patients.	Heterogeneous patterns of altered diurnal rhythmicity in skin temperature and melatonin secretion parameters were observed in the majority of patients treated for NFMAs. On a group level, both NFMA and craniopharyngioma patients showed a lower daytime proximal skin temperature than control subjects, but other group averages were not significantly different. The observations suggest altered function of central (or peripheral) clock machinery, possibly by disturbed entrainment or damage of the hypothalamic SCN by the suprasellar macroadenoma or its treatment.	
24825404	Improvement of uremic pruritus has been reported under short-term administration of oral zinc sulfate. Objective of the study was to confirm efficacy and safety of oral zinc sulfate in pruritus of hemodialytic patientsA pilot randomized, triple-blind study was conducted to evaluate the pruritus of hemodialytic patients. Forty eligible patients were screened and assigned to receive either zinc sulfate (220 mg/d) or matched placebo for a 4-week trial. Pruritus scale was evaluated at the initiation of the study and 1, 2, 3, and 4 weeks after the treatment. We used a modified score proposed by Duo assessing pruritus severity, distribution of pruritus, and frequency of pruritus-related sleep disturbance.	Thirty-six patients completed the study. The mean pruritus score decreased in both groups during the first and the second weeks of trial; however, it was more prominent in zinc group than placebo one. In the zinc group, 4 (20%) patients showed pruritus discontinuation during treatment period whereas, in the placebo group, the number was only 1 (5%) patient. Nonetheless, T-test revealed no statistically significant difference between the zinc and placebo groups (P=0.88 and P=0.56, respectively).	Our findings demonstrated that oral zinc sulfate (220 mg/d) during four weeks treatment might be safe and effective in discontinuation of uremic pruritus, but it was not significant. This could be because of the small number of patients; therefore, we suggest conducting more studies with larger sample size.	
24824827	Delirium in the ICU affects as many as 60-80% of mechanically ventilated patients and a smaller but substantial percentage of other critically ill patients. Poor sleep quality has been consistently observed in critically ill patients. These problems are associated with worse ICU outcomes and, in many cases, delirium and poor sleep quality may be related. This review will summarize the recent literature relevant to both the problems and provide a potential pathway toward improvement.Many cases of delirium and the poor sleep experienced by ICU patients may be iatrogenic. How critical care practitioners prescribe sedatives and analgesics and, perhaps more broadly, how all medications are administered to critically ill patients, may be at the root of some of these problems. Reducing the administration of some commonly used ICU medications, especially some sedatives and anticholinergic medications, and keeping patients more awake and actively engaged in their care during the day may lead to better outcomes.	It is our responsibility to apply the best available, evidence-based medicine to our practice. Adherence to new guidelines for the treatment of pain, agitation, and delirium may be the best pathway toward reducing delirium, improving sleep quality, and improving related outcomes.	
24824747	To assess circadian preference with a score, the Morningness-Eveningness Questionnaire (MEQ) has been used for more than 3 decades now. More recently, the Munich ChronoType Questionnaire (MCTQ) was developed: it asks for sleep-wake behavior on work and free days and uses the midpoint of sleep on free days (MSF), corrected for sleep debt accumulated during the work week as an indicator of chronotype (MSFsc). In this study, we developed a Japanese version of the MCTQ by using a translation/back-translation approach including an examination of its semantic validity. In a subsequent questionnaire survey, 450 adult men and women completed the Japanese versions of the MCTQ and MEQ. Results showed that MEQ scores were significantly negatively correlated with mid-sleep parameters assessed by the MCTQ, on both, work and free days, as well as with the chronotype measure MSFsc (r = -0.580 to -0.652, all p < 0.001). As in the original German version, the strongest correlation was observed between MEQ score and MSF. A physiological validation study using dim light melatonin onset as a circadian phase marker (N = 37) showed a high correlation between chronotype as assessed with the MSFsc (r = 0.542, p < 0.001), and less so for MEQ score (r = -0.402, p = 0.055). These results demonstrate the validity of the Japanese MCTQ and provide further support of the adequacy of the MCTQ as a chronotype measure. 
24824340	Conventional scoring of sleep provides little information about the process of transitioning between vigilance-states. We used the state space technique to explore whether rats with chronic upper airway obstruction (UAO) have abnormal sleep/wake states, faster movements between states, or abnormal transitions between states.The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed to increase upper airway resistance with no evidence for frank obstructed apneas or hypopneas; 24-h electroencephalography of sleep/wake recordings of UAO and sham-control animals was analyzed using state space technique. This non-categorical approach allows quantitative and unbiased examination of vigilance-states and state transitions. Measurements were performed 2 weeks post-surgery at baseline and following administration of ritanserin (5-HT2 receptor antagonist) the next day to stimulate sleep.	UAO rats spent less time in deep (delta-rich) slow wave sleep (SWS) and near transition zones between states. State transitions from light SWS to wake and vice versa and microarousals were more frequent and rapid in UAO rats, indicating that obstructed animals have more regions where vigilance-states are unstable. Ritanserin consolidated sleep in both groups by decreasing the number of microarousals and trajectories between wake and light SWS, and increasing deep SWS in UAO.	State space technique enables visualization of vigilance-state transitions and velocities that were not evident by traditional scoring methods. This analysis provides new quantitative assessment of abnormal vigilance-state dynamics in UAO in the absence of frank obstructed apneas or hypopneas.	
24822040	Inability to solve complex problems or errors in decision making is often attributed to poor brain processing, and raises the issue of brain augmentation. Investigation of neuronal activity in the cerebral cortex in the sleep-wake cycle offers insights into the mechanisms underlying the reduction in mental abilities for complex problem solving. Some cortical areas may transit into a sleep state while an organism is still awake. Such local sleep would reduce behavioral ability in the tasks for which the sleeping areas are crucial. The studies of this phenomenon have indicated that local sleep develops in high order cortical areas. This is why complex problem solving is mostly affected by local sleep, and prevention of local sleep might be a potential way of augmentation of brain function. For this approach to brain augmentation not to entail negative consequences for the organism, it is necessary to understand the functional role of sleep. Our studies have given an unexpected answer to this question. It was shown that cortical areas that process signals from extero- and proprioreceptors during wakefulness, switch to the processing of interoceptive information during sleep. It became clear that during sleep all "computational power" of the brain is directed to the restoration of the vital functions of internal organs. These results explain the logic behind the initiation of total and local sleep. Indeed, a mismatch between the current parameters of any visceral system and the genetically determined normal range would provide the feeling of tiredness, or sleep pressure. If an environmental situation allows falling asleep, the organism would transit to a normal total sleep in all cortical areas. However, if it is impossible to go to sleep immediately, partial sleep may develop in some cortical areas in the still behaviorally awake organism. This local sleep may reduce both the "intellectual power" and the restorative function of sleep for visceral organs. 
24821401	Accumulating data continue to support the therapeutic potential of glutamate metabotropic (mGluR2) receptors for treatment of psychiatric disorders such as depression, anxiety and schizophrenia. Glutamate neurotransmission is an integral component of sleep-wake mechanisms, which have translational relevance to assess on-target activity of drugs. Here, we investigated the influence of mGluR2 inactivation upon sleep-wake electroencephalogram (EEG) in rodents. Rats were administered with vehicle, the specific mGluR2 antagonist LY341495 (2.5, 5, 10mg/kg) or negative allosteric modulator (NAM) Ro-4491533 (2.5, 10 and 40 mg/kg) at lights onset. mGluR2 (-/-) mice were used to confirm the selectivity of functional response. Both LY341495 and Ro-4491533 induced an immediate and endured desynchronized cortical activity during 3-6h associated with enhanced theta and gamma oscillations and depressed slow oscillations during sleep. The arousal-promoting effect is consistent with the marked lengthening of sleep onset latency, an increased number of state transitions from light sleep to waking and the gradual increase in homeostatic compensatory sleep. The arousal response to mGluR2 blockade was not accompanied by sharp rebound hypersomnolence as found with the classical psycho-stimulant amphetamine. mGluR2 (-/-) mice and their WT littermates exhibited similar sleep-wake phenotype, while Ro-4491533 (40 mg/kg) enhanced waking associated with increased locomotor activity and body temperature in WT but not in mGluR2 (-/-) mice, which confirm the role of mGluR2 inactivation in the arousal response. Our results lend support for a role of mGluR2 blockade in promoting cortical arousal associated with theta/gamma oscillations as well as high thresholds transitions from sleep to waking.
24821311	The basic elements of animal behavior that are critical to survival include energy, arousal, and motivation: Energy intake and expenditure are fundamental to all organisms for the performance of any type of function; according to the Yerkes-Dodson law, an optimal level of arousal is required for animals to perform normal functions; and motivation is critical to goal-oriented behaviors in higher animals. The brain is the primary organ that controls these elements and, through evolution, has developed specialized structures to accomplish this task. The orexin/hypocretin system in the perifornical/lateral hypothalamus, which was discovered 15 years ago, is one such specialized area. This review summarizes a fast-growing body of evidence discerning how the orexin/hypocretin system integrates internal and external cues to regulate energy intake that can then be used to generate sufficient arousal for animals to perform innate and goal-oriented behaviors. 
24820165	While acute rehabilitation following neurotrauma has evolved over the past 30 years to include the common use of pharmacologic agents to promote synaptogenesis and improve recovery potential, little guidance exists for a similar strategy in the post-acute or community re-entry phases of injury. Drawing upon the existing scientific literature, models of pharmacologic intervention in promoting stability in other disease states and the authors' collective clinical experience, this article provides a potential structure by which to implement methods to create a stable physiologic platform to facilitate behavioral intervention.This article reviews basic foundations for physiologic optimization, pharmacologic strategies for facilitation, and dyscompliance after neurotrauma.	Literature review, case analysis, clinical experience.	Guidelines for facilitation of behavioral intervention with physiologic stabilization and with pharmacologic agents are presented with clinical rationale for their utilization.	Improving physiologic readiness for behavioral intervention in the post-acute and community re-entry phases following neurotrauma has potential to improve both the efficiency and durability of these efforts.	


24818445	This article reviews the research at the Department of Human Biology at the Christian-Albrechts-University in Kiel since 2006. The research focuses on the investigation of recent human populations with respect to aging, chronobiology, and adaptation to high altitude. The research areas are outlined presenting findings, ongoing projects and future directions. Aging research examines biological changes in humans considering that aging is a multidimensional process. Changes in body composition, resting energy metabolism, oxidative stress, and sleep have been examined. The applicability of specific research methods to older people has been tested. Chronobiological research concentrates on investigating circadian rhythms of humans. The emphasis lies on the sleep-wake rhythm, body temperature rhythms, hormonal rhythms (cortisol and melatonin) and the circadian expression of so-called clock genes which are involved in the generation of circadian rhythms. Association studies examine the relationship between defined chronobiological phenotypes and clock gene polymorphisms. Genetic aspects are as well investigated within the third research area on the adaptation of native populations to life at high altitude in the South American Andes. Both candidate gene analysis and epigenetic parameters are investigated. Future research will concentrate on the aging of the circadian system.
24816545	Like many chronic illnesses, Behçet's disease (BD) has been reported to negatively affect the quality of life and mental health of the individuals diagnosed with this disease. This study aims to investigate the relationship between disease activity and depression and sleep quality in BD. Forty patients with BD and 30 healthy subjects (controls), aged 18-65, were included in this study, and all of the subjects enrolled in this study were assessed in terms of depression and sleep quality using the Beck depression index (BDI) and Pittsburg sleep quality index (PSQI). Additionally, the subjects with BD were also assessed using the Behçet's disease current activity form (BDCAF). It was determined that the depression and sleep quality scores were significantly higher in the BD group compared to those in the control group (p = 0.012 and p = 0.020, respectively), and in the BD group, significant positive correlations were determined between the BDCAF and depression and sleep quality scores (r = 0.559, p < 0.001 and r = 0.462, p = 0.003, respectively). We believe that the assessment of BD patients for depressive symptoms and sleep quality, and providing medical support to those who need it, will contribute to the treatment and follow-up processes of BD.
24816469	Based on the literature data in the last two decades, growth hormone deficiency (GHD) in adults has been accepted as a clinical entity. Due to the presence of GH and IGF-I receptors throughout the body, the physiological effects of the GH-IGF-I axis are still under investigation. The effects of GH on skin, sleep, and coagulation parameters in adults have only been investigated in detail only in the recent years. In this review, our aim was to summarize the literature regarding the effects of GHD and GH replacement treatment on the skin, sleep, and coagulation parameters in adults. 
24814637	Studies of the long-term stability of sleep in pre-schoolers are scarce. The aim of the present study was to investigate objectively assessed sleep via actigraphy in pre-schoolers longitudinally, and to predict sleep, psychological functioning and cortisol secretion prospectively as a function of sleep 12 months earlier.A total of 73 pre-schoolers (mean age: 5.45 years; 53% females) were assessed again after 12 (mean age: 6.4 years). Sleep-actigraphy recordings were performed, saliva cortisol was analysed, and parents and experts rated children's psychological functioning.	Longitudinally, poor sleep at age 5.45 years was associated with poor sleep and internalizing and peer problems but not with externalizing problems and hyperactivity, and cortisol secretion 12 months later. At age 6.4 years and cross-sectionally, poor sleep was concurrently associated with greater psychological difficulties and increased cortisol secretion.	In pre-schoolers, poor sleep objectively assessed at age five was associated with psychological difficulties and poor sleep as assessed via actigraph and one year later. Results indicate that in pre-schoolers sleep remains stable over a 12-mont interval. Pre-schoolers with poor sleep appear to be at risk for developing further psychological difficulties.	
24814312	Musculoskeletal chronic pain is a costly public health threat. The aim of our study was to investigate mental health indicators, including self-reported symptoms of depression, sleep disruption, stress, well-being, and quality of life (QoL), among men and women with musculoskeletal chronic pain in a general population.This was a cross-sectional study; a postal questionnaire was mailed to a stratified random sample of 9807 eligible Icelanders retrieved from a national registry, of whom 5906 responded (response rate = 60.2%). Chronic pain conditions included reports of current chronic back pain, chronic neck symptoms, and/or fibromyalgia. Gender-stratified associations of chronic pain conditions with mental health indicators were estimated with logistic regression analyses adjusting for age, income, body mass index (BMI), smoking, education, and residence.	We observed higher odds of low satisfaction with life [adjusted odds ratio (OR(adj)) women 2.0, 95% confidence interval (CI) 1.5-2.6; OR(adj) men 2.3, 95% CI 1.7-3.1], higher levels of perceived stress (OR(adj) women 1.7, 95% CI 1.3-2.2; OR(adj) men = 1.5, 95% CI 1.1-2.1), depressive symptoms (OR(adj) women 2.4, 95% CI 1.9-3.0; OR(adj) men 2.8, 95% CI 2.1-3.7), and sleep disruption (OR(adj) women 2.8, 95% CI 2.2-3.5; OR(adj) men 2.2, 95% CI 1.5-3.1), and diminished QoL (OR(adj) women 1.6, 95% CI 1.2-2.1; OR(adj) men 1.5, 95% CI 1.0-2.1) among individuals with chronic pain compared with those without the condition.	Our data indicate that individuals with musculoskeletal chronic pain have increased risk of poor mental health and diminished QoL. Further studies are needed on treatment and preventative measures of a decline in mental health among individuals with chronic pain.	
24813585	Several measuring devices are available to assess specific behavioural problems of dementia patients residing in nursing homes but only a few have been translated and validated in French. This study's main objective was to determine the factorial structure of the French version of the Nursing Home Behavior Problem Scale (NHBPS) with people suffering from dementia. A secondary objective was to document the variables associated with the global score of the NHBPS and the underlying dimensions of the instrument. Participants (n = 155) were diagnosed with dementia and resided in three nursing homes and a hospital's long-term care unit. The presence of behavioural problems and other characteristics were assessed by two nurses. A factor analysis revealed five key dimensions in the francophone version of the questionnaire. Several variables were associated with the total score of the NHBPS and its five underlying dimensions. Although the factorial solution of the French version of the NHBPS is similar to the English versions, our results also show differences that may depend on methodological characteristics.
24813556	The aim of this study was to measure the brain activity of preterm infants treated with caffeine citrate and doxapram for preterm apnoea, using amplitude-integrated electroencephalography (aEEG), to identify any adverse effects on cerebral function.We analysed the aEEG tracings of 13 preterm infants <30 weeks of gestation before, during and after doxapram treatment, with regard to background activity (percentages of continuous and discontinuous patterns), occurrence of sleep-wake cycling and appearance of electrographic seizure activity. They were also compared with 61 controls without doxapram treatment.	During doxapram treatment, aEEG tracings showed an increase in continuous background activity (19 ± 30% before treatment, 38 ± 35% during treatment) and a decrease in discontinuous patterns. In addition, they showed more frequent electrographic seizure activity (0% before treatment, 15 ± 37% during treatment) and less frequent sleep-wake cycling (92 ± 27% before treatment, 85 ± 37% during treatment) could be observed. These results were confirmed when compared to the control group.	Doxapram treatment influences aEEG in preterm infants, showing higher percentages of continuous activity as well as more electrographic seizure activity and less sleep-wake cycling. It should, therefore, be used with caution in very preterm infants.	

24812539	Cerebellar ataxia comprises a group of debilitating diseases that are the result of progressive cerebellar degeneration. Recent studies suggest that, like other neurodegenerative diseases, sleep impairments are common in cerebellar ataxia. In light of the role of sleep in mood regulation and cognition, we sought to assess interactions between sleep, cognition, and affect in individuals with cerebellar ataxia.A survey of 176 individuals with cerebellar ataxia was conducted. The battery of instruments included a modified International Cooperative Ataxia Rating Scale, Pittsburgh Sleep Quality Index, Restless Leg Syndrome Questionnaire, REM Behavior Disorder Questionnaire, Beck Depression Inventory, Epworth Sleepiness Scale, and a Composite Cognitive Questionnaire.	Fifty-one percent of individuals indicated significant sleep disturbances on the Pittsburgh Sleep Quality Index, 73% of participants had two or more symptoms of restless leg syndrome, and 88% had two or more symptoms of REM behavior disorder. Ataxia severity, based on the modified International Cooperative Ataxia Rating Scale, predicted scores on the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and REM Behavior Disorder Questionnaire. Median split analyses revealed that cognitive function appeared to be reduced and depressive symptoms were greater for those individuals with poor subjective sleep quality and severe RLS. Importantly, sleep appears to play a mediatory role between disease severity and depressive symptoms.	These results suggest that disturbed sleep may have detrimental effects on cognition and affect in individuals with cerebellar ataxia. While objective measures are needed, such results suggest that treating sleep deficits in these individuals may improve cognitive and mental health as well as overall quality of life.	
24812132	Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments. 
24809311	The aim of this study was to investigate the longitudinal effect of work-related stress, sleep deficiency, and physical activity on 10-year cardiometabolic risk among an all-female worker population.Data on patient care workers (n=99) was collected 2 years apart. Baseline measures included: job stress, physical activity, night work, and sleep deficiency. Biomarkers and objective measurements were used to estimate 10-year cardiometabolic risk at follow-up. Significant associations (P<0.05) from baseline analyses were used to build a multivariable linear regression model.	The participants were mostly white nurses with a mean age of 41 years. Adjusted linear regression showed that having sleep maintenance problems, a different occupation than nurse, and/or not exercising at recommended levels at baseline increased the 10-year cardiometabolic risk at follow-up.	In female workers prone to work-related stress and sleep deficiency, maintaining sleep and exercise patterns had a strong impact on modifiable 10-year cardiometabolic risk.	

24807838	The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating an equivalent homeostatic stress between individuals than other methods. Individual variation in the homeostatic stress associated with each training session would result in individuals experiencing a different exercise 'stimulus' and contribute to individual variation in the adaptive responses incurred over the course of the training program. Furthermore, recovery between the sessions of a standardized training program may vary amongst individuals due to factors such as training status, sleep, psychological stress, and habitual physical activity. If there is an imbalance between overall stress and recovery, some individuals may develop fatigue and even maladaptation, contributing to variation in pre-post training responses. There is some evidence that training response can be modulated by the timing and composition of dietary intake, and hence nutritional factors could also potentially contribute to individual variation in training responses. Finally, a certain amount of individual variation in responses may also be attributed to measurement error, a factor that should be accounted for wherever possible in future studies. In conclusion, there are several factors that could contribute to individual variation in response to standardized training. However, more studies are required to help clarify and quantify the role of these factors. Future studies addressing such topics may aid in the early prediction of high or low training responses and provide further insight into the mechanisms of training adaptation. 

24806676	The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertal orexin-tTA;TetO DTA mice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when ∼5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep/wake regulation, orexin-tTA; TetO DTA mice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost. 
24806564	To explore sleep risk factors and their association with adverse events in transportation operators.Self-reported sleep-related behaviors were analyzed in transportation operators (drivers, pilots, and rail operators) aged 26 to 78 years who completed the National Sleep Foundation's 2012 "Planes, Trains, Automobiles, and Sleep" survey. Regression analyses were used to assess the associations of various sleep-related variables with the combined outcome of self-reported accidents and near misses.	Age- and body mass-adjusted predictors of accidents/near misses included an accident while commuting (odds ratio [OR] = 4.6; confidence interval [CI], 2.1 to 9.8), driving drowsy (OR = 4.1; CI, 2.5 to 6.7), and Sheehan Disability Scale score greater than 15 (OR = 3.5; CI, 2.2 to 5.5). Sleeping more than 7 hours nightly was protective for accident/near misses (OR = 0.6; CI, 0.4 to 0.9).	Recognized risk factors for poor sleep or excessive daytime sleepiness were significantly associated with self-reported near misses and/or accidents in transportation operators.	
24804716	Throughout history, people have suffered from physical symptoms that they have attributed to modern technologies. Often these attributions are strongly held, but not supported by scientific evidence. Symptoms attributed to the operation of wind turbines (called "wind turbine syndrome" by some) may fit into this category. Several psychological mechanisms might account for symptoms attributed to wind turbines. First, the "nocebo effect" is a well-recognized phenomenon in which the expectation of symptoms can become self-fulfilling. Second, misattribution of pre-existing or new symptoms to a novel technology can also occur. Third worry about a modern technology increases the chances of someone attributing symptoms to it. Fourth, social factors, including media reporting and interaction with lobby groups can increase symptom reporting. For wind turbines, there is already some evidence that a nocebo effect can explain the attributed symptoms while misattribution seems likely. Although worry has not been directly studied, research has shown that people who are annoyed by the sound that turbines produce are more likely to report symptoms and that annoyance is associated with attitudes toward the visual impact of wind farms and whether a person benefits economically from a wind farm. Given that these mechanisms may be sufficient to account for the experiences reported by sufferers, policy-makers, clinicians and patients should insist on good-quality evidence before accepting a more direct causal link. 
24804513	The use of actigraphy, which can be used to estimate sleep-wake patterns from activity levels, has become common in sleep research. Actigraphy is a simple, cost-effective and non-invasive method for healthcare providers and researchers to assess patients sleep quality and screen for potential sleep disorders in recent years. But, there is no wide recognition and application of actigraphy in China up till now. This review summarized the application of actigraphy in evaluation of sleep and diagnosis of sleep disorders.
24803913	Obstructive sleep apnea (OSA) patients have increased upper airway muscle activity, including such lingual muscles as the genioglossus (GG), geniohyoid (GH), and hyoglossus (HG). This adaptation partially protects their upper airway against obstructions. Rodents are used to study the central neural control of sleep and breathing but they do not naturally exhibit OSA. We investigated whether, in chronically instrumented, behaving rats, disconnecting the GH and HG muscles from the hyoid (H) apparatus would result in a compensatory increase of other upper airway muscle activity (electromyogram, EMG) and/or other signs of upper airway instability. We first determined that, in intact rats, lingual (GG and intrinsic) muscles maintained stable activity levels when quantified based on 2 h-long recordings conducted on days 6 through 22 after instrumentation. We then studied five rats in which the tendons connecting the GH and HG muscles to the H apparatus were experimentally severed. When quantified across all recording days, lingual EMG during slow-wave sleep (SWS) was modestly but significantly increased in rats with surgically altered upper airway [8.6 ± 0.7% (SE) vs. 6.1 ± 0.7% of the mean during wakefulness; p = 0.012]. Respiratory modulation of lingual EMG occurred mainly during SWS and was similarly infrequent in both groups, and the incidence of sighs and central apneas also was similar. Thus, a weakened action of selected lingual muscles did not produce sleep-disordered breathing but resulted in a relatively elevated activity in other lingual muscles during SWS. These results encourage more extensive surgical manipulations with the aim to obtain a rodent model with collapsible upper airway. 
24802904	Data on the relationship between sleep disturbances and refractory epileptic encephalopathies (EEs) are scarce. Our aim was to assess, by means of nocturnal polysomnography, if children with EEs present with objective alterations in sleep organization. Twenty-three children with EEs (12 males; mean age: 8.7±1.4years) and 40 healthy controls (22 males; mean age: 8.8±1.1years) underwent an overnight full polysomnography (PSG). Relative to controls, children with EEs showed a significant reduction in all PSG parameters related to sleep duration time in bed (TIB-min p<0.001), total sleep time (TST-min p<0.001), and sleep percentage (SPT-min p<0.001), as well as significantly higher REM latency (FRL-min p<0.001), rate in stage shifting (p=0.005), and number of awakenings/hour (p=0.002). Relative to controls, children with EEs also showed significant differences in respiratory parameters (AHI/h p<0.001, ODI/h p<0.001, SpO2% p<0.001, SpO2 nadir% p<0.001) and a higher rate of periodic limb movements (PLMs% p<0.001). Our findings suggest that sleep evaluation could be considered mandatory in children with refractory epileptic encephalopathy in order to improve the clinical management and the therapeutic strategies. 
24802313	Septo-Optic Dysplasia (SOD) is a rare disorder with postulated genetic and environmental etiology. Whilst initially considered as a very rare disease (defined as incidence of approx. 1 in 50,000 births) recent data gave a reported incidence of 1 in 10,000, with equal sex distribution. The diagnosis of SOD is predominantly a clinical one, and made with the presence of two or more features of the classic triad: 1) hypopituitarism, 2) optic nerve hypoplasia, and 3) midline brain defects, typically absence or hypoplasia of the septum pellucidum and/or corpus callosum. Hypopituitarism ranges from isolated to multiple hormone deficits, with diabetes insipidus in a minority. The condition is heterogeneous and may also manifest additional brain defects. Although homozygous mutations in the homeobox gene HESX1 have been identified in SOD, these are uncommon and genetic diagnosis can be made in only <1% of patients with autosomal recessive inheritance. Autosomal dominant inheritance has also been reported. SOX2, SOX3 and OTX2 mutations have also been identified in some forms of SOD. The aetiology of SOD is uncertain but viral infections, environmental teratogens and vascular or degenerative damage have been postulated to account for its sporadic occurrence. Other factors (endogenous or exogenous) include parental age, parity, smoking, alcohol and substance abuse, antenatal bleeding, and ethnicity. Cocaine abuse during pregnancy, which is a potent vasoconstrictor has recently been identified as a potential external cause. The phenotype of SOD is highly variable; the clinical picture may include visual impairment, short stature, obesity and sleep-wake inversion. Approximately 75-80% of patients exhibit optic nerve hypoplasia, which may be the first presenting feature. Pituitary insufficiency may evolve over time, and children with possible SOD must be kept under careful endocrine follow-up. Untreated hormonal abnormalities will further jeopardize neurodevelopment of children with SOD and could also lead to life-threatening adrenal crises. The attention should be focussed on early diagnosis and treatment and education of paediatricians how to recognize this complex disorder.
24800863	Periodic oscillations play an important role in many biomedical systems. Proper functioning of biological systems that respond to periodic signals requires the ability to synchronize with the periodic excitation. For example, the sleep/wake cycle is a manifestation of an internal timing system that synchronizes to the solar day. In the terminology of systems theory, the biological system must entrain or phase-lock to the periodic excitation. Entrainment is also important in synthetic biology. For example, connecting several artificial biological systems that entrain to a common clock may lead to a well-functioning modular system. The cell-cycle is a periodic program that regulates DNA synthesis and cell division. Recent biological studies suggest that cell-cycle related genes entrain to this periodic program at the gene translation level, leading to periodically-varying protein levels of these genes. The ribosome flow model (RFM) is a deterministic model obtained via a mean-field approximation of a stochastic model from statistical physics that has been used to model numerous processes including ribosome flow along the mRNA. Here we analyze the RFM under the assumption that the initiation and/or transition rates vary periodically with a common period T. We show that the ribosome distribution profile in the RFM entrains to this periodic excitation. In particular, the protein synthesis pattern converges to a unique periodic solution with period T. To the best of our knowledge, this is the first proof of entrainment in a mathematical model for translation that encapsulates aspects such as initiation and termination rates, ribosomal movement and interactions, and non-homogeneous elongation speeds along the mRNA. Our results support the conjecture that periodic oscillations in tRNA levels and other factors related to the translation process can induce periodic oscillations in protein levels, and may suggest a new approach for re-engineering genetic systems to obtain a desired, periodic, protein synthesis rate.
24800763	Long-term aircraft noise exposure may increase the risk of cardiovascular disease, but no study has investigated chronic effects on the metabolic system.The aim of this study was to investigate effects of long-term aircraft noise exposure on body mass index (BMI), waist circumference, and type 2 diabetes. Furthermore, we explored the modifying effects of sleep disturbance.	This prospective cohort study of residents of Stockholm County, Sweden, followed 5,156 participants with normal baseline oral glucose tolerance tests (OGTT) for up to 10 years. Exposure to aircraft noise was estimated based on residential history. Information on outcomes and confounders was obtained from baseline and follow-up surveys and examinations, and participants who developed prediabetes or type 2 diabetes were identified by self-reported physician diagnosis or OGTT at follow-up. Adjusted associations were assessed by linear, logistic, and random-effects models.	The mean (± SD) increases in BMI and waist circumference during follow-up were 1.09 ± 1.97 kg/m2 and 4.39 ± 6.39 cm, respectively. The cumulative incidence of prediabetes and type 2 diabetes was 8% and 3%, respectively. Based on an ordinal noise variable, a 5-dB(A) increase in aircraft noise was associated with a greater increase in waist circumference of 1.51 cm (95% CI: 1.13, 1.89), fully adjusted. This association appeared particularly strong among those who did not change their home address during the study period, which may be a result of lower exposure misclassification. However, no clear associations were found for BMI or type 2 diabetes. Furthermore, sleep disturbances did not appear to modify the associations with aircraft noise.	Long-term aircraft noise exposure may be linked to metabolic outcomes, in particular increased waist circumference.	
24798635	To characterize clusters of neuropsychiatric symptoms targeted for tracking the disease course in people with dementia, in relation to stage.Baseline symptoms from 2922 subjects from two datasets (one clinic based, one online) were aggregated. Common neuropsychiatric symptoms identified by patients/carers as targets of treatment using a dementia SymptomGuide™ were selected. The Global Deterioration Scale was used for clinic staging, and an artificial neural network algorithm, for staging online subjects. Symptom clusters were detected using multiple correspondence analysis and connectivity graph analysis based on relative risk (RR). In a connectivity graph, each pair of nodes (representing symptoms) is connected if their co-occurrence is statistically significant; direction is indicated as positive if RR > 1 and negative otherwise.	Neuropsychiatric symptoms were targeted for treatment in 1072 patients (37%). Agitation (37%) and sleep disturbances (28%) were most common symptoms. One cluster (in people with cognitive impairment, no dementia (CIND) or mild dementia) showed significant co-occurrence of anxiety and restlessness; decreased initiative was chiefly seen in isolation. A second cluster (in moderate/severe dementia) was defined by significant co-occurrence of delusions and hallucinations with sleep disturbances; in these subjects, decreased initiative was related to aggression.	Two analytical methods identified neuropsychiatric symptom clusters targeted to track the disease course. In CIND/mild dementia, a profile of decreased initiative distinct from depression suggests possible executive dysfunction. In moderate/severe dementia, targets more reflected psychotic symptoms. Visual data displays allow the relationships between multiple symptoms to be considered simultaneously, which commonly is how they present in patients.	
24797355	Nicotine may affect sleep by influencing sleep-regulating neurotransmitters. Sleep disorders can increase the risk for depression and substance dependency. To detect the influence of sleep disturbances on the effect of smoking cessation, we investigated polysomnographically (PSG) the sleep of smoking subjects during a period of smoking, during withdrawal and after a period of abstinence from nicotine. Thirty-three smokers (23 male, 10 female, median age 29 years, Fagerström Test for Nicotine Dependence score 6.3) were examined during smoking, 24-36 hours after smoking and 3 months after cessation. All subjects had an adaptation night followed by the PSG night. Compared with the smoking state, we found increased arousal index and wake time during nicotine withdrawal. Smokers who later relapsed (11) presented a higher degree of nicotine dependence and more withdrawal symptoms than those who abstained (22) and were characterized by less rapid eye movement (REM) sleep, a longer REM latency as well as by more intense sleep impairments in the subjective sleep rating during the withdrawal. Impairments of sleep during the withdrawal phase may reflect more severe nicotine dependence and may contribute to earlier relapse into smoking behaviours. 
24796235	Sleep disorders in patients with Parkinson's disease (PD) are very common and have an immense negative impact on their quality of life. Insomnia, daytime sleepiness with sleep attacks, restless-legs syndrome (RLS) and REM-sleep behaviour disorder (RBD) are the most frequent sleep disorders in PD. Neurodegenerative processes within sleep regulatory brain circuitries, antiparkinsonian (e.g., levodopa and dopamine agonists) and concomitant medication (e.g., antidepressants) as well as comorbidities or other non-motor symptoms (such as depression) are discussed as causative factors. For the diagnosis of sleep disturbances we recommend regular screening using validated questionnaires such as the Pittsburgh Sleep Quality Index (PSQI) or the Medical Outcomes Study Sleep Scale (MOS), for evaluating daytime sleepiness we would suggest to use the Epworth Sleepiness Scale (ESS), the inappropriate sleep composite score (ISCS) or the Stanford sleepiness scale (SSS). All of these questionnaires should be used in combination with a detailed medical history focusing on common sleep disorders and medication. If necessary, patients should be referred to sleep specialists or sleep laboratories for further investigations. Management of sleep disorders in PD patients usually starts with optimization of (dopaminergic) antiparkinsonian therapy followed by specific treatment of the sleep disturbances. Aside from these clinical issues of sleep disorders in PD, the concept of REM-sleep behaviour disorder (RBD) as an early sign for emerging neurodegenerative diseases is of pivotal interest for future research on biomarkers and neuroprotective treatment strategies of neurodegenerative diseases, and particularly PD. 
24796108	Some sleep disorders and sleep problems are reported as risk of dementia. It is reported that 50-80% of idiopathic REM sleep behavior had a later conversion to a synucleinopathy, thus this parasomnia is regarded as early marker of Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Obstructive sleep apnea syndrome causes reversible decline of cognitive functions in children and adults, and it increases the risk of dementia and mild cognitive impairment in elderly women. A decrease of amplitude of circadian activity rhythm and habitual long sleep duration (> or = 9 hours) are reported to increase the risk of dementia in elderly people. Some reports indicate that hypnotic use may be a risk factor of dementia. However, it is not cleared whether insomnia itself related with dementia or not, since no study evaluated the risk of insomnia without hypnotic treatment.
24795216	This study sought to examine the prevalence and correlates of psychological distress among incarcerated youth in Taiwan using the 5-item Brief Symptom Rating Scale (BSRS-5).This cross-sectional census survey study was conducted in 2007 among all the juveniles incarcerated in 23 correctional institutions (n = 1505) in Taiwan using a self-administered anonymous questionnaire. Of the total 1505 participants, 1363 completed the questionnaire (91% response rate). We excluded 494 participants as they were aged either over 17 years or under 12 years. Psychological distress was measured among the final 869 participants using the BSRS-5. Psychological distress was defined as a total score of at least 6 out of 20. Those identified as having psychological distress were then pooled into a case group and compared with control participants without psychological distress.	The prevalence of psychological distress was 44.1%. Among the case group, sleep disturbance (36.8%) had the highest prevalence of severe or very severe symptoms, followed by depression (34.7%), and hostility (27.9%). Multivariate logistic regression analysis revealed that correlates of psychological distress included the following: being female; having a poor self-rated health status; having joined a gang; having experienced life disturbances prior to the current imprisonment; and having ever had a smoking habit.	Significant sex differences were found for both the overall BSRS-5, as well as for each individual item of the BSRS-5. Treatment programs and interventions should be carefully tailored to address the mental health needs of juvenile inmates in a sex-specific manner using a multifaceted approach.	
24794949	Poststroke sleep disturbances (PSSDs) are frequent and reported to be associated with unfavorable clinical outcomes. PSSDs appear to be related to a multitude of factors including lesion location and environmental causes. Moreover, depression and fatigue, which frequently develop in stroke patients may also contribute to PSSD development. The purpose of this study was to evaluate the prevalence and characteristics of PSSDs and factors related to PSSDs including depression and fatigue in hospitalized stroke patients.Patients who were hospitalized with acute stroke at the Asan Medical Center were evaluated. The quality (Verran-Snyder-Halpern [VSH] Sleep Scale score), duration and latency of night-time sleep, the frequency of waking after sleep onset, and daytime sleepiness were evaluated during the hospitalization period. To validate the self-reported night-time sleep, an actigraphy was performed in a subset of patients. The location, circulation, and laterality of each lesion were determined from brain magnetic resonance images obtained within 7 days of stroke onset. Depression and fatigue were assessed using the Beck Depression Inventory and the Fatigue Severity Scale, respectively. For environmental factors, the duration of hospitalization and the number of other patients in the same room were recorded. Univariate, multiple regression, and multiple logistic regression analyses were used to evaluate predictors of PSSD development.	A total of 282 patients completed the study. The mean age of the patients was 62.3 (±12.76) years and 58.9% of them were male. Sixty patients (21.3%) reported sleep duration less than 6 hours/night and 110 (39.0%) reported more daytime sleepiness than before the stroke. In 54 patients who agreed to wear an actigraph, self-reported sleep duration was significantly correlated with time in bed measured with an actigraph (r = .407, P = .002) and, VSH Sleep Scale score and sleep efficiency in actigraphy were also significantly correlated (r = .305, P = .026). Quality of night-time sleep was independently related to cortical lesion location (P = .002), diabetes mellitus (P = .020), and depression (P < .001), whereas increased daytime sleepiness was independently associated with subcortical lesion location (P = .031), fatigue (P = .001), and quality of night-time sleep (P = .001).	PSSDs are common in hospitalized stroke patients. The most powerful factor predicting night-time sleep disturbances in stroke patients was depression. Cortical brain lesion and diabetes mellitus were also associated with night-time sleep disturbances. On the other hand, although poststroke daytime sleepiness is in part caused by night-time sleep disturbance, it is more closely associated with fatigue and subcortical lesion location.	
24791913	Sleep has numerous important physiological and cognitive functions that may be particularly important to elite athletes. Recent evidence, as well as anecdotal information, suggests that athletes may experience a reduced quality and/or quantity of sleep. Sleep deprivation can have significant effects on athletic performance, especially submaximal, prolonged exercise. Compromised sleep may also influence learning, memory, cognition, pain perception, immunity and inflammation. Furthermore, changes in glucose metabolism and neuroendocrine function as a result of chronic, partial sleep deprivation may result in alterations in carbohydrate metabolism, appetite, food intake and protein synthesis. These factors can ultimately have a negative influence on an athlete's nutritional, metabolic and endocrine status and hence potentially reduce athletic performance. Research has identified a number of neurotransmitters associated with the sleep-wake cycle. These include serotonin, gamma-aminobutyric acid, orexin, melanin-concentrating hormone, cholinergic, galanin, noradrenaline, and histamine. Therefore, nutritional interventions that may act on these neurotransmitters in the brain may also influence sleep. Carbohydrate, tryptophan, valerian, melatonin and other nutritional interventions have been investigated as possible sleep inducers and represent promising potential interventions. In this review, the factors influencing sleep quality and quantity in athletic populations are examined and the potential impact of nutritional interventions is considered. While there is some research investigating the effects of nutritional interventions on sleep, future research may highlight the importance of nutritional and dietary interventions to enhance sleep. 


24791255	Obstructive sleep apnea (OSA) is a common diagnosis in clinical practice. Excessive daytime sleepiness may be a warning for possible OSA.To assess the prevalence of excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) in a rural community population; potential risk factors for OSA were also assessed.	In 2010, a baseline respiratory health questionnaire within the Saskatchewan Rural Health Study was mailed to 11,982 households in Saskatchewan. A total of 7597 adults within the 4624 (42%) respondent households completed the ESS questionnaire. Participants were categorized according to normal or high (>10) ESS scores. Data obtained included respiratory symptoms, doctor-diagnosed sleep apnea, snoring, hypertension, smoking and demographics. Body mass index was calculated. Multivariable logistic regression analysis examined associations between high ESS scores and possible risk factors. Generalized estimating equations accounted for the two-tiered sampling procedure of the study design.	The mean age of respondents was 55.0 years and 49.2% were male. The prevalence of ESS>10 and 'doctor diagnosed' OSA were 15.9% and 6.0%, respectively. Approximately 23% of respondents reported loud snoring and 30% had a body mass index >30 kg⁄m2. Of those with 'doctor-diagnosed' OSA, 37.7% reported ESS>10 (P<0.0001) and 47.7% reported loud snoring (P<0.0001). Risk of having an ESS>10 score increased with age, male sex, obesity, lower socioeconomic status, marriage, loud snoring and doctor-diagnosed sinus trouble.	High levels of excessive daytime sleepiness in this particular rural population are common and men >55 years of age are at highest risk. Examination of reasons for residual sleepiness and snoring in persons with and without sleep apnea is warranted.	
24790280	The hypocretins (HCRTs) are two hypothalamic peptides predominantly localized to neurons in the perifornical, dorsomedial, and lateral hypothalamic area (PF-LHA). Evidence suggests that HCRT signaling is critical for the promotion and stabilization of active-arousal and its loss or malfunction leads to symptoms of narcolepsy. In the PF-LHA, HCRT neurons are intermingled with glutamate-expressing neurons and also co-express glutamate. Evidence suggests that HCRT-glutamate interactions within the PF-LHA may play a critical role in maintaining behavioral arousal. However, the relative contributions of the glutamate and HCRT in sleep-wake regulation are not known.We determined whether a lack of HCRT signaling in the prepro-orexin-knockout (HCRT-KO) mouse attenuates/compromises the wake-promoting ability of glutamatergic activation of the PF-LHA region. We used reverse microdialysis to deliver N-methyl-D-aspartate (NMDA) into the HCRT zone of the PF-LHA in HCRT-KO and wild-type (WT) mice to evaluate the contributions of glutamatergic vs. HCRT signaling in sleep-wake regulation.	As compared to respective controls, local perfusion of NMDA into the PF-LHA, dose-dependently increased active-waking with concomitant reductions in nonREM and REM sleep in spontaneously sleeping WT as well as HCRT-KO mice. However, compared to WT, the NMDA-induced behavioral changes in HCRT-KO mice were significantly attenuated, as evidenced by the higher dose of NMDA needed and lower magnitude of changes induced in sleep-wake parameters. Although not observed in WT mice, the number of cataplectic events increased significantly during NMDA-induced behavioral arousal in HCRT-KO mice.	The findings of this study are consistent with a hypothesis that synergistic interactions between hypocretin and glutamatergic mechanisms within the perifornical, dorsomedial, and lateral hypothalamic area are critical for maintaining behavioral arousal, especially arousal involving elevated muscle tone.	
24790278	Chronic upper airway obstruction (UAO) elicits a cascade of complex endocrine derangements that affect growth, sleep, and energy metabolism. We hypothesized that elevated hypothalamic orexin has a role in maintaining ventilation during UAO, while at the same time altering sleep-wake activity and energy metabolism. Here, we sought to explore the UAO-induced changes in hypothalamic orexin and their role in sleep-wake balance, respiratory activity, and energy metabolism.The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed; UAO and sham-operated control animals were monitored for 7 weeks. We measured food intake, body weight, temperature, locomotion, and sleep-wake activity. Magnetic resonance imaging was used to quantify subcutaneous and visceral fat tissue volumes. In week 7, the rats were sacrificed and levels of hypothalamic orexin, serum leptin, and corticosterone were determined. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and respiration was also explored.	UAO increased hypothalamic orexin mRNA and protein content by 64% and 65%, respectively. UAO led to 30% chronic sleep loss, excessive active phase sleepiness, decreased body temperature, increased food intake, reduction of abdominal and subcutaneous fat tissue volume, and growth retardation. Administration of almorexant normalized sleep but induced severe breathing difficulties in UAO rats, while it had no effect on sleep or on breathing of control animals.	In upper airway obstruction animals, enhanced orexin secretion, while crucially important for respiratory homeostasis maintenance, is also responsible for chronic partial sleep loss, as well as considerable impairment of energy metabolism and growth.	
24790263	Impaired sleep is an established risk factor for the development of cardiovascular disease, whereas less is known about how impaired sleep affects cardiovascular prognosis. The aim of this study is to determine how different aspects of impaired sleep affect the risk of case fatality and subsequent cardiovascular events following first-time acute myocardial infarction (AMI).Prospective cohort study.	The Stockholm Heart Epidemiology Program, Sweden.	There were 2,246 first-time AMI cases.	Sleep impairment was assessed by the Karolinska Sleep Questionnaire, which covers various indices of impaired sleep: disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Case fatality, defined as death within 28 days of initial AMI, and new cardiovascular events within up to 10 y of follow-up were identified through national registries. In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95-3.00), stroke (HR = 2.61; 95% CI: 1.19-5.76), and heart failure (HR = 2.43; 95% CI: 1.18-4.97), whereas no clear effect of impaired sleep on case fatality was found in women. In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76-6.06) was observed in regard to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis.	Results suggest sex-specific effects of impaired sleep that differ by short- and long-term prognosis. Sleep complaints are frequent, easily recognizable, and potentially manageable. Evaluation of sleep complaints may, even if they represent prognostic markers rather than risk factors, provide additional information in clinical risk assessment that could benefit secondary cardiovascular prevention.	
24786696	The aim of this study was to assess the primary concerns of parents/caregivers regarding their young child's sleep. A total of 1,287 consecutive sleep-related questions were analyzed from submissions to an Ask the Expert section of a publicly available iPhone-based application for sleep in young children. Questions regarding infants were most likely to be submitted (53.9%), followed by newborns (23.76%) and toddlers (17.8%), with an average age of 10.94 months. The primary concerns regarded night wakings, sleep schedules, and bedtime problems, accounting for almost 85% of all questions. Results align with common concerns noted in epidemiological studies. Understanding the types of concerns for which parents seek advice is beneficial in the continued development of resources for caregivers. 
24784787	Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves sleep in patients affected by Parkinson's disease (PD). Since microsubthalamotomy (mSTN) shows positive effects on motor symptoms, it could improve sleep in PD patients. Our goals were: to assess the effects of mSTN on sleep in patients affected by advanced PD; and to look for a correlation between sleep and motor features after the neurosurgical procedure.Fifteen patients who underwent bilateral STN-DBS were enrolled. Subjective sleep evaluation was assessed using the Parkinson's Disease Sleep Scale (PDSS). Data on sleep schedule and presence of restless legs syndrome (RLS) were obtained. Objective sleep features were investigated by polysomnography (PSG). To evaluate the mSTN effect, we compared motor state and sleep features before and after the neurosurgical procedure, before the programmable pulse generator was switched on.	mSTN had beneficial effects on motor state and sleep features. After the surgery, the mean total PDSS score increased from 84.0±25.2 to 115.2±16.6 (P<0.001). PD patients reported longer total sleep time duration, decreased daytime sleepiness, and improvement in RLS symptoms. PSG data showed an increase in total sleep time and sleep efficiency with a decrease in wakefulness after sleep onset and arousal index. No correlation between motor improvements and sleep features modifications was observed after mSTN.	mSTN improves sleep quality and ameliorates several sleep complaints, as well as motor symptoms, in advanced PD patients who have undergone STN-DBS.	
24782698	There is a strong correlation between signature EEG frequency patterns and the relative levels of distinct neuromodulators. These associations become particularly evident during the sleep-wake cycle. The monoamine-acetylcholine balance hypothesis is a theory of neurophysiological markers of the EEG and a detailed description of the findings that support this proposal are presented in this paper. According to this model alpha rhythm reflects the relative predominance of cholinergic muscarinic signals and delta rhythm that of monoaminergic receptor effects. Both high voltage synchronized rhythms are likely mediated by inhibitory Gαi/o-mediated transduction of inhibitory interneurons. Cognitively, alpha and delta EEG measures are proposed to indicate automatic and flexible strategies, respectively. Sleep is associated with marked changes in relative neuromodulator levels corresponding to EEG markers of distinct stages. Sleep studies on memory consolidation present some of the strongest evidence yet for the respective roles of monoaminergic and cholinergic projections in declarative and non-declarative memory processes, a key theoretical premise for understanding the data. Affective dysregulation is reflected in altered EEG patterns during sleep. 
24782195	Recent research suggests that sleep quality and pain intensity are intimately linked. Although sleep problems are common in patients with low back pain, the effect of sleep quality on the levels of pain intensity is currently unknown. The aim of this study was to investigate the effect of sleep quality on subsequent pain intensity in patients with recent-onset low back pain.Data on 1,246 patients with acute low back pain were included in the analysis. Sleep quality was assessed using the sleep quality item of the Pittsburgh Sleep Quality Index, scored on a 0-3-point scale, where 0 = very good sleep quality and 3 = very bad sleep quality. Pain intensity was assessed on a numerical rating scale (range 0-10). A generalized estimating equation (GEE) analysis modeled with an exchangeable correlation structure was used to examine the relationship between sleep quality and pain intensity. The model further controlled for symptoms of depression and prognostic factors for low back pain.	The GEE analysis demonstrated a large effect of poor sleep on subsequent pain intensity, such that for every 1-point decrease in sleep quality (based on a 0-3-point scale), pain intensity (based on a 0-10-point scale) increased by 2.08 points (95% confidence interval 1.99-2.16). This effect was independent of depression and common prognostic factors for low back pain.	Sleep quality is strongly related to subsequent pain intensity in patients with acute low back pain. Future research is needed to determine whether targeting sleep improvement contributes to pain reduction.	
24781854	During the menopausal transition and early postmenopause, participants in the Seattle Midlife Women's Health Study were likely to belong to one of three symptom severity classes: severe hot flashes with moderate sleep, mood, cognitive, and pain symptoms (high-severity hot flash); moderate levels of all but hot flashes (moderate severity); and low levels of all (low severity). We tested models of the differential effects of hypothalamic-pituitary-ovarian (HPO) axis, hypothalamic-pituitary-adrenal (HPA) axis, and autonomic nervous system (ANS) biomarkers on the three symptom severity classes.The Seattle Midlife Women's Health Study participants recorded symptoms monthly in diaries and provided overnight urine samples several times per year that were analyzed for estrone, follicle-stimulating hormone (FSH), cortisol, testosterone, epinephrine, and norepinephrine. Multilevel latent class analysis with multinomial regression was used to determine the effects of HPO axis, HPA axis, and ANS biomarkers on symptom severity class membership.	Having lower estrogen and higher FSH levels was significantly associated with belonging to the high-severity hot flash class versus the low-severity class. Having lower epinephrine and higher norepinephrine levels increased the likelihood of belonging to the high-severity hot flash class versus the low-severity class. Having lower epinephrine levels was significantly associated with belonging to the moderate-severity class versus the low-severity class. Cortisol and testosterone were unrelated to symptom severity class membership.	The association of HPO axis biomarkers (estrogen and FSH) with the high-severity hot flash class is anticipated based on prior hot flash research, and the associations of HPA axis biomarkers are as expected based on earlier laboratory studies. The association of lower epinephrine levels with the moderate-severity class suggests that these symptoms may be mediated by the ANS.	
24780146	The present study examined age-related changes in the sleep of children with autism spectrum disorders (ASD) compared to age-related changes in the sleep of typically developing (TD) children. Participants were 108 mothers of children with ASD and 108 mothers of TD children. Participants completed a questionnaire on children's overall sleep quality that also tapped specific sleep-domains (i.e., bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, disordered breathing, daytime sleepiness). Results confirm significantly poorer sleep quantity and quality in children with ASD, particularly children age 6-9 years. Unlike TD children, the sleep problems of children with ASD were unlikely to diminish with age. Our findings suggest that it is important to exam specific domains of sleep as well as overall sleep patterns. Finding of significant age-related interactions suggests that the practice of combining children from wide age-ranges into a single category obfuscates potentially important developmental differences.
24780136	We aimed to describe and report the initial validity of a newly developed structured interview for sleep disorders (Diagnostic Interview for Sleep Patterns and Disorders [DISP]) administered by trained lay interviewers.A total of 225 patients with various sleep disorders were recruited from two nationally recognized sleep centers in the United States. The International Classification of Sleep Disorders, second edition (ICSD-2) criteria, were used to classify sleep disorders (e.g., delayed sleep phase disorder, hypersomnia, narcolepsy with cataplexy [NC], restless legs syndrome [RLS], periodic limb movement disorder [PLMD], insomnia, rapid eye movement sleep behavior disorder [RBD], and obstructive sleep apnea [OSA]). Interview diagnoses were compared with final diagnoses by sleep specialists (reference diagnosis based on clinical history, examination, and polysomnography [PSG] when indicated).	DISP diagnoses had fair to substantial concordance with clinician diagnoses for various sleep disorders, with area under the receiver operator characteristic curves (AUC) ranging from 0.65 to 0.84. Participants classified by the clinician as having a sleep disorder were moderately well-detected (sensitivity ranging from 0.50 for RBD disorder to 0.87 for insomnia). Substantial specificity (>0.8) also was seen for five of the eight sleep disorders (i.e., delayed sleep phase, hypersomnia, NC, PLMD, and RBD). Interviews were more likely than clinicians to detect disorders secondary to the primary sleep problem.	The DISP provides an important tool for the detection of a wide range of sleep disorders in clinical settings and is particularly valuable in the detection of secondary disorders that were not the primary referral diagnosis.	
24780133	Narcolepsy, a chronic neurologic condition resulting from dysregulation of the sleep-wake cycle, usually has an onset at an early age. However, a long delay until diagnosis has been consistently reported in the literature across countries and several publications have focused on characterizing this delay. Most studies report a mean delay to diagnosis of up to 15 years, with individual cases of >60 years, although a trend over time toward a shorter diagnostic delay has been suggested. While variables associated with this delay have been identified, a lack of symptom recognition resulting in misdiagnosis prior to reaching the narcolepsy diagnosis is the likely underlying reason. This lack of symptom recognition is especially relevant considering the high comorbidity burden that has been shown in patients with narcolepsy as some disorders manifest with symptoms that overlap with narcolepsy. A consequence of delayed diagnosis is delayed treatment, which affects the burden of disease. Substantial detrimental effects on health-care resource utilization, employment, and quality of life have been described after narcolepsy onset and prior to the diagnosis of narcolepsy. This review highlights the importance of closing the diagnostic gap by expanding awareness of narcolepsy and its symptoms.
24779591	We evaluated nocturnal sleep-wake rhythms and subjective sleep quality on the first postoperative night compared with the preoperative night in 34 patients who had total hip arthroplasty (mean age: 61.9 years; 82.4% female) under spinal anaesthesia. We also examined secondary factors related to sleep disturbances after surgery. Patients wore an accelerometer (actigraph) during the preoperative period and the first postoperative night to track sleep-wake rhythms. Secondary end-points were postsurgical pain and low back pain. Sleep parameters were measured objectively by actigraphy, and subjective sleep quality was measured by the Oguri-Shirakawa-Azumi Sleep Inventory, Middle-Aged and Aged Version and found to worsen significantly after surgery. Actigram data showed a reduction in actual sleep time from 353.7 ± 121.2 min preoperatively to 263.8 ± 104.4 min postoperatively. The data indicate that normalized continuous sleep time is important for patient healing and well-being and that postoperative sleep disturbance is related to low back pain more than to postsurgical pain. 
24773912	To determine if disturbed sleep-wake cycle patterns in young people with evolving mental disorder are associated with stages of illness.The sleep-wake cycle was monitored using actigraphy across 4 to 22 days. Participants (21 healthy controls and 154 persons seeking help for mental health problems) were aged between 12 and 30 years. Those persons seeking mental health care were categorized as having mild symptoms (stage 1a), an 'attenuated syndrome' (stage 1b) or an 'established mental disorder' (stage 2+).	The proportions of individuals with a delayed weekdays sleep schedule increased progressively across illness stages: 9.5% of controls, 11.1% of stage 1a, 25.6% of stage 1b, and 50.0% of stage 2+ (χ(2) (3 d.f.) = 18.4, P < 0.001). A similar pattern was found for weekends (χ(2) (3 d.f.) = 7.6, P = 0.048). Compared with controls, stage 1b participants had later sleep onset on weekends (P = 0.015), and participants at stages 1b and 2+ had later sleep offset on both weekdays and weekends (P < 0.020). Compared with controls, all participants with mental disorders had more wake after sleep onset (P < 0.029) and those at stages 1a and 2+ had lower sleep efficiency (P < 0.040). Older age, medicated status and later weekdays sleep offset were found to be the three strongest correlates of later versus earlier clinical stages.	In relation to clinical staging of common mental disorders in young people, the extent of delayed sleep phase is associated with more severe or persistent phases of illness.	
24773429	Sleep and circadian functioning has been of particular interest to researchers focused on improving treatments for psychiatric illness. The goal of the present paper is to highlight the exciting research that utilizes basic sleep and circadian science as building blocks for intervention in the mood disorders. The reviewed evidence suggests that the sleep and circadian systems are a) disrupted in the mood disorders and linked to symptoms, b) open systems that can be modified, c) the focus of interventions which have been developed to effectively treat sleep disturbance within mood disorders, and d) intimately linked with mood, such that improvements in sleep are associated with improvements in mood. Although significant positive treatment effects are evident, more research is needed to fill the gap in our basic understanding of the relationship between sleep and mood.
24773428	The use of alcohol is an important part of the daily lives of many individuals that may be experienced as a single nightly drink with a meal or a debilitating pattern of intoxication. The circadian timing system imposes a daily temporal order throughout the brain and body. Ethanol, with its complex and broad pharmacology, can thereby alter circadian physiology at multiple levels of organization. Here, we review data from animal models demonstrating that (a) perturbations of the circadian timing system are often, but not necessarily, reflected in altered drinking behaviors or ethanol response; (b) alcohol can act to alter the circadian entrainment and pacemaking functions of the suprachiasmatic nuclei; and (c) the temporal patterning of alcohol exposure and withdrawal in a circadian context can influence processes related to addiction development, particularly increased voluntary alcohol consumption and development of physical dependence as reflected in the physiological withdrawal reaction. New data are presented to show that the withdrawal reaction elicited after long-duration alcohol vapor sessions is significantly modulated according to the time of day that it is initiated. Further application of chronobiological principles to alcohol research should enhance mechanistic understanding and suggest potential therapeutic approaches.
24772943	Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.
24772582	The objective of the present study was to compare a physician's diagnosis of sleep disorders in patients with Parkinson's disease (PD) during clinical evaluation of sleep disorders diagnosed by validated questionnaires.Patients with PD at the Parkinson's clinic at Siriraj Hospital were included in this prospective cross-sectional study. Patients completed the Modified Parkinson's Disease Sleep Scale (MPDSS), Thai Epworth Sleepiness Scale (Thai-ESS), Scales for Outcomes in Parkinson's Disease-Sleep Scale questionnaire (SCOPA), Berlin questionnaire (Thai version), and Siriraj sleep questionnaire (SSQ). Thereafter, attending physicians diagnosed sleep disorders based on patient evaluation.	One hundred twenty patients with PD participated in the present study. Among them, 73 (60.8%) were males, the mean age was 61.5 +/- 12.0 years, and the mean body mass index (BMI) was 22.7 +/- 3.5 kg/m2 (BMI > or = 30 kg/m2 in 1.7% of patients). The study demonstrated a prevalence of overall sleep disorders in 59.2% of patients based on physician diagnosis and 81.7% of patients based on the MPDSS questionnaire. The ESS was > 10 in 29.2% of the patients. High risk for obstructive sleep apnea was observed in 28.3% (Berlin) and 42% (MPDSS) of patients (15% by both). SSQ detected all sleep disorders in 86.7% of the population, and its results correlated with the MPDSS.	Sleep disorders are common in patients with PD but remain underestimated because they are not routinely screened in clinical practice. This study demonstrates the use of validated questionnaires to efficiently detect and classify patients with PD at risk for common sleep disorders.	
24770646	Genetic variations in the wild-derived inbred mouse strains are more diverse than that of classical laboratory inbred mouse strains, including C57BL/6J (B6). The sleep/wake and monoamine properties of six wild-derived inbred mouse strains (PGN2, NJL, BLG2, KJR, MSM, HMI) were characterized and compared with those of B6 mice. All examined mice were nocturnal and had a polyphasic sleep pattern with a "main sleep period" identified during the light period. However, there were three sleep/wake phenotypic differences between the wild-derived mouse strains and B6 strain. First, the amount of sleep during the dark phase was comparable with that of B6 mice. However, the amount of sleep during the light phase was more varied among strains, in particular, NJL and HMI had significantly less sleep compared with that of B6 mice. Second, PGN2, NJL, BLG2, and KJR mice showed a "highly awake period" (in which the hourly total sleep time was <10%) immediately after the onset of the dark period, which was not seen in B6 mice. Third, relative to that of B6 mice, PGN2 and KJR mice showed longer duration of wakefulness episodes during the 12-h dark phase. Differences in whole brain noradrenaline, dopamine, and 5-hydroxy-tryptamine contents between the wild-derived mouse strains and B6 strain were also found. These identified phenotypes might be potentially under strong genetic control. Hence, wild-derived inbred mice could be useful for identifying the genetic factors underlying the regulation of sleep and wakefulness. 
24767722	The aim of our study was to examine the association between sleep disturbances and social anxiety disorder (SAD). Another aim was to explore the impact of cognitive behavioral group therapy (CBGT) for SAD on co-occurring sleep difficulties.Data were obtained retrospectively from patient files receiving CBGT for SAD. The sample included 63 patients with SAD (mean age, 30.42 years [standard deviation, 6.92 years]). There were 41 men and 22 women, of whom 41 participants completed the treatment protocol. Before treatment onset participants completed the Liebowitz Social Anxiety Scale (LSAS), the Beck Depression Inventory (BDI), the Pittsburgh Sleep Quality Index, and several sociodemographic questions. On completion of the treatment protocol, the same measures were completed, with the addition of the Sheehan Disabilities Scale (SDS).	The results of our study suggest that: (1) subjective insomnia is associated with SAD severity even after controlling for depression severity and additional variables; (2) participants with SAD with co-occurring clinical levels of subjective insomnia present a more severe clinical picture both at treatment onset and termination; and (3) although CBGT lead to reduction in SAD and depression symptoms severity, it had no significant impact on co-occurring sleep difficulties.	Sleep difficulties predict SAD severity regardless of depressive symptoms and may be linked to a more severe clinical picture. Clinicians should be aware of these sleep difficulties co-occurring with SAD and consider implementing specific sleep interventions. Future studies should incorporate larger samples sizes from clinical populations outside of Israel.	
24767377	The aims of this project were to explore the factors contributing to poor sleep quality at 1 to 3 years after heart transplantation (post-HT), and to explore economic problems and social support for HT recipients (HTRs).This study used a cross-sectional retrospective triangulation approach combining qualitative and quantitative research method designs. Quantitative data included data from the visual analog scale and the Taiwanese version of the World Health Organization Quality of Life questionnaire. Qualitative data were derived from questions that explored physiological, psychological, and economic factors contributing to poor sleep quality postprocedure for HTRs.	Sixty-four subjects (81% male, 19% female) participated in this research. Their ages ranged from 20 to 70 (M = 46.88 ± 12.12) years old. Their post-HT timeframe ranged from 1 to 4.10 years; 33% received preoperative extracorporeal membrane oxygenation support. Sleeping disturbances were reported by 72.7% of subjects after HT. Poor sleeping quality at 2 to 3 years post-HT (P = .028) was a complaint, and was worse than at 1 to 2 years post-HT (P = .008). Six physiological (62.5%) and 3 psychological (37.5%) contributing factors were further identified in qualitative interviews. Physiological factors were the major causes affecting their sleep quality 2 to 3 years after HT, whereas psychological factors arose from various family roles, responsibilities, and economic-related pressures.	Medical teams should find the causes that lead to sleep disturbances and use the findings to improve HTR sleep quality. When the family financial status is affected, these teams should offer assistance and suggestions for patients who are unable to work due to post-HT physical decline. Establishing and providing good family support systems or patient support groups may allow patients to obtain physical, psychological, and spiritual comfort.	
24766454	There has been an increased focus on the neurological sequelae of repetitive mild traumatic brain injury (TBI), particularly neurodegenerative syndromes, such as chronic traumatic encephalopathy (CTE); however, no animal model exists that captures the behavioral spectrum of this phenomenon. We sought to develop an animal model of CTE. Our novel model is a modification and fusion of two of the most popular models of TBI and allows for controlled closed-head impacts to unanesthetized mice. Two-hundred and eighty 12-week-old mice were divided into control, single mild TBI (mTBI), and repetitive mTBI groups. Repetitive mTBI mice received six concussive impacts daily for 7 days. Behavior was assessed at various time points. Neurological Severity Score (NSS) was computed and vestibulomotor function tested with the wire grip test (WGT). Cognitive function was assessed with the Morris water maze (MWM), anxiety/risk-taking behavior with the elevated plus maze, and depression-like behavior with the forced swim/tail suspension tests. Sleep electroencephalogram/electromyography studies were performed at 1 month. NSS was elevated, compared to controls, in both TBI groups and improved over time. Repetitive mTBI mice demonstrated transient vestibulomotor deficits on WGT. Repetitive mTBI mice also demonstrated deficits in MWM testing. Both mTBI groups demonstrated increased anxiety at 2 weeks, but repetitive mTBI mice developed increased risk-taking behaviors at 1 month that persist at 6 months. Repetitive mTBI mice exhibit depression-like behavior at 1 month. Both groups demonstrate sleep disturbances. We describe the neurological sequelae of repetitive mTBI in a novel mouse model, which resemble several of the neuropsychiatric behaviors observed clinically in patients sustaining repetitive mild head injury.
24763506	Although portable instruments have been used in the assessment of sleep disturbance for patients with low back pain (LBP), the accuracy of the instruments in detecting sleep/wake episodes for this population is unknown. This study investigated the criterion validity of two portable instruments (Armband and Actiwatch) for assessing sleep disturbance in patients with LBP. 50 patients with LBP performed simultaneous overnight sleep recordings in a university sleep laboratory. All 50 participants were assessed by Polysomnography (PSG) and the Armband and a subgroup of 33 participants wore an Actiwatch. Criterion validity was determined by calculating epoch-by-epoch agreement, sensitivity, specificity and prevalence and bias- adjusted kappa (PABAK) for sleep versus wake between each instrument and PSG. The relationship between PSG and the two instruments was assessed using intraclass correlation coefficients (ICC 2, 1). The study participants showed symptoms of sub-threshold insomnia (mean ISI = 13.2, 95% CI = 6.36) and poor sleep quality (mean PSQI = 9.20, 95% CI = 4.27). Observed agreement with PSG was 85% and 88% for the Armband and Actiwatch. Sensitivity was 0.90 for both instruments and specificity was 0.54 and 0.67 and PABAK of 0.69 and 0.77 for the Armband and Actiwatch respectively. The ICC (95%CI) was 0.76 (0.61 to 0.86) and 0.80 (0.46 to 0.92) for total sleep time, 0.52 (0.29 to 0.70) and 0.55 (0.14 to 0.77) for sleep efficiency, 0.64 (0.45 to 0.78) and 0.52 (0.23 to 0.73) for wake after sleep onset and 0.13 (-0.15 to 0.39) and 0.33 (-0.05 to 0.63) for sleep onset latency, for the Armband and Actiwatch, respectively. The findings showed that both instruments have varied criterion validity across the sleep parameters from excellent validity for measures of total sleep time, good validity for measures of sleep efficiency and wake after onset to poor validity for sleep onset latency. 
24760861	Histaminergic neurons in the tuberomammillary nucleus (TMN) are an important component of the ascending arousal system and may form part of a "flip-flop switch" hypothesized to regulate sleep and wakefulness. Anatomical studies have shown that the wake-active TMN and sleep-active ventrolateral preoptic nucleus (VLPO) are reciprocally connected, suggesting that each region can inhibit its counterpart when active. In this study, we determined how histamine affects the two branches of this circuit. We selectively expressed channelrhodopsin-2 (ChR2) in TMN neurons and used patch-clamp recordings in mouse brain slices to examine the effects of photo-evoked histamine release in the ventrolateral TMN and VLPO. Photostimulation decreased inhibitory GABAergic inputs to the ventrolateral TMN neurons but produced a membrane hyperpolarization and increased inhibitory synaptic input to the VLPO neurons. We found that in VLPO the response to histamine was indirect, most likely via a GABAergic interneuron. Our experiments demonstrate that release of histamine from TMN neurons can disinhibit the TMN and suppresses the activity of sleep-active VLPO neurons to promote TMN neuronal firing. This further supports the sleep-wake "flip-flop switch" hypothesis and a role for histamine in stabilizing the switch to favor wake states. 
24760214	Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV) still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV.Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service.	Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life.	None of the ten patients (0%) presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life.	Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population.	
24759325	The Pittsburgh Sleep Quality Index (PSQI) is used extensively to assess subjective sleep disturbance in cancer populations. Although previous studies on the PSQI suggested a better fit for a two- or three-factor model than the original one-factor model, none accounted for the indicator-specific effect between sleep duration and habitual sleep efficiency. This study evaluated the PSQI's dimensionality and its convergent validity with cancer-related psychopathological states in female breast cancer patients.The PSQI was administered to 197 women with breast cancer. Confirmatory factor analysis examined the relative fit of one-, two-, three-, and revised one-factor models. The PSQI's convergent validity was evaluated via bivariate correlations between the PSQI factor scores and measures of anxiety, depression, fatigue, pain, and quality of life.	Confirmatory factor analyses showed an adequate fit for the revised one-factor model with the PSQI global score as the overall index of sleep disturbance. Although the revised one- and two-factor solutions showed statistically equivalent model fits, the one-factor model was selected due to utility reasons. The severity of sleep dysfunction that the PSQI global score represented was positively correlated with anxiety, depression, fatigue, pain, and reduced quality of life.	The results support the PSQI's original unidimensional structure, demonstrating that the PSQI global score is a valid and parsimonious measure for assessing and screening sleep dysfunction in cancer patients.	


24757362	Ibrutinib (Imbruvica) for chronic lymphocytic leukemia, tasimelteon (Hetlioz) for non-24-hour sleep-wake disorder, and anti-inhibitor coagulant complex (Feiba) to prevent or reduce bleeding in hemophilia A or B. 
24757113	Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson's disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment.
24756217	Sleep disorders are very prevalent in Parkinson's disease (PD) and include a diversity of disturbances. Rating scales and questionnaires are widely used to assess the presence and severity of the sleep disorders. The objective is to review rating scales and questionnaires used for assessment of sleep disorders in PD. To this purpose, a description and update of the sleep scales reviewed by the ad hoc Movement Disorder Society task force (MDS-TF) and other sleep disorder assessments was performed. Two specific (Parkinson's Disease Sleep Scale and Scales for Outcomes in PD Sleep) and two generic scales (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale) were "Recommended" by the MDS-TF as they were used in PD patients, by researchers others than their developers and properly validated. Two other generic scales (Inappropriate Sleep Composite Score and Stanford Sleepiness Scale), "Suggested" due to incomplete validation, are also reviewed. Other instruments included in this review are three comprehensive PD-specific instruments for assessing multiple domains in addition to sleep problems (e.g., Non-Motor Symptoms Questionnaire, Non-Motor Symptoms Scale, MDS-UPDRS), and three generic instruments focused on particular disturbances (e.g., International Restless Legs Syndrome Study Group Rating Scale, REM behavioral disorders questionnaires), although these latter lack formal validation in PD populations. The "Recommended" instruments cover satisfactorily the needs for screening and evaluation of the nocturnal sleep disorders and daytime sleepiness in PD patients. It would be convenient to validate or complete the validation in PD populations of those instruments that cannot be recommended due to the lack of information on their clinimetric attributes. 
24756186	Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077-0.80]), giving a NNT of 3.0 [95 % CI 1.7-11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.
24755900	This study aims to evaluate subjective sleep quality in premenopausal and postmenopausal women and to study its association with night sweats, hot flashes, and depressive symptoms.A total of 158 healthy women were recruited; 107 were premenopausal (44-48 y) and 51 were postmenopausal (53-58 y). Sleep quality was evaluated with the Basic Nordic Sleep Questionnaire, night sweats and hot flashes were evaluated with a specific symptom questionnaire, and depressive symptoms were evaluated with the Beck Depression Inventory.	Postmenopausal women had poorer general sleep quality (P < 0.001), slept more restlessly (P = 0.020), and had more nocturnal awakenings (P = 0.015). However, the frequency of difficulty falling asleep, snoring, witnessed apnea, or use of sleep medication was similar between the groups. Furthermore, sleep latency, morning tiredness, or daytime tiredness did not differ between the groups. Postmenopausal women did not report more unintentional falling asleep at work or during leisure time; however, when not active, they dozed off more easily than premenopausal women (P < 0.001). Postmenopausal women had more night sweats (P < 0.001), hot flashes (P < 0.001), and depressive symptoms (P < 0.001). Even a low frequency of night sweats disturbed sleep in postmenopausal women, whereas only frequent night sweats were disturbing in premenopausal women. Depressive symptoms disturbed sleep regardless of menopause status.	Maintenance insomnia, most evidently because of night sweats and hot flashes, seems to be the major type of insomnia in postmenopausal women and has to be considered when choosing insomnia treatment for this group. Initiation of sleep and daytime vitality are not, in general, affected by menopause.	

24755400	This pilot study aimed to gain empirical data on the social and economic impacts of child burns on children and parents, in the context of the outpatient setting.A questionnaire was completed by 52 parents of paediatric patients attending the burns outpatient department at Queen Victoria Hospital (QVH), East Grinstead, for at least the third time. Children's medical notes were used to extract demographic and medical data. Quantitative data was analyzed statistically and qualitative data was analyzed manually using content analysis.	The financial burden related to the injury posed the greatest impact on parents, and was mainly associated with making the journey to the hospital, with lower income households being most affected. Self-employed parents and those who had to attend more than 6 hospital appointments also ran into difficulties. On the whole, there was not a considerable social impact on the burn-injured child, which may reflect the minor nature of burns in this study (mean depth partial thickness, median TBSA 1.0%).	Parents were shown to perceive a greater impact from their child's burn injury than their child. Certain groups of parents were identified as requiring additional support following the burn injury.	
24755136	The aim of this study was to evaluate the effect of sleep disturbance on the pharmacokinetics, especially on the absorption, of lorazepam in humans. Eight healthy male volunteers received a single oral dose of lorazepam 1 mg before sleep on two occasions in a cross-over design. In either of the two doses, subjects were intermittently exposed to noise for 1.5 hours after oral lorazepam administration. Plasma lorazepam concentrations were measured by HPLC. The exposure to noise significantly prolonged tmax (control vs. noise: 2.0 vs. 3.0 hours) and significantly decreased AUC of lorazepam in the absorption phase. The reduction was 54% (95% CI, 15 - 75%) and 24% (3 - 40%) for AUC (0 - 1 hours) and AUC (0 - 3 hours), respectively. No significant changes were observed in other pharmacokinetic parameters. The results of this study suggest that the onset of drug action after oral lorazepam administration can be altered by sleep disturbance. 
24755040	This study examines the association between suicidal ideation and sleep disturbances in a sample of treatment-seeking Canadian Forces members and veterans, after controlling for probable posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalised anxiety disorder (GAD), and alcohol use disorder (AUD). Subjects included members and veterans of Canadian Forces seeking treatment at a hospital-based Operational Stress Injury Clinic (n=404). Sleep disturbances and nightmares were measured using individual items on the PTSD Checklist - Military Version (PCL - M), while the suicidality item of the Patient Health Questionnaire (PHQ-9) was used as a stand-alone item to assess presence or absence of suicidal ideation. Regression analyses were used to determine the respective impact of (1) insomnia and (2) nightmares on suicidal ideation, while controlling for presence of probable PTSD, MDD, GAD, and AUD. We found that 86.9% of patients reported having problems falling or staying asleep and 67.9% of patients reported being bothered by nightmares related to military-specific traumatic events. Neither sleep disturbances nor nightmares significantly predicted suicidal ideation; instead, probable MDD emerged as the most significant predictor. The clinical implications of these findings and their potential impact on treatment guidelines are discussed. 
24754981	To evaluate the clinical value of transcutaneous carbon dioxide (TcPCO2) measurement during sleep respiratory monitoring.A total of 29 patients were prospectively recruited. Their age range was (49.5 ± 12.9) years and body mass index (BMI) (28.2 ± 3.6) kg/m(2). All of them underwent polysomnography (PSG) at Sleep Center, Peking University People's Hospital during the period of January-August 2013. TcPCO2 signal was entered into PSG systems and TcPCO2 (TCM4, Radiometer,Demark) measured simultaneously. Arterial blood gas (ABG) analysis for arterial pressure of CO2 (PaCO2) was undertaken to validate TcPCO2 measurement. The data were statistically analyzed by Pearson's product-moment correlation. Dynamic change of TcPCO2 was monitored during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. The effect of noninvasive positive airway pressure ventilation (NPPV) treatment on TcPCO2 during sleep was also observed.	TcPCO2 (44.2 ± 4.0) mmHg (1 mmHg = 0.133 kPa) was highly correlated with PaCO2 (43.2 ± 4.7) mmHg (Pearson's correlation, r = 0.896, P = 0.000), TcPCO2 (45.8 ± 5.4) mmHg level during wakefulness correlated significantly with that during N1, N2, N3 and REM sleep stages (r = 0.658, 0.871, 0.898,0.775; P = 0.009, 0.000, 0.003, 0.000). TcPCO2 levels during different sleep stages were all higher than that of wakefulness.However, TcPCO2 levels did not differ between two sleep stages. During both NREM and REM, elevated TcPCO2 returned to the level during wakefulness on NPPV treatment.	Continuous monitoring of PCO2 is well-tolerated during PSG testing. And the signal is stable. During whole night sleep, TcPCO2 monitoring provides more accurate and clinically acceptable estimation of PaCO2 so that it helps to titrate the NPPV pressure levels.	
24754483	This study examines the relationship among prenatal maternal stress, sleep quality and unplanned Caesarean delivery. For this research, we adopted a prospective survey design and a sample of 200 women in the early stages of labour. The findings were as follows: (i) 11.5% of the participants underwent unplanned Caesarean sections; (ii) based on a Pittsburg Sleep Quality Index split point of 5, approximately 90.5% of the participants experienced poor sleep quality; and (iii) the odds ratio for primiparas undergoing an unplanned Caesarean section was 4.183 times that for multiparas (95% confidence interval (CI) = 1.177 to 14.864), indicating a statistically significant difference. The results also showed that stress was a significant factor related to unplanned Caesarean sections; a 1-point increase on the Pregnancy Stress Rating Scale was associated with a 1.033-fold higher probability of undergoing an unplanned Caesarean section (95% CI = 1.002 to 1.065). Furthermore, prenatal stress was a significant variable that can be used to predict unplanned Caesarean deliveries.
24754427	The psychological factors and their association with chronic inflammatory disease, aren't well recognized, yet their importance in oral lichen planus is still debated.The aim of this study was to investigate the prevalence of sleep disturbances, anxiety, depression and their association in patient with oral lichen planus.	50 patients with oral lichen planus vs. equal number of age and sex-matched healthy controls were enrolled. Questionnaires examining insomnia symptoms, excessive daytime sleepiness (Pittsburgh sleep quality index and Epworth aleepiness scale) depression and anxiety (The Hamilton rating scale for Depression and Anxiety) were used.	The patients with oral lichen planus had statistically higher scores in all items of the Pittsburgh sleep quality index, the Hamilton rating scale for depression and anxiety and Epworth sleepiness scale than the healthy controls. The median and inter-quartile range of the Pittsburgh sleep quality index was 5-2 and for the oral lichen planus patients and 4-2 for the healthy controls (P < 0.011). In the study group, a depressed mood and anxiety correlated positively with sleep disturbances. The Pearson correlations were 0.76 for Pittsburgh sleep quality Index vs. Hamilton rating scale for depression (P < 0.001) and 0.77 for Pittsburgh sleep quality Index vs. Hamilton rating scale for anxiety (P < 0.001).	Oral lichen planus patients report a greater degree of sleep problems, depressed mood and anxiety as compared with controls.	We suggest to screen sleep disturbances in patients with oral lichen planus because they could be considered a prodromal symptoms of mood disorders.	
24753534	Although anxiety is common in children with attention-deficit/hyperactivity disorder (ADHD), it is unclear how anxiety influences the lives of these children. This study examined the association between anxiety comorbidities and functioning by comparing children with ADHD and no, 1, or ≥2 anxiety comorbidities. Differential associations were examined by current ADHD presentation (subtype).Children with diagnostically confirmed ADHD (N = 392; 5-13 years) were recruited via 21 pediatrician practices across Victoria, Australia. Anxiety was assessed by using the Anxiety Disorders Interview Schedule for Children-IV. Functional measures included parent-reported: quality of life (QoL; Pediatric Quality of Life Inventory 4.0), behavior and peer problems (Strengths and Difficulties Questionnaire), daily functioning (Daily Parent Rating of Evening and Morning Behavior), and school attendance. Teacher-reported behavior and peer problems (Strengths and Difficulties Questionnaire) were also examined. Linear and logistic regression controlled for ADHD severity, medication use, comorbidities, and demographic factors.	Children with ≥2 anxiety comorbidities (n = 143; 39%) had poorer QoL (effect size: -0.8) and more difficulties with behavior (effect size: 0.4) and daily functioning (effect size: 0.3) than children without anxiety (n = 132; 36%). Poorer functioning was not observed for children with 1 anxiety comorbidity (n = 95; 26%). Two or more anxiety comorbidities were associated with poorer functioning for children with both ADHD-Inattentive and ADHD-Combined presentation.	Children with ADHD demonstrate poorer QoL, daily functioning and behavior when ≥2 anxiety comorbidities are present. Future research should examine whether treating anxiety in children with ADHD improves functional outcomes.	
24751916	Night eating is a complex behavior associated with disruptions in eating, sleep, and mood regulation. While night eating has been associated with alterations in neuroendocrine functioning, night eating and Night Eating Syndrome (NES) are not well understood in patients with prevalent metabolic conditions, such as diabetes. In this study, 194 adults with Type 2 diabetes completed questionnaires assessing night eating symptoms as well as eating, sleep, and depressive symptoms. Glycemic control data, as measured by hemoglobin A1c (HbA1c), were gathered from patient medical charts. Results indicated that 7% of participants met criteria for NES. Increased symptoms of night eating were associated with poorer glycemic control and disruptions in eating, sleep, and mood, including significantly increased likelihood of having HbA1c levels >7% and endorsing clinical levels of depressive symptoms. Increasing understanding of the relationship between night eating and metabolic and psychosocial functioning in patients with diabetes may provide new avenues for treatment of these patients. 
24751311	Using laboratory-based polysomnography (PSG) we recently provided evidence of significantly prolonged sleep onset latency (SOL) and reduced latency to rapid eye movement (REM) sleep among non-depressed children with generalized anxiety disorder (GAD) compared to healthy age-matched controls. In the current study we conducted unattended ambulatory PSG in a new sample of children with GAD and controls in order to examine sleeping characteristics in the home environment.Thirty-two children (ages of 7-11 years) including 16 children with primary GAD and 16 controls receiving no psychotropic medications were studied. The anxious group had a primary diagnosis of GAD without secondary mood disorders and controls were free of any medical or psychiatric diagnoses. All participants underwent structured diagnostic assessments and completed one night of home-based polysomnography (PSG).	Children with GAD exhibited significantly higher sleep efficiency (SE) and fewer rapid eye movement (REM) sleep periods compared to controls. Self-reported somatic arousal during the pre-sleep period was negatively correlated with the percentage of total REM sleep among controls, but positively correlated with REM sleep percentage in the GAD group.	A small sample size and one night of PSG only.	Home-based PSG recording do not provide evidence of disrupted sleep patterns in children with GAD. Contextual factors that better elucidate differences between laboratory and home-based sleep findings are suggested as important directions for future research.	
24750691	Sleep disorders are common in patients with HIV/AIDS, and can lead to poor quality of life. Although many studies have investigated the aetiology of these disorders, it is still unclear whether impaired sleep quality is associated with HIV itself, social problems, or side effects of antiretroviral therapy (ART). Moreover, despite its known neurological associations, little is known about the role of the trans-activator of transcription (Tat) protein in sleep disorders in patients with HIV/AIDS. The purpose of this study was to test the hypothesis that the sleep quality of patients with HIV/AIDS affected by an altered circadian rhythm correlates with cerebrospinal HIV Tat protein concentration.Ninety-six patients with HIV/AIDS between 20 and 69 years old completed the Pittsburgh Sleep Quality Index. Their circadian rhythm parameters of blood pressure, Tat concentration in cerebrospinal fluid, melatonin concentration, CD4 cell count and HIV RNA viral load in serum were measured.	The circadian amplitude of systolic blood pressure and the score for sleep quality (Pittsburgh Sleep Quality Index) were negatively correlated with HIV Tat protein concentration, while the melatonin value was positively correlated with Tat protein concentration.	The HIV Tat protein affects circadian rhythmicity by interfering with the circadian system in patients with HIV/AIDS and further increases the melatonin excretion value. A Tat protein-related high melatonin value may counteract HIV-related poor sleep quality during the progression of HIV infection. This study provides the first clinical evidence offering an explanation for why sleep quality did not show an association with progression of HIV infection in previous studies.	
24750268	This study aims to evaluate the effect of light therapy on depression and sleep disruption in older adults residing in a long-term care facility. Psychological morbidity is a problem commonly seen in older adults residing in long-term care facilities. Limited research has addressed the effect of light therapy on depression in this population. A quasi-experimental pretest and posttest design was used. Thirty-four participants in the experimental group received light therapy by sitting in front of a 10000-lux light box 30 min in the morning, three times a week for 4 weeks. Thirty-one participants in the control group received routine care without light therapy. Depression was measured by Geriatric Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of light therapy, the mean depression score in the experimental group decreased from 7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant reduction (t = 2.22, P = 0.03). However, there was no significant difference in depression score and sleep disruption between the experimental group and control group. Light therapy might have the potential to reduce depressive symptoms and sleep disruption and may be a viable intervention to improve mental health of older adults in the long-term care facilities. 
24749793	Sleep disorders are associated with cardiovascular complications and preterm delivery (PTD). Insufficient sleep results in metabolic alterations and increased inflammation, both known to contribute to placental abruption (abruption), a determinant of PTD. We examined associations of abruption with sleep duration and complaints of vital exhaustion.The study included 164 abruption cases and 160 controls in a multicenter study in Peru. Data on habitual sleep duration and vital exhaustion during the first 6 months of pregnancy were elicited during interviews conducted following delivery. Women were categorized according to short, normal and long sleep duration (≤6, 7-8 and ≥9 h); and frequency of feeling exhausted. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.	Short and long sleep durations were associated with increased odds of abruption. The ORs of abruption in relation to short (≤6 h) and long (≥9 h) sleep duration were 2.0 (95% CI 1.1-3.7) and 2.1 (95% CI 1.1-4.1), compared with normal sleep duration (7-8 h). Complaints of vital exhaustion were also associated with abruption (OR = 2.37; 95% CI 1.46-3.85), and were independent of sleep duration.	We extend the existing literature and support the thesis that maternal sleep habits and disorders should be assessed among pregnant women.	
24747999	Textile factory is among the most common manufacturing industries that has higher rate of work-related injuries. Knowing the associated factors of work-related injuries can be a critical step for improving the working condition of workers in the sector.To assess the major determinants of occupational injury among workers in Kombolcha textile factory, North-East Ethiopia.	An institution-based cross-sectional study was conducted from April 1 to 15, 2013 on 455 randomly selected workers after stratification by working departments. The data was collected using a structured questionnaire through face-to-face interview by data collectors of 6 occupational health experts and 6 nurses.	Working >48 hrs/wk (aOR: 2.71, 95% CI: 1.18-6.24), handling objects >20 kg (aOR: 2.35, 95% CI: 1.24-4.45), visual concentration (aOR: 3.10, 95% CI: 1.42-6.75), timely maintenance of machine (aOR: 1.80, 95% CI: 1.11-2.93), and sleep disorder (aOR: 2.95, 95% CI: 1.47-5.92) were significant factors for the occurrence of occupational injuries.	Many factors including working for a long time with accurate instruments and sleep disorders can cause occupational injury in textile industries.	
24746674	Previous studies investigating cerebral metabolic changes associated with continuous spike-waves during sleep (CSWS) compared the metabolism of children with CSWS with that of healthy adults, precluding any assessment in brain areas showing physiologic age-related metabolic changes. Here, we investigated the metabolic and connectivity changes characterizing the acute phase of CSWS activity by comparing awake brain metabolism of children with CSWS with that of pediatric pseudo-controls. Positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) was performed in 17 awake children with cryptogenic CSWS (5 girls, age: 5-11 years). Voxel-based analyses identified significant metabolic changes in CSWS patients compared with 18 pediatric pseudo-controls (12 girls, age: 6-11 years, non-CSWS focal cryptogenic epilepsy with normal FDG-PET). CSWS-induced changes in the contribution of brain areas displaying metabolic changes to the level of metabolic activity in other brain areas were investigated using pathophysiological interaction. Hypermetabolism in perisylvian regions bilaterally and hypometabolism in lateral and mesial prefrontal cortex, precuneus, posterior cingulate cortex and parahippocampal gyri characterized the acute phase of CSWS (p<0.05 FWE). No change in thalamic metabolism was disclosed. Altered functional connectivity was found between hyper- and hypometabolic regions in CSWS patients compared with pediatric pseudo-controls. This study demonstrates hypometabolism in key nodes of the default mode network (DMN) in awake patients with CSWS, in relation with a possible phenomenon of sustained remote inhibition from the epileptic foci. This hypometabolism might account for some of the acquired cognitive or behavioral features of CSWS epileptic encephalopathies. This study failed to find any evidence of thalamic metabolic changes, which supports the primary involvement of the cortex in CSWS genesis. 
24746115	Few studies have been conducted examining the genuine sleep condition and memory in patients with euthymic bipolar disorder. Thus we evaluated sleep complaints and memory functions in psychotropic drug-free euthymic patients with bipolar disorder.Twenty-two psychotropic drug-free euthymic patients with bipolar disorder and 44 healthy controls matched by age and sex were recruited and assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Wechsler Memory Scale-Revised (WMS-R).	The quality of sleep and memory function of the euthymic patients with bipolar disorder were significantly poorer than those of the controls. Both years of education and the hypnotic use sub-item of the PSQI were significantly correlated with visual memory index of the WMS-R.	Sleep complaints management is important in euthymic patients with bipolar disorder.	
24746052	Hypoglossal (XII) motoneurons innervate muscles of the tongue whose tonic and inspiratory modulated activity protects the upper airway from collapse in patients affected by the obstructive sleep apnea (OSA) syndrome. Both norepinephrine and serotonin provide wakefulness-related excitatory drives that maintain activity in XII motoneurons, with the noradrenergic system playing a particularly prominent role in rats. When noradrenergic and serotonergic drives are antagonized, no further decline of XII nerve activity occurs during pharmacologically induced rapid eye movement (REM) sleep-like state. This is the best evidence to date that, at least in this model, the entire REM sleep-related decline of upper airway muscle tone results from withdrawal of these two excitatory inputs. A major component of noradrenergic input to XII motoneurons originates from pontine noradrenergic neurons that have state-dependent patterns of activity, maximal during wakefulness, and minimal, or absent during REM sleep. Our data suggest that not all ventrolateral medullary catecholaminergic neurons follow this pattern, with adrenergic C1 neurons probably increasing their activity during REM sleep. When rats are subjected to chronic-intermittent hypoxia, noradrenergic drive to XII motoneurons is increased by mechanisms that include sprouting of noradrenergic terminals in the XII nucleus, and increased expression of α1-adrenoceptors; an outcome that may underlie the elevated baseline activity of upper airway muscles during wakefulness in OSA patients. 
24745954	We tested whether sleep problems co-occur with, precede, and/or follow common psychiatric disorders during childhood and adolescence. We also clarified the role of comorbidity and tested for specificity of associations among sleep problems and psychiatric disorders.Data came from the Great Smoky Mountains Study, a representative population sample of 1,420 children, assessed 4 to 7 times per person between ages 9 and 16 years for major Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) disorders and sleep problems. Sleep-related symptoms were removed from diagnostic criteria when applicable.	Sleep problems during childhood and adolescence were common, with restless sleep and difficulty falling asleep being the most common symptoms. Cross-sectional analyses showed that sleep problems co-occurred with many psychiatric disorders. Longitudinal analyses revealed that sleep problems predicted increases in the prevalence of later generalized anxiety disorder (GAD) and high GAD/depression symptoms, and oppositional defiant disorder (ODD). In turn, GAD and/or depression and ODD predicted increases in sleep problems over time.	Sleep problems both predict and are predicted by a diagnostic cluster that includes ODD, GAD, and depression. Screening children for sleep problems could offer promising opportunities for reducing the burden of mental illness during the early life course.	
24745778	The Brief Insomnia Questionnaire (BIQ) was first validated in the U.S. for insomnia disorders according to the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR), International Classification of Diseases, Tenth Edition (ICD-10) and research diagnostic criteria/International Classification of Sleep Disorders, Second Edition (RDC/ICSD-2). We aimed to determine the validity and reliability of a Hong Kong Chinese version of the BIQ to derive the DSM-5 in addition to other insomnia diagnoses in a general population sample.Probability subsamples of population-based epidemiological survey respondents (n=2011) completed test-retest (n=120) and clinical reappraisal (n=176) interviews.	Short-term test-retest reliability was moderate for most BIQ items (Pearson r>0.40), except for the number of nights with problems staying asleep, amount of time awake, duration of sleep problems and sleep onset latency. The areas under the receiver operating characteristic curve for the DSM-IV-TR, DSM-5, ICD-10 and RDC/ICSD-2 insomnia disorder ranged from 0.76 to 0.86, indicating high individual-level concordance between BIQ and clinical-interview diagnoses. The use of super-normal control and BIQ symptom-level data further improves the diagnostic concordance. Prevalence estimates based on the BIQ dichotomous classification were comparable with estimates based on clinical interviews for the DSM-5, RDC/ICSD-2 and any of the DSM-IV-TR, ICD-10 and RDC/ICSD-2 insomnia disorders.	The Hong Kong Chinese version of the BIQ generates accurate prevalence estimates for insomnia disorders in the general population. Modification of the BIQ scoring algorithms and use of trained interviewers may further improve its diagnostic performance.	
24745777	High rates of sleep disturbances occur in depression. Sleep disturbances are linked to heightened inflammation. We sought to determine if sleep disturbances explain a portion of the putative inflammation - depression association among older adults. In late life, age-related immunoregulation changes may modify the inflammation-depression relationship.Cross-sectional associations of a panel of serum inflammatory markers with probable depression (measured with the Geriatric Depression Scale) were assessed among 2560 community-dwelling older men. We tested whether inflammatory marker - probable depression associations were independent of chronic diseases, as well as objective and subjectively measured sleep disturbances. We also tested whether inflammation-probable depression associations were moderated by age.	Inflammatory markers were not independently associated with higher odds of probable depression. A significant age by C-reactive protein (CRP) interaction (p=0.01) was detected such that the strength of the CRP-probable depression association decreased with age. When stratifying by the median age of 76, elevated odds of probable depression were found for men with CRP levels above the median only among the younger group (OR=2.08, 95% CI 1.18-3.69). In the final adjusted model, independent effects of chronic diseases and subjective sleep disturbances contributed to a total of 37% attenuation of the original OR (adjusted OR=1.68, 95% CI 0.911-3.10, p=.09).	In late-life, associations between inflammatory markers and mood may be explained by both chronic diseases and subjectively reported sleep disturbances. Our findings indicate that the association of CRP with probable depression diminishes in strength with age.	
24745776	Insomnia is commonly co-morbid with obstructive sleep apnea. Among patients reporting insomnia symptoms, sleep misperception occurs when self-reported sleep duration under-estimates objective measures. Misperception represents a clinical challenge since insomnia management is based entirely on patient self-report. We tested the hypothesis that misperception occurring in sleep apnea patients would improve with subsequent treatment.We compared subjective sleep-wake reports with objective sleep in adults with obstructive sleep apnea (n=405) in two nights of polysomnography (diagnostic and treatment) within a median interval of 92 days.	Sleep latency was generally over-estimated, while wake after sleep onset and number of awakenings were under-estimated. None of these estimations differed between diagnostic and treatment polysomnograms. We observed a large spectrum of total sleep time misperception values during the diagnostic polysomnogram, with one third of the cohort under-estimating their total sleep time by at least 60 min. Of those with >60 minute misperception, we observed improved total sleep time perception during treatment polysomnography. Improved perception correlated with improvements in self-reported sleep quality and response confidence. We found no polysomnogram or demographic predictors of total sleep time misperception for the diagnostic polysomnogram, nor did we find objective correlates of improved perception during titration.	Our results suggest that misperception may improve with treatment of obstructive sleep apnea in patients who also exhibit misperception. Within subject changes in misperception are consistent with misperception being, at least to some extent, a state characteristic, which has implications for management of patients with comorbid insomnia and sleep apnea.	
24743941	Diabetes and depression occur together approximately twice as frequently as would be predicted by chance alone. Comorbid diabetes and depression are a major clinical challenge as the outcomes of both conditions are worsened by the other. Although the psychological burden of diabetes may contribute to depression, this explanation does not fully explain the relationship between these 2 conditions. Both conditions may be driven by shared underlying biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors. Depression is frequently missed in people with diabetes despite effective screening tools being available. Both psychological interventions and antidepressants are effective in treating depressive symptoms in people with diabetes but have mixed effects on glycemic control. Clear care pathways involving a multidisciplinary team are needed to obtain optimal medical and psychiatric outcomes for people with comorbid diabetes and depression. 
24743876	Particular interest has been generated regarding the possible influence of statin use on sleep quality. However, no conclusive evidence exists that a particular statin is more likely to be associated with sleep disturbances versus others. It remains uncertain whether different statins produce different risks for sleep disturbance.To examine the association between statin use and the risk of sleep disturbances, we conducted data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and a large organized database of prescriptions constructed by a database vendor (Japan Medical Information Research Institute, Inc. Japan).	Relevant reports in the FAERS were identified and analyzed. Data from the first quarter of 2004 through the end of 2012 [corrected] were included in this study.The reporting odds ratio (ROR) was used to detect spontaneous report signals, calculated using the case/non-case method. For the ROR, a signal was detected if the lower limit of 95 % two-sided confidence interval (95 % CI) was >1. Additionally, signal detection using the IC was conducted using the IC025 metric, a lower limit of the 95 % CI of the IC, where a signal is detected if the IC025 value exceeds 0. In addition, symmetry analysis was used to identify the risk of insomnia after using statins over the period of January 2006 to August 2013.	In the analyses of the FAERS database, significant signals for sleep disturbances including disturbances in initiating and maintaining sleep, sleep disorders NEC, sleeping disorders due to a general medical condition, and parasomnias were found. In the prescription sequence symmetry analysis, a significant association between statin use and hypnotic drug use was found, with adjusted sequence ratios of 1.14 (1.03-1.26), 1.20 (1.11-1.29), and 1.18 (1.11-1.25) at intervals of 91, 182, and 365 days, respectively.	Multi-methodological approaches using different algorithms and databases strongly suggest that statin use is associated with an increased risk for sleep disturbances including insomnia.	
24743466	Numerous randomized controlled trials have been conducted to determine efficacy of exercise on cancer-related fatigue. However, many trials lacked sufficient power to demonstrate significant differences, and little is known about how the effect of exercise differs depending on patient- and intervention-level characteristics. A meta-analysis was performed to determine whether exercise reduces fatigue compared with usual care or nonexercise control intervention in patients with cancer. The authors searched Ovid MEDLINE, EMBASE, PsycINFO, The Cochrane Central Register of Controlled Trials, and CINAHL. Two authors independently extracted the data. Randomized controlled trials comparing exercise with control intervention in cancer patients in which fatigue was quantified were eligible. Seventy-two randomized controlled trials were identified, 71 in adults and 1 in children. Exercise had a moderate effect on reducing fatigue compared with control intervention. Exercise also improved depression and sleep disturbance. Type of exercise did not significantly influence the effect on fatigue, depression, or sleep disturbance. Exercise effect was larger in the studies published 2009 or later. There was only one pediatric study. The results of this study suggest that exercise is effective for the management of cancer-related fatigue. 
24742264	This study examined the factor structure of the Adolescent Sleep-Wake Scale (ASWS) among 491 adolescents (12-18 years) with and without pediatric health conditions. Exploratory factor analyses were conducted using iterated principal axis factoring with varimax rotation. Highly cross-loading items were systematically removed and analyses were rerun until a clean solution was attained. The final solution explained 57.1% of the total model variance, including 10 items and three factors: Falling Asleep and Reinitiating Sleep-Revised, returning to Wakefulness-Revised, and Going to Bed-Revised. Internal consistency reliability scores were acceptable to good, with the exception of the Going to Bed-Revised subscale for the healthy sample. Adolescents with chronic pain reported significantly poorer overall sleep quality and more problems in falling asleep, reinitiating sleep, and returning to wakefulness as compared to healthy adolescents, providing preliminary evidence for construct validity of the new factors. The resulting ASWS version is a concise assessment tool with empirically derived, distinct behavioral sleep dimensions that can be used for clinical and research purposes. 
24741970	To improve the method for monitoring sleep state and respiratory rhythm of SD rats, providing a solution for rats' chewing on the wires, signal loss and instability problems in the animal model of sleep apnea syndrome (SAS).We improved monitoring electrodes of both electrocorticogram (ECoG) and electromyogram (EMG), signal circuit and animal operation.	Operation time was shortened and wound exposure time was reduced, which made it easier for postoperative recovery. The ECoG and EMG signals were more stable with sharp image, and signal circuit lines had better conductivity and material durability, achieving continuous monitoring for a long time and high success rate. We could precisely distinguish the sleep wake state and the sleep apnea events in rats according to these signals.	The improved method is more reliable and practical to test the small animal model of SAS, and is more easily to operate and the signals are more stable.	
24740871	Disturbed sleep is a prominent feature of posttraumatic stress disorder (PTSD). PTSD and disrupted sleep have been independently linked to cognitive deficits; however, synergistic effects of PTSD and poor sleep on cognition have not been investigated. The purpose of this study was to examine the effects of PTSD symptoms and objectively measured disruptions to sleep on cognitive function. Forty-four young-adult African American urban residents comprised the study sample. The Clinician-Administered PTSD Scale (CAPS; Blake et al., 1995) was utilized to determine the severity of PTSD symptoms. Participants underwent 2 consecutive nights of polysomnography. The Automated Neuropsychological Assessment Metrics (Reeves, Winter, Bleiberg, & Kang, ) was utilized to assess sustained attention and the Rey Auditory Verbal Learning Test (Schmidt, ) was used to evaluate verbal memory. PTSD symptom severity, r(42) = .40, p = .007, was significantly associated with omission errors on the sustained attention task, and sleep duration, r(42) = .41, p = .006, and rapid eye movement sleep, r(42) = .43, p = .003, were positively correlated with verbal memory. There was an interaction of PTSD symptom severity and sleep duration on omission errors such that more than 7 hours 12 minutes of sleep mitigated attentional lapses that were associated with PTSD.
24740235	Several diagnoses in the new DSM-5 chapter on 'Obsessive-Compulsive and Related Disorders' directly relate to psychodermatology. The new excoriation (skin-picking) disorder (SPD) and trichotillomania (TTM) both manifest as recurrent body-focused repetitive behaviors that have compulsive and dissociative features, the latter being more prevalent in TTM than SPD. The DSM-5 refers to SPD and TTM occurring without full awareness or preceding tension, however does not specifically mention the possible role of dissociation. This has important treatment implications, as patients with high dissociative symptoms are not likely to respond to the standard treatments for obsessive-compulsive disorder. Body dysmorphic disorder (BDD), which is frequently associated with cutaneous body image (CBI) dissatisfaction, is present in 9%-15% of dermatology patients. Treatment guidelines in dermatology are increasingly considering the psychosocial morbidity related to CBI in their treatment outcome measures. The presence of BDD, if unrecognized, may therefore directly affect the dermatologic treatment regimens offered to the patient.
24739309	This review describes evolving concepts and recent data on the relationship between serum testosterone levels and normal and disordered sleep.Sex-related differences in circadian rhythms and sleep physiology are in part due to organizational and activational effects of sex steroids. Testosterone affects the organization of circadian rhythms and the timing, but not the duration, of sleep. Increasing testosterone during puberty leads to later bedtimes. The diurnal variation in testosterone depends on sleep rather than circadian rhythm or season. Pubertal onset is heralded, well before virilization, by a luteinizing hormone level at least 3.7 U/l during sleep. Total sleep deprivation lowers testosterone, but sleep restriction only does so if it occurs in the first half of the night. The recovery of testosterone from sleep disruption is impaired in old as compared with young rodents. In men with obstructive sleep apnoea (OSA), low testosterone is related to obesity rather than the OSA itself, and improves with weight loss but inconsistently with continuous positive airway pressure (CPAP). Testosterone treatment only transiently worsens severity of OSA, which need not be considered a contraindication to its use.	Testosterone treatment is unlikely to benefit sleep in men with secondary hypogonadism, for example due to obesity or depression, in contrast to the management of the underlying abnormality.	
24738970	A young male patient was successfully treated for parasomnia overlap disorder (POD) using hypnosis. In 2006, this 16-year-old patient underwent a clinical evaluation for episodes of sleep talking, sleepwalking, and dream enactment. This initial assessment was followed by polysomnographic evaluation, a brain MRI, and three sessions of treatment using hypnosis. From the beginning, until the last contact in December 2011, benefits from the hypnotic suggestions were noted and documented. 
24737221	This study characterizes psychiatric manifestations as a primary symptom of neurosyphilis (NS). Fifty-two of the 169 NS patients presented with psychiatric manifestations, many patients had characteristics of more than one syndrome, including cognitive impairment, personality disorders, delirium, hostility, dysarthria, confusion, disruption of their sleep-wake cycle, fecal and urinary incontinence, dysphoria, paranoia, hallucinations, expansive mood, and mania. Fifty-two patients had positive sera RPR and T. pallidum particle agglutination (TPPA), 75% had positive CSF RPR, 96.2% had positive CSF TPPA, 44.2% had CSF pleocytosis and elevated CSF proteins, and 70.0% had nonspecific, abnormal brain MRIs. These results indicate that NS mimics almost all psychiatric disorders. 
24736200	This study aims to determine whether vitamin D levels are associated with menopause-related symptoms in older women.A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were included in these analyses.	Borderline significant associations between 25(OH)D levels and total number of menopausal symptoms were observed (with P values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. No associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue were observed (P's > 0.10 for fully adjusted models).	There is no evidence for a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.	
24735203	Numerous studies have explored the effectiveness of bright light therapy as a treatment of sleep disorders in nursing home and long-stay geriatric hospital residents, most of whom have dementia. A recent Cochrane Collaboration meta-analysis of 10 selected studies concluded that there was insufficient evidence to assess its therapeutic efficacy as most available studies had methodological problems. We sought to remedy this situation by developing proposals to guide research methods in future studies.Based on the literature and our own clinical and research experience, we developed a series of proposals relating to study design, participant selection, light delivery modalities and outcome measures that we believe will maximize the chances of identifying a bright light treatment effect. We then checked adherence to these proposals in all relevant published experimental studies.	Of the 18 studies published in the last two decades that met our selection criteria, only half the studies had selected participants with a sleep disorder. Eleven studies excluded people with severe vision loss; seven included a clinical rating of sleep, and five measured baseline lighting levels. Most checked psychoactive medication prescriptions but few reported changes in prescriptions over the course of the study. Most also checked treatment adherence and included some control for differences in amount of social contact.	Evidence for the effectiveness of bright white light treatment in people residing in nursing homes is equivocal. We anticipate that the quality of this evidence will be improved if researchers refine their study methods and adopt a more uniform approach.	
24733992	The suprachiasmatic nucleus (SCN) plays a critical role in maintaining melatonin and sleep-wake cycles.We report a case of 38-year-old woman who, after gunshot wound to the right temple, developed a sleep complaint of multiple nocturnal awakenings and several naps throughout the day.	Computerized tomography and magnetic resonance imaging revealed bilateral optic nerve and optic chiasm damage. Diagnostic polysomnography and actigraphy revealed an irregular sleep wake rhythm.	We speculate concurrent damage of the SCN and optic nerves bilaterally resulted in the posttraumatic irregular sleep-wake rhythm.	
24733989	To examine the link between disturbed sleep and depression scores in Mexican Americans and non-Hispanic Whites.Data were analyzed for 566 participants (45% Mexican Americans) who were part of a rural healthcare study, Project FRONTIER. Mean age was 55.5 years for Mexican Americans (70% female) and 65.6 years for non-Hispanic Whites (69% female). Self-reported sleep disturbance was entered as the predictor, GDS-30 total and factor scores as the outcome variables, and age, sex, education, BMI, and medical diagnoses (hyperlipidemia, diabetes mellitus, and hypertension) entered as covariates.	Mexican Americans reported higher rates of sleep disturbances (25%) than non-Hispanic whites (17%). Sleep disturbances were significantly associated with GDS-30 total scores and the factors Dysphoria and Cognitive Impairment in both Mexican Americans and non-Hispanic whites.	In this study, Mexican Americans reported higher rates of sleep disturbances than non-Hispanic whites. Disturbed sleep was positively associated with depression and the factor scores for Dysphoria and Cognitive Impairment in both groups. Given the paucity of research on sleep disorders in Mexican Americans, identifying what sleep disorders are present and the impact treating these sleep disorders have on depression warrant further investigation.	
24733988	This study examined documented treatment recommendations provided for sleep disorders and sleep problems in pediatric primary care, the persistence of sleep problems and sleep disorders in children and adolescents, and the relationship between sleep issues and health care utilization.In-depth chart review of pediatric primary care patient visits (n = 750 patients) from 2007 through 2010.	Only 26 children (5.2% of those with a sleep disorder/ problem) received a treatment recommendation, with half of these recommendations behavioral in nature. Sleep disorders and sleep problems were highly persistent across time for up to a third of children. Children with sleep disorders had significantly more sick visits/calls (mean = 8.84, 95% CI 7.77-9.90) than children without a sleep disorder (mean = 6.34, 95% CI 5.56-7.12).	Very few children or adolescents were found to have documented treatment recommendations or referrals for diagnosed sleep disorders or sleep problems. In addition, given that sleep disorders and sleep problems are highly persistent, as well as result in more sick visits/calls, it is important that pediatric primary care providers screen for and identify these issues across development. Furthermore, it is essential to provide health care providers with more education and support on sleep disorders and sleep problems in pediatric primary care.	
24733987	Down syndrome (DS) is a neurodevelopmental disorder characterized by multiple comorbidities. Sleep disorders are common among children with DS and can cause significant distress for families. However, research is limited describing sleep problems and correlates in large population-based samples. Accordingly, we aimed to describe sleep behavior among children with DS and its relationship with medical conditions in this population.We conducted a population-based, cross-sectional study (2009-2011) of sleep disturbances in children and adolescents with DS 7 to 17 years of age (N = 107). We assessed sleep problems using caregiver report on two validated screening tools: the Childhood Sleep Habits Questionnaire (CSHQ) and the Pediatric Sleep Questionnaire (PSQ). The prevalence of sleep problems was compared in children with and without important comorbidities using modified Poisson regression with robust standard errors.	65% of children screened positive on the CSHQ for significant sleep problems in the past month, but their parents often did not report sleeping difficulties in their children. On the PSQ, 46% screened positive for sleep related breathing problems and 21% screened positive for sleep related movement disorders. Children with asthma, autism, and a history of enlarged adenoids and tonsils had more current sleep problems than children without these comorbidities.	Our findings suggest that sleep problems may be an important but under-recognized problem in children with DS. Sleep problems appear to be correlated with prevalent comorbidities, which may provide guidance to augment current practice guidelines to evaluate sleep problems in this population.	
24733738	Early and repeated experiences of pain may have long-term effects on vulnerable newborns hospitalized in the Neonatal Intensive Care Unit (NICU), and neonatal pain responses may be affected by a variety of factors that neonates encounter. We tested the hypothesis that male preterm neonates exhibited greater pain sensitivity than females by assessing biobehavioural pain reactivity and recovery patterns to painful procedure.Fifty-three infants born preterm and low birthweight who were admitted to NICU were observed during five phases (baseline, antisepsis, puncture, recovery-dressing and recovery-resting). Behavioural pain reactivity was measured using the Neonatal Facial Coding System (NFCS) and the Sleep-Wake States Scale (SWS). The heart rate (HR) was continuously recorded. All measures were assessed based on scores and magnitude of responses.	We found that male and female preterm neonates had similar patterns of behavioural pain reactivity and recovery; there were no statistical differences between groups in NFCS and SWS scores. However, male preterm infants presented higher HR immediately in the first minute of the puncture phase and also higher change in maximum HR between the baseline and puncture phases, than female preterm infants.	Although we found that male infants showed higher physiological reactivity to painful stimulus in some HR parameters than female infants, the evidences were not sufficient to confirm the influence of sex on biobehavioural response to pain in vulnerable neonates.	
24733634	Sleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory.Sixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year).	Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values <0.05). At cycle 4, BC showed worse sleep, increased fatigue, more depressive symptoms, and more disrupted CARs compared to their own baseline levels and to NC (all p values <0.05). By 1 year, BC's fatigue, depressive symptoms, and QoL returned to baseline levels but were still worse than those of NC, while NAPTIME and CARs did not differ from NC's.	Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time.	
24733375	Pre-school children placed in local authority care show elevated rates of mental health disorders when compared to the general population. This study investigated risk factors for mental health disorders relating to the period prior to entering care and while in care. A representative sample of 43 children in care aged 0-72 months in an inner London borough underwent comprehensive multidimensional assessments. Presence of emotional, behavioural, attachment and adaptive disorders was ascertained. Exposure to two pre-placement risk factors and six placement risk factors was compared between children with and without a disorder. A total of 26 children (60.5%) had at least one mental health disorder. The two pre-placement risk factors, multiple types of maltreatment and entry into care after the age of 6 months, were both significantly associated with mental health disorders. The three placement risk factors of sudden placement moves, multiple placement moves and child-carer alienation showed a significant association with mental health disorders. There was a strong correlation between the number of risk factors and the number of co-morbid mental health disorders per child (r = .67, p < .001). In conclusion, this study identified five modifiable risk factors related to the quality of safeguarding and fostering services which showed a significant association with pre-school mental health. 
24731962	Sleep disorders are common among patients with systemic lupus erythematosus (SLE) with unclear underlying mechanisms. We assessed the role of vitamin D in sleep quality of patients with SLE.A retrospective study was conducted on women with SLE for whom the following data were available at the same time; sleep quality (Pittsburgh Sleep Quality Index (PSQI)), disease activity, cumulative disease damage, psychological state (Hospital Anxiety and Depression Scale (HADS)), and serum vitamin D level. Bivariate and regression analyses were computed to find contributors of sleep quality.	In total, 63 women were studied. Serum vitamin D level was correlated with physical activity (r=0.310, p=0.015), season of assessment (r=-0.302, p=0.016), the PSQI global score (r=-0.262, p=0.043), anxiety score (r=-0.298, p=0.021), and non-significantly with depression score (r=-0.218, p=0.094). Including all variables into a linear regression model, vitamin D level was independently associated with the global PSQI score (beta=-0.364, p=0.042). Association of vitamin D level with psychological state disappeared after controlling for season of assessment (beta=-0.248, p=0.154).	We found a role for vitamin D in sleep quality of SLE patients. Further studies are warranted to confirm these results and to find possible mechanisms of action.	
24731536	In parallel with the increasing prevalence of obesity and type 2 diabetes, sleep loss has become common in modern societies. An increasing number of epidemiological studies show an association between short sleep duration, sleep disturbances, and circadian desynchronisation of sleep with adverse metabolic traits, in particular obesity and type 2 diabetes. Furthermore, experimental studies point to distinct mechanisms by which insufficient sleep adversely affects metabolic health. Changes in the activity of neuroendocrine systems seem to be major mediators of the detrimental metabolic effects of insufficient sleep, through favouring neurobehavioural outcomes such as increased appetite, enhanced sensitivity to food stimuli, and, ultimately, a surplus in energy intake. The effect of curtailed sleep on physical activity and energy expenditure is less clear, but changes are unlikely to outweigh increases in food intake. Although long-term interventional studies proving a cause and effect association are still scarce, sleep loss seems to be an appealing target for the prevention, and probably treatment, of metabolic disease.
24730888	Turnover is a typical intermittent body movement while asleep. Exploring its behavior may provide insights into the mechanisms and management of sleep. However, little is understood about the dynamic nature of turnover in healthy humans and how it can be modified in disease. Here we present a detailed analysis of turnover signals that are collected by accelerometry from healthy elderly subjects and age-matched patients with neurodegenerative disorders such as Parkinson's disease. In healthy subjects, the time intervals between consecutive turnover events exhibit a well-separated bimodal distribution with one mode at ⩽10 s and the other at ⩾100 s, whereas such bimodality tends to disappear in neurodegenerative patients. The discovery of bimodality and fine temporal structures (⩽10 s) is a contribution that is not revealed by conventional sleep recordings with less time resolution (≈30 s). Moreover, we estimate the scaling exponent of the interval fluctuations, which also shows a clear difference between healthy subjects and patients. We incorporate these experimental results into a computational model of human decision making. A decision is to be made at each simulation step between two choices: to keep on sleeping or to make a turnover, the selection of which is determined dynamically by comparing a pair of random numbers assigned to each choice. This decision is weighted by a single parameter that reflects the depth of sleep. The resulting simulated behavior accurately replicates many aspects of observed turnover patterns, including the appearance or disappearance of bimodality and leads to several predictions, suggesting that the depth parameter may be useful as a quantitative measure for differentiating between normal and pathological sleep. These findings have significant clinical implications and may pave the way for the development of practical sleep assessment technologies. 
24729150	Nocturia, awaking from sleep to void, has a negative impact on health and well-being. Nocturia affects men and women and is more prevalent among the elderly. More than two nocturnal voids is considered to be a clinically meaningful threshold associated with significant negative outcomes for health and well-being, and the timing of awakening has a significant bearing on the negative consequences of nocturia. Several serious underlying pathophysiologic conditions may be associated with nocturia. A thorough history and assessment of number and times of voids, void volume, and fluid intake is essential for determining the etiology of a patient's nocturia. With data obtained from the frequency-volume chart (FVC), which is used to collect quantitative voiding data, a patient's nocturia may be classified as global polyuria, nocturnal polyuria, reduced bladder capacity, or a combination of these categories. Global polyuria is defined as 24-hr urinary output that exceeds 40 ml/kg body weight and results in increased 24-hr urinary frequency. Nocturnal polyuria is defined as more than 20% of daily urine output at night in young patients and more than 33% in elderly patients. Reduced bladder capacity may be a result of idiopathic or neurogenic detrusor overactivity, bladder outlet obstruction, or reduced nocturnal bladder capacity. The pathophysiology underlying the findings of the FVC falls into five main categories: global polyuria, nocturnal polyuria, reduced bladder capacity, sleep disorders, and circadian clock disorders. This review discusses the epidemiology, etiology, and pathophysiology of nocturia.
24729148	Nocturia, the need to awaken at night to void, is a highly prevalent disorder that negatively affects nocturnal sleep, increases daytime tiredness, and adversely impacts quality of life. In this selective review, we provide the reader an overview of current work in this area. From the perspective of disturbed sleep, two divergent perspectives have emerged from the literature when discussing nocturia. The first is that a patient awakens because of an urge to urinate. The second is that a patient awakens during the night for some reason unrelated to urinary urge (e.g., an awakening from an environmental source or from intrinsic lightening of sleep) and then decides to void while awake. In the few studies that have inquired about nocturia as a cause of awakenings, nocturia often ranks above the traditional psychological or physical factors. Not only is nocturia likely to disrupt sleep, but it may impact waking quality of life as well. A number of generic and nocturia-related questionnaires have been used to quantify the effect of nocturia on quality of life. In this short paper, we introduce the reader to several key studies in these important areas.
24728141	To evaluate the effects of a change in water intake on mood and sensation in 22 habitual high-volume (HIGH; 2-4 L/d) and 30 low-volume (LOW; <1.2 L/d) drinkers who were asked to respectively decrease and increase their daily water intake.During baseline HIGH consumed 2.5 L and LOW 1 L of water/day. During 3 controlled intervention days HIGH's water intake was restricted to 1 L/day whereas LOW's was increased to 2.5 L water/day. Several mood scales (Bond & Lader Visual Analog Scale (VAS), Profile of Mood States, Karolinska Sleepiness Scale, Thirst & Emotional VAS) were administered at different time points during the study. ANOVA including intervention, time point and intervention by time point as fixed effects on mean values (i.e.; baseline data vs. mean of 3 intervention days) for each mood scale was performed.	At baseline HIGH and LOW were comparable in mood state, except for thirst scores (estimate = 17.16, p<0.001) and POMS depression-dejection scores (estimate = 0.55, p<0.05) which were both higher in the HIGH vs. LOW. In HIGH the restricted water intake resulted in a significant increase in thirst (p<0.001) and a decrease in contentedness (p<0.05), calmness (p<0.01), positive emotions (p<0.05) and vigor/activity (p<0.001). In LOW, increased water consumption resulted in a significant decrease in fatigue/inertia (p<0.001), confusion/bewilderment (p = 0.05) and thirst (p<0.001) and a trend to lower sleepiness (p = 0.07) compared to baseline.	Increasing water intake has beneficial effects in LOW, especially sleep/wake feelings, whereas decreasing water intake has detrimental effects on HIGH's mood. These deleterious effects in HIGH were observed in some sleep/wake moods as well as calmness, satisfaction and positive emotions.	
24726572	The purpose of this systematic review was to examine the evidence for sleep-related disturbances among adolescents with cancer, particularly the types of disturbances reported, using single and mixed paediatric oncology samples.Electronic searches of Medline, PubMed, and the Cochrane Database of Systematic Reviews since inception to September 2013 were conducted to identify all relevant studies. Search terms included sleep, a second term including adolescent, juvenile, youth, child, or childhood, and a third term including cancer, leukaemia, or brain tumour. A total of 41 articles met inclusion criteria and were included in the review. Of these, 32 included patients with leukaemia and 21 included patients with brain tumours. Sleep-related disturbances included difficulty initiating sleep, fragmented sleep, disordered breathing, parasomnias, napping, daytime sleepiness/fatigue, and unspecified disturbances. Adolescents with cancer experience many problems related to sleep. Given the increase in survival rates of the youth diagnosed with leukaemia or brain tumours, symptom management is an essential area of research in order to continue improving quality of life.	
24725849	This study aimed at characterizing the functional stability of sleep in schizophrenia by quantifying dissociated stages of sleep (DSS), and to explore their correlation with psychopathology. The sleep of 10 first-break, drug-naive young adults with schizophrenia and 10 controls was recorded. Four basic DSS patterns were scored: 1) the transitional EEG-mixed intermediate stage (EMIS); 2) Rapid-eye-movement (REM) sleep without rapid eye movement (RSWR); 3) REM sleep without atonia (RSWA); and 4) non-REM sleep with rapid eye movements. An intermediate sleep (IS) score was calculated by summing EMIS and RSWR scores, and the durations of intra-REM sleep periods IS (IRSPIS) and IS scored "at the expense" of REM sleep (ISERS) were determined. Patients were administered the Brief Psychiatric Rating Scale (BPRS) at the time of recording. Proportions of each DSS variables over total sleep time and proportions of IRSPIS and ISERS over REM sleep duration were compared between patients and controls. Correlation coefficients between DSS variables and BPRS total scores were calculated. The proportion of total DSS did not differ between patients and controls. Among DSS subtypes, RSWA was significantly increased in patients while other comparisons showed no significant differences. Significant positive correlations were found between BPRS scores and proportions of DSS, IS, RSWR, IRSPIS and ISERS over total sleep and REM sleep durations. These results demonstrate the functional instability of REM sleep in first-break, drug naive young adults with schizophrenia and unveil a pattern reminiscent of REM sleep behavior disorder. The significant correlation suggests that schizophrenia and REM sleep share common neuronal control mechanisms. 
24725785	Prolonged poor sleeping quality can decrease women's ability to perform their maternal and family duties after delivery. The aim of this study was to investigate the effects of a Pilates training program on sleep quality in primigravida postpartum women in a randomized clinical trial. Eighty postpartum women were randomly divided into intervention and control groups (n = 40). Home-based 30-min Pilates exercises were started 72 h after the delivery and performed five times per week for consecutive 8 weeks. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) prior to the intervention and 4th and 8th weeks afterwards. The intervention group showed a significant improvement in subjective sleep quality, sleep latency, daytime dysfunction and global PSQI score (P < 0.001); however, there was no difference in sleep duration, habitual sleep efficiency and sleep disturbance between the groups. In conclusion, Pilates exercises appeared to improve sleep quality in primigravida postpartum women.
24725022	Attention-deficit hyperactivity disorder (ADHD) is a complex disorder that can affect individuals across the lifespan. It is associated with substantial heterogeneity in terms of aetiology, clinical presentation and treatment outcome and is the subject of extensive research. Because of this, it can be difficult for clinicians to stay up to date with the most relevant findings and know how best to respond to parents' questions and concerns about the disorder and interventions. This is a narrative review that aims to summarize key findings from recent research into ADHD and its treatment that clinicians can share with families in order to increase their knowledge about ADHD and intervention options. ADHD develops as a result of complex interplay between interdependent genetic and non-genetic factors. The disorder is associated with substantial impairments in functioning and poor long-term outcomes. Pharmacological and non-pharmacological treatment options are available for symptom management and to improve function, but functioning outcomes often fail to normalize in children with ADHD. Despite extensive advances in understanding this complex disorder, it is clear that there is still a long way to go. In particular, we address the need for future non-pharmacological interventions to be more specifically targeted for ADHD symptoms and its commonly associated functioning deficits in order to ensure the best long-term outcomes for children with ADHD. 
24724691	This paper examines the efficacy of non-behavioural and non-pharmacological approaches to the treatment of sleep disturbance in individuals with autism spectrum disorder.A systematic search of electronic databases and reference lists identified eight studies that met inclusion criteria. Studies were evaluated according to (a) treatment used, (b) participants, (c) experimental design, (d) baseline measures, (e) dependent variables, (f) follow-up measures, (g) reliability and treatment integrity, (h) results and certainty of evidence and (i) implications for treatment.	Positive outcomes were reported for the use of massage therapy and vitamin supplements. Aromatherapy was reported to have no effect on sleep. No studies were found that examined other non-traditional treatment approaches, nor did any of the studies provide conclusive evidence.	The limited corpus of evidence and the methodological limitations suggests that the efficacy of non-traditional approaches to treatment of sleep problems in individuals with autism is yet to be demonstrated.	

24724527	The purpose of this study was to profile characteristics of people with traumatic brain injury (TBI) who self-reported arthritis 7 to 24 yr. post-injury. Pre- and post-injury socio-demographic factors, injury-related factors, and postinjury standardized assessments measuring health, activity, and participation outcomes were assessed in a retrospective cohort study of 274 participants. The group self-reporting arthritis had significantly more sleep disturbances, poorer overall health, lower mental health and physical function, and decreased productivity. Also, they were older and reported a shorter length of loss of consciousness from TBI. These resulted suggest that musculoskeletal complaints from long-term survivors of TBI sholud be addressed in post-acute care and could guide future research on arthritis in the TBI population.
24723098	The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways. 
24722664	Adequate sleep is essential for maintaining homeostasis, especially when recovering from an illness; however, studies have shown that sleep disruption and sleep deprivation are common in intensive care unit patients, including children who have sustained burn injury. The purpose of this study was to evaluate the effect of diphenhydramine (DPH) on sleep in pediatric intensive care unit burn patients using Myra Levine's Conservation Model as the organizing framework. For this study, secondary analysis of polysomnography data and retrospective chart review were used. Twelve DPH patients were pair matched in terms of morphine, midazolam, and methadone with 12 non-DPH patients. The data were analyzed using paired t-tests for each dependent variable and χ analysis was used for frequency determinations. There was no difference in demographics between the two groups. DPH patients took 4.3 ± 1.6 minutes to fall asleep whereas non-DPH patients took 15.8 ± 1.6 minutes to achieve sleep onset (P = .06). Patients receiving DPH achieved 297.6 ± 29.9 minutes of total sleep time whereas those not receiving DPH achieved only 209.2 ± 29.9 minutes (P < .05). There was minimal difference in the mean percentage of sleep time in stages 3 and 4 between the two groups. The DPH group did have 50% more rapid eye movement sleep time compared with the non-DPH group. Even though DPH did not result in a statistical improvement in sleep quality, sleep quantity was increased in this study. More research is needed to find an effective sleep intervention in pediatric burn patients. 
24722577	Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM) sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data required that activity of the wake-promoting population modulated the interaction between the REM-on and REM-off populations. This analysis suggests neuronal processes to be targeted in further experimental studies of the regulatory mechanisms of REM sleep. 
24722127	In subjects at high risk for sleep apnea (SA), aldosterone concentrations correlate with severity of SA and primary aldosteronism (PA) is very often diagnosed. Patients with PA show a high prevalence of SA. Treatment of PA either by adrenalectomy (ADX) or mineralocorticoid receptor (MR) blockade is thought to abolish the increased comorbidities. However, no data are available regarding effectiveness of different PA treatments on quality of sleep.This prospective multi-center study included 15 patients with newly diagnosed PA evaluated before and 0.7 ± 0.2 years after treatment initiation, and a second cohort including 81 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Biochemical parameters, 24h blood pressure and three validated self-assessment questionnaires (Giessen Complaint List (GBB-24), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality-Index (PSQI)) were analyzed.	Z-scores of exhaustion tendency of GBB significantly improved in newly diagnosed PA patients after treatment initiation (1.8 ± 1.4 vs. 1.0 ± 1.2, p=0.034). In the second cohort no differences were found in GBB-24, ESS and PSQI. No differences were found in all three questionnaires independently of type of PA therapy. However, female patients scored significantly higher than males in the PSQI (8.7 ± 3.6 vs 5.7 ± 4.2, p<0.005), indicating lower sleep quality, independently of the type of therapy.	For the first time, we analyzed quality of sleep in patients with PA, demonstrating that therapy initiation improves exhaustion tendency. Surprisingly, female PA patients showed significantly more sleep disturbances than male PA patients several years after treatment initiation.	
24721733	Hibernation is a physiological state that by putting vital biological processes at rest enables mammals to protect all organs, especially the brain against ischemic insults and reperfusion injuries. Earlier studies have highlighted the role of hypothalamic (HTH) sites like the periventricular nucleus (Pe) toward sleep-wake and cardiovascular activities of hibernators. In the present work, infusions of Pe with the orexigenic neuropeptide orexin-A (ORX-A) or the novel anti-obesity sympathoinhibitory neuroactive peptide catestatin (CST) have been correlated to differing feeding and motor behaviors in the facultative hibernating hamster Mesocricetus auratus. Behavioral observations showed that treatment with CST provided an anti-obesity activity via the reduction of food intake and body weight for all hibernating states, while ORX-A promoted orexigenic events during mainly the entrance phase. Moreover, hamsters treated with this neuropeptide during the entrance and the arousal hypertensive phases also featured elevated ORX 2 receptor (ORX2R) levels in the third layer of the parietal cortex and lateral HTH (LH), areas involved with feeding, motor plus sleep-wake rhythms. Conversely, ORX-A down-regulated ORX2Rs in the ventromedial (VMH) and supraoptic (SO) HTH nuclei that are associated with anorexigenic effects. Even CST induced mixed ORX2R expression patterns in mostly HTH areas like the evident down-regulation in LH along with the up-regulation in VMH and SO. Overall treatments, especially ORX-A+CST led to reduced neurodegenerative phenomena in HTH supporting their importance together with ORX2Rs in preserving hemodynamic activities, feeding and sleep-wake rhythms of this diencephalic station, which may supply useful therapeutic indications for treating cardiovascular disturbances linked with brain dysfunctions. 
24721551	Recent case reports suggest that zolpidem usage may be associated with infection events. The aim of this study was to determine the risk of infection events in patients with sleep disturbance taking zolpidem in a full 3-year follow-up study.A total of 17474 subjects with a diagnosis of sleep disturbance in 2002 and 2003 were identified, of whom 5882 had used zolpidem after recruitment. A Cox proportional hazard model was used to estimate the 3-year infection event-free rates for the patients using zolpidem and those not using zolpidem after adjusting for confounding factors. To maximize case ascertainment, only patients hospitalized for infection events were included.	A total of 646 patients had had infection events, 331 (5.63%) of whom had been taking zolpidem and 315 (2.71%) had not. Zolpidem usage increased the risk of infection events. After adjustments for gender, age, co-morbidities, and other medications, patients using zolpidem with cDDD 1-28, 29-84, and >84 had hazard ratios of 1.67 (95% CI, 1.32-2.11), 1.91 (95% CI, 1.47-2.49) and 1.62 (95% CI, 1.32-1.98) respectively, compared with patients who did not use zolpidem.	Zolpidem increased the risk of infection events in sleep disturbance patients. This increased risk of infection should be explained to sleep disturbance patients, and prescriptions of zolpidem to chronic insomnia patients should be restricted.	
24720812	Sleep disturbances are recognized as an important health and public health problem that affects physical, mental, and emotional health and well-being. Inhalation of essential oils may be a safe alternative to pharmaceutical interventions for mild to moderate sleep disturbances. Quantitative human studies on the effect of inhaled essential oils on sleep that were published between 1990 to 2012 were reviewed.Ovid Medline, PsychINFO, CINAHL, Science Direct, and PubMed databases were searched to extract articles that evaluated the effect of inhaled essential oils on sleep in humans.	The search yielded 15 quantitative studies, including 11 randomized controlled trials that examined hypnotic effects of inhalation of essential oils. A majority of the study findings suggested a positive effect of essential oils on sleep. Lavender was the most frequently studied essential oil. No adverse events were reported.	Inhalation of essential oils may be considered for people with mild sleep disturbances. Further studies with larger samples and stronger methods and endpoints are needed to build on the findings.	
24717700	This study's purpose was to investigate how young children's and parent/caregivers' oral health-related quality of life and children's dental fears were affected by dental rehabilitation under general anesthesia (DRGA).A consecutive clinical sample of dyads of parents/caregivers and their four- to six-year-old children who received DRGA were surveyed before and after DRGA. Parents/caregivers responded through a self-administered questionnaire [Early Childhood Oral Health Impact Scale (ECOHIS)], and children received a dentist-administered questionnaire [children's fear survey schedule-dental subscale (CFSS-DS)].	The final sample consisted of 311 children/caregiver dyads. One to six teeth were extracted in 91 percent of children. There was a 44 percent decrease in total ECOHIS scores following treatment (P<.001). Overall child impact section scores decreased 34 percent following treatment (P<.001), and family impact section scores decreased 65 percent (P<.001). CFSS-DS anxiety scores after dental treatment were significantly higher for 14 of 15 situations/conditions assessed (P<.001). There was a trend of higher CFSS-DS scores in children who received increasing numbers of extractions.	Children's and parent/caregivers' quality of life improved after the children received dental rehabilitation under general anesthesia, and children's fears increased for all situations tested. The number of extractions the children received was associated with increased levels of fear.	
24717334	Sleep-wake patterns and the electroencephalogram (EEG) during sleep undergo fundamental changes during adolescence. Scientific evidence indicates that these changes represent components of an extensive maturational brain remodeling process. Sleep during periods of brain maturation appears to be particularly important for health and behavior. Adolescents' sleep problems affect their cognitive and psychobehavioral functioning, making insufficient sleep during this developmental stage a significant international health concern. In this review, we summarize some key data concerning developmental changes in sleep behavior and regulation, and the association between sleep EEG changes and brain maturation. This review extends our understanding of adolescent sleep and highlights its significance for healthy development. We discuss the possibility to follow brain maturation and to detect errors in this maturational process by monitoring the developmental sleep EEG changes.
24716856	Chronic pain and sleep disturbance frequently coexist and often complicate the course of treatment. Despite the well-established comorbidity, there are no studies that have investigated concurrent changes in sleep and pain among patients participating in an interdisciplinary chronic pain rehabilitation program (ICPRP). The goal of this study was to investigate the daily changes in sleep and pain among patients participating in an ICPRP.Multilevel modeling techniques were used to evaluate the daily changes in total sleep time (TST) and pain among a sample of 50 patients with chronic noncancer pain participating in the ICPRP.	Increases in TST were predictive of less pain the following treatment day, although daily pain ratings were not predictive of that night's TST. Time in treatment was a significant predictor of both TST and pain reduction, even while controlling for age, gender, anxiety, and depression. Additional analyses revealed significant individual variability in the relationship between TST and next day pain. Individuals with stronger associations between previous night's TST and next day pain were found to experience the greatest treatment benefits overall, in terms of pain reduction and TST.	Our results provide compelling support for individual variability of the pain-sleep relationship in patients with intractable pain conditions participating in an ICPRP. Importantly, these findings suggest that when pain and sleep are comorbid, both must be addressed to reap the maximum response to treatment programs such as an ICPRP.	This study demonstrates the utility of treating sleep problems in patients participating in an interdisciplinary chronic pain rehabilitation program. Results highlight the benefits of accounting for individual variability in the pain-sleep relationship in a clinical setting and targeting sleep interventions for those individuals whose pain and sleep problems are comorbid.	
24716479	Intensive care unit (ICU) patients are known to experience severely disturbed sleep, with possible detrimental effects on short- and long- term outcomes. Investigation into the exact causes and effects of disturbed sleep has been hampered by cumbersome and time consuming methods of measuring and staging sleep. We introduce a novel method for ICU depth of sleep analysis, the ICU depth of sleep index (IDOS index), using single channel electroencephalography (EEG) and apply it to outpatient recordings. A proof of concept is shown in non-sedated ICU patients.Polysomnographic (PSG) recordings of five ICU patients and 15 healthy outpatients were analyzed using the IDOS index, based on the ratio between gamma and delta band power. Manual selection of thresholds was used to classify data as either wake, sleep or slow wave sleep (SWS). This classification was compared to visual sleep scoring by Rechtschaffen & Kales criteria in normal outpatient recordings and ICU recordings to illustrate face validity of the IDOS index.	When reduced to two or three classes, the scoring of sleep by IDOS index and manual scoring show high agreement for normal sleep recordings. The obtained overall agreements, as quantified by the kappa coefficient, were 0.84 for sleep/wake classification and 0.82 for classification into three classes (wake, non-SWS and SWS). Sensitivity and specificity were highest for the wake state (93% and 93%, respectively) and lowest for SWS (82% and 76%, respectively). For ICU recordings, agreement was similar to agreement between visual scorers previously reported in literature.	Besides the most satisfying visual resemblance with manually scored normal PSG recordings, the established face-validity of the IDOS index as an estimator of depth of sleep was excellent. This technique enables real-time, automated, single channel visualization of depth of sleep, facilitating the monitoring of sleep in the ICU.	

24713051	This study examined factors that influence sleep quality in older African American women (N = 181) reporting chronic pain. Participants completed a series of questions assessing demographic and behavioral characteristics, health status, pain intensity, and sleep disturbance. Findings indicated that younger participants and those experiencing poorer physical functioning reported more difficulty sleeping due to pain. Similarly, participants who reported being awakened from sleep due to pain were younger and experienced greater pain intensity. Understanding the relationship between sleep and pain in this group of women may be useful in promoting effective disease management and sleep awareness among patients, caregivers, and healthcare professionals. 

24711162	A prospective longitudinal study to profile patient-reported symptoms during radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) for head and neck cancer was performed. The goals were to understand the onset and trajectory of specific symptoms and their severity, identify clusters, and facilitate symptom interventions and clinical trial design.Participants in this questionnaire-based study received RT or CCRT. They completed the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module before and weekly during treatment. Symptom scores were compared between treatment groups, and hierarchical cluster analysis was used to depict clustering of symptoms at treatment end. Variables believed to predict symptom severity were assessed using a multivariate mixed model.	Among the 149 patients studied, the majority (47%) had oropharyngeal tumors, and nearly one-half received CCRT. Overall symptom severity (P < .001) and symptom interference (P < .0001) became progressively more severe and were more severe for those receiving CCRT. On multivariate analysis, baseline Eastern Cooperative Oncology Group performance status (P < .001) and receipt of CCRT (P < .04) correlated with higher symptom severity. Fatigue, drowsiness, lack of appetite, problem with mouth/throat mucus, and problem tasting food were more severe for those receiving CCRT. Both local and systemic symptom clusters were identified.	The findings from this prospective longitudinal study identified a pattern of local and systemic symptoms, symptom clusters, and symptom interference that was temporally distinct and marked by increased magnitude and a shift in individual symptom rank order during the treatment course. These inform clinicians about symptom intervention needs, and are a benchmark for future symptom intervention clinical trials.	
24709825	The presence of extraintestinal manifestations (EIM) in children with gastrointestinal (GI) food allergy (GIFA) is greatly debated. In the present study we assessed the prevalence of EIM in children with GIFA and investigated whether their presence is helpful in the allergy-focused history-taking process.The medical records of all children with a proven diagnosis of GIFA were reviewed along with those of children diagnosed as having inflammatory bowel disease (IBD) as controls. Data regarding age at onset, age at diagnosis, atopic family history, atopic comorbidities, GI symptoms, and EIM were recorded.	Data from 436 children with GIFA and 74 children with IBD were included in the analysis. EIM were documented in 368 children with GIFA, including fatigue (53.0%), allergic shiners (49.1%), mouth ulcers (39.0%), joint pain/hypermobility (35.8%), poor sleep (34.4%), night sweats (34.4%), headache (22.7%), and bed-wetting (17.7%). The proportion of patients with EIM was higher in the GIFA group compared with that in the IBD group (368/436 [84.4%] vs 40/74 [54.1%]; P < 0.001). Segregating the GIFA group into children with and without atopic comorbidities, both atopic (276/30; 89.9%) and nonatopic (93/130; 71.5%) children showed higher proportion of EIM than children with IBD ([40/74; 54.1%], P < 0.01 and <0.05, respectively).	GIFA are commonly associated with a wide range of EIM, which appear to represent important and specific clinical features of this group of conditions. Their recognition in taking an allergy-focused history may play an important role for both diagnosis and management.	
24709308	We aimed to identify the effect of environmental factors on sleep in the summertime in Japan.A self-reported questionnaire survey was conducted in Japan. Age of participants ranged from 20 to 70 years.	The mean Pittsburgh Sleep Quality Index (PSQI) score was 4.9 (±2.7), and 123 (35.0%) participants had scores of >5. According to the results of multivariate logistic regression analysis, the adjusted odds ratio (aOR) for PSQI scores of >5 without installation of air conditioner was 1.8 (95% confidence interval [CI], 1.0-3.3; P<.05), use of a light bulb was 3.7 (95% CI, 1.1-12.6; P<.05), and noise was 2.1 (95% CI, 1.1-4.1; P<.05) after controlling for several confounding variables. Difficulty initiating sleep (DIS) was associated with installation of an air conditioner (1 [reference] to 3 [aOR, 2.5 {95% CI, 1.2-5.1}] and 4 [aOR, 2.8 {95% CI, 1.1-7.1}]) and noise (1 [reference] to 3 [aOR, 2.4 {95% CI, 1.0-5.9}] and 4 [aOR, 8.8 {95% CI, 3.1-25.0}]). Difficulty maintaining sleep (DMS) was associated with installation of a fan (1 [reference] to 2 [aOR, 0.4 {95% CI, 0.2-0.8}] and noise (1 [reference] to 3 [aOR, 2.3 {95% CI, 1.0-5.3}]) after controlling for several confounding variables.	Our finding using analysis of the association between residential environments and subjective sleep statuses, which determined that the installation of an air conditioner and lighting equipment might affect sleep, may be useful to discuss sleep environments and improve sleep quality.	
24709182	The prevalence of sleep disorders has been shown to be high in patients with chronic dialysis patients and may contribute to impaired quality of life and higher mortality in this population. However, there are few data on the relationship of sleep disorders and their risk factors in chronic dialysis patients. The aim of this study was to evaluate the relationship of sleep disorders and their risk factors in chronic dialysis patients.A total of 42 continuous ambulatory peritoneal dialysis (CAPD) patients were involved in this cross-sectional study. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Restless legs syndrome (RLS) was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group. And depression was assessed by Hamilton depression scale. General information and laboratory data were collected.	The prevalence of sleep disorders was 47.6% in the CAPD patients. According to the PSQI, the 42 CAPD patients were divided into sleep disturbance group and non-sleep disorders group. There were no significant differences in age, gender, dialysis duration, hemoglobin, serum creatinine, urea nitrogen, β2-microglobulin, parathyroid hormone, calcium, and phosphorus between CAPD patients with sleep disorders and those without sleep disorders. But the level of serum albumin (Alb) in CAPD patients with sleep disorders was significantly lower than that in CAPD patients without sleep disorders (31.3 ± 1.4 vs. 34.3 ± 3.7, t = 3.603, P = 0.001) . And the prevalence of RLS and depression was significantly higher than that in CAPD patients without sleep disorders (RLS: 11/22 vs. 1/20, χ(2) = 10.395, P = 0.001; depression: 7/22 vs. 1/20, χ(2) = 4.886, P = 0.027). In CAPD patients with RLS, the prevalence of sleep disorders was significantly higher than that in CAPD patients without RLS (11/22 vs. 11/30, χ(2) = 10.395, P = 0.001). And in CAPD patients with depression, the prevalence of sleep disorders was significantly higher than that in CAPD patients without depression (7/8 vs. 15/34, χ(2) = 4.886, P = 0.027). In CAPD patients, bivariate correlation analysis showed that sleep disorders was negatively correlated with serum Alb (r = -0.606, P = 0.000) and positively correlated with RLS (r = 0.497, P = 0.001) and depression (r = 0.341, P = 0.029). Multivariate regression analysis revealed that the odds ratio of RLS, depression, and low serum Alb was 22.900, 42.209, and 0.597, respectively.	The prevalence of sleep disorders was relatively high in CAPD patients. RLS, depression, and low serum Alb were the risk factors for CAPD patients with sleep disorders.	
24708924	Neurons containing the hypothalamic peptides orexin-A (hypocretin 1) and melanin-concentrating hormone (MCH) have been reported numerous roles in the regulation of the sleep-wake cycle, energy balance and feeding behavior. We investigated the response of these cells to repeated administration of low doses of endotoxin lipopolysaccharide (LPS) in mice. Adult male C57/6J mice where intraperitoneally (i.p.) injected with either LPS or phosphate-buffered saline (PBS) weekly for either 4 or 8 weeks, and afterwards were sacrificed at different time intervals from last injection. A significant drop in orexin-containing neuron number, but not in numbers of MCH or neuronal nuclear antigen (NeuN)-immunoreactive neurons, was observed after 8 weeks of LPS treatment, as compared to PBS treatment. Orexin expression entirely returned to control levels 30 days after the last LPS injection in mice treated for 8 weeks. These data strongly suggest the occurrence of selective alterations of orexinergic system, reversible over time, following repeated and intermittent systemic inflammatory challenge in mice. 
24708298	Despite the predominance of sleep in early infancy, developmental science has yet to play a major role in shaping concepts and theories about sleep and its associated ultradian and circadian rhythms. Here we argue that developmental analyses help us to elucidate the relative contributions of the brainstem and forebrain to sleep-wake control and to dissect the neural components of sleep-wake rhythms. Developmental analysis also makes it clear that sleep-wake processes in infants are the foundation for those of adults. For example, the infant brainstem alone contains a fundamental sleep-wake circuit that is sufficient to produce transitions among wakefulness, quiet sleep, and active sleep. In addition, consistent with the requirements of a "flip-flop" model of sleep-wake processes, this brainstem circuit supports rapid transitions between states. Later in development, strengthening bidirectional interactions between the brainstem and forebrain contribute to the consolidation of sleep and wake bouts, the elaboration of sleep homeostatic processes, and the emergence of diurnal or nocturnal circadian rhythms. The developmental perspective promoted here critically constrains theories of sleep-wake control and provides a needed framework for the creation of fully realized computational models. Finally, with a better understanding of how this system is constructed developmentally, we will gain insight into the processes that govern its disintegration due to aging and disease.

24705593	Although nocturnal disturbances are increasingly recognized as an integral part of the continuum of daytime manifestations of Parkinson's disease (PD), there is still little evidence in the medical literature to support the occurrence of these complex phenomena in patients with atypical parkinsonian disorders (APDs). Based on the anatomical substrates in APDs, which are considered to be more extensive outside the basal ganglia than in PD, we might expect that patients with APDs encounter the whole range of nocturnal disturbances, including motor, sleep disorders, autonomic dysfunctions, and neuropsychiatric manifestations at a similar, or even greater, frequency than in PD. This article is a review of the current literature on the problems at nighttime of patients with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. MEDLINE, life science journals and online books were searched by querying appropriate key words. Reports were included if the studies were related to nocturnal manifestations in APDs. Forty articles fulfilled the selection criteria. Differences between these symptoms in APDs and PD are highlighted, given the evidence available about each manifestation. This analysis of nocturnal manifestations of APDs suggests the need for future studies to address these issues to improve the quality of life not only of patients with APDs but the caregivers who encounter the challenges of supporting these patients on a daily basis. 
24704178	The study compared sleep disturbances and behavior problems in school-age children with and without juvenile idiopathic arthritis (JIA). Children 6-to-11 years of age, with (n=70) and without (n=46) JIA, and their parent participated. Parents completed questionnaires on sleep habits and behavior problems. Compared to control children, JIA children had significantly higher total sleep disturbances and higher scores on six of eight subscales. Sleep disturbances predicted externalizing behavior problems, controlling for age, medications, study group, and pain. Sleep disturbances such as, sleep disordered breathing are often overlooked or unrecognized in JIA and may contribute to behavioral problems.
24703829	Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up. They are usually painless, but associated with fear and distress. In spite of the fact that its characteristic symptomatology was first described approximately 150 y ago, exploding head syndrome has received relatively little empirical and clinical attention. Therefore, a comprehensive review of the scientific literature using Medline, PsycINFO, Google Scholar, and PubMed was undertaken. After first discussing the history, prevalence, and associated features, the available polysomnography data and five main etiological theories for exploding head syndrome are summarized. None of these theories has yet reached dominance in the field. Next, the various methods used to assess and treat exploding head syndrome are discussed, as well as the limited outcome data. Finally, recommendations for future measure construction, treatment options, and differential diagnosis are provided.
24702469	To test if the current model of diffuse brain injury produces chronic sleep disturbances similar to those reported by TBI patients.Adult male C57BL/6 mice were subjected to moderate midline fluid percussion injury (n = 7; 1.4 atm; 6-10 minutes righting reflex time) or sham injury (n = 5). Sleep-wake activity was measured post-injury using a non-invasive, piezoelectric cage system. Chronic sleep patterns were analysed weekly for increases or decreases in percentage sleep (hypersomnia or insomnia) and changes in bout length (fragmentation).	During the first week after diffuse TBI, brain-injured mice exhibited increased mean percentage sleep and mean bout length compared to sham-injured mice. Further analysis indicated the increase in mean percentage sleep occurred during the dark cycle. Injury-induced changes in sleep, however, did not extend beyond the first week post-injury and were not present in weeks 2-5 post-injury.	Previously, it has been shown that the midline fluid percussion model used in this study immediately increased post-traumatic sleep. The current study extended the timeline of investigation to show that sleep disturbances extended into the first week post-injury, but did not develop into chronic sleep disturbances. However, the clinical prevalence of TBI-related sleep-wake disturbances warrants further experimental investigation.	
24701564	Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor "lansoprazole" on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg) were injected intraperitoneally in the same animal (n = 7) and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was 9.26 ± 1.03 and 9.09 ± 0.54, respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle) and 34.21% (from low dose). Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker "amiloride" (10 mg/kg; i.p.) (n = 5) did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.
24700622	The chronic pain (CP) and chronic multi-site pain (CMP) condition is a highly prevalent health problem. Several studies have reported a high (31-64%) prevalence of co-morbid restless legs syndrome (RLS) in patients with fibromyalgia, one specifically defined form of chronic widespread pain. The current study explored the association between CMP and RLS.The study included 4040 respondents to a postal questionnaire sent to 10,000 women in the age range of 18-64 years and randomly selected from the general population. Complete questionnaire data on type (acute/chronic), degree (mild to severe) and spreading (0-5 body zones) of pain, as well as RLS symptoms (validated questionnaire), were obtained from 3060 subjects. Information on lifestyle, anthropometrics, co-morbidities and medication was collected.	RLS prevalence increased from 9.6% in subjects with no report of pain to 23,9%, 26.4%, 39.2%, 44.9% and 54.8% in those reporting one, two, three, four and five pain areas, respectively (p < 0.001). Further, RLS prevalence increased from 9.6% (no pain) to 27.9%, 37.9% and 42.4% in subjects with mild, moderate and severe chronic pain (p < 0.001). Multi-site pain, pain localized in the leg, extended pain duration and co-morbid psychiatric disorder were all independently associated with a RLS diagnosis in a multiple regression analysis.	The prevalence of RLS increased progressively with pain severity and even more sharply with the degree of pain spreading in women recruited from the general population. Both acute and chronic pain was associated with RLS-related symptoms.	
24700387	An effective and safe treatment of insomnia in patients with neuropathic pain remains an unmet need. Melatonin and its analogs have been shown to have both analgesic and hypnotic effects; however, capacity of them on sleep disturbance with neuropathic pain as well as the precise mechanism is unclear.The present study evaluated effects of piromelatine, a novel melatonin receptor agonist, on sleep disturbance in a neuropathic pain-like condition as well as the underlying mechanisms.	A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSL) was employed. The antinociceptive and hypnotic effects of piromelatine were evaluated by measurement of thermal hyperalgesia, mechanical allodynia, and electroencephalogram (EEG) recordings in PSL mice. Pharmacological approaches were used to clarify the mechanisms of action of piromelatine.	PSL significantly lowered thermal and mechanical latencies and decreased non-rapid eye movement (NREM) sleep, and PSL mice exhibited sleep fragmentation. Treatment with 25, 50, or 100 mg/kg of piromelatine significantly prolonged thermal and mechanical latencies and increased NREM sleep. Moreover, the antinociceptive effect of piromelatine was prevented by melatonin antagonist luzindole, opioid receptor antagonist naloxone, or 5HT1A receptor antagonist WAY-100635. The hypnotic effect of piromelatine was blocked by luzindole but neither by naloxone nor WAY-100635.	These data indicate that piromelatine is an effective treatment for both neuropathic pain and sleep disturbance in PSL mice. The antinociceptive effect of piromelatine is likely mediated by melatonin, opioid, and 5HT1A receptors; however, the hypnotic effect of piromelatine appears to be mediated by melatonin receptors.	
24699238	To characterize sleep and its relationship with disability and pain in patients with spine pathology.A survey study.	A university-based hospital spine clinic.	Subjects (N=121) with mixed-etiology spine pathology.	Not applicable.	Self-reported disability (Oswestry Disability Index [ODI]), back and leg pain intensity, the effect of back or leg pain on function, and sleep (Pittsburgh Sleep Quality Index [PSQI]) assessments were completed.	Severe disability was evident with a mean ODI ± SD of 54.9±14, with mean pain intensities ± SD of 50±30 mm and 54±27 mm of 100mm for the leg and back, respectively. The mean PSQI ± SD was 10.4±5.3, with 87% of participants scoring greater than the sleep-disordered threshold of 5. PSQI was correlated to ODI (r=.53, P<.001), and ODI without the sleep component (r=.47, P<.001). Six of the subscales of PSQI were all also significantly correlated to ODI (.25<r<.42, P<.05). Stepwise regression (ODI dependent variables; PSQI, pain intensity and function, age, body mass index as independent variables) was performed. PSQI was retained in the model along with 2 pain measures (r(2)=.50, P<.001). Substitution of the 7 subscales for the overall PSQI score revealed 2 subscales (sleep quality, use of sleep medications) as predictors of ODI (r(2)=.490, P<.001).	Despite its being intuitive that sleep disorders will be present in patients with spinal disorders, it was surprising that sleep quality was an independent predictor of disability along with pain. Furthermore, sleep quality is more closely correlated to disability than leg pain, which is the current focus of medical interventions.	
24696217	Sleep disturbances in Parkinson's disease and parkinsonism (such as atypical parkinsonian disorders like multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies and corticobasal degeneration) are multifactorial and as such treatment needs to be tailored to the specific patient case and sleep dysfunction. One also has to consider drug-related effects on sleep architecture. This article provides an overview of the therapeutic options for nocturnal problems in Parkinson`s disease and atypical parkinsonian disorders. 
24695508	Up to 50% of children will experience a sleep problem. Early identification of sleep problems may prevent negative consequences, such as daytime sleepiness, irritability, behavioral problems, learning difficulties, motor vehicle crashes in teenagers, and poor academic performance. Obstructive sleep apnea occurs in 1% to 5% of children. Polysomnography is needed to diagnose the condition because it may not be detected through history and physical examination alone. Adenotonsillectomy is the primary treatment for most children with obstructive sleep apnea. Parasomnias are common in childhood; sleepwalking, sleep talking, confusional arousals, and sleep terrors tend to occur in the first half of the night, whereas nightmares are more common in the second half of the night. Only 4% of parasomnias will persist past adolescence; thus, the best management is parental reassurance and proper safety measures. Behavioral insomnia of childhood is common and is characterized by a learned inability to fall and/or stay asleep. Management begins with consistent implementation of good sleep hygiene practices, and, in some cases, use of extinction techniques may be appropriate. Delayed sleep phase disorder is most common in adolescence, presenting as difficulty falling asleep and awakening at socially acceptable times. Treatment involves good sleep hygiene and a consistent sleep-wake schedule, with nighttime melatonin and/or morning bright light therapy as needed. Diagnosing restless legs syndrome in children can be difficult; management focuses on trigger avoidance and treatment of iron deficiency, if present. 
24693819	College students regularly report increased sleep disturbances as well as concomitant reductions in performance (e.g., academic grades) upon entering college. Sleep hygiene refers to healthy sleep practices that are commonly used as first interventions in sleep disturbances. One widely used practice of this sort involves arranging the sleep environment to minimize disturbances from excessive noise and light at bedtime. Communal sleep situations such as those in college residence halls do not easily support this intervention. Following several focus groups, a questionnaire was designed to gather self-reported information on sleep disturbances in a college population. The present study used The Young Adult Sleep Environment Inventory (YASEI) and sleep logs to investigate the sleep environment of college students living in residential halls. A summary of responses indicated that noise and light are significant sleep disturbances in these environments. Recommendations are presented related to these findings.
24693810	Evening orientation and sleep duration have been linked with aggression and problematic behaviors, but no study has used an explicit aggression questionnaire. The present study used the Buss-Perry Aggression Questionnaire based on physical aggression, verbal aggression, anger, and hostility, as well as questionnaires on the timing of sleep and sleep duration to assess this relationship in young adult men. The Composite Scale of Morningness was used to assess circadian preference; sleep-wake variables (wake time and sleep onset time on weekdays and on weekend days) were used to calculate midpoint of sleep, social jetlag, and sleep duration. Results indicated that sleep duration correlated negatively with verbal aggression, physical aggression, and anger. Short sleepers were more aggressive. Using multivariate analysis of variance, shorter sleep duration was a significant predictor of verbal aggression and anger. Concerning physical aggression, social jetlag also contributed to the model. Morningness-eveningness was associated with the hostility scale with eveningness related to higher hostility. Men scored higher than women in physical and verbal aggression.
24693600	U.S. veterans present with complex medical and psychosocial concerns postdeployment. Identification of psychosocial concerns is necessary for appropriate and targeted social work interventions to improve delivery and receipt of health care through the U.S. Department of Veterans Affairs. The purpose of this article is to identify specific psychosocial concerns of veterans of Operations Iraqi Freedom and Enduring Freedom (OIF/OEF) presenting at the War Related Illness and Injury Study Center. A retrospective chart review of psychosocial concerns from all OIF/OEF veterans seen fromJune 2008 toJune 2010 provided data for this mixed methods study. Veterans in the sample (N= 356) reported an average of 5.2 psychosocial concerns (SD = 2.32, range = 0 to 11). The most commonly reported concerns were pain (72 percent), sleep (62 percent), cognition (61 percent), vocational issues (53 percent), education (49 percent), finances (42 percent), relationships (37 percent), anger (30 percent), substance abuse (23 percent), and social support (20 percent), though these categories were not exclusive and many veterans endorsed more than one category. Multiple psychosocial concerns reported by veterans suggest the need for targeted social work intervention.
24691757	Changes in a subject's state have been shown to modulate the perceptual update of his or her action capabilities. In parallel, sleep deprivation impairs in cognitive functions. It involves common neural structures that support the perception of successfully achieving a motor task. Thus, the study investigated the effect of 24 h of sleep deprivation on the perception of action capabilities. Twenty-four healthy participants were randomly separated into two groups (control group vs. 24 h sleep deprivation group). Participants in the control group slept at home according to their habitual sleep-wake schedule. The 24-h sleep deprivation group stayed awake in the laboratory. Participants estimated the limit of their maximal height of stepping-over a bar before and after the sleep intervention. These estimations were compared to each participant's actual maximal stepping-over height. Physical performance (measured by maximal voluntary quadriceps contraction and repetitive vertical jumping tests) and perceptual inhibition tests (measured by choice reaction time tasks) were also performed for three sessions at three time points t 0, t +12h, and t +24h with t 0 = 8:00 a.m. for all participants. Participants in the 24-h sleep deprivation group showed impairments in perceived over-stepping performance and impaired cognitive functioning (higher reaction time), while no changes were observed in actual performance in the over-stepping, voluntary quadriceps contraction, or jumping tasks. The cognitive processing of inputs that specify the estimated consequences of motor action is discussed as the main explanation for the inability to successfully update the perception of action capabilities after sleep deprivation.
24691298	To identify factors that influence diurnal and sleep/wake seizure timing in children undergoing tapered drug withdrawal in an epilepsy monitoring unit.Medical charts of patients that underwent video-EEG were reviewed. Seizures were evaluated based on their occurrence in three-hour time intervals (bins) and between wakefulness and sleep. Patients were classified according to EEG localisation and age: infants (≤3 years), children (3-12 years), and adolescents (>12-21 years). Analysis utilising generalised estimating equations with a negative binomial distribution was performed.	A total of 390 patients (188 girls; mean age: 9.2 years; SD: 6.0) had 1,754 seizures. Generalised seizures (109 patients; 490 seizures) occurred more during wakefulness (p<0.001) and during the day (p<0.001). Modelling revealed a greater occurrence of seizures at night with increasing age (p=0.046). Temporal lobe seizures (62 patients; 271 seizures) occurred overall more frequently during wakefulness (p=0.03). Frontal lobe seizures (41 patients; 184 seizures) occurred more frequently during wakefulness in infants (p<0.05) and more frequently during sleep in adolescents (p<0.0001). Adolescents with frontal lobe seizures were 3.6 times more likely to have seizures during sleep compared to other children (95% CI: 1.8-7.2).	These findings are suggestive of changes in circadian rhythmicity that may alter seizure susceptibility in different age groups. The results may assist in prediction of periods of greatest seizure propensity.	
24687357	Frequency of cognitive impairment among people over 65 years old in community pharmacy. Study of asssociated factors, referral of cases to the specialist and inclusion in a program of health education.Cross-sectional study of prevalence, frequency, conducted in four pharmacies (two urban and two rural pharmacies) in the Autonomous Community of Valencia.	people over 65 years old who come to the pharmacy and who agree to participate in the study after signing an informed consent. It is used as the initial screening test, the Short Portable Mental State Questionnaire of Pfeiffer. Pfeiffer positive cases undergo a second test (Mini-Mental State Examination, NORMACODEM version). A questionnaire designed specifically for the study has been used to collect information. It includes questions to gain demographic data, questions on lifestyle and chronic diseases. We used analysis logistic regression multilevel.	245 patients have participated (76% of respondents). 12.65% were detected to have cognitive impairment. In the Logistic regression analysis multivariate there is a relation between cognitive impairment and some variables: age, lack of reading habit, unusual reading habit, sleeping less than 6 or more than 8 hours a day. Only 12.9% wanted to be referred for clinical evaluation and 42% were included in a cognitive training program.	There are asssociation between lifestyle habits that are modifiable and cognitive impairment.	
24687189	To investigate the prevalence of and contributors to poor sleep quality in patients with mild cognitive impairment (MCI).Data were collected for 158 patients meeting the criteria for MCI. Measures included the Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Mini-Mental State Examination. Demographic, lifestyle, medication, and substance use data were also collected.	A total of 63% of patients with MCI demonstrated sleep disturbance, a significantly higher rate than that of the controls (44%; chi-square = 8.77; P = .003). Depressive symptoms, cognition, antidepressant usage, alcohol consumption, age, and education were identified as significant predictors of self-reported sleep quality in patients with MCI (R(2) = .327, F 6,145 = 11.729, P < .0001).	Sleep disturbance occurs in around two-thirds of patients with MCI. Interventions addressing depression, cognition, and substance and medication use may improve sleep quality in MCI.	
24683060	The aim of this study is to assess the mutual relationships between burnout and sleep disorders in students in the preclinical phase of medical school.This study collected data on 127 medical students who filled in the Maslach Burnout Inventory-Student Survey, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Inventory, and Beck Anxiety Inventory. Hierarchical logistic regressions tested the reciprocal influence between sleep disorders and burnout, controlling for depression and anxiety.	Regular occurrence of emotional exhaustion, poor sleep quality, and excessive daytime sleepiness affected 60, 65, and 63% of medical students, respectively. Emotional exhaustion and daytime sleepiness influenced each other. Daytime sleep dysfunctions affected unidirectionally the occurrence of cynicism and academic efficacy. The odds of emotional exhaustion (odds ratio (OR)=1.21, 95% confidence interval (CI)=1.08 to 1.35) and cynicism (OR=2.47, 95% CI=1.25 to 4.90) increased when daytime sleepiness increased. Reciprocally, the odds of excessive daytime sleepiness (OR=2.13, 95% CI=1.22 to 3.73) increased when emotional exhaustion worsened. Finally, the odds of academic efficacy decreased (OR=0.86, 95% CI=0.75 to 0.98) when daytime sleepiness increased.	Burnout and sleep disorders have relevant bidirectional effects in medical students in the early phase of medical school. Emotional exhaustion and daytime sleepiness showed an important mutual influence. Daytime sleepiness linked unidirectionally with cynicism and academic efficacy.	
24682900	To assess the influence of craniopharyngioma or consequent surgery on melatonin secretion, and the association with fatigue, sleepiness, sleep pattern and sleep quality.Cross-sectional study.	A total of 15 craniopharyngioma patients were individually matched to healthy controls. In this study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns were characterised by actigraphy and sleep diaries recorded for 2 weeks. Sleepiness, fatigue, sleep quality and general health were assessed by Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Short-Form 36.	Patients had increased mental fatigue, daytime dysfunction, sleep latency and lower general health (all, P≤0.05), and they tended to have increased daytime sleepiness, general fatigue and impaired sleep quality compared with controls. The degree of hypothalamic injury was associated with an increased BMI and lower mental health (P=0.01). High BMI was associated with increased daytime sleepiness, daytime dysfunction, mental fatigue and lower mental health (all, P≤0.01). Low midnight melatonin was associated with reduced sleep time and efficiency (P≤0.03) and a tendency for increased sleepiness, impaired sleep quality and physical health. Midnight melatonin remained independently related to sleep time after adjustment for cortisol. Three different patterns of melatonin profiles were observed; normal (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients with absent midnight peak had impaired sleep quality, increased daytime sleepiness and general and mental fatigue.	Craniopharyngioma patients present with changes in circadian pattern and daytime symptoms, which may be due to the influence of the craniopharyngioma or its treatment on the hypothalamic circadian and sleep regulatory nuclei.	
24682359	Nocturnal manifestations of Parkinson's disease (PD) are myriad, have diverse etiologies and include motor, sleep, urinary, and neuropsychiatric symptoms which are often associated with daytime somnolence. While most patients perceive these symptoms as troublesome, the recognition of nocturnal problems related to PD is still low in clinical practice. We conducted a survey using semi-structured interviews and self-rated questionnaires of 215 consecutive patients with PD enrolled in three centers in Thailand to determine the prevalence and risk factors of nocturnal disabilities and their relationship to daytime symptoms. We found that 96.6% of patients reported the presence of nocturnal symptoms as determined by the modified version of Parkinson's Disease Sleep Scale (MPDSS). Our survey indicated that the most frequent and distressing symptom was the interruption of sleep to pass urine (56.7%, 4.4 ± 3.9). The severity of symptoms revealed in the MPDSS increased along with the disease duration (p < 0.05) and Hoehn and Yahr stages (p = 0.01). There were similar to findings of the Nocturnal Akinesia Dystonia and Cramp Score (NADCS) where patients with advanced disease had significantly higher NADCS scores than early/moderate disease (p < 0.001). There was a significant correlation of total MPDSS scores with the total scores of the 9-item Wearing-Off Questionnaire (WOQ-9); (r = -0.43, p < 0.05) [motor (r = -0.35, p < 0.05) and nonmotor subscores (r = -0.43, p < 0.05)]; total nonmotor symptoms (NMS) scores (r = -0.55, p < 0.05); Parkinson's Disease Questionnaire-8 Summary Index (PDQ-8 SI) (r = -0.52, p < 0.05); and the total NADCS (r = -0.35, p < 0.05). Multiple regression analysis identified PDQ-8 SI (β = -0.27, p = 0.005) as the most significant predictor of nocturnal manifestations of PD, followed by the nonmotor subscore of WOQ (β = -0.24, p = 0.006), and the NMS item 20 (feeling light-headed, dizzy, or weak when standing from sitting or lying) (β = -0.22, p = 0.003). Our study found that nocturnal symptoms of PD are very common and we suggest that good clinical practice should include a comprehensive review of nighttime manifestations, particularly for those patients who already experience "wearing-off" symptoms.
24682206	Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss-related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was no longer present when sleep pressure was reduced by the application of multiple naps. Concomitantly, well-being was worse in the G/A genotype under sleep loss when compared to the nap protocol, and n-back working memory performance appeared to be specifically susceptible to sleep-wake manipulation in this genotype. When considering psychomotor vigilance performance, however, a higher sensitivity to sleep-wake manipulation was detected in homozygous participants, but specifically at the end of the night and only for optimal task performance. Although these data are based on a small sample size and hence require replication (12 G/A- and 12 G/G-allele carriers), they confirm the assumption that interindividual differences regarding the effect of sleep manipulation highly depend on the cognitive task and circadian phase, and thus emphasize the necessity of a multimethodological approach. Moreover, they indicate that napping might be suitable to counteract endogenously heightened sleep pressure depending on the neurobehavioral domain.
24681431	Different approaches have been followed to characterize the role of 5-hydroxytryptamine (serotonin) receptor 7 (5-HT7) in the regulation of sleep-wake behavior: (1) 5-HT7 receptor knockout mice spend less time in rapid eye movement sleep than their wild-type counterparts, mainly during the light period. In contrast, there is no difference between the genotypes in time spent in wakefulness or slow-wave sleep. (2) Systemic administration of the selective 5-HT7 receptor agonist LP-211 significantly increased wakefulness (time spent awake) and reduced rapid eye movement sleep in the rat. Direct infusion of LP-211 into the dorsal raphe nucleus, locus coeruleus nucleus, basal forebrain (horizontal limb of the diagonal band of Broca), or laterodorsal tegmental nucleus also produced a decrease in rapid eye movement sleep. Additionally, microinjection of the 5-HT7 receptor agonist into the basal forebrain augmented the time animals remained awake. Local injection of the 5-HT7 receptor agonist LP-44 into the dorsal raphe nucleus also suppressed rapid eye movement sleep in the rat. (3) A similar reduction of rapid eye movement sleep has been described following intraperitoneal injection of the selective 5-HT7 receptor antagonists SB-269970 and SB-656104 in the rat and oral administration of the 5-HT7 receptor antagonist NJ-18038683 to rat and man. Local microinjection of SB-269970 into the dorsal raphe nucleus and basal forebrain also induced a decrease in rapid eye movement sleep in the rat. This tends to suggest that the on-off (activation/blockade), two-state ligand-receptor interaction model is not tenable for the 5-HT7 receptor.
24679947	In this study we report the results of surgery in a large population of patients affected by drug-resistant focal sleep related epilepsy (SRE) and the identified prognostic factors. We conducted a retrospective analysis of a case series of 955 patients operated on for drug-resistant focal epilepsy from 1997 to 2009. Ninety-five patients with focal SRE and a follow-up of at least 2 years were identified. Presurgical, surgical and histopathological variables were analyzed. Risk of seizures recurrence was assessed by univariate and multivariate analysis. Mean age at epilepsy onset was 5.6 ± 4.9 years. MRI revealed a focal abnormality in 78.9% of cases. Sixty-two percent of patients required a Stereo-EEG investigation. The cortical resection involved the frontal lobe in 61.1% of cases, while in 38.9% an extrafrontal resection was performed. Focal cortical dysplasia (FCD) type II was the most frequent histopathological finding. Mean postoperative follow-up was 82.3 months. Seventy-three patients (76.8%) were in Engel's class I. At univariate analysis, variables associated with a favorable outcome were: absence of Stereo-EEG investigation; positive MRI; complete removal of the epileptogenic zone (EZ); presence of FCD type II and FCD type IIb. A diagnosis of FCD type I was associated with postoperative recurrence of seizures. Multivariate analysis identified the complete removal of the EZ and FCD type I as independent predictors of a favorable and unfavorable outcome respectively. SRE can frequently originate outside the frontal lobe and a favorable surgical outcome is achieved in three-fourths of cases independently from the location of the EZ.
24679223	Little is known about human entrainment under natural conditions, partly due to the complexity of human behavior, torn between biological and social time and influenced by zeitgebers (light-dark cycles) that are progressively "polluted" (and thereby weakened) by artificial light. In addition, data about seasonal variations in sleep parameters are scarce. We, therefore, investigated seasonal variation in cross-sectional assessments of sleep/wake times of 9765 subjects from four European populations (EGCUT = Estonian Genome Centre, University of Tartu in Estonia; KORA = Cooperative Health Research in the Region of Augsburg in Germany; KORCULA = The Korcula study in Croatia; and ORCADES = The Orkney Complex Disease Study in Scotland). We identified time-of-year dependencies for the distribution of chronotype (phase of entrainment assessed as the mid-sleep time point on free days adjusted for sleep deficit of workdays) in cohorts from Estonia (EGCUT) and Germany (KORA). Our results indicate that season (defined as daylight saving time - DST and standard zonetime periods - SZT) specifications of photoperiod influence the distribution of chronotype (adjusted for age and sex). Second, in the largest investigated sample, from Estonia (EGCUT; N = 5878), we could detect that seasonal variation in weekly average sleep duration was dependent on individual chronotype. Later chronotypes in this cohort showed significant variation in their average sleep duration across the year, especially during DST (1 h advance in social time from the end of March to end of October), while earlier chronotypes did not. Later chronotypes not only slept less during the DST period but the average chronotype of the population assessed during this period was earlier than during the SZT (local time for a respective time zone) period. More in detail, hierarchical multiple regression analyses showed that, beyond season of assessment (DST or SZT), social jetlag (SJl; the discrepancy between the mid sleep on free and work days - which varied with age and sex) contributed to a greater extent to the variation in sleep duration than chronotype (after taking into account factors that are known to influence sleep duration, i.e. age, sex and body mass index). Variation in chronotype was also dependent on age, sex, season of assessment and SJl (which is highly correlated with chronotype - SJl was larger among later chronotypes). In summary, subjective assessments of sleep/wake times are very reliable to assess internal time and sleep duration (e.g. reproducing sleep duration and timing tendencies related to age and sex across the investigated populations), but season of assessment should be regarded as a potential confounder. We identified in this study photoperiod (seasonal adaptation) and SJl as two main factors influencing seasonal variation in chronotype and sleep duration. In conclusion, season of assessment, sex and age have an effect on epidemiological variation in sleep duration, chronotype and SJl, and should be included in studies investigating associations between these phenotypes and health parameters, and on the development of optimal prevention strategies. 
24677015	The purpose was to document 4 patients with different epilepsy syndromes, showing electrical status epilepticus during sleep (ESES), without marked cognitive and behavioral regression in the long-term follow-up. The mean age at onset of seizures was 8 years. Absences, myoclonic, focal motor, or generalized tonic - clonic seizures and drop attacks were the prominent seizure types. The neurological examination and neuroimaging findings revealed no abnormality. Focal epileptiform electroencephalographic (EEG) activity was seen in 3 cases, whereas generalized photosensitive epileptic discharges were detected in 1 patient with juvenile myoclonic epilepsy. Neuropsychological evaluations of all cases were within the normal range, and deterioration in mental status was not observed during their mean follow-up duration of 14 years. Our data support the view that ESES can emerge along with different types of childhood epilepsy syndromes, including idiopathic generalized epilepsies, and may not always be a poor prognostic factor. 
24676018	To evaluate the frequency of sleep disorders, such as obstructive sleep apnea, restless leg syndrome and insomnia in overweight/obese postmenopausal women seen in a climacteric sleep disorders clinic.Thirty-four postmenopausal women were selected using the following inclusion criteria: age between 50 and 70 years; at least 12 months of amenorrhea; body mass index (BMI) greater than or equal to 25 kg/m2; and sleep-related complaints with at least one previous polysomnography. Patients provided responses to 6 questionnaires related to sleep characteristics and menopausal symptoms. Weight and height were measured using standardized scales, and abdomen and hip circumferences were also measured. The statistical analyses were performed using the χ² test for qualitative variables and using Student's t-test for quantitative variables.	Patients' characteristics were as follows: mean age of 60.35 years; mean BMI of 31.62; an average of 11.61 postmenopausal years and an average Kupperman Index of 19. A total of 85.2% of the patients had a waist/hip ratio of less than 0.8. The Epworth Scale score was greater than or equal to 9 in 50% of patients; 68% had sleep disturbances according to the Pittsburgh Index, and 68% were classified as high-risk for sleep apnea by the Berlin Questionnaire. On polysomnography, 70.58% of the patients had a sleep efficiency lower than 85%; 79.41% had a sleep latency of less than 30 min; 58.82% had a REM sleep latency of less than 90 min, and 44.11% had mild apnea. When the groups were compared, a linear association was identified between BMI and the AHI average, and a relationship between high BMI and use of drugs for thyroid treatment was found.	There was a high prevalence of sleep-disordered breathing, initial insomnia, fragmented sleep, and thyroid disorders in the group with higher BMI.	
24675720	Behavioral health risks are among the most serious and difficult to mitigate risks of confinement in space craft during long-duration space exploration missions. We report on behavioral and psychological reactions of a multinational crew of 6 healthy males confined in a 550 m(3) chamber for 520 days during the first Earth-based, high-fidelity simulated mission to Mars. Rest-activity of crewmembers was objectively measured throughout the mission with wrist-worn actigraphs. Once weekly throughout the mission crewmembers completed the Beck Depression Inventory-II (BDI-II), Profile of Moods State short form (POMS), conflict questionnaire, the Psychomotor Vigilance Test (PVT-B), and series of visual analogue scales on stress and fatigue. We observed substantial inter-individual differences in the behavioral responses of crewmembers to the prolonged mission confinement and isolation. The crewmember with the highest average POMS total mood disturbance score throughout the mission also reported symptoms of depression in 93% of mission weeks, which reached mild-to-moderate levels in >10% of mission weeks. Conflicts with mission control were reported five times more often than conflicts among crewmembers. Two crewmembers who had the highest ratings of stress and physical exhaustion accounted for 85% of the perceived conflicts. One of them developed a persistent sleep onset insomnia with ratings of poor sleep quality, which resulted in chronic partial sleep deprivation, elevated ratings of daytime tiredness, and frequent deficits in behavioral alertness. Sleep-wake timing was altered in two other crewmembers, beginning in the first few months of the mission and persisting throughout. Two crewmembers showed neither behavioral disturbances nor reports of psychological distress during the 17-month period of mission confinement. These results highlight the importance of identifying behavioral, psychological, and biological markers of characteristics that predispose prospective crewmembers to both effective and ineffective behavioral reactions during the confinement of prolonged spaceflight, to inform crew selection, training, and individualized countermeasures.
24673553	Treatment-induced early menopause occurs in > 80% of premenopausal women diagnosed with breast cancer. This study explored the relationship between vasomotor symptoms (VMS), sleep and mood in women aged 40-51 years with non-metastatic breast cancer.Cross-sectional study using validated questionnaires (Greene Climacteric scale and Hospital Anxiety and Depression Scale, HADS). Women (n = 114) were recruited from the community and hospital outpatient clinics. Frequency determination and structural equation modeling (SEMod) were used to examine the relationship between the latent variables: VMS, anxiety, and depression, and the indicator variable: difficulty sleeping.	Participants' mean age was 47 years and 94% became menopausal after breast cancer diagnosis. Difficulty sleeping was reported by 82% of women with 46% reporting (Likert scale) 'quite a bit/extremely'. Most women reported night sweats (77% of women: 47% reporting 'quite a bit/extremely') and hot flushes (84% of women: 50% reporting 'quite a bit/extremely'). HADS scores indicated clinically relevant depression and anxiety in 98% and 99% of women, respectively. SEMod revealed that VMS contributed to difficulty sleeping (standardized coefficient = 0.54; p < 0.001) and difficulty sleeping mediated the relationship between VMS and anxiety (standardized coefficient = 0.34; p = 0.03). However, difficulty sleeping did not have a significant direct impact on depression (standardized coefficient = -0.03; p = 0.8), although anxiety was a strong predictor of depression (standardized coefficient = 0.83; p = 0.015).	VMS, sleep and mood disturbance are commonly experienced by younger women with breast cancer. Using SEMod, we demonstrate for the first time that VMS may directly influence sleep in these women. VMS may have an indirect effect on mood, partly mediated by sleep difficulty.	
24673066	Experiences of needling techniques of Professor LI Ya- fang is introduced in this article. Gentle and superficial insertion is adopted by Professor LI in clinic. Emphases are put on the qi regulation function, needling sensation to the affected region and insertion with both hands, especially the function of the left hand as pressing hand. The gentle and superficial insertion should be done as the follows: hold the needle with the right hand, press gently along the running course of meridians with the left hand to promote qi circulation, hard pressing should be applied at acupoints to disperse the local qi and blood, insert the needle gently and quickly into the subcutaneous region with the right hand, and stop the insertion when patient has the needling sensation. While the fast needling is characterized with shallow insertion and swift manipulation: the left hand of the manipulator should press first along the running course of the meridian, and fix the local skin, hold the needle with the right hand and insert the needle quickly into the acupoint. Withdrawal of the needle should be done immediately after the reinforcing and reducing manipulations. Professor LI is accomplished in qi regulation. It is held by him that regulating qi circulation is essence of acupuncture, letting the patient get the needling sensation is the most important task of needling. Lifting, thrusting and rotation manipulations should be applied to do reinforcing or reducing. The tissue around the tip of the needle should not be too contracted or too relaxed, and the resistance should not be too strong or too weak. The feeling of the insertion hand of the practitioner should not be too smooth or too hesitant. Needle should be inserted into the skin quickly at the moment of hard pressing by the left hand. And then, slow rotation and gentle lifting and thrusting can be applied to promote the needling sensation like electric current pass through and to reach the affected region along the running course of meridians.
24672016	Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping-waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep-wake states, cortical activity, and muscle tone. We found that all cholinergic neurons were maximally active during W and PS in positive correlation with fast (γ) cortical activity, as "W/PS-max active neurons." Like cholinergic neurons, many GABAergic and glutamatergic neurons were also "W/PS-max active." Other GABAergic and glutamatergic neurons were "PS-max active," being minimally active during W and maximally active during PS in negative correlation with muscle tone. Conversely, some glutamatergic neurons were "W-max active," being maximally active during W and minimally active during PS in positive correlation with muscle tone. Through different discharge profiles, the cholinergic, GABAergic, and glutamatergic neurons of the LDT, SubLDT, and MPPT thus appear to play distinct roles in promoting W and PS with cortical activation, PS with muscle atonia, or W with muscle tone. 
24671311	Pulmonary hypertension (PH) commonly occurs in patients with cystic fibrosis (CF), but there is no current data regarding alterations of sleep in patients with PH.A single-center, retrospective review was performed in patients with advanced lung disease due to CF who completed both nocturnal polysomnography and right heart catheterization (RHC) from January 2010 to June 2013. For statistical analysis, two-tailed unpaired t tests and Pearson correlation coefficient analysis were performed after normal distribution was confirmed.	A total of 18 consecutive CF patients were enrolled with RHC identifying PH in 56 % (10/18) of patients. The PH group had significantly lower mean sleep efficiency (72 ± 4 vs. 87 ± 3 %, p = 0.01), significantly higher ETCO(2) levels (54.5 ± 2.2 vs. 43.8 ± 3.0 mmHg, p = 0.01) on capnography, and significantly lower PO(2) (53.8 ± 3.1 vs. 65.5 ± 3.9 mmHg, p = 0.03) on capillary blood gas. Correlations with poor sleep efficiency included mean PAP (r = - 0.55, p = 0.01), systolic PAP (r = -0.5, p = 0.03), ETCO(2) (r = - 0.53, p = 0.02), and PO(2)) (r = 0.62, p = 0.01); ETCO(2) with systolic PAP (r = 0.47, p = 0.04) and PCO(2) (r = - 0.57, p = 0.01); and PO(2) to 6-min walk distance (r = 0.55, p = 0.02).	We found significant differences in sleep efficiency and gas exchange associated with PH in CF patients with advanced lung disease.	
24669681	To assess the accuracy of a wrist worn Watch PAT 200 in diagnosing obstructive sleep apnea hypopnea syndrome (OSAHS) by comparing with the standard polysomnography (PSG).Twenty-eight adults with suspected OSAHS underwent a standard in-lab PSG while wearing a Watch PAT 200. PSG events were manually scored according to standard criteria (AASM). Watch PAT data were collected including changes of apnea hypopnea, sleep stages, peripheral arterial volume, signal oxygen saturation and heart rate, and then apnea hypopnea index (AHI) was analyzed by an automatic algorithm.	For PSG, the mean score of AHI was (23.00 +/- 21.55)/h, and for Watch PAT, a mean score of AHI was (25.99 +/- 19.09)/h. There is a statistically positive correlation between PSG-AHI and PAT-AHI (r = 0.92, P < 0.01). The Coincidence rate of the sleep-wake assessment based on 30-second bins between the PSG and Watch PAT 200 was (89 +/- 6)%.	Watch PAT 200 could detected OSAHS based on AHI with comparable accuracy with standard PSG. And it would provide a reasonably accurate estimation of sleep and wakefulness stages in patients with OSAHS.	
24669357	Little is known about the physical activity (PA) of young adults (YAs) during cancer therapy. In this feasibility study, 14 YAs (20-34 years old) completed a six-minute walk test, recorded their steps per day for one week, and answered weekly self-reports about physical activity, fatigue, sleep-wake disturbances, and depression during one cycle of chemotherapy. Findings suggest YAs are willing to complete a PA study during chemotherapy and have variable sleep and activity schedules. Their symptoms varied in severity, with highest scores for fatigue. Studies to improve PA in YAs during chemotherapy are warranted to manage short- and long-term treatment effects.
24668399	Delirium is a common acute neuropsychiatric syndrome. It is characterized by concurrent disturbances of consciousness and attention, perception, reasoning, memory, emotionality, the sleep-wake cycle as well as psychomotor symptoms. Delirium caused by alcohol or medication withdrawal is not the subject of the current review. Specific predisposing and precipitating factors have been identified in delirium which converge in a common final pathway of global brain dysfunction. The major predisposing factors are older age, cognitive impairment or dementia, sensory deficits, multimorbidity and polypharmacy. Delirium is always caused by one or more underlying pathologies which need to be identified. In neurology both primary triggers of delirium, such as stroke or epileptic seizures and also secondary triggers, such as metabolic factors or medication side effects play a major role. Nonpharmacological interventions are important in the prevention of delirium and lead to an improvement in prognosis. Delirium is associated with increased mortality and in the long term the development of cognitive deficits and functional impairment. 
24666716	Disturbances of the sleep-wake cycle and seasonality have been reported in patients with bipolar disorder (BD). Considering that BD seems to be a spectrum condition in terms of clinical and biological characteristics, circadian and seasonal rhythm related to BD could be detected in non-clinical individuals with subthreshold bipolarity. The aim of this study was to screen past hypomanic symptoms in non-clinical samples and investigate their association with deviated sleep-wake cycle and seasonality.Lifetime history of hypomanic symptoms was assessed with the Hypomania Checklist-32 (HCL-32). Circadian preference, variability of sleep-wake time and seasonal changes in mood and behavior were evaluated on a lifetime-basis in non-clinical adult samples (n=313), using the Composite Scale of Morningness (CSM), the Sleep Timing Questionnaire (STQ), and the Seasonal Pattern Assessment Questionnaire (SPAQ).	Two subdomains of hypomanic symptoms were identified through factor analysis of HCL-32, i.e., "active/elated" factor and "irritable/risk-taking" factor. The HCL-32 total score (p<0.001) and the "active/elated" factor score (p=0.028) were weakly correlated only with seasonality, whereas the "irritable/risk-taking" factor score was associated not only with seasonality (p<0.001), but also with evening preference (p<0.001) and irregularity of sleep-wake times (p=0.001~0.011).	Circadian and seasonal characteristics related to BD are also associated with a past history of hypomanic symptoms in non-clinical samples, especially "irritable/risk-taking" symptoms, suggesting the existence of subclinical presentation of BD and their biological traits.	
24666675	Difficulty falling asleep (sleep latency) and staying asleep (sleep maintenance) are common problems for persons living with pain. Research demonstrates that sleep problems are, in turn, related to exacerbation of chronic pain. There is a growing body of evidence for a range of pragmatic, non-pharmacological sleep interventions that can potentially be incorporated into pain management programs. This study looks at the outcome of teaching patients with musculoskeletal pain standardized pre-bedtime hand self-Shiatsu (HSS) to reduce sleep latency.A case series design, with participants acting as their own controls, was selected to facilitate hypothesis generation for this novel, under-researched intervention. Sleep efficiency, latency and maintenance, sleep beliefs, pain intensity and basic participant demographics were collected at baseline with actigraphy and standardized self-report questionnaires. After one week of baseline data collection, the HSS intervention was taught to participants. Follow-up data were collected at 2 and 8 weeks post-intervention.	Data collected at baseline and the two follow-up periods revealed no apparent changes in the objective actigraphy data. However a trend toward improved self-reported sleep latency (time to fall asleep) and sleep duration (time spent asleep) emerged. A number of participants reported they were more concerned with increasing their period of unbroken sleep as opposed to their total sleep time and it is possible that HSS may be useful to be applied during nighttime awakenings as well as before bed. None of the participants reported adverse effects of the intervention.	These preliminary findings are promising and future studies exploring the mechanism of action and with stronger control of treatment fidelity are indicated.	
24666180	This paper presents findings from a larger study that explored losses from mental illness. Losses associated with occupations--a key theme from this participatory action research study--are the focus of this paper.Semi-structured in-depth interviews were carried out with 16 people who had been diagnosed with a mental illness and attended a community mental health centre. Interviews were transcribed verbatim and thematically analysed, guided by processes proposed by Dey.	Numerous losses influenced participants' ability to initiate or engage in daily occupations. Some losses perpetuated further loss, at times with profound consequences, such as the loss of a house following a loss of work. Engaging in chosen occupations was often described as a longer-term goal or something participants did infrequently, due to losses such as motivation, energy, or normal sleeping patterns. The desire to work and participate in everyday occupations was emphasized and its benefits highlighted, despite previous difficulties.	Implications for occupational therapists include the importance of exploring, validating, and responding to losses when these are shared, and being aware of and striving to support people experiencing losses in the areas of work, motivation, sleep patterns, and energy, which were perceived as especially challenging for participants in this study.	
24665961	This study examined the effect of traumatic brain injury (TBI) in young children on sleep problems and the relationship of sleep problems to neuropsychological and psychosocial functioning. Participants were drawn from an ongoing longitudinal study of injury in young children recruited from 3 to 6 years of age. They constituted three groups: orthopedic injury (OI; n=92), complicated mild/moderate TBI (mTBI; n=55); and severe TBI (sTBI; n=20). Caregivers completed the Children's Sleep Habits Questionnaire (CSHQ), as well as ratings of behavioral adjustment, adaptive functioning, and everyday executive function at 1, 6, 12, and 18 months postinjury. Retrospective ratings of preinjury sleep and psychosocial functioning were obtained at the initial assessment. Children completed neuropsychological testing at all occasions. Children with complicated mTBI demonstrated more total sleep problems than children with OI at 6 months postinjury, but not at 12 or 18 months. Children with sTBI displayed more bedtime resistance and shorter sleep duration than those with complicated mTBI or OI at several occasions. Across groups, total sleep problems predicted more emotional and behavioral problems and worse everyday executive function as rated by parents across follow-up occasions. In contrast, sleep problems were generally not related to neuropsychological test performance. The results suggest that young children with TBI demonstrate more sleep problems than children with injuries not involving the head. Sleep problems, in turn, significantly increase the risk of poor psychosocial outcomes across time, but are not associated with worse neuropsychological test performance.
24664948	To investigate the relationship between common psychiatric disorders (CPDs) and sleep characteristics (evening chronotype, poor sleep quality and daytime sleepiness) among Thai college students.A cross-sectional study was conducted among 2,970 undergraduate students in Thailand. Students were asked to complete a self-administered questionnaire that collected information about lifestyle and demographic characteristics. The Horne and Ostberg Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate circadian preference, sleep quality and daytime sleepiness, respectively. The General Health Questionnaire-12 (GHQ-12) was used to evaluate presence of CPDs. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of CPDs in relation to the covariates of interest.	A total of 337 students were classified as having CPDs (11.2%; 95% CI 10.1-12.3%). Evening chronotype (OR = 3.35; 95% CI 2.09-5.37), poor sleep quality (OR = 4.89; 95% CI 3.66-6.54) and excessive daytime sleepiness (OR = 1.95; 95% CI 1.54-2.47) were statistically significantly associated with CPDs.	Our study demonstrated that CPDs are common among Thai college students. Further, evening chronotype, poor sleep quality and excessive daytime sleepiness were strongly associated with increased risk of CPDs. These findings highlight the importance of educating students and school administrators about the importance of sleep and their impact on mental health.	
24661963	Disturbed sleep is common in Parkinson's disease and has a detrimental impact on functioning and quality of life. While the progression of the disease contributes to the aetiology of sleep problems in Parkinson's disease, it is unknown whether an individual's beliefs and attitudes about sleep play a role. In this study we sought to investigate whether dysfunctional beliefs and attitudes about sleep could be related to subjective and objective measures of sleep disturbance in Parkinson's disease. Ninety-three patients with Parkinson's disease completed the Dysfunctional Beliefs and Attitudes about Sleep 16 item questionnaire, which comprises four domains: Expectations, Worry/Helplessness, Consequences and Medication. Patients also completed the Pittsburgh Sleep Quality Index questionnaire and Beck Depression Inventory-II. Patients wore actigraphy watches and completed sleep diaries for 2 consecutive weeks, recording measures of sleep disturbance including Sleep Onset and Offset, Wake After Sleep Onset, Sleep Efficiency, and Wake Bouts per hour. Greater dysfunctional beliefs and attitudes in the domains of Worry/Helplessness and Medication were associated with lower perceived sleep quality and greater depressive symptoms. However, no relationships were found between dysfunctional beliefs and attitudes about sleep and any objective actigraphic measure of sleep disturbance. These findings suggest that beliefs and attitudes about sleep in Parkinson's disease are associated with mood disturbance, rather than objective measures of sleep. Thus it is possible that interventions targeting mood may lead to more accurate perceptions of sleep and improved quality of life in Parkinson's disease patients. 
24661455	Sleep-disordered breathing (SDB) may develop in primary ciliary dyskinesia (PCD), leading to these diseases worsening one another.Sixteen stable PCD patients (4.9-17.2 years) and 42 controls underwent overnight respiratory polysomnography (rPSG) and Sleep Disturbances Scale for Children (SDSC). In PCD we assessed nasal endoscopy, pulmonary function tests and chest high-resolution computed tomography (HRCT).	Compared with controls, PCD had higher obstructive apnoea (4.7 vs 0.2, P < 0.001), central apnoea (0.8 vs 0.2, P < 0.001), hypopnoea (1.8 vs 0.2, P < 0.001), apnoea-hypopnoea (7.8 vs 0.6, P < 0.001), oxygen desaturation indexes (ODI; 0.7 vs 0.2, P = 0.002), and mean oxygen desaturation (4% vs 1%, P < 0.001), while mean and nadir oxygen saturation (97.1% vs 98.1, P < 0.001) (93% vs 97.2%, P < 0.001) were lower, respectively. In PCD, SDSC was unrelated to rPSG (P > 0.05), with total score and subscores of disorders in initiating and maintaining sleep, and sleep-wake transition lower than controls. PCD patients had chronic rhinosinusitis (100%) and adenoidal hypertrophy (50%). Total HRCT score was 7 (range 0-14). ODI correlated with functional residual capacity (r = 0.8, P = 0.02), total HRCT (r = 0.6, P = 0.03) and peribronchial thickening scores (r = 0.7, P = 0.02). Oxygen saturation was associated with bronchiectasis severity score (r = -0.6, P = 0.02).	PCD's parents may underestimate SDB. As nocturnal desaturation is associated with lung function and structure abnormalities, SDB may significantly contribute to pulmonary morbidity.	
24660887	Higher wake promotion against sleep drive boosts cognitive processing, but it also seems to increase the risk of insomnia by reinforcing an obsession with sleep in neurotic patients. To explore whether a personality trait of neuroticism simultaneously facilitates wake-promoting ability and sleep devaluation via a common regional prefrontal function under a sleep-restricted condition, working memory tasks were administered to 49 healthy humans after a 2-h sleep restriction. Higher wake-promoting ability demonstrated in a high-load task was correlated with lower bilateral prefrontal activation, as measured by near-infrared spectroscopy. Structural equation modeling revealed that neuroticism predicts sleep devaluation and wake-promoting ability via left and right regional prefrontal efficiency, respectively. Our results indicate that neuroticism-related neural efficiency increases resilience to sleepiness, but decreases sleep satisfaction. 
24660657	An association between circadian clock function and mood regulation is well established and has been proposed as a factor in the development of mood disorders. Patients with depression or mania suffer disturbed sleep-wake cycles and altered rhythms in daily activities. Environmentally disrupted circadian rhythms increase the risk of mood disorders in the general population. However, proof that a disturbance of circadian rhythms is causally involved in the development of psychiatric disorders remains elusive. Using clock gene mutants, manipulations of sleep-wake and light-dark cycles, and brain lesions affecting clock function, animal models have been developed to investigate whether circadian rhythm disruptions alter mood. In this review, selected animal models are examined to address the issue of causality between circadian rhythms and affective behavior.
24660648	Headaches are a common complaint in temporomandibular disorder (TMD) patients. However, few studies have compared the symptom characteristics between TMD patients with and without a complaint of headache. The aim of this study was to compare subjective symptoms and treatment outcomes between myofascial TMD patients who had a chief complaint of headache and those who did not.One hundred sixty one patients underwent comprehensive examinations and scored their pre- and post-treatment symptoms on a form (4 items assessing pain intensity and 1 assessing sleeping difficulty). On the basis of the primary diagnosis, patients were divided into two groups: myofascial pain with and without a chief complaint of headache (MPH and MP).	Before treatment, patients in the MPH group scored significantly higher with respect to pain intensity and level of sleeping difficulty than did patients in the MP group (jaw/face pain, P = 0.015; headache, P < 0.001; neck pain, P < 0.001, and difficulty in sleeping, P = 0.005; Mann-Whitney U-test). Patients in the two groups demonstrated similar treatment outcomes, except for neck pain.	Significant differences in symptom characteristics and outcomes were observed between primarily myofascial TMD patients with and without a chief complaint of headache.	
24659320	Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering and daytime sleepiness are common clinical problems in dementia due to Alzheimer's disease (AD), and are associated with significant caregiver distress, increased healthcare costs and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population.To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with Alzheimer's disease through identification and analysis of all relevant randomized controlled trials (RCTs).	We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 31 March 2013 using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, "rest-activity", sundowning.	We included RCTs that compared a drug with placebo and that had the primary aim of improving sleep in people with Alzheimer's disease who had an identified sleep disturbance at baseline. Trials could also include non-pharmacological interventions as long as both drug and placebo groups had the same exposure to them.	Two authors working independently extracted data on study design, risk of bias and results from the included study reports. Additional information was obtained from study authors where necessary. We used the mean difference as the measure of treatment effect and, where possible, synthesized results using a fixed-effect model.	We found RCTs eligible for inclusion for three drugs: melatonin (209 participants, three studies, but only two yielded data suitable for meta-analysis), trazodone (30 participants, one study) and ramelteon (74 participants, one study, no peer-reviewed publication, very limited information available).The melatonin and trazodone studies were of people with moderate-to-severe AD; the ramelteon study was of people with mild-to-moderate AD. In all studies participants had a variety of common sleep problems. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. Only two studies made a systematic assessment of adverse effects. Overall, the published studies were at low risk of bias, although there were areas of incomplete reporting and some problems with participant attrition, related largely to poor tolerance of actigraphy and technical difficulties. The risk of bias in the ramelteon study was unclear due to incomplete reporting.We found no evidence that melatonin, either immediate- or slow-release, improved any major sleep outcome in patients with AD. We were able to synthesize data for two sleep outcomes: total nocturnal sleep time (MD 10.68 minutes, 95% CI -16.22 to 37.59, two studies), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03, two studies). Other outcomes were reported in single studies. We found no difference between intervention and control groups for sleep efficiency, time awake after sleep onset or number of night-time awakenings, nor in cognition or performance of activities of daily living (ADLs). No serious adverse effects of melatonin were reported in the included studies.Trazodone 50 mg administered at night for two weeks significantly improved total nocturnal sleep time (MD 42.46 minutes, 95% CI 0.9 to 84.0, one study) and sleep efficiency (MD 8.53, 95% CI 1.9 to 15.1, one study), but there was no clear evidence of any effect on the amount of time spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6, one study) or the number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8, one study). No effect was seen on daytime sleep, nor on cognition or ADLs. No serious adverse effects were reported.Results from a phase 2 trial investigating ramelteon 8 mg administered at night were available in summary form in a sponsor's synopsis. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or eight weeks (end of treatment). The synopsis reported few significant differences from placebo for any sleep, behavioural or cognitive outcomes; none were likely to be of clinical significance. There were no serious adverse effects of ramelteon.	We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in AD. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in AD, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin is beneficial to AD patients with moderate to severe dementia and sleep problems. There is some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in AD. Systematic assessment of adverse effects is essential.	
24659108	On-call duties have been rated to be among the most stressful aspects of physicians' work. On-call work has been associated, for example, with medical errors, injuries and lower well-being. Thus, because it is not possible to remove on-call duties, measures to decrease the negative ramifications of on-call work are needed.To examine whether working on-call would predict psychological distress, job satisfaction and work ability in a 4-year follow-up and whether sleeping problems or work interference with family (WIF) would act as mechanisms in these associations.	Questionnaires in 2006 and 2010 among physicians in Finland. The mediation analyses were conducted using methods suggested by Preacher and Hayes to examine direct and indirect effects with multiple mediators.	There were 1541 respondents (60% women) of whom 52% had on-call duties. Sleeping problems and WIF acted as mechanisms in the association of existence of on-call duties with high distress, low job satisfaction and low work ability. On-call work was associated with higher levels of sleeping problems and WIF, and the number of active on-call hours was associated with higher levels of WIF, but not with sleeping problems.	According to our results, one way to attenuate on-call work's negative ramifications is to make it easier for on-call physicians to connect work and family lives and develop work arrangements to promote better sleep and protected sleep time.	

24657202	This case-control psychological autopsy study aimed to explore a relationship between sleep disturbances and suicide among Japanese, as well as determine the importance and usability of screening for sleep disturbances in suicide prevention.A semi-structured interview was conducted with the close family members of 49 adult suicide completers and 145 gender-, age-, and residential municipality-matched living controls. The survey included sections on demographics, sleep disturbances, and mental disorders. Conditional logistic regression analyses were performed to compare sleep disturbance prevalence between the two groups.	A significantly higher prevalence of sleep disturbances was found among the suicide group (75.5%) compared to the controls (11.0%) (odds ratio [OR]=21.6, p<0.001). The association remained significant after adjusting for mental disorders (OR=12.7, p<0.001). The population attributable risk percent of suicide associated with sleep disturbances and mental disorders was estimated to be 56.4% and 35.3%, respectively.	The study confirmed that sleep disturbances are an important risk factor of suicide, independent of mental disorders. Sleep disturbances accounted for a greater proportion of suicide cases than did mental disorders in the Japanese population given the higher prevalence, and could thus be considered an important target in suicide prevention in Japan.	
24656426	To assess the prevalence of insomnia symptoms in Chronic Obstructive Pulmonary Disease (COPD) participants, their association with psychiatric disorders and their impact on health care utilization and quality of life.It is a cross-sectional telephone study using a representative sample consisting of 10,854 non-institutionalized individuals aged 15 or over living in Germany, Spain and the United Kingdom. Interviews were managed by the Sleep-EVAL expert system. The questionnaire included questions on sleeping habits, life habits, health, DSM-IV mental disorders, DSM-IV and ICSD sleep disorders. COPD was defined as chronic bronchitis or emphysema (treated or not) diagnosed by a physician.	A total of 2.5% [2.1%-2.8%] of the sample reported having been diagnosed with COPD. As many as 48.1% of COPD had insomnia symptoms, which was twice higher than the rate observed in non-COPD (OR: 2.4). Only 11.8% of COPD addressed their sleep difficulties to their physician. Mental disorders were higher in COPD compared to non-COPD participants: Major Depressive disorder (AOR: 2.8); Generalized Anxiety Disorder (AOR: 11.0); Panic Disorder (AOR: 7.1) and Specific Phobia (AOR: 3.7). As many as 84.4% of COPD with depression and 59.7% of those with an Anxiety Disorder had associated insomnia symptoms. The co-occurrence of both conditions increased by five times the likelihood of hospitalizations in the previous year among COPD. Both conditions were associated with a diminished Quality of Life in COPD.	COPD is a debilitating disease accompanied with psychiatric disorders and sleep disturbances in the overwhelming majority of cases. This high comorbidity is associated with greater health care utilization and great deterioration of the quality of life.	
24656221	Cognitive behaviour therapy (CBT) has been found to reduce the impact of menopausal symptoms, hot flushes and night sweats. This study investigates the moderators and mediators of CBT for women who had problematic menopausal symptoms following breast cancer treatment.Analysis of 96 patients with breast cancer induced menopausal symptoms recruited to the MENOS1 trial; 47 were randomly assigned to Group CBT and 49 to usual care. Questionnaires were completed at baseline, 9 and 26 weeks post randomisation. Potential moderators and mediators, including sociodemographic, clinical and psychological factors, of the treatment effect on the primary outcome were examined.	Hot Flush Problem Rating.	CBT was effective at reducing problem rating at 9 weeks regardless of age, BMI, time since breast cancer diagnosis, menopausal status at time of diagnosis, or type of cancer treatment (radiotherapy or chemotherapy or endocrine treatment). The treatment effect was significantly greater in women not receiving chemotherapy, those with higher levels of psychological distress at baseline and for non-white women. Beliefs about control/coping with hot flushes were the main mediators of improvement in problem rating following CBT. Beliefs about hot flushes in a social context, depressed mood and sleep problems were also identified as mediators.	These findings suggest that CBT is widely applicable for breast cancer patients who are experiencing treatment related menopausal symptoms, and that CBT works mainly by changing beliefs and improving mood and sleep.	
24655758	Findings from actigraphic studies suggesting that sleep and circadian rhythms are disrupted in bipolar disorder (BD) patients have been undermined by methodological heterogeneity and the failure to adequately address potential confounders.Twenty-six euthymic BD cases and 29 healthy controls (HC), recruited from University Paris-Est and matched for age and gender, were compared on subjective (Pittsburgh Sleep Questionnaire Inventory; PQSI) and objective (mean scores and variability in actigraphy) measures of sleep as recorded by over 21 consecutive days.	Multivariate generalized linear modelling (GLM) revealed significant differences between BD cases and HC for five PSQI items (total score and four subscales), four actigraphy variables (mean scores) and five actigraphy variability measures. Backward stepwise linear regression (BSLR) indicated that a combination of four variables (mean sleep duration, mean sleep latency, variability of the fragmentation index over 21 days, and mean score on PSQI daytime dysfunction sub-scale) correctly classified 89% of study participants as cases or controls (Chi-square=39.81; df=6; p=0.001).	The sample size (although larger than most actigraphy studies) and incomplete matching of cases and controls may have influenced our findings. It was not possible to control for potential effects of psychotropic medication or differences in employment status between groups.	When potential confounders of sleep and circadian profiles are adequately taken into account (particularly age, gender, daytime sleepiness, mood symptoms, body mass index, and risk of sleep apnoea), a selected subset of quantitative (mean scores) and qualitative (variability) features differentiated euthymic BD cases from HC.	
24655719	The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities. 
24654988	Addressing sleep disturbance can help to slow functional decline, delay nursing home admission, and improve overall health among older adults; however, sleep is not widely studied in high-risk older adults such as Adult Day Health Care (ADHC) participants. Sixty-eight ADHC participants were interviewed for sleep disturbance using a 28-item screening questionnaire. More than two thirds (n = 48, 70.6%) reported one or more characteristics of poor sleep, and 38% of participants met basic criteria for insomnia. Individuals with insomnia attended ADHC less frequently, reported worse sleep quality and shorter sleep duration, and were more likely to endorse trouble falling asleep, staying asleep, and waking up too early (ps < 0.001). Research is needed to better understand perceptions, predictors, and outcomes of sleep disturbance within ADHC participants. 
24654933	This study used a case-control design to compare sleep disturbances in 40 adolescents who attempted suicide with 40 never-suicidal adolescents. Using hierarchical logistic regression analyses, we found that self-reported nighttime awakenings were significantly associated with attempted suicide, after controlling for antidepressant use, antipsychotic use, affective problems, and being bullied. In a separate regression analysis, the parent-reported total sleep problems score also predicted suicide attempt status, controlling for key covariates. No associations were found between suicide attempts and other distinct sleep problems, including falling asleep at bedtime, sleeping a lot during the day, trouble waking up in the morning, sleep duration, and parent-reported nightmares. Clinicians should be aware of sleep problems as potential risk factors for suicide attempts for adolescents. 
24654884	To identify possible changes in the sleep patterns according to chronotype in undergraduate students during the daylight saving time (DST) transition.A total of 378 students answered the Morningness-Eveningness Questionnaire (MEQ) to determine their chronotype and kept a diary about sleep-wake schedules 1 week before and after the DST transition. Oral mucosal cell samples were collected for genetic analysis.	After the DST transition, intermediate types (I-types) delayed bedtime and increased their time in bed and all groups delayed their wake-up time. All groups presented a shorter phase angle between sunset and the bedtime after the DST transition. On the other hand, only E-types showed a tendency to reduce the phase angle between sunrise and wake-up time, while I-types and M-types kept the same phase angles between sunrise and wake-up time after the DST transition. The polymorphisms in the human genes CLOCK and PER3 were not associated with individual differences in sleep patterns, nor were they associated with an adjustment to the DST transition.	Under the new set of social times determined by DST, the adjustment was only partial. I-types delayed bedtime and all groups delayed their wake-up times after the beginning of DST. Consequently, the time in bed after the DST transition was not reduced; Morning (M-types) and Evening-types (E-types) kept the same time in bed and I-types showed an increase on it.	
24654443	The role of sleep in different memory processes is debated. Probably it plays an active role in the memory consolidation or possibly it prevents forgetting by protecting against interference or it makes the memory performance more efficient by facilitating the forgetting. The beneficial effect of sleep in explicit memory is well demonstrated, while the role of sleep in implicit mechanisms has not been comprehensively characterized so far. There are several factors which affect the appearance of sleep effect, such as the structure, the length and the complexity of sequence being used, the awareness of the sequence, the length of the learning blocks and the offline period. Besides the classical sleep deprivation methods with healthy participants, examining patients with sleep disorders could be a new method of the investigation of the sleep effect which enables us to enrich our knowledge not only about the sleep-dependent memory consolidation but also the cognitive dysfunction related to sleep pathologies. This new line of research can help the development of more effective rehabilitation programs.
24652608	Sleep quality and architecture as well as sleep's homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep's (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as well as a phase advance (moved earlier in time) of the brain's circadian clock. With mild cognitive impairment (MCI) there are further reductions of sleep quality, SWS, spindles, and percent REM, all of which further diminish, along with a profound disruption of circadian rhythmicity, with the conversion to Alzheimer's disease (AD). Sleep disorders may represent risk factors for dementias (e.g., REM Behavior Disorder presages Parkinson's disease) and sleep disorders are themselves extremely prevalent in neurodegenerative diseases. Working memory , formation of new episodic memories, and processing speed all decline with healthy aging whereas semantic, recognition, and emotional declarative memory are spared. In MCI, episodic and working memory further decline along with declines in semantic memory. In young adults, sleep-dependent memory consolidation (SDC) is widely observed for both declarative and procedural memory tasks. However, with healthy aging, although SDC for declarative memory is preserved, certain procedural tasks, such as motor-sequence learning, do not show SDC. In younger adults, fragmentation of sleep can reduce SDC, and a normative increase in sleep fragmentation may account for reduced SDC with healthy aging. Whereas sleep disorders such as insomnia, obstructive sleep apnea, and narcolepsy can impair SDC in the absence of neurodegenerative changes, the incidence of sleep disorders increases both with normal aging and, further, with neurodegenerative disease. Specific features of sleep architecture, such as sleep spindles and SWS are strongly linked to SDC. Diminution of these features with healthy aging and their further decline with MCI may account for concomitant declines in SDC. Notably these same sleep features further markedly decline, in concert with declining cognitive function, with the progression to AD. Therefore, progressive changes in sleep quality, architecture, and neural regulation may constitute a contributing factor to cognitive decline that is seen both with healthy aging and, to a much greater extent, with neurodegenerative disease. 
24651580	The orexinergic neurons of the lateral hypothalamus (Orx) are essential for regulating sleep-wake dynamics, and their loss causes narcolepsy, a disorder characterized by severe instability of sleep and wake states. However, the mechanisms through which Orx stabilize sleep and wake are not well understood. In this work, an explanation of the stabilizing effects of Orx is presented using a quantitative model of important physiological connections between Orx and the sleep-wake switch. In addition to Orx and the sleep-wake switch, which is composed of mutually inhibitory wake-active monoaminergic neurons in brainstem and hypothalamus (MA) and the sleep-active ventrolateral preoptic neurons of the hypothalamus (VLPO), the model also includes the circadian and homeostatic sleep drives. It is shown that Orx stabilizes prolonged waking episodes via its excitatory input to MA and by relaying a circadian input to MA, thus sustaining MA firing activity during the circadian day. During sleep, both Orx and MA are inhibited by the VLPO, and the subsequent reduction in Orx input to the MA indirectly stabilizes sustained sleep episodes. Simulating a loss of Orx, the model produces dynamics resembling narcolepsy, including frequent transitions between states, reduced waking arousal levels, and a normal daily amount of total sleep. The model predicts a change in sleep timing with differences in orexin levels, with higher orexin levels delaying the normal sleep episode, suggesting that individual differences in Orx signaling may contribute to chronotype. Dynamics resembling sleep inertia also emerge from the model as a gradual sleep-to-wake transition on a timescale that varies with that of Orx dynamics. The quantitative, physiologically based model developed in this work thus provides a new explanation of how Orx stabilizes prolonged episodes of sleep and wake, and makes a range of experimentally testable predictions, including a role for Orx in chronotype and sleep inertia. 
24650740	Despite evidence suggesting that social and neighbourhood contexts may relate to sleep in adults, the underlying social and demographic mechanisms involved remain relatively unexplored. This study proposes a conceptual framework for examining the link between social environments and restless sleep, and assesses whether associations among restless sleep, social capital, and neighbourhood environments differ by gender. Data come from the 2008 Montreal Neighborhood Networks and Healthy Aging Study (n = 2707). Participants self-reported restless sleep. Network and cognitive dimensions of social capital were examined. Neighbourhood disadvantage and population density were measured using 2006 Canada Census data. Multilevel logistic analyses adjusting for socio-economic and -demographic variables were used to estimate associations among study variables. The final sample size for this study was 2643 adults (nmen = 930; nwomen = 1713). Women were more likely to experience restless sleep than men (OR: 1.29; 95% CIs: 1.07, 1.55). Network capital increased the likelihood of restless sleep in men (OR = 1.25; 95% CI: 1.04-1.50) but not women. High generalized trust decreased the odds of restless sleep in women (OR = 0.75; 95% CI: 0.59-0.94); neighbourhood disadvantage increased the odds of restless sleep in women but not men (OR = 1.18; 95% CI: 1.01-1.38). The association among restless sleep, social capital, and neighbourhood environmental factors differed in male and female Montreal adults. This study contributes to a greater understanding of possible differential associations between social environments and health in men and women. Greater knowledge of the social and environmental factors that contribute to poor sleep in men and women can aid in the design of interventions to improve sleep patterns in the general population. Social and health promotion interventions might aim to improve general neighbourhood environmental conditions to improve the sleep health of women. 
24647377	This study examined the use of self-care strategies to address difficulty sleeping among community-dwelling older adults. Data were collected from a series of 18 questionnaires administered to 195 rural African American and white older adults in North Carolina. Participants reported whether they had experienced difficulty sleeping and strategies used to respond to the symptom. The most widely used strategies included ignoring the symptom, staying in bed or resting, and praying. Herb and supplement use were not reported. Ethnicity, income, and education were associated with use of specific self-care strategies for sleep. This variation suggests that older adults may draw on cultural understandings to interpret the significance of difficulty sleeping and influence their use of self-care strategies, including complementary and alternative medicine use. This information may enable health care providers to communicate with the older patients about sleep difficulty strategies to minimize sleep problems. 
24647242	admission to nursing homes is often associated with major changes in the way the elderly live, possibly leading to sleep disorders. The aim of our study was to assess sleep quality in the elderly without dementia living in nursing homes, to determine the prevalence of sleep disorders, and to examine the links between sleep quality and sociodemographic features, comorbidities, and degree of dependency.we carried out a cross-sectional survey, involving old people living in Manouba nursing home. Assessment of sleep was performed using Pittsburgh Sleep Quality Index. We excluded subjects with severe motor or sensory impairments as well as individuals with cognitive impairment.	thirty-two patients were included in the study. The majority (68.8%) were male, institutionalized for an average period of 6.3 years. Mean age was 71.6 years. More than half of the subjects (56.3%) had depression, and 93.8% had one or more chronic conditions. About one third (37.5%) of residents were dependent in one or more activities of daily living and 25% were confined to bed or to a wheelchair. The majority of residents (73%) were identified as "poor sleepers" based on a global Pittsburgh Sleep Quality Index score >5. Sleep disorders were attributed to nocturia, nocturnal or premature awakenings and pain. We noted a fairly large percentage (18.8%) of hypnotic drugs intake among participants. Our results also showed a strong association between poor sleep quality and depression (p<0.001).	early detection of sleep disorders in nursing home residents can help them to get an optimized and efficacious treatment.	
24646366	Three studies were conducted to validate the Training Distress Scale (TDS), a 19-item measure of training-related distress and performance readiness. Study 1 was a randomized, controlled laboratory experiment in which a treatment group undertook daily interval training until a 25% decrement occurred in time-to-fatigue performance. Comparisons with a control group showed that TDS scores increased over time within the treatment group but not in the control group. Study 2 was a randomized, controlled field investigation in which performance capabilities and TDS responses were compared across a high-intensity interval training group and a control group that continued normal training. Running performance decreased significantly in the training group but not in the control group, and scores on the TDS mirrored those changes in performance capabilities. Study 3 examined the relationship between TDS scores obtained over a 2-week period before major swimming competitions and subsequent performance in those competitions. Significantly, better performance was observed for swimmers with low TDS scores compared with those with moderate or high TDS scores. These findings provide both laboratory and field evidence for the validity of the TDS as a measure of short-term training distress and performance readiness. 
24645570	Over the past 60 years a great progress has been made in our understanding of the pathogenesis of essential hypertension. The contribution of excessive sympathetic nerves activity in the development of hypertension and target organ damage has been demonstrated in experimental and clinical studies. Also the important role of the renin-angiotensin-aldosteron in the pathophysiology of arterial hypertension has been confirmed in many studies. During the last three decades many studies revealed the relationship between low birth weight and arterial hypertension. Sleep disturbances--short sleep duration, insomnia are proposed as a possible pathophysiological factor of hypertension. The novel concept that immune system may play an important role in the pathogenesis of essential hypertension has gained support in recent years. The multifactorial nature of essential hypertension is now widely accepted.

24644258	The aim of the study was to investigate the parameters of tryptophan and phenylalanine metabolism and their associations to immune system activation and to behavioural symptoms during medium-term withdrawal (4-12 weeks of abstinence) in alcohol-dependent patients.Biochemical assays and clinical assessments at the beginning of treatment (fourth week of alcohol abstinence in average) and prior to the discharge after 8 weeks of treatment.	Kynurenine to tryptophan ratio (Kyn/Trp) slightly correlated with neopterin levels in early post-withdrawal period (Week 4 of abstinence) but this association disappeared after 12 weeks of abstinence. Phenylalanine and tyrosine concentrations as well as phenylalanine to tyrosine ratio (Phe/Tyr) decreased between Weeks 4 and 12 of abstinence. Kynurenine and Kyn/Trp increased significantly at 12th week of abstinence when compared with the beginning of the study (Week 4 of abstinence). At Week 12, Kyn/Trp significantly correlated with such behavioural symptoms as fatigue, irritability and sleep disturbances.	Tryptophan breakdown in early stages may be influenced by the increased activity of indoleamine 2,3-dioxygenase but the increase of Kyn/Trp between Weeks 4 and 12 of abstinence seems to be independent of immune changes and correlates with behavioural symptoms in later stages of the post-withdrawal course. A possible role of kynurenine metabolites in mediation of the increased stress sensibility in post-withdrawal alcohol-dependent patients is discussed.	
24643830	Most individuals with mental disorders complain about the problems they experience with sleeping and waking. It is becoming evident that careful diagnosis of sleep-wake disorders is of great importance for the prevention and treatment of mental disorders. Since the introduction of the DSM-IV, clinical scientific research has provided important new insights in this field.To find out whether the new classification of sleep-wake disorders in DSM-5 is likely to improve the diagnosis of disorders of this type.	We discuss the main changes in the DSM-5 classification of sleep- wake disorders, comparing the new version with the version in DSM-IV.	Because considerable attention is being given to the symptom-orientated and dimensional approach, the classification of sleep-wake disorders in the DSM-5 is closer to current psychiatric practice and it does justice to the current scientific insights into the dimensional nature of psychiatric disorders.	The DSM-5 classification takes recent scientific insights into account and might help to improve the diagnosis of sleep-wake disorders in psychiatry.	
24643168	Describe the development and psychometric validation of a brief scale (the Sleep Condition Indicator (SCI)) to evaluate insomnia disorder in everyday clinical practice.The SCI was evaluated across five study samples. Content validity, internal consistency and concurrent validity were investigated.	30 941 individuals (71% female) completed the SCI along with other descriptive demographic and clinical information.	Data acquired on dedicated websites.	The eight-item SCI (concerns about getting to sleep, remaining asleep, sleep quality, daytime personal functioning, daytime performance, duration of sleep problem, nights per week having a sleep problem and extent troubled by poor sleep) had robust internal consistency (α≥0.86) and showed convergent validity with the Pittsburgh Sleep Quality Index and Insomnia Severity Index. A two-item short-form (SCI-02: nights per week having a sleep problem, extent troubled by poor sleep), derived using linear regression modelling, correlated strongly with the SCI total score (r=0.90).	The SCI has potential as a clinical screening tool for appraising insomnia symptoms against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.	
24643100	The aim of this study was to compare the sleep quality of patients who underwent total knee arthroplasty before and after the surgery and analyze the effect of total knee arthroplasty on sleep quality.The study included 42 patients (32 females, 10 males) who underwent total knee arthroplasty for primary knee osteoarthritis. For each patient the preoperative 1 day and postoperative 3 months results of Pittsburgh Sleep Quality Index (PSQI) and 100-mm visual analogue scale (VAS) were compared.	The preoperative mean PSQI was 9. VAS score decreased in 97.6% of the patients, while sleep quality increased in 78.6%. 85.7% of the patients reported to have less episodes of pain related sleep disturbances. While both the PSQI and VAS improved after the surgery, there was no correlation between the parameters (p>0.05).	Our results suggested that total knee arthroplasty surgery relieves pain and improves sleep quality. The improvement in sleep quality does not appear to be related to pain relief.	

24641293	Asthma is a heterogeneous inflammatory disease and eosinophilic, non-eosinophilic and neutrophilic forms are recognised. While clinically similar to eosinophilic asthma, patients with non-eosinophilic asthma have different responses to treatment and little is known about the triggers of symptoms and inflammation.This study sought to characterise asthma control, exacerbation frequency and potential triggers of non-eosinophilic and specifically neutrophilic asthma such as infection, gastroesophageal reflux disease, and rhinosinusitis.	Adults with asthma (n=65; doctor's diagnosis plus demonstrated response to bronchodilator and/or airways hyperresponsiveness to hypertonic saline) were recruited from the Respiratory and Sleep Medicine Ambulatory Care Service at John Hunter Hospital, NSW, Australia. Questionnaires were administered to assess gastroesophageal reflux disease, rhinosinusitis and asthma control. A sputum induction was performed and sputum was processed for assessment of inflammatory cells, infection, and lipid laden macrophages (Oil Red O).	Participants with neutrophilic asthma (n=11, 23%) had a higher frequency of primary care doctor visits for asthma exacerbations and a high prevalence (> 70%) of chest infections in the previous 12 months. There was also an increased prevalence of rhinosinusitis (64%) and increased symptoms of gastroesophageal reflux disease compared to those with eosinophilic asthma.	The clinical pattern of neutrophilic asthma is different from paucigranulocytic and eosinophilic asthma with evidence of abnormal upper airways responses. Specific and targeted treatment of these airway problems may assist in the control and management of neutrophilic asthma.	
24639634	Under sleep loss, vigilance is reduced and attentional failures emerge progressively. It becomes difficult to maintain stable performance over time, leading to growing performance variability (i.e., state instability) in an individual and among subjects. Task duration plays a major role in the maintenance of stable vigilance levels, such that the longer the task, the more likely state instability will be observed. Vulnerability to sleep-loss-dependent performance decrements is highly individual and is also modulated by a polymorphism in the human clock gene PERIOD3 (PER3). By combining two different protocols, we manipulated sleep-wake history by once extending wakefulness for 40 h (high sleep pressure condition) and once by imposing a short sleep-wake cycle by alternating 160 min of wakefulness and 80 min naps (low sleep pressure condition) in a within-subject design. We observed that homozygous carriers of the long repeat allele of PER3 (PER3 (5/5) ) experienced a greater time-on-task dependent performance decrement (i.e., a steeper increase in the number of lapses) in the Psychomotor Vigilance Task compared to the carriers of the short repeat allele (PER3 (4/4) ). These genotype-dependent effects disappeared under low sleep pressure conditions, and neither motivation, nor perceived effort accounted for these differences. Our data thus suggest that greater sleep-loss related attentional vulnerability based on the PER3 polymorphism is mirrored by a greater state instability under extended wakefulness in the short compared to the long allele carriers. Our results undermine the importance of time-on-task related aspects when investigating inter-individual differences in sleep loss-induced behavioral vulnerability. 
24636782	Delirium is a disturbance of consciousness and cognition that results in a confusional state. It tends to fluctuate in intensity and is often observed in older patients. Sleep is a window of vulnerability for the occurrence of delirium and sleep disorders can play a role in its appearance. In particular, delirious episodes have been associated with obstructive sleep apnoea syndrome, which is reported to be frequent in the elderly. Hereby, we present a case-report documenting the sudden onset of a confusional state triggered by obstructive sleep apnoea-induced arousal, together with a review of the literature on the topic. We emphasise that, among the many pathogenic factors implicated in delirium, it is worth considering the possible link between nocturnal delirium and the occurrence of impaired arousals. Indeed, the complex confusional manifestations of delirium could be due, in part, to persistence of dysfunctional sleep activity resulting in an inability to sustain full arousal during behavioural wakefulness. Arousals can be triggered by sleep disturbances or other medical conditions. Clinicians should be aware that older patients may present disordered sleep patterns, and make investigation of sleep patterns and disorders potentially affecting sleep continuity a key part of their clinical workup, especially in the presence of cognitive comorbidities. Correct diagnosis and optimal treatment of sleep disorders and disrupted sleep can have a significant impact in the elderly, improving sleep quality and reducing the occurrence of abnormal sleep-related behaviours. 
24636462	Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition. Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study. Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS. 
24636002	We aimed to present psychometric properties and describe the score distributions of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P), a guardian-reported survey questionnaire for assessing sleep disturbances and problematic sleep habits among preschool children.Guardians of 2998 toddlers in three communities and guardians of 102 patients diagnosed with sleep disorders in two clinics completed the JSQ-P.	Exploratory factor analysis (EFA) revealed the 10 domains of the JSQ-P to be similar to our previous small-scale study and confirmed the robustness of the JSQ-P. The JSQ-P showed acceptable internal consistency; α coefficients ranged from 0.622 (insufficient sleep) to 0.912 (restless legs syndrome [RLS], motor) for the community sample and 0.696 (insufficient sleep) to 0.959 (RLS, motor) for the clinical sample. The score differentiations between the community and clinical samples associated with RLS, obstructive sleep apnea syndrome (OSAS), morning symptoms, parasomnias, excessive daytime sleepiness, and daytime behaviors were demonstrated in our study. The distributions of percentile T scores for each subscale and age and gender differentiation of scores also were evaluated.	We confirmed that the JSQ-P is a valid and reliable instrument to evaluate Japanese sleep habits using a large population-based sample. The JSQ-P may be useful in both clinical and academic settings.	
24635644	Fluctuations in sleep-wake state are thought to contribute to the respiratory instability of Cheyne-Stokes respiration in patients with heart failure by promoting the rhythmic occurrence of central apnea and ventilatory overshoot. There are no data, however, on the relationship between vigilance state and respiratory events. In this study we used a novel method to detect the occurrence of state transitions (time resolution: 0.25 s, minimum duration of state changes: 2 s) and to assess their time relationship with apnoeic events. We also evaluated whether end-apnoeic arousals are associated with a ventilatory overshoot. A polysomnographic, daytime laboratory recording (25 min) was performed during Cheyne-Stokes respiration in 16 patients with heart failure. Automatic state classification included wakefulness and non-rapid eye movement sleep stages 1-2. As a rule, wakefulness occurred during hyperpnoeic phases, and non-rapid eye movement sleep occurred during apnoeic events. Ninety-two percent of the observed central apneas (N = 272) were associated with a concurrent wakefulness → non-rapid eye movement sleep → wakefulness transition. The delay between wakefulness → non-rapid eye movement sleep transitions and apnea onset was -0.3 [-3.1, 3.0] s [median (lower quartile, upper quartile); P = 0.99 testing the null hypothesis: median delay = 0], and the delay between non-rapid eye movement sleep → wakefulness transitions and apnea termination was 0.2 [-0.5, 1.2] s (P = 0.7). A positive/negative delay indicates that the state transition occurred before/after the onset or termination of apnea. Non-rapid eye movement sleep → wakefulness transitions synchronous with apnea termination were associated with a threefold increase in tidal volume and a twofold increase in ventilation (all P < 0.001), indicating ventilatory overshoot. These findings highlight that wakefulness → non-rapid eye movement sleep → wakefulness transitions parallel apnoeic events during Cheyne-Stokes respiration in patients with heart failure. The relationships between state changes and respiratory events are consistent with the notion that state fluctuations promote ventilatory instability. 
24635581	It has been reported that sleep problems and neurocognitive deficit in asthmatic children is prevalent. However, systematic studies on these problems in stable asthma using polysomnography have rarely been performed. We therefore investigated sleep and neurocognitive functioning in children with well-controlled asthma. Forty-three children with well-controlled, stable asthma and 31 controls (age range: 6-9 years) were enrolled in the study. Subjects were questioned for daytime sleepiness using the Paediatric Daytime Sleepiness Scale. Complete overnight polysomnography and neurocognitive function tests were performed on all subjects. Children with stable asthma had lower pulmonary function in comparison to their age-matched controls. Asthmatic children had a higher apnea-hypopnea index (P < 0.001) and apnea-hypopnea-related arousal index (P < 0.001) as compared with non-asthmatics. Deep sleep was decreased in asthmatics (P = 0.001). In the vigilance test, the mean number of correct answers was lower (P = 0.005) and the mean reaction time was slower (P = 0.002) in asthmatic children. A hierarchical multiple linear regression showed that deep sleep and apnea-hypopnea-related arousal index were significant predictors of vigilance. The data suggest that the prevalence of paediatric sleep-disordered breathing and sleep fragmentation could be very high among children with well-controlled asthma. Moreover, vigilance, the ability to maintain attention and alertness, was worse in stable asthmatic children when compared with healthy controls. Sleep-disordered breathing should be checked even in stable asthmatic children as they are at risk for developing neurobehavioural deterioration associated with frequent arousals during sleep. Furthermore, early treatment for asthma may be required in order to prevent airway remodelling that could cause sleep problems.


24634631	Previous studies have demonstrated pronounced reduction of REM sleep on the first nights following major surgery which may influence pain, analgesic use, and recovery. This placebo-controlled, randomized, double-blind study set out to evaluate the effect of zolpidem on sleep architecture in an elderly population undergoing fast-track total hip and knee arthroplasty (THA/TKA) with length of stay < 3 days.Twenty patients (≥ 60 years) undergoing THA or TKA in a standardized setup with spinal anesthesia and multimodal opioid-sparing postoperative analgesia were included. Polysomnography measures were performed for 2 nights, 1 night at home prior to surgery and on the first night after surgery, when the patient received placebo or zolpidem 10 mg. Analgesic use, pain levels, and subjective measures of fatigue and sleep quality were recorded. Analysis of sleep data was performed according to the American Academy of Sleep Medicine manual.	Objective sleep data did not show a significant difference between groups in any of the sleep stages. However, subjective data on sleep quality and fatigue showed significantly less fatigue and better sleep quality in the zolpidem group (p < 0.05), and reduced objectively recorded number of arousals (p = 0.004). Levels of pain and opioid use were similar in the 2 groups.	Our objective data did not support the primary hypothesis that one night's treatment with zolpidem would significantly improve sleep architecture following major surgery, although there was improved feeling of sleep quality and fatigue associated with fewer postoperative arousals.	Krenk L; Jennum P; Kehlet H. Postoperative sleep disturbances after zolpidem treatment in fast-track hip and knee replacement.	

24633694	Behavioral sleep problems are common in children with attention-deficit/hyperactivity disorder (ADHD), as are internalizing and externalizing comorbidities. The prevalence of these difficulties and the extent to which they co-exist in children with ADHD could inform clinical practice, but remains unclear. Therefore, we examined the association between sleep problems and internalizing and externalizing comorbidities in children with ADHD. Children aged 5-13 years were recruited from 21 pediatric practices across Victoria, Australia (N = 392). Internalizing and externalizing comorbidities (none, internalizing, externalizing, co-occurring) were assessed by the telephone-administered Anxiety Disorders Interview Schedule for Children IV/Parent version. Sleep problem severity was assessed by primary caregiver report (no, mild, moderate or severe problem). Moderate/severe sleep problems were confirmed using International Classification of Sleep Disorders. Seven specific sleep problem domains (bedtime resistance, sleep anxiety, sleep onset delay, sleep duration, night waking, parasomnias and daytime sleepiness) were assessed using the Children's Sleep Habits Questionnaire. Data were analyzed using adjusted logistic and linear regression models. Compared to children without comorbidities, children with co-occurring internalizing and externalizing comorbidities were more likely to have moderate/severe sleep problems (adjusted OR 2.4, 95 % CI 1.2; 4.5, p = 0.009) and problematic sleep across six of seven sleep domains. Children with either comorbidity alone were not at risk of moderate/severe sleep problems, but at the sleep domain level, children with internalizing alone had more sleep anxiety, and those with externalizing alone had less night waking. In conclusion, children with ADHD experiencing co-occurring internalizing and externalizing comorbidities are at an increased risk of sleep problems.
24631194	Somatosensory amplification is the experience of sensing everyday bodily sensations as intense, agitating, and unpleasant. Using data from menopausal breast cancer survivors and midlife women without cancer, the study purposes were to (1) explore the psychometric properties of the Somatosensory Amplification Scale and (2) to describe somatosensory amplification and its relationship to menopausal symptoms of hot flashes, mood and sleep disturbance.This was a cross-sectional, descriptive, correlational study using demographic, e-diary, and questionnaire data from 99 breast cancer survivors and 138 midlife women.	Somatosensory amplification, hot flashes (frequency, severity, bother, interference, perceived control), mood, and sleep.	Cronbach's alphas for the scale were low. When an 8-item version of the scale was evaluated, alphas improved and item-total correlations remained strong or improved. Midlife women and breast cancer survivors did not have significantly different somatosensory amplification total or item scores after adjusting for group differences in demographics. Somatosensory amplification was significantly correlated with hot flash interference, perceived control over hot flashes, and mood and sleep disturbance in both groups but the patterns of correlations differed slightly between groups and depending on whether the 10-item or 8-item scale was used.	Somatosensory amplification may be a relevant concept to assess in relation to the menopausal symptom experience of midlife women with and without breast cancer as it may represent a potential intervention target to improve the menopausal symptom experience.	
24630177	Fatigue is related to a number of serious diseases, as well as to general well-being. It is also a major cause of sickness absence and use of health facilities. Still, the determinants of variations in fatigue are little investigated. The purpose of present study was to investigate the relationships between the daily variations of fatigue with sleep during the previous night, stress or disease symptoms during the same day - across 42 consecutive days of normal life.50 individuals participated and gave diary reports and used an actigraph across the 42days. The data was analyzed using a multilevel approach with mixed model regression.	The analyses showed that the day-to-day variation in fatigue was related to (poor) sleep quality (p<.001) and (reduced) sleep duration (p<.01) the previous night, as well as to higher stress (p<.05), and to the occurrence of a cold or fever (p<.001) during the same day as the fatigue rating. Fatigue was also strongly related to poorer subjective health (p<.001) and sleepiness (p<.001) during the same day.	The results indicate that prior sleep (and sleepiness) as well as stress and illness are consistently connected to how fatigue is experienced during normal living conditions.	
24629828	The main aim of this paper is to consider relevant theoretical and empirical factors defining optimal sleep, and assess the relative importance of each in developing a working definition for, or guidelines about, optimal sleep, particularly in children. We consider whether optimal sleep is an issue of sleep quantity or of sleep quality. Sleep quantity is discussed in terms of duration, timing, variability and dose-response relationships. Sleep quality is explored in relation to continuity, sleepiness, sleep architecture and daytime behaviour. Potential limitations of sleep research in children are discussed, specifically the loss of research precision inherent in sleep deprivation protocols involving children. We discuss which outcomes are the most important to measure. We consider the notion that insufficient sleep may be a totally subjective finding, is impacted by the age of the reporter, driven by socio-cultural patterns and sleep-wake habits, and that, in some individuals, the driver for insufficient sleep can be viewed in terms of a cost-benefit relationship, curtailing sleep in order to perform better while awake. We conclude that defining optimal sleep is complex. The only method of capturing this elusive concept may be by somnotypology, taking into account duration, quality, age, gender, race, culture, the task at hand, and an individual's position in both sleep-alert and morningness-eveningness continuums. At the experimental level, a unified approach by researchers to establish standardized protocols to evaluate optimal sleep across paediatric age groups is required. 

24628120	This study investigated levels of symptoms, caregiver burden, and changes over time in 278 family caregivers (FC) of cancer patients. FCs experienced high levels of depressive symptoms and sleep disturbance, low levels of fatigue, and low to moderate levels of caregiver burden, yet these symptoms remained relatively stable over time. Being female and not being employed were factors associated with an increased risk of symptoms and caregiver burden. The understanding evolving from this study can enhance social- and health care professionals' awareness of FCs' challenging situation and the potential impact this has on the FCs' ability to provide care to the patient. 

24626947	Depression is the most important neuropsychiatric complication in chronic kidney disease because it reduces quality of life and increases mortality. Evidence demonstrating the association between dialysis shift and depression is lacking; thus, obtaining such evidence was the main objective of this study.This cross-sectional study included patients attending a hemodialysis program. Depression was diagnosed using Beck's Depression Inventory. Excessive daytime sleepiness was evaluated using the Epworth Sleepiness Scale.	A total of 96 patients were enrolled (55 males, age 48±14 years). Depression and excessive daytime sleepiness were observed in 42.7% and 49% of the patients, respectively. When comparing variables among the three dialysis shifts, there were no differences in age, dialysis vintage, employment status, excessive daytime sleepiness, hemoglobin, phosphorus levels, or albumin levels. Patients in the morning shift were more likely to live in rural areas (p<0.0001), although patients in rural areas did not have a higher prevalence of depression (p = 0.30). Patients with depression were more likely to be dialyzed during the morning shift (p = 0.008). Independent risk factors for depression were age (p<0.03), lower levels of hemoglobin (p<0.01) and phosphorus (p<0.01), and dialysis during the morning shift (p = 0.0009). The hospitalization risk of depressive patients was 4.5 times higher than that of nondepressive patients (p<0.008).	These data suggest that depression is associated with dialysis shift, higher levels of phosphorus, and lower levels of hemoglobin. The results highlight the need for randomized trials to determine whether this association occurs by chance or whether circadian rhythm disorders may play a role.	
24625639	To explore the interactions of sleep quality and sleep duration and their effects on impaired fasting glucose (IFG) in Chinese adults.Cross-sectional survey.	Community-based investigation in Xuzhou, China.	15 145 Chinese men and women aged 18-75 years old who fulfilled the inclusion criteria.	The Pittsburgh Sleep Quality Index was used to produce sleep quality categories of good, common and poor. Fasting blood glucose levels were assessed for IFG. Sleep duration was measured by average hours of sleep per night, with categories of <6, 6-8 and >8 h. The products of sleep and family history of diabetes, obesity and age were added to the logistic regression model to evaluate the addictive interaction and relative excess risk of interaction (RERI) on IFG. The attributable proportion (AP) of the interaction and the synergy index (S) were applied to evaluate the additive interaction of two factors. Bootstrap measures were used to calculate 95% CI of RERI, AP and S.	The prevalence of IFG was greatest in those with poor sleep quality and short sleep duration (OR 6.37, 95% CI 4.66 to 8.67; p<0.001) compared with those who had good sleep quality and 6-8 h sleep duration, after adjusting for confounders. After adjusting for potential confounders RERI, AP and S values (and their 95% CI) were 1.69 (0.31 to 3.76), 0.42 (0.15 to 0.61) and 2.85 (2.14 to 3.92), respectively, for the interaction between poor sleep quality and short sleep duration, and 0.78 (0.12 to 1.43), 0.61 (0.26 to 0.87) and -65 (-0.94 to -0.27) for the interaction between good sleep quality and long sleep duration.	The results suggest that there are additive interactions between poor sleep quality and short sleep duration.	
24625311	Accumulating evidence suggests that dopamine plays a key role in sleep-wake regulation. Cerebral dopamine levels are regulated primarily by the dopamine transporter (DAT) in the striatum and by catechol-O-methyl-transferase (COMT) in the prefrontal cortex. We hypothesized that the variable-number-tandem-repeat (VNTR) polymorphism in the 3'-untranslated region of the gene encoding DAT (DAT1, SLC6A3; rs28363170) and the Val158Met polymorphism of COMT (rs4680) differently affect actigraphy-derived rest-activity cycles and sleep estimates in healthy adults (65 men; 45 women; age range: 19-35 years). Daytime sleepiness, continuous rest-actigraphy and sleep diary data during roughly 4-weeks were analyzed. Nine-repeat (9R) allele carriers of DAT1 (n = 48) more often reported elevated sleepiness (Epworth sleepiness score ≥10) than 10-repeat (10R) allele homozygotes (n = 62, p < 0.02). Moreover, male 9R allele carriers showed higher wrist activity, whereas this difference was not present in women ("DAT1 genotype" × "gender" interaction: p < 0.005). Rest-activity patterns did not differ among COMT genotypes. Nevertheless, a significant "COMT genotype" × "type of day" (workdays vs. rest days) interaction for sleep duration was observed (p = 0.04). The Val/Val (n = 36) and Met/Met (n = 24) homozygotes habitually prolonged sleep on rest days compared to workdays by more than 30 min, while Val/Met heterozygotes (n = 50) did not significantly extend their sleep (mean difference: 7 min). Moreover, whereas the proportion of women among the genotype groups did not differ, COMT genotype affected body-mass-index (BMI), such that Val/Met individuals had lower BMI than the homozygous genotypes (p < 0.04). While awaiting independent replication and confirmation, our data support an association of genetically-determined differences in cerebral dopaminergic neurotransmission with daytime sleepiness and individual rest-activity profiles, as well as other sleep-associated health characteristics such as the regulation of BMI. The differential associations of DAT1 and COMT polymorphisms may reflect the distinct local expression of the encoded proteins in the brain. 

24623507	Involuntarily exercising rats undergo more physical and mental stress than voluntarily exercising rats; however, these findings still lack electrophysiological evidence. Many studies have reported that theta rhythm appears when there is mental stress and that it is affected by emotional status. Thus we hypothesized that the differences between voluntary and involuntary movement should also exist in the hippocampal theta rhythm. Using the wheel and treadmill exercise models as voluntary and involuntary exercise models, respectively, this study wirelessly recorded the hippocampal electroencephalogram, electrocardiogram, and three-dimensional accelerations of young male rats. Treadmill and wheel exercise produced different theta patterns in the rats before and during running. Even though the waking baselines for the two exercise types were recorded in different environments, there did not exist any significant difference after distinguishing the rats' sleep/wake status. When the same movement-related parameters are considered, the treadmill running group showed more changes in their theta frequency (4-12 Hz), in their theta power between 9.5-12 Hz, and in their heart rate than the wheel running group. A positive correlation between the changes in high-frequency (9.5-12 Hz) theta power and heart rate was identified. Our results reveal various voluntary and involuntary changes in hippocampal theta rhythm as well as divergences in heart rate and high-frequency theta activity that may represent the effects of an additional emotional state or the sensory interaction during involuntary running by rats. 
24623353	Post-traumatic stress disorder (PTSD) is characterized by intrusive memories of a traumatic event, avoidance behavior related to cues of the trauma, emotional numbing, and hyper-arousal. Sleep abnormalities and nightmares are core symptoms of this disorder. In this review, we propose a model which implicates abnormal activity in the locus coeruleus (LC), an important modifier of sleep-wake regulation, as the source of sleep abnormalities and memory abnormalities seen in PTSD. Abnormal LC activity may be playing a key role in symptom formation in PTSD via sleep dysregulation and suppression of hippocampal bidirectional plasticity. 
24621477	The prevalence of osteoporosis and the incidence of age-related fragility fracture vary by ethnicity. There is greater than 10-fold variation in fracture probabilities between countries across the world. Mineral and bone metabolism are intimately interlinked, and both are known to exhibit patterns of daily variation, known as the diurnal rhythm (DR). Ethnic differences are described for Ca and P metabolism. The importance of these differences is described in detail between select ethnic groups, within the USA between African-Americans and White-Americans, between the Gambia and the UK and between China and the UK. Dietary Ca intake is higher in White-Americans compared with African-Americans, and is higher in White-British compared with Gambian and Chinese adults. Differences are observed also for plasma 25-hydroxy vitamin D, related to lifestyle differences, skin pigmentation and skin exposure to UVB-containing sunshine. Higher plasma 1,25-dihydroxy vitamin D and parathyroid hormone are observed in African-American compared with White-American adults. Plasma parathyroid hormone is also higher in Gambian adults and, in winter, in Chinese compared with White-British adults. There may be ethnic differences in the bone resorptive effects of parathyroid hormone, with a relative skeletal resistance to parathyroid hormone observed in some, but not all ethnic groups. Renal mineral excretion is also influenced by ethnicity; urinary Ca (uCa) and urinary P (uP) excretions are lower in African-Americans compared with White-Americans, and in Gambians compared with their White-British counterparts. Little is known about ethnic differences in the DR of Ca and P metabolism, but differences may be expected due to known differences in lifestyle factors, such as dietary intake and sleep/wake pattern. The ethnic-specific DR of Ca and P metabolism may influence the net balance of Ca and P conservation and bone remodelling. These ethnic differences in Ca, P and the bone metabolism may be important factors in the variation in skeletal health. 
24620624	Recently, reports have suggested grouping different autoimmune conditions that are triggered by external stimuli as a single syndrome called autoimmune syndrome induced by adjuvants (ASIA). This syndrome is characterized by the appearance of myalgia, myositis, muscle weakness, arthralgia, arthritis, chronic fatigue, sleep disturbances, cognitive impairment and memory loss, and the possible emergence of a demyelinating autoimmune disease caused by systemic exposure after vaccines and adjuvants. As there are no markers for ASIA, the authors intend to present ASIA, or Shoenfeld's syndrome, as an autoimmune syndrome induced by adjuvants.
24617761	To evaluate the effect of socioeconomic status on measures of sleep quality, continuity, and quantity in a large cohort of pregnant women.Prospective, longitudinal study.	One hundred seventy (170) pregnant women at 10-20 weeks gestation.	Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Sleep duration and continuity (sleep fragmentation index [SFI]) were assessed with actigraphy at 10-12, 14-16, and 18-20 weeks gestation. Because sleep did not significantly differ across time, averages across all three time points were used in analyses. Socioeconomic status (SES) was defined by self-reported annual household income. Linear regression analyses were used to model the independent associations of SES on sleep after adjusting for age, race, parity, marital status, body mass index (BMI), perceived stress, depressive symptoms, and financial strain.	On average, women reported modestly poor sleep quality (M = 5.4, SD = 2.7), short sleep duration (391 [55.6] min) and fragmented sleep (SFI M = 33.9, SD = 10.4. A household income < $50,000/year was associated with poorer sleep quality (β = -.18, p < 0.05) and greater sleep fragmentation (β = -.18, p < 0.05) following covariate adjustment.	Low SES was associated with poorer sleep quality and fragmented sleep, even after statistical adjustments. Perceived stress and financial strain attenuated SES-sleep associations indicating that psychosocial situations preceding pregnancy are also important to consider.	
24616658	The tight regulation of sleep/wake states is critical for mental and physiological wellbeing. For example, dysregulation of sleep/wake systems predisposes individuals to metabolic disorders such as obesity and psychiatric problems, including depression. Contributing to this understanding, the last decade has seen significant advances in our appreciation of the complex interactions between brain systems that control the transition between sleep and wake states. Pivotal to our increased understanding of this pathway was the description of a group of neurons in the lateral hypothalamus (LH) that express the neuropeptides orexin A and B (hypocretin, Hcrt-1 and Hcrt-2). Orexin neurons were quickly placed at center stage with the demonstration that loss of normal orexin function is associated with the development of narcolepsy-a condition in which sufferers fail to maintain normal levels of daytime wakefulness. Since these initial seminal findings, much progress has been made in our understanding of the physiology and function of the orexin system. For example, the orexin system has been identified as a key modulator of autonomic and neuroendocrine function, arousal, reward and attention. Notably, studies in animals suggest that dysregulation of orexin function is associated with neuropsychiatric states such as addiction and mood disorders including depression and anxiety. This review discusses the progress associated with therapeutic attempts to restore orexin system function and treat neuropsychiatric conditions such as addiction, depression and anxiety. We also highlight potential pitfalls and challenges associated with targeting this system to treat these neuropsychiatric states. 
24616334	The role of noise as an environmental pollutant and its impact on health are being increasingly recognized. Beyond its effects on the auditory system, noise causes annoyance and disturbs sleep, and it impairs cognitive performance. Furthermore, evidence from epidemiologic studies demonstrates that environmental noise is associated with an increased incidence of arterial hypertension, myocardial infarction, and stroke. Both observational and experimental studies indicate that in particular night-time noise can cause disruptions of sleep structure, vegetative arousals (e.g. increases of blood pressure and heart rate) and increases in stress hormone levels and oxidative stress, which in turn may result in endothelial dysfunction and arterial hypertension. This review focuses on the cardiovascular consequences of environmental noise exposure and stresses the importance of noise mitigation strategies for public health. 
24616231	This study aimed to better understand how minor mental health problems (MMPs) are perceived by well-educated urban dwellers in China who are influenced by Western values. Urban China is a rapidly changing society in which traditional Chinese culture and Western thought coexist. As a result, the established processes of interdependent self-appraisal have been challenged and a sense of a bicultural self has developed among a growing proportion of the population. The fieldwork for this study included interviews and observations. The results are derived mainly from interviews with professional practitioners, students, and lay people from three urban sites. One of the main findings was that respondents who referred to traditional and collectivistic Chinese values tended not to label MMPs as psychiatric disorders or illnesses but as challenges in daily life and relationships strain. While the Western medical model of MMPs considers them a form of illness, they were not viewed in this way in traditional collectivistic China in the past, even among educated urban dwellers. However, the urban and educated Chinese who have developed a stronger sense of a bicultural self are now more likely to perceive and deal with MMPs from a Western viewpoint. 
24614968	This paper aims to compare the absolute performance of three noncontact sleep measurement devices for measuring sleep parameters in normal subjects against polysomnography and to assess their relative performance.The devices investigated were two noncontact radio-frequency biomotion sensors (SleepMinder (SM) and SleepDesign (HSL-101)) and an actigraphy-based system (Actiwatch). Overnight polysomnography measurements were carried out in 20 normal subjects, with simultaneous assessment of sleep parameters using the three devices. The parameters measured included total sleep time (TST), sleep efficiency (SE), sleep-onset latency (SOL), and wake-after-sleep onset (WASO). The per-epoch agreement level for sleep/wake distinction was evaluated.	The TSTs reported by the three devices were 426 ± 34, 434 ± 22, and 441 ± 16 min, for the SM, HSL-101, and Actiwatch, respectively, against polysomnogram (PSG)-reported TST of 391 ± 49 min. The SOLs were 10 ± 10, 5 ± 6, and 3 ± 2 min for the SM, HSL-101 and Actiwatch, respectively against PSG SOL of 19 ± 13 min. The WASO times were 46 ± 33, 43 ± 22, and 38 ± 17 min, as against PSG-reported 69 ± 46 min. All three devices had a statistically significant bias to overestimate sleep time and underestimate WASO and SOL compared with PSG. The performance of the three devices was basically equivalent, with only minor interdevice differences. The overall per-epoch agreement levels were 86 % for the SM, 86 % for the HSL-101, and 85 % for the Actiwatch.	Noncontact biomotion approaches to sleep measurement provided reasonable estimates of TST, but with a bias to over-estimation of sleep. The radio-frequency biomotion sensors provided similar accuracies for sleep/wake determination in normal subjects as the actigraph used in this study and slightly improved estimates of TST, SOL, and WASO.	
24613865	Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for patients with Parkinson's disease (PD), especially those with advanced motor complications. The effect of STN DBS on non motor symptoms (NMS) of PD is less well studied. In this article, we review the pertinent literature on the impact of STN DBS on NMS when they co-exist with disabling motor symptoms in PD patients. We also present evidence that the number and the severity of most NMS decrease after STN DBS which can have a major impact on patients' quality of life. 
24613533	A majority of women will experience bothersome symptoms related to declining and/or fluctuating levels of estrogen during their menopausal transition. Vasomotor symptoms, vaginal dryness, poor sleep, and depressed mood have all been found to worsen during the menopausal transition. While vasomotor symptoms gradually improve after menopause, the time course can be many years. Vaginal dryness does not improve without treatment, while the long-term course of sleep and mood deterioration is not clearly defined at this time. A small minority of women have vasomotor symptoms that persist throughout the remainder of their lives. These common menopausal symptoms all improve with estrogen treatment. Over the last 10 years, we have witnessed a dramatic reduction in enthusiasm for menopausal hormone therapy, despite its high efficacy relative to other treatments. We have also seen the emergence of sound, evidence-based clinical trials of non-hormonal alternatives that can control the common menopausal symptoms. Understanding the natural history of menopausal symptoms, and the risks and benefits of both hormonal and non-hormonal alternatives, helps the clinician individualize management plans to improve quality of life. 
24613308	The basal forebrain (BF) plays a crucial role in cortical activation [1, 2]. However, the exact role of cholinergic BF (ch-BF) neurons in the sleep-wake cycle remains unclear [3, 4]. We demonstrated that photostimulation of ch-BF neurons genetically targeted with channelrhodopsin 2 (ChR2) was sufficient to induce an immediate transition to waking or rapid eye movement (REM) sleep from slow-wave sleep (SWS). Light stimulation was most likely to induce behavioral arousal during SWS, but not during REM sleep, a result in contrast to the previously reported photostimulation of noradrenergic or hypocretin neurons that induces wake transitions from both SWS and REM sleep. Furthermore, the ratio of light-induced transitions from SWS to wakefulness or to REM sleep did not significantly differ from that of natural transitions, suggesting that activation of ch-BF neurons facilitates the transition from SWS but does not change the direction of the transition. Excitation of ch-BF neurons during wakefulness or REM sleep sustained the cortical activation. Stimulation of these neurons for 1 hr induced a delayed increase in the duration of wakefulness in the subsequent inactive period. Our results suggest that activation of ch-BF neurons alone is sufficient to suppress SWS and promote wakefulness and REM sleep.
24612632	Few studies have examined the broad health effects of occupational exposures in flight attendants apart from disease-specific morbidity and mortality studies. We describe the health status of flight attendants and compare it to the U.S. population. In addition, we explore whether the prevalence of major health conditions in flight attendants is associated with length of exposure to the aircraft environment using job tenure as a proxy.We surveyed flight attendants from two domestic U.S. airlines in 2007 and compared the prevalence of their health conditions to contemporaneous cohorts in the National Health and Nutrition Survey (NHANES), 2005-2006 and 2007-2008. We weighted the prevalence of flight attendant conditions to match the age distribution in the NHANES and compared the two populations stratified by gender using the Standardized Prevalence Ratio (SPR). For leading health conditions in flight attendants, we analyzed the association between job tenure and health outcomes in logistic regression models.	Compared to the NHANES population (n =5,713), flight attendants (n = 4,011) had about a 3-fold increase in the age-adjusted prevalence of chronic bronchitis despite considerably lower levels of smoking. In addition, the prevalence of cardiac disease in female flight attendants was 3.5 times greater than the general population while their prevalence of hypertension and being overweight was significantly lower. Flight attendants reported 2 to 5.7 times more sleep disorders, depression, and fatigue, than the general population. Female flight attendants reported 34% more reproductive cancers. Health conditions that increased with longer job tenure as a flight attendant were chronic bronchitis, heart disease in females, skin cancer, hearing loss, depression and anxiety, even after adjusting for age, gender, body mass index (BMI), education, and smoking.	This study found higher rates of specific diseases in flight attendants than the general population. Longer tenure appears to explain some of the higher disease prevalence. Conclusions are limited by the cross-sectional design and recall bias. Further study is needed to determine the source of risk and to elucidate specific exposure-disease relationships over time.	
24612225	We aimed to determine Axis-I psychiatric disorders in patients with chronic pain (CP) and compare control subjects determined by a structured clinical interview. Another objective of the study was to examine whether there is an association between psychiatric disorders and quality of sleep, quality of life, and demographic and clinical characteristics in patients with CP.The study sample was comprised of 108 patients with CP and 54 control subjects without pain. Psychiatric interviews were conducted with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (SCID). Also used were the Hospital Anxiety and Depression Scale, Hamilton Depression Inventory, Short Form-36, and Pittsburgh Sleep Quality Index (PSQI).	The rate of any Axis-I psychiatric disorder stood at 66.7% (any mood disorder, 50%; any anxiety disorder, 33.3%; any somatoform disorder, 20.4%; any substance use disorder, 16.6%), significantly more common in the patients' group compared with the control group. The most common psychiatric disorder was major depression (49.1%) in subjects with CP. Female gender, numbers of localization, and neck and back localizations were significantly higher in the SCID (+) group than the SCID (-) group. A statistically significant difference was observed between the SCID (+) and SCID (-) groups regarding visual analogue scale, depression and anxiety scores, mental component summary score, and global PSQI scores.	Results of this study suggest that psychiatric morbidity in patients with CP is frequently seen and may adversely affect quality of sleep and quality of life of the patients. Therefore, the patients with CP should be examined with respect to their mental status.	
24611789	Sluggish cognitive tempo (SCT) and daytime sleepiness are both common in individuals with attention-deficit/hyperactivity disorder (ADHD). There appears to be considerable overlap between the tired and lethargic aspects of SCT and behaviors frequently exhibited by individuals with daytime sleepiness. However, no studies have examined the degree to which these constructs overlap and whether or not they are empirically distinct. In Study 1, a confirmatory factor analysis with the SCT subscale of the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) and the Epworth Sleepiness Scale (ESS) was conducted in a sample of 768 college students. Results demonstrated that SCT and daytime sleepiness exhibit considerable overlap but are empirically distinct. In Study 2, we examined the relation between SCT and daytime sleepiness and also the impact of comorbid SCT and sleepiness on the functioning of 58 college students rigorously diagnosed with ADHD. Regression analyses in both Study 1 and Study 2 showed that SCT predicts daytime sleepiness above and beyond symptoms of ADHD, anxiety, and depression. The 2 constructs were significantly related (r = .51), with the highest correlations occurring between the SCT tired and lethargic items with daytime sleepiness. College students with ADHD + SCT and daytime sleepiness were significantly more impaired than college students diagnosed with ADHD without SCT or daytime sleepiness. Together, these results fill an important gap in the literature by confirming SCT to be overlapping but empirically distinct from daytime sleepiness and demonstrating that SCT and daytime sleepiness are associated with functioning in college students with ADHD.
24611534	Sleep-temperament associations have not yet been examined among university students, despite awareness of the high incidence of sleep problems in this population. The present study was conducted (a) to examine whether sleep quality was associated with temperament among university-attending young adults and (b) to determine whether particular components of sleep quality were differentially associated with temperament. University students completed questionnaires designed to assess sleep quality and temperament. Poor sleep quality was associated with increased negative affect and orienting sensitivity as well as decreased effortful control; regression analyses revealed differential associations between components of nighttime sleep quality and temperament ratings. The presented study reveals conceptual continuity in sleep-temperament relations from infancy to young adulthood and highlights important avenues for future research. 
24611503	The aims of this investigation are to determine whether loneliness is associated with a person's own sleep quality and sleep quality of their partner, and to test stress as a potential mediator. Participants were 255 couples in married (75%) or cohabiting relationships who completed self-report measures of loneliness, sleep quality, stress, and depression. Results of Actor-Partner Interdependence analyses replicated findings in the literature showing an association between loneliness and poor sleep quality. The more lonely a male participant was, the lower his partner's sleep quality. In addition, the more lonely participants were, the higher they rated their partner's sleep disturbance. There were significant indirect effects of loneliness on poor sleep quality through increased stress, even after controlling for depression. 

24610704	Tasimelteon (HETLIOZ™) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder. It is the first US FDA-approved medication for this orphan indication. Melatonin is thought to play a role in governing the body's natural sleep-wake cycle through physiological processes regulated in the suprachiasmatic nucleus of the hypothalamus. The hormone is secreted by the pineal gland, with onset typically occurring when daylight begins to dim. In healthy, sighted individuals, the endogenous circadian period is a little over 24 hours, but is entrained to the 24-hour day through exposure to environmental cues, such as light and darkness. In the absence of these cues, synchronisation is lost and the circadian rhythm follows the intrinsic non-24-hour clock, resulting in disorders like non-24-hour sleep-wake disorder. Because the rhythm of endogenous melatonin is considered to be a measure of the human circadian phase, the carefully timed administration of melatonin analogues, such as tasimelteon, can potentially promote circadian readjustment. This article summarizes the milestones in the development of tasimelteon leading to this first approval for the treatment of non-24-hour sleep-wake disorder. 
24607658	Particulate matter with aerodynamic diameter of <2.5 μm (PM2.5) is associated with blood pressure and hemodynamic changes. Blunted nocturnal blood pressure dipping is a major risk factor for cardiovascular events; limited information is available on whether PM2.5 exposure-related hemodynamic changes vary with day-night blood pressure circadian rhythms. In this study, we enrolled 161 subjects and monitored the changes in ambulatory blood pressure and hemodynamics for 24h. The day-night blood pressure and cardiovascular metrics were calculated according to the sleep-wake cycles logged in the subject׳s diary. The effects of PM2.5 exposure on blood pressure and hemodynamic changes were analyzed using generalized linear mixed-effect model. After adjusting for potential confounders, a 10-μg/m(3) increase in PM2.5 was associated with 1.0 mmHg [95% confidence interval (CI): 0.2-1.8 mmHg] narrowing in the pulse pressure, 3.1% (95% CI: 1.4-4.8%) decrease in the maximum rate of left ventricular pressure rise, and 3.6% (95% CI: 1.6-5.7%) increase in systemic vascular resistance among 79 subjects with nocturnal blood pressure dip of <10%. In contrast, PM2.5 was not associated with any changes in cardiovascular metrics among 82 subjects with nocturnal blood pressure dip of ≥10%. Our findings demonstrate that short-term exposure to PM2.5 contributes to pulse pressure narrowing along with cardiac and vasomotor dysfunctions in subjects with nocturnal blood pressure dip of <10%.
24606809	Circadian rhythms are known to influence a variety of biological phenomena such as cell cycle, sleep-wake rhythm, hormone release and other important physiological functions. Given that cell cycle entry of hibernating hematopoietic stem cells (HSCs) plays a critical role in controlling hematopoiesis, we asked functional significance of the clock gene Bmal1, which plays a central role in regulating circadian rhythms as a transcription factor. Here we investigated the necessity of Bmal1 for HSC functions using Bmal1 deficient (Bmal1⁻/⁻) mice.Using colony-forming assays in vitro, we found that the frequency of mixed colony formation between Bmal1⁺/⁺ and Bmal1⁻/⁻ CD34-KSL cells does not differ significantly. Competitive bone marrow assays also revealed that Bmal1⁻/⁻ bone marrow cells competed normally with wild-type cells and displayed long-term multi-hematopoietic lineage reconstitution. In addition, there were no significant differences in the frequencies and hibernation state of bone marrow HSCs between Bmal1⁺/⁺ and Bmal1⁻/⁻ mice, suggesting that they are independent of circadian rhythms.	This paper discusses the necessity of circadian rhythms for HSC functions. Our data clearly shows that a key circadian clock gene Bmal1 is dispensable for intrinsic functions of HSCs, such as differentiation, proliferation and repopulating ability.	
24605819	Sleep problems in children are associated with poor health, behavioural and cognitive problems, as are deficiencies of long-chain omega-3 fatty acids such as docosahexaenoic acid. Theory and some evidence support a role for these fatty acids in sleep regulation, but this issue has received little formal investigation. We examined associations between blood fatty acid concentrations (from fingerstick blood samples) and subjective sleep (using an age-standardized parent questionnaire) in a large epidemiological sample of healthy children aged 7-9 years (n = 395) from mainstream UK schools. In a randomized controlled trial, we then explored whether 16-week supplementation (600 mg day(-1) ) with algal docosahexaenoic acid versus placebo might improve sleep in a subset of those children (n = 362) who were underperforming in reading. In a randomly selected subsample (n = 43), sleep was also assessed objectively via actigraphy. In 40% of the epidemiological sample, Child Sleep Habits Questionnaire scores indicated clinical-level sleep problems. Furthermore, poorer total sleep disturbance scores were associated weakly but significantly with lower blood docosahexaenoic acid (std coeff. -0.105*) and a lower docosahexaenoic acid : arachidonic acid ratio (std coeff. -0.119**). The treatment trial showed no significant effects on subjective sleep measures. However, in the small actigraphy subsample, docosahexaenoic acid supplementation led on average to seven fewer wake episodes and 58 min more sleep per night. Cautiously, we conclude that higher blood levels of docosahexaenoic acid may relate to better child sleep, as rated by parents. Exploratory pilot objective evidence from actigraphy suggests that docosahexaenoic acid supplementation may improve children's sleep, but further investigations are needed.
24605542	In elderly, biological changes cause circadian rhythm disturbance, and sleep disorders are often observed. The risk of sleep disorders is higher in dementia patients, sleep disorders are causes of care burden increase. In treatments of sleep disorders in dementia patients, it is important to evaluate correctly about sleep disorders and to check BPSD which merges to insomnia. In clinical, nonpharmacological therapies, such as an improvement of a lifestyle and cause removal of insomnia, are first choices. In medication, when other psychological symptoms and BPSDs merge, use of an easy sleeping drug is avoided, and medication of antidepressants or atypical antipsychotics is considered, but these medications use requires cautions about insurance adaptation and side effects.
24604714	Behavioral contributions to the pathogenesis of prediabetes and Type 2 diabetes (T2D) include lifestyle behaviors including dietary intake, exercise, sedentariness, sleep, and stress. The purpose of this paper is to review evidence for the metabolic pathways by which the behavior is linked to T2D. Evidence for interventions, which change each of the lifestyle behaviors, is discussed. The article will close with a brief discussion on how new technologies may provide opportunities to better understand relationships between moment-to-moment fluctuations in behaviors and diabetes pathogenesis, as well as provide opportunities to personalize and adapt interventions to achieve successful behavior change and maintenance of that change. Especially promising are new technologies, which assist in tracking lifestyle behaviors along with clinical and metabolic outcomes. 
24604677	Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most common spinocerebellar ataxia. In this neurological disease, anatomical, physiological, clinical, and functional neuroimaging demonstrate a degenerative process besides the cerebellum. We performed neurophysiological and neuroimaging studies-polysomnography, transcranial sonography, vestibular-evoked myogenic potential, single-photon emission computed tomography (SPECT) with (99m)Tc-TRODAT-1, and a formal neuropsychological evaluation in a patient with sleep complaints and positive testing for Machado-Joseph disease, without cerebellar atrophy, ataxia, or cognitive complaints. Polysomnography disclosed paradoxical high amplitude of submental muscle, characterizing REM sleep without atonia phenomenon. Transcranial sonography showed hyperechogenicity of the substantia nigra. There was an absence of vestibular-evoked myogenic potentials on both sides in the patient under study, in opposite to 20 healthy subjects. Brain imaging SPECT with (99m)Tc-TRODAT-1 demonstrated a significant lower DAT density than the average observed in six healthy controls. Electroneuromyography was normal. Neuropsychological evaluation demonstrated visuospatial and memory deficits. Impairment of midbrain cholinergic and pontine noradrenergic systems, dysfunction of the pre-synaptic nigrostriatal system, changes in echogenicity of the substantia nigra, and damage to vestibulo-cervical pathways are supposed to occur previous to cerebellar involvement in Machado-Joseph disease. 
24604478	Motor vehicle accidents associated with commercial driving are an important cause of occupational death and impact public safety.We summarise the evidence regarding the type, prevalence and impact of medical conditions discovered during health assessment of commercial drivers.	We conducted a systematic review of multiple electronic databases and made a manual search for relevant studies that enrolled commercial drivers in any country and reported the outcomes of health assessment carried out in the context of commercial driving through November 2012. Data were extracted by a pair of independent reviewers and synthesised using a metanarrative approach.	We identified 32 studies of moderate methodological quality enrolling 151 644 commercial drivers (98% men). The prevalence of multiple health conditions was high (sleep disorders 19%, diabetes 33%, hypertension 23% and obesity 45%). Some conditions, such as sleep disorders and obesity, were linked to increased risk of crashes. Evidence on several other highly relevant medical conditions was lacking. Cost-effectiveness data were sparse.	Several medical conditions are highly prevalent in commercial drivers and can be associated with increased risk of crashes, thus providing a rationale for health assessment of commercial drivers.	
24604461	To explore the effect of cognitive behavioral therapy (CBT) in combination with systemic family therapy (SFT) on mild to moderate postpartum depression and sleep quality.249 primiparous women with mild to moderate postpartum depression were recruited and randomly assigned to a control group (n=128), which received conventional postpartum care, or to a psychological intervention group (n=121), which received conventional postpartum care combined with psychological intervention. The Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate depression and sleep quality, respectively.	104 patients in the intervention group and 109 in the control group completed the study. After intervention, the EPDS score, PSQI score, sleep quality score, sleep latency score, sleep duration score, habitual sleep efficiency score, sleep disturbance score, and daytime dysfunction score were significantly lower in the intervention group than in the control group. The EPDS and PSQI scores of each group at different time points after intervention were markedly decreased compared with those before intervention, and the reduction in the intervention group was more evident than that in the control group.	CBT in combination with SFT can improve depression and sleep quality in patients with mild to moderate postpartum depression.	
24604372	Sleep medicine is a relatively new field among Medical Sciences. Its legal aspects are still obscure, either for lack of knowledge of the biological mechanisms underlying violent behaviour during sleep or the virtual absence of clear legal and uniformly accepted guidelines as to whether to punish or treat those disorders. An updated review of the pertinent literature was performed to determine the most prevalent pathological conditions involving violence and sleep and to identify their most common precipitating factors, attempting to provide some technical support to aid Brazilian medical-experts or assistants in preparing substantial and scientific-based reports in a legal environment. 
24603053	The pontine Kölliker-Fuse nucleus (KF) has established functions in the regulation of inspiratory-expiratory phase transition and the regulation of upper airway patency via laryngeal valving mechanisms. Here we studied the role of the KF in the gating and modulation of eupneic hypoglossal motor activity (HNA) using the in situ perfused brainstem preparation, which displays robust inspiratory HNA. Microinjection of glutamate into the KF area triggered complex and often biphasic modulation (excitation/inhibition or inhibition/excitation) of HNA. Subsequent transient pharmacological inhibition of KF by unilateral microinjection of GABA-A receptor agonist isoguvacine reduced HNA and while bilateral microinjections completely abolished HNA. Our results indicate that mixed and overlapping KF pre-motor neurons provide eupneic drive for inspiratory HNA and postinspiratory vagal nerve activity. Both motor activities have important functions in the regulation of upper airway patency during eupnea but also during various oro-pharyngeal behaviors. These results have potential implications in the contribution of state-dependent modulation of KF hypoglossal pre-motor neurons during sleep-wake cycle to obstructive sleep apnea. 
24602983	Short duration immobilization stress (IS) in younger rats is followed by a sleep rebound involving slow wave sleep (SWS) and, more particularly, rapid eye movement (REM) sleep. This rebound, expressing the ability of the brain to confront a stress challenge, is now accepted as a marker of the homeostasis. In older rats (24-25 months), however, an IS of 1h is not followed by a sleep rebound. To determine whether this impairment is reversible, we analyzed the effects of the antidepressant agomelatine, on stress-related sleep rebound in older animals. Older and younger (3-5 months) rats were equipped with electroencephalographic (EEG) and electromyographic (EMG) electrodes and polygraphic recordings were achieved under basal conditions with a digitized set-up. Older rats were pretreated with agomelatine (40mg/kg/day) for 3 days, with IS applied on the third day, whereas younger rats were only subjected to IS. Polygraphic recordings achieved under basal conditions confirmed the conventional impairments of the sleep/wake architecture in older animals, including decreased delta power, shortened REM sleep bouts, and modified sleep/wake circadian rhythms. Older rats pretreated with agomelatine for 3 days showed a reversal of the deficit observed in the beta-1, but not in the delta, EEG power band. Application of an IS to older rats after agomelatine pretreatment resulted in a REM sleep rebound in response to stress. These findings indicate that agomelatine, by improving beta-1 EEG power band and by inducing stress-related sleep rebound in older animals, contributes to the homeostasis maintenance. 
24599632	To evaluate the accuracy of a neck-worn device in measuring sleep/wake, detecting supine airway position, and using loud snoring to screen for obstructive sleep apnea. Study A included 20 subjects who wore the neck-device during polysomnography (PSG), with 31 records obtained from diagnostic and split-night studies. Study B included 24 community-based snorers studied in-home for up to three-nights with obstructive sleep apnea (OSA) severity measured with a validated Level III recorder. The accuracy of neck actigraphy-based sleep/wake was measured by assessing sleep efficiency (SE). Differences in sleep position measured at the chest and neck during PSG were compared to video-editing. Loud snoring acquired with an acoustic microphone was compared to the apnea-hypopnea index (AHI) by- and acrosspositions. Over-reported SE by neck actigraphy was inversely related to OSA severity. Measurement of neck and chest supine position were highly correlated with video-edits (r=0.93, 0.78). Chest was bias toward over-estimating supine time while the majority of neck-device supine position errors occurred during CPAP titrations. Snoring was highly correlated with the overall, supine, and non-supine PSG-AHI (r=0.79, 0.74, 0.83) and was both sensitive and specific in detecting overall, supine, and non-supine PSGAHI>10 (sensitivity=81, 88, 82%; specificity=87, 79, 100%). At home sleep testing-AHI>10, the sensitivity and specificity of loud snoring was superior when users were predominantly non-supine as compared to baseline (sensitivity=100, 92%; specificity=88, 77%). Neck actigraphy appears capable of estimating sleep/wake. The accuracy of supine airway detection with the neck-device warrants further investigation. Measurement of loud snoring appears to provide a screening tool for differentiating positional apneic and benign snorers.
24599302	The present study had two main objectives. The first objective was to compare the sleep architecture of young and older adults, with an emphasis on sleep spindle density and REM density. The second objective was to examine two aspects of age differences that have not been considered in previous studies: age differences in the variability of sleep measures as well as the magnitude of age differences in phasic events across the distribution of values (i.e., at each decile rather than a single measure of location such as the mean or median. A total of 24 young (mean age=20.75 ± 1.78 years) and 24 older (mean age=71.17 ± 6.15 years) adults underwent in-home polysomnography. Whole-night spindle density was significantly higher in young adults than older adults. The two age groups did not differ significantly in whole-night REM density, although significant increases in REM density across the night were observed in both age groups. These results suggest that spindle density is more affected by age than REM density. Although age differences were observed in the degree of absolute variability (older adults had significantly larger variances than young adults for sleep efficiency and time spent awake after sleep onset), a similar pattern was also observed within the two age groups: the four sleep measures with the lowest degrees of relative variability were the same and included time spent in REM and Stage 2 sleep, total sleep time, and sleep efficiency. The distributional analysis of age differences in sleep spindle density revealed that the largest age differences were initially observed in the middle of the distributions, but as the night progressed, they were seen at the upper end of the distributions. The results reported here have potential implications for the causes and functional implications of age-related changes in sleep architecture.
24597158	Implementation of Fatigue Risk Management Systems (FRMS) is gaining momentum; however, agreed safety performance indicators (SPIs) are lacking. This paper proposes an initial set of SPIs based on measures of crewmember sleep, performance, and subjective fatigue and sleepiness, together with methods for interpreting them.Data were included from 133 landing crewmembers on 2 long-range and 3 ultra-long-range trips (4-person crews, 3 airlines, 220 flights). Studies had airline, labor, and regulatory support, and underwent independent ethical review. SPIs evaluated preflight and at top of descent (TOD) were: total sleep in the prior 24 h and time awake at duty start and at TOD (actigraphy); subjective sleepiness (Karolinska Sleepiness Scale) and fatigue (Samn-Perelli scale); and psychomotor vigilance task (PVT) performance. Kruskal-Wallis nonparametric ANOVA with post hoc tests was used to identify significant differences between flights for each SPI.	Visual and preliminary quantitative comparisons of SPIs between flights were made using box plots and bar graphs. Statistical analyses identified significant differences between flights across a range of SPls.	In an FRMS, crew fatigue SPIs are envisaged as a decision aid alongside operational SPIs, which need to reflect the relevant causes of fatigue in different operations. We advocate comparing multiple SPIs between flights rather than defining safe/unsafe thresholds on individual SPIs. More comprehensive data sets are needed to identify the operational and biological factors contributing to the differences between flights reported here. Global sharing of an agreed core set of SPIs would greatly facilitate implementation and improvement of FRMS.	

24596244	We studied the interaction between glucocorticoid (GC) level and sleep/wake state during memory consolidation. Recent research has accumulated evidence that sleep supports memory consolidation in a unique physiological process, qualitatively distinct from consolidation occurring during wakefulness. This appears particularly true for memories that rely on the hippocampus, a region with abundant expression of GC receptors. Against this backdrop we hypothesized that GC effects on consolidation depend on the brain state, i.e., sleep and wakefulness. Following exploration of two objects in an open field, during 80 min retention periods rats received an intrahippocampal infusion of corticosterone (10 ng) or vehicle while asleep or awake. Then the memory was tested in the hippocampus-dependent object-place recognition paradigm. GCs impaired memory consolidation when administered during sleep but improved consolidation during the wake retention interval. Intrahippocampal infusion of GC or sleep/wake manipulations did not alter novel-object recognition performance that does not require the hippocampus. This work corroborates the notion of distinct consolidation processes occurring in sleep and wakefulnesss, and identifies GCs as a key player controlling distinct hippocampal memory consolidation processes in sleep and wake conditions.
24594864	This study aims to develop the Menopausal Interpretations/Perceptions Questionnaire (MIPQ) using confirmatory factor analysis.A descriptive cross-sectional design was used to examine the MIPQ. We recruited 228 women through mail-outs and word of mouth. The women were aged between 45 and 64 years (mean [SD], 55.6 [5.2] y) and were able to read and write English. Most were non-Hispanic white (63.4%), college-educated (74.2%), and postmenopausal (76.8%). We modified the Revised Illness Perception Questionnaire to reflect menopausal perception by substituting the word "menopause" or "menopausal symptoms" for the word "illness" to develop the MIPQ.	Using confirmatory factor analysis to test the MIPQ model, we deleted 22 items that did not reflect their respective subscales (latent variable). The fit indices indicated acceptable fit (χ209 = 425.5; P = 0.000; goodness of fit = 0.96; comparative fit index = 0.93; root mean square error of approximation = 0.07; 90% CI, 0.06-0.08; Akaike information criterion = 559.5). There were significant correlations among the MIPQ constructs. Correlations between the MIPQ subscales and the Greene Climacteric Scale were significant and in the expected direction, supporting construct validity. The intercorrelations between the MIPQ subscales supported the discriminant validity of the constructs.	The MIPQ provides a comprehensive measure of menopausal experience to more fully understand women's interpretations/perceptions of their experiences. Future researchers should further examine the construct validity of the MIPQ.	

24590405	No data are available regarding the occurrence of sleep disorders in spinal and bulbar muscular atrophy (SBMA). We investigated the sleep-wake cycle in SBMA patients compared with healthy subjects. Nine SBMA outpatients and nine age-matched and sex-matched healthy controls were evaluated. Subjective quality of sleep was assessed by means of the Pittsburgh Sleep Quality Index (PSQI). The Epworth Sleepiness Scale was used in order to evaluate excessive daytime sleepiness. All participants underwent a 48-h polysomnography followed by the multiple sleep latency test. Time in bed, total sleep time and sleep efficiency were significantly lower in SBMA than controls. Furthermore, the apnea-hypopnea index (AHI) was significantly higher in SBMA than controls. Obstructive sleep apnea (OSA: AHI >5/h) was evident in 6/9 patients (66.6 %). REM sleep without atonia was evident in three patients also affected by OSA and higher AHI in REM; 2/9 (22.2 %) SBMA patients showed periodic limb movements in sleep. The global PSQI score was higher in SBMA versus controls. Sleep quality in SBMA is poorer than in controls. OSA is the most common sleep disorder in SBMA. The sleep impairment could be induced both by OSA or/and the neurodegenerative processes involving crucial areas regulating the sleep-wake cycle.

24589672	Sleep duration and media use (ie, computer use and television viewing) have important implications for the health and well-being of children. Population data suggest that shorter sleep duration and excessive screen time are growing problems among children and could be interacting issues.To examine whether bidirectional relationships exist between sleep duration and media use among children, and whether these associations are moderated by child- and household-related factors.	Cohort study of a representative sample of 3427 Australian children (4-5 years of age at baseline [51.2%male children]), obtained from the Longitudinal Study of Australian Children. Data were available from 3 waves (2004, 2006, and 2008) when children were 4, 6, and 8 years of age, respectively.	Sleep duration and media use. RESULTS Bidirectional relationships were observed between sleep duration and media use; for instance, total media use at 4 years of age was significantly associated with sleep duration at 6 years of age (â = .0.06 [95%CI, .0.10 to .0.02]), with media use at 6 years of age predicting sleep duration at 8 years of age (â = .0.06 [95%CI, .0.11 to .0.02]). Sleep duration at 4 years of age was associated with media use at 6 years of age (â = .0.10 [95%CI, .0.14 to .0.05]), with sleep duration at 6 years of age predicting media use at 8 years of age (â = .0.08 [95%CI, .0.13 to .0.03]). Several of these bidirectional relationships varied by socioeconomic status.	The results supported the hypotheses that bidirectional relationships exist between sleep duration and media use among children. These findings are important given recent population trends for increased media use and shorter sleep durations among children.	
24588507	The present paper summarizes and compares data from our studies on subjective and objective sleep quality and pain thresholds in tension-type headache (TTH), migraine, and controls.In a blinded controlled explorative study, we recorded polysomnography (PSG) and pressure, heat, and cold pain thresholds in 34 controls, 20 TTH, and 53 migraine patients. Sleep quality was assessed by questionnaires, sleep diaries, and PSG. Migraineurs who had their recordings more than 2 days from an attack were classified as interictal while the rest were classified as either preictal or postictal. Interictal migraineurs (n=33) were also divided into two groups if their headache onsets mainly were during sleep and awakening (sleep migraine, SM), or during daytime and no regular onset pattern (non-sleep migraine, NSM). TTH patients were divided into a chronic or episodic group according to headache days per month.	Compared to controls, all headache groups reported more anxiety and sleep-related symptoms. TTH and NSM patients reported more daytime tiredness and tended to have lower pain thresholds. Despite normal sleep times in diary, TTH and NSM had increased slow-wave sleep as seen after sleep deprivation. Migraineurs in the preictal phase had shorter latency to sleep onset than controls. Except for a slight but significantly increased awakening index SM, patients differed little from controls in objective measurements.	We hypothesize that TTH and NSM patients on the average need more sleep than healthy controls. SM patients seem more susceptible to sleep disturbances. Inadequate rest might be an attack-precipitating- and hyperalgesia-inducing factor.	
24588270	Sleep problems and alcohol misuse are common issues experienced by college students that can have detrimental effects on overall health. Previous work indicates a strong relationship between poor sleep quality and alcohol risk in this population. This study explored the moderating effect of drinking motives in the relationship between global sleep quality and experience of alcohol-related negative consequences.College students (N = 1,878) who reported past-month drinking.	Participants completed online surveys assessing sleep and alcohol-related behaviors.	Poorer sleep quality and higher drinking motives (coping, conformity, and enhancement) predicted greater alcohol-related consequences, controlling for drinking. Further, coping motives moderated the relationship between sleep quality and consequences such that participants reporting poor sleep and high coping motives experienced heightened levels of consequences.	These findings advance the understanding of the relationship between sleep problems and alcohol-related risk and provide implications for targeted campus-based health promotion interventions.	
24587581	To investigate the association between sleeping problems in adolescence and subsequent hospital admission for self-harm (SH).Prospective cohort study, linking health survey information on sleep problems to hospital-based patient records.	Residents of Nord-Trøndelag County, Norway, aged 13-19 years in 1995-97.	10,202 adolescents were invited to participate in the Young-HUNT study; 8,983 (88%) completed the health survey.	10% of participants reported difficulties initiating sleep, 4% reported early morning wakening. Ninety-eight participants (27% male) were hospitalized following SH over a mean 12 years follow-up. Difficulties initiating sleep/early morning wakening were associated with increased risk of SH (HR 2.11, 95% CI 1.29-3.46, sex- and age-adjusted) compared with no problems, yet coexistent symptoms of combined anxiety/depression explained most of the association with sleep problems (fully adjusted HR 1.19, 95% CI 0.66-2.16). The HR of combined difficulties initiating sleep/early morning wakening differed in those with and without anxiety/depression at baseline (P interaction = 0.03); among those without caseness symptoms of anxiety/depression it was 5.58 (95% CI 2.02-15.40), while in those with caseness symptoms of anxiety/ depression it was 0.82 (95% CI 0.19-3.44).	Sleep problems are common among Norwegian adolescents. The strong association between sleep problems and subsequent hospitalization for self-harm could mainly be related to coexistent symptoms of anxiety and depression. Prevention of adolescent sleep problems, anxiety and depression should be targeted when seeking to reduce and prevent self-harm.	
24587574	Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice.This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization.	Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity.	Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization.	Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved.	
24587566	To investigate whether subjective sleep quality is associated with brain volume independent of comorbid psychiatric conditions.Cross-sectional.	Department of Veterans Affairs (VA) Medical Center.	One hundred forty-four Gulf War Veterans (mean age 45 years; range: 31-70 years; 14% female).	None.	Total cortical, lobar gray matter, and hippocampal volumes were quantified from 1.5 Tesla magnetic resonance images using Freesurfer version 4.5. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regressions were used to determine the association of sleep quality with total and regional brain volumes. The global PSQI score was positively correlated with lifetime and current posttraumatic stress disorder (PTSD) and current depressive symptoms (P < 0.001) and was higher in veterans with Gulf War Illness, trauma exposure, and those using psychotropic medication (P ≤ 0.03). After adjusting for these comorbid variables, age, intracranial volume, and multiple comparisons, global PSQI was inversely associated with total cortical and frontal gray matter volume (adjusted P ≤ 0.03). Within the frontal lobe, total PSQI was inversely associated with the superior and middle frontal, orbitofrontal, anterior cingulate, and frontal pole volumes (adjusted P ≤ 0.02). Examination of the 3-factor structure of the PSQI revealed that the associations were driven by perceived sleep quality.	Poorer subjective sleep quality was associated with reduced total cortical and regional frontal lobe volumes independent of comorbid psychiatric conditions. Future work will be needed to examine if effective treatment of disturbed sleep leads to improved structural and functional integrity of the frontal lobes.	
24586290	Considering the marked changes in sleep and circadian rhythms across the lifespan, age may contribute to the heterogeneity in sleep-wake profiles linked to mood disorders. This study aimed to investigate the contributions of age and depression severity to sleep-wake disturbances. The Hamilton Depression Rating Scale (HDRS) was administered to assess current symptoms severity in 238 persons with a history of a mood disorder between 12 and 90 years of age (y.o.). Actigraphy was recorded over five to 22 days. Regression analyses and analyses of variance [age (12-19 y.o., 20-39 y.o., 40-59 y.o., and ≥ 60 y.o.) by depression severity (HDRS< and ≥ 8)] were conducted. The 12-19 y.o. and 20-39 y.o. groups had a delayed sleep schedule and acrophase compared to all other groups. The ≥ 60 y.o. group had a lower rhythmicity and amplitude (p ≤ .006) than the 12-19 y.o. group (p ≤ .046). Participants with a HDRS ≥ 8 spent longer time in bed, had later sleep offset times and had lower circadian rhythmicity than those with a HDRS<8 (p ≤ .036). Younger age and higher HDRS score correlated with later sleep onset and offset times, longer time in bed, higher WASO, lower sleep efficiency and later acrophase (p ≤ .023). Age was a significant predictor of delayed sleep and activity schedules (p ≤ .001). The profile of sleep-wake cycle disturbances associated with mood disorders changes with age, with prominent sleep phase delay during youth and reduced circadian strength in older persons. Conversely, disruptions in sleep consolidation seem more stable across age.
24583680	The concept of noise sensitivity emerged in public health and psychoacoustic research to help explain individual differences in reactions to noise. Noise sensitivity has been associated with health problems, but the mechanisms underlying this relationship have yet to be fully examined. Participants (n = 1102) were residents of Auckland, New Zealand, who completed questionnaires and returned them through the post. Models of noise sensitivity and health were tested in the analyses using bootstrapping methods to examine indirect effects. Results indicated that gender and noise exposure were not significant moderators in the model. Perceived stress and sleep problems were significant mediators of the relationship between noise sensitivity and subjective health complaints, even after controlling for the influence of neuroticism. However, the relationship between noise sensitivity and mental health complaints (anxiety and depression) was accounted for by the variance explained by neuroticism. Overall, this study provides considerable understanding of the relationship between noise sensitivity and health problems and identifies areas for further research in the field. 
24582668	As mammals, birds exhibit two sleep phases, slow wave sleep (SWS) and REM (Rapid Eye Movement) sleep characterized by presenting different electrophysiological patterns of brain activity. During SWS a high amplitude slow wave pattern in brain activity is observed. This activity is substituted by a low amplitude fast frequency pattern during REM sleep. Common quail (Coturnix coturnix) is an animal model that has provided information related to different physiological mechanisms present in man. There are reports related to its electrophysiological brain activity, however the sleep characteristics that have been described are not. The objectives of this study is describing the sleep characteristics throughout the nychthemeral cycle of the common quail and consider this bird species as an avian model to analyze the regulatory mechanisms of sleep. Experiments were carried out in implanted exemplars of C. coturnix. Under general anesthesia induced by ether inhalation, stainless steel electrodes were placed to register brain activity from the anterior and posterior areas during 24 continuous hours throughout the sleep-wake cycle. Ocular and motor activities were visually monitored. Quail showed four electrophysiologically and behaviorally different states of vigilance: wakefulness (53.28%), drowsiness (14.27%), slow wave sleep (30.47%) and REM sleep (1.98%). The animals presented 202 REM sleep episodes throughout the nychthemeral cycle. Sleep distribution was polyphasic; however sleep amount was significantly greater during the period corresponding to the night. The number of nocturnal REM sleep episodes was significantly greater than that of diurnal one.The quail C. coturnix shows a polyphasic distribution of sleep; however the amount of this state of vigilance is significantly greater during the nocturnal period.	
24581914	To describe the 1-year course of symptoms following mild traumatic brain injury (MTBI) sustained in a motor vehicle collision as well as patterns of care-seeking.One-year follow-up of a population-based inception cohort.	The province of Saskatchewan, Canada, with a population of about 1,000,000 inhabitants.	Persons (N=1716) sustaining an MTBI during a car collision between November 1997 and December 1999.	Not applicable.	We report the prevalence of sleep disturbances, tiredness, dizziness, forgetfulness, vision problems, hearing problems, headache, neck pain, mid back pain, and low back pain at 6 weeks and 3, 6, 9, and 12 months postcollision. At the same time points, we report self-reported care-seeking from registered health care professionals.	A total of 1716 adults suffered MTBI after a motor vehicle collision over the 2-year inception period. Six weeks after the collision, 75% reported having more than 3 symptoms and 30% had clinically significant pain in more than 3 body sites. Over time, the prevalence of symptoms and pain decreased but they were still common after 1 year. Almost all participants sought care for their symptoms at all time points, most commonly from a physician. Care-seeking from physiotherapists, chiropractors, and massage therapists was also very common, and most participants sought care from 2 or 3 providers at all follow-up points.	Up to 1 year after sustaining an MTBI during a motor vehicle collision, multiple symptoms and pain in several anatomical sites are common. Care-seeking from multiple providers continues throughout the first year postinjury.	
24581904	To synthesize the best available evidence on prognosis after pediatric mild traumatic brain injury (MTBI).We searched MEDLINE, Embase, PsycINFO, CINAHL, and SPORTDiscus (2001-2012), as well as reference lists of eligible articles, and relevant systematic reviews and meta-analyses.	Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI pediatric cases. After 77,914 records were screened for the entire review, 299 studies were eligible and assessed for scientific rigor.	Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables.	Evidence from 25 accepted articles was synthesized qualitatively according to SIGN criteria, and prognostic information was prioritized according to design as exploratory or confirmatory. Most studies show that postconcussion symptoms and cognitive deficits resolve over time. Limited evidence suggests that postconcussion symptoms may persist in those with lower cognitive ability and intracranial pathology on neuroimaging. Preliminary evidence suggests that the risk of epilepsy is increased for up to 10 years after MTBI; however, there is insufficient high-quality evidence at this time to support this link.	Common post-MTBI symptoms and deficits in children are not specific to MTBI and appear to resolve with time; however, limited evidence suggests that children with intracranial pathology on imaging may experience persisting symptoms or deficits. Well-designed, long-term studies are needed to confirm these findings.	
24581825	Bipolar depression is one of the most serious psychiatric conditions. In addition, sleep disturbance in bipolar disorder is common, and therapeutic agents restoring sleep disturbances in bipolar disorder patients will be clinically beneficial. In the current study, we compared the effect of quetiapine XR with lithium on depressive symptoms and sleep in bipolar depression patients during 8 weeks of trial.An open-label, randomized comparison of sleep-activity and depressive symptoms between 8-week quetiapine XR monotherapy and lithium monotherapy for bipolar depression was conducted. Each assessment consisted of HDRS-17, Clinical Global Impression-severity (CGI-S), and self-reported Pittsburgh Sleep Quality Index (PSQI). Actigraphy-measured sleep parameters were assessed.	A total of 42 patients (35.7±10.9 years; gender: male 15, female 27) with bipolar depression were screened out. Out of 42 patients, six patients were excluded before randomization. After randomization, seven patients were withdrawn. Twenty-nine patients with more than two visits after randomization (lithium group: 17, quetiapine XR group: 12, mean age: 36.1±10.4, gender: male 13, female 16) were included in the final analysis. In both groups, Hamilton Depression Rating Scale (HDRS) scores were significantly decreased at weeks 1, 2, 4, 6, and 8 compared with baseline. Remission rate (HDRS≤7) in the quetiapine XR was significantly higher than that of the lithium group. In the quetiapine XR group, PSQI scores at weeks 1, 2, 4, 6, and 8 was significantly decreased compared with baseline. Sleep efficiency at weeks 6 and 8 was significantly increased. WASO at week 8 was significantly decreased.	First, the present study was conducted with the relatively small number of study subjects. Second, bias could have affected the study results due to its open-label design. Third, study subjects were made up of high proportion of bipolar II disorder patients.	Quetiapine XR monotherapy was more effective in treating bipolar depression than lithium. In particular, quetiapine XR treatment improved both subjective and objective sleep quality in patients with bipolar depression. However, relationship between favorable sleep quality and depressive symptom improvement were limited.	
24579982	To clinically and genetically characterize a large Brazilian family with autosomal dominant partial epilepsy with auditory features (ADPEAF) not related to leucine-rich, glioma-inactivated 1 (LGI1) gene.Seventy family members (four married-ins) participating in the study were assessed by a detailed clinical interview and a complete neurologic examination. Genetic mapping was conducted through autosome-wide single nucleotide polymorphism (SNP) genotyping and subsequent linkage analysis on 16 and haplotype analysis on 25 subjects, respectively.	The pedigree comprised 15 affected members, of whom 11 were included in the study (male/female: 6/5; mean age 39.5 years). All but two (III:22 and IV:92) had focal seizures with auditory aura followed by secondary generalization in 44.4%. The mean age at onset of epilepsy seizures was 13.7 years. Initial autosome-wide SNP linkage analysis conducted on 12 subjects (8 affected) pointed to a single genomic region on chromosome 19 with a maximum multipoint logarithm of the odds (LOD) score of 2.60. Further refinement of this region through SNP and microsatellite genotyping on 16 subjects (11 affected) increased the LOD score to 3.41, thereby establishing 19q13.11-q13.31 as a novel ADPEAF locus. Haplotype analysis indicated that the underlying mutation is most likely located in a 9.74 Mb interval between markers D19S416 and D19S420. Sequence analysis of the most prominent candidate genes within this critical interval (SCN1B, LGI4, KCNK6, and LRFN1) did not reveal any mutation.	This study disclosed a novel ADPEAF locus on chromosome 19q13.11-q13.31, contributing to future identification of a second dominant gene for this epileptic syndrome. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.	
24578222	Despite the growing body of research linking sleep problems and social ties, research investigating the direction of effects between these two constructs is lacking. Furthermore, there remains a dearth of research examining the mechanisms that may explain the association between sleep problems and social ties within a longitudinal design. The present 3-year longitudinal study addressed two research questions: (1) Is there a bidirectional association between sleep problems and social ties at university? and (2) Does emotion regulation mediate the association between sleep problems and social ties at university? Participants (N = 942, 71.5% female; M = 19.01 years at Time 1, SD = 0.90) were university students who completed annual assessments of sleep problems, social ties, and emotion regulation, for three consecutive years. Results of path analysis indicated that the bidirectional association between sleep problems and social ties was statistically significant (controlling for demographics, sleep-wake inconsistency, sleep duration, and alcohol). Analyses of indirect effects indicated that emotion regulation mediated this link, such that better sleep quality (i.e., less sleep problems) led to more effective emotion regulation, which, subsequently, led to more positive social ties. In addition, more positive social ties led to more effective emotion regulation, which, in turn, led to less sleep problems. The findings highlight the critical role that emotional regulation plays in the link between sleep problems and social ties, and emphasize the need for students as well as university administration to pay close attention to both the sleep and social environment of university students.
24576643	Cancer-related fatigue (CRF) is a serious clinical problem and is one of the most common symptoms experienced by cancer patients. CRF has deleterious effects on many aspects of patient quality of life including their physical, psychological and social well-being. It can also limit their ability to function, socialise and participate in previously enjoyable activities. The aetiology of CRF is complex and multidimensional, involving many potentially contributing elements. These include tumour-related factors and comorbid medical/psychological conditions and also side effects associated with anti-cancer therapies or other medications. Barriers to the effective management of CRF exist both on the side of physicians and patients, and as a result CRF often remains unrecognised and undiscussed in clinical practice. A change of approach is required, where fatigue is treated as central to patient management during and after systemic anti-cancer treatment. In this review we summarise factors involved in the aetiology of CRF and the barriers to its effective management, as well as factors involved in the screening, diagnosis and treatment of cancer patients experiencing fatigue. Pharmacological and non-pharmacological approaches to its management are also reviewed. We suggest an algorithm for the process of managing CRF, guided by our experiences in The Netherlands, which we hope may provide a useful tool to healthcare professionals dealing with cancer patients in their daily practice. Although CRF is a serious and complex clinical problem, if it is worked through in a structured and comprehensive way, effective management has the potential to much improve patient quality of life. 
24576397	The aim of this study was to determine the prevalence of painful musculoskeletal conditions and migraine headache or any other headache in a sample of Spanish adults with disabilities and their association with anxiety, depression, and sleep disorders.This cross-sectional study analyzed data from the Spanish national disability and dependence survey (2007-2008) of 16,932 adults aged 18 or older who have disabilities. The prevalence (95% confidence interval [CI]) of painful musculoskeletal conditions was determined according to a diagnosis of arthritis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, muscular dystrophy, and neck or back pain. The prevalence of migraine or other headache was also calculated. Factors associated with these painful conditions were analyzed separately for men and women by using a logistic regression model.	The prevalence of painful musculoskeletal conditions was 66.9% (95% CI, 66.2%-67.6%) and that of migraine or other headache was 23.4% (95% CI, 22.8%-24.1%), both of which were higher in women than in men. Factors associated with these conditions in both men and women included older age, a sleep disorder, and concomitant chronic anxiety and/or depression.	The prevalence of painful musculoskeletal conditions and migraine or other headache is high in people with disability in Spain, especially in women, and these conditions often coexist with depression, anxiety, and/or a sleep disorder. To design programs for rehabilitating and improving the quality of life of adults with disability and painful conditions, treatments for mental and/or sleep disorders should be considered in addition to conventional treatments.	
26483902	Narcolepsy, a chronic disorder of the sleep-wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment. 
24574061	Rest-activity and sleep-wake cycles are controlled by the endogenous circadian rhythm generated by the suprachiasmatic nuclei (SCN) of the hypothalamus. Degenerative changes in the SCN appear to be a biological basis for circadian disturbances in people with dementia, and might be reversed by stimulation of the SCN by light.The review examines the effectiveness of light therapy in improving cognition, activities of daily living (ADLs), sleep, challenging behaviour, and psychiatric symptoms associated with dementia.	ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 20 January 2014 using the terms: "bright light*", "light box*", "light visor*", "dawn-dusk*", phototherapy, "photo therapy", "light therapy" "light treatment", light* . The CDCIG Specialized Register contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources.	All relevant, randomized controlled trials were included in which light therapy, at any intensity and duration, was compared with a control group for the effect of improving cognition, ADLs, sleep, challenging behaviour, and psychiatric symptoms associated with dementia (as well as institutionalization rates or cost of care). Included were people with dementia of any type and degree of severity.	Two review authors independently assessed the retrieved articles for relevance, and four review authors independently assessed the selected studies for risk of bias and extracted the data. Statistically significant differences in outcomes between the treatment and control groups at the end of treatment and follow-up were examined. Each study was summarized using a measure of effect (for example mean difference).	Eleven trials (13 articles) met the inclusion criteria. However, three of the studies could not be included in the analyses either because the reported data could not be used in the meta-analysis or we were unable to retrieve the required data from the authors.This updated review found no effect of light therapy on cognitive function, sleep, challenging behaviour (for example agitation), or psychiatric symptoms associated with dementia. Reduction in the development of ADL limitations was reported in one study, at three of five time points, and light therapy was found to have an effect after six weeks and two years but not after one year.	There is insufficient evidence to justify the use of bright light therapy in dementia. Further research should concentrate on replicating the suggested effect on ADLs, and establishing the biological mechanism for how light therapy improves these important outcomes.	
24573063	Non-motor symptoms (NMS) are important preclinical features of Parkinson's disease (PD) and have become the leading cause of poor quality of life with disease progression. There are little data on how antiparkinsonian medications influence the NMS in PD at early stage. In this study, we explored the distribution of NMS in treated and untreated PD and investigated the association between NMS and antiparkinsonian medications in Chinese patients with early PD. Subjects were enrolled from a Chinese PD patient cohort based on 2 clinical trials. Face-to-face interviews and evaluations were performed for clinical information. NMS were compared in patients with or without antiparkinsonian treatment, and between subgroups of dopaminergic medications. Eight hundred and sixteen PD patients were enrolled in this study, of whom 428 were newly diagnosed PD. Only 5 in 646 patients who completed all these NMS measurements (0.6%) were free of NMS. PD patients with antiparkinsonian medications had a significantly higher frequency of poor sleep (p = 0.001), depression (p = 0.0001) and constipation (p = 0.0001) after adjusted gender, onset age, duration, and Hoehn & Yahr stage. Moreover, patients treated by levodopa plus dopamine agonist had a higher percentage of bad sleepers (adjusted p = 0.040), and correlation analysis revealed that Levodopa Equivalent Dose (LED) was associated with constipation (coefficient 0.146, p = 0.005). These findings suggest that although NMS exist in the prodromal stage of PD, antiparkinsonian treatment is associated with increased frequency of some NMS, which may challenge the management for PD. 
24572815	The circadian clock system in mammals drives many physiological processes including the daily rhythms of sleep-wake behavior, hormonal secretion, and metabolism. This system responds to daily environmental changes, such as the light-dark cycle, food intake, and drug administration. In this review, we focus on the central and peripheral circadian clock systems in response to drugs, food, and nutrition. We also discuss the adaptation and anticipation mechanisms of our body with regard to clock system regulation of various kinetic and dynamic pathways, including absorption, distribution, metabolism, and excretion of drugs and nutrients. "Chrono-pharmacology" and "chrono-nutrition" are likely to become important research fields in chrono-biological studies. 
24571367	We examined qualitative data from a larger study of benzodiazepine-using women older than 65 years, living in the United States, for subjective experiences of loneliness and social isolation.Data from semistructured interviews with seven participants discussed aspects of social isolation or loneliness. Following a phenomenological design, data were coded and analysed for experiences.	Three themes emerged: 'Dislike being alone'; 'Loneliness and isolation'; and 'Social isolation causes negative feelings'.	Social isolation and loneliness are negative aspects of the lived experience for older benzodiazepine-using women and the loss of companions and transportation is important to this experience. Being isolated can cause depression, fear and insecurity. Future research should consider the role psychotropic medications have in coping with social isolation and loneliness among older adults. Clinicians should be aware of social isolation and loneliness in late life and discuss non-pharmacologic treatment options with their ageing patients.	
24569619	Sleep disturbance is an important change in menopause because it affects quality of life and can lead to other conditions such as depression. This study measured sleep alterations and explored associated physical, emotional, hormonal, and lifestyle factors during perimenopause and postmenopause.This cross-sectional study enrolled 160 women who were classified as perimenopausal (n = 85) or postmenopausal (n = 75). Using diaries, we collected data on duration of sleep, time awake in bed, and sleep efficiency. Follicle-stimulating hormone, 17β-estradiol, and cortisol levels were quantified by radioimmunoassay, and serum anti-Müllerian hormone levels were measured using enzyme-linked immunosorbent assay. Correlations between sleep measurements and symptoms were assessed using a generalized linear model.	The reported duration of sleep was similar for both groups of women (close to 6.9 h), and sleep efficiency was 88%. We did not find any factor that was associated with duration of sleep. Sleep efficiency was negatively associated with age, perimenopause/postmenopause status, loss of sexual interest, hot flashes, and depressed mood. Time awake in bed was positively associated with depressed mood (P < 0.000001), cigarette smoking (P < 0.000041), menopause status (P < 0.00009), and age (P < 0.0009). These associations remained after controlling for exercise, alcohol consumption, and caffeine consumption as confounding variables. Finally, morning salivary cortisol was reduced in postmenopausal women.	Time awake in bed shows the most significant associations. Depressed mood, age, and menopause status are the main factors associated with sleep disturbances.	
24569552	Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM), and modifying cardiovascular risk through lifestyle intervention and pharmacologic therapy is paramount. This review focuses on recent advances in treatment of classical (traditional) cardiovascular risk factors and highlights the impact of novel risk factors, including sleep disorders, socioeconomic status and chronic psychological stress on CVD in T2DM.Obesity is a substantial cardiovascular risk factor, and recently, large trials of lifestyle and surgical (e.g. gastric bypass) interventions impact on CVD in overweight and obese patients have been reported. Lifestyle intervention including low calorie diet and exercise reduced individual cardiovascular risk factors but did not decrease the rate of long-term cardiovascular events. Bariatric surgery was beneficial in reducing cardiovascular risk factors and long-term cardiovascular events. Sleep insufficiency, poor sleep quality and obstructive sleep apnoea lead to higher CVD and further research is needed to characterize the benefit of treating sleep disorders on long-term cardiovascular events in T2DM. Lastly, socioeconomic status and chronic psychological stress independently have a major impact on increasing CVD in T2DM, and public health policies to reduce this burden will be important to address over the coming decade.	CVD in T2DM is multifactorial and requires a multifaceted approach in reducing known cardiovascular risks at the individual patient level through lifestyle, pharmacotherapy and surgical interventions and at the societal level through public health policies that support reduction in classical and novel cardiovascular risk factors.	
24568742	The DSM-5 currently includes a dissociative-PTSD subtype within its nomenclature. Several studies have confirmed the dissociative-PTSD subtype in both American Veteran and American civilian samples. Studies have begun to assess specific factors which differentiate between dissociative vs. non-dissociative PTSD. The current study takes a novel approach to investigating the presence of a dissociative-PTSD subtype in its use of European victims of sexual assault and rape (N=351). Utilizing Latent Profile Analyses, we hypothesized that a discrete group of individuals would represent a dissociative-PTSD subtype. We additionally hypothesized that levels of depression, anger, hostility, and sleeping difficulties would differentiate dissociative-PTSD from a similarly severe form of PTSD in the absence of dissociation. Results concluded that there were four discrete groups termed baseline, moderate PTSD, high PTSD, and dissociative-PTSD. The dissociative-PTSD group encompassed 13.1% of the sample and evidenced significantly higher mean scores on measures of depression, anxiety, hostility, and sleeping difficulties. Implications are discussed in relation to both treatment planning and the newly published DSM-5. 
24568642	Identifying patients with increased risk of suicidal behaviors is a constant challenge and concern for clinicians caring for patients with psychiatric conditions. We conducted a systematic review to assess the association between suicidal behaviors and sleep disturbances in psychiatric patients.A systematic literature search of Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycInfo, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus was conducted using earliest inclusive dates to 28 June 2013. Eligible studies were comparative observational studies that reported sleep disturbances in psychiatric patients and the outcome of interest (any type of suicidal behaviors). Pairs of reviewers extracted descriptive data, study quality, and outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were pooled across studies using the random-effects model. Newcastle-Ottawa scale was used to critically appraise study quality.	Nineteen studies met the inclusion criteria. Compared to those without sleep disturbances, patients with psychiatric diagnoses and co-morbid sleep disturbances were significantly more likely to report suicidal behaviors (OR = 1.99, 95% CI 1.72, 2.30, P <0.001). The association was also demonstrated across several psychiatric conditions including depression (OR = 3.05, 95% CI 2.07, 4.48, P <0.001), post-traumatic stress disorder (PTSD) (OR = 2.56, 95% CI 1.91, 3.43, P <0.001), panic disorder (OR = 3.22, 95% CI 1.09, 9.45, P = 0.03), and schizophrenia (OR = 12.66, 95% CI 1.40, 114.44, P = 0.02). In subgroup analysis based on the type of sleep disorder, we also found suicidal behavior to be significantly associated with the presence of insomnia, parasomnias, and sleep-related breathing disorders, but not hypersomnias.	This systematic review and meta-analysis suggests that in patients with psychiatric diagnoses, sleep disturbances are associated with the increased risk of suicidal behaviors.	
24568300	To summarize the literature on post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) and their co-morbidity, focusing on diagnosis, clinical symptoms and treatment issues relevant to the clinician.Review of the literature.	Pubmed searches were performed using the terms post-traumatic stress disorder, traumatic brain injury, sleep, cognitive, depression, anxiety, treatment and combinations of these terms. Those articles relevant to the objective were included.	This study presents pathophysiological, neuroimaging and clinical data on co-morbid PTSD and TBI. It reviews associated conditions, emphasizing the impact of cognitive and sleep problems. It summarizes the emerging literature on treatment effectiveness for co-morbid PTSD and TBI, including psychotherapy, pharmacotherapy and cognitive rehabilitation.	Both PTSD and TBI commonly occur in the general population, both share some pathophysiological characteristics and both are associated with cognitive impairment and sleep disruption. PTSD and TBI present with a number of overlapping symptoms, which can lead to over-diagnosis or misdiagnosis. Both conditions are associated with co-morbidities important in diagnosis and treatment planning. More research is needed to elucidate what treatments are effective in PTSD and TBI co-morbidity and on factors predictive of treatment success.	
24566763	Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD.To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics.	A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University.	Twenty-four hour monitoring of serum melatonin secretion.	Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm.	Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm.	Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.	
24566056	The relation between responses to survey questions on noise annoyance and self-reported sleep disturbance has been analysed to gain insight in its dependency on noise source or noise type and on individual characteristics. The results show a high correlation between responses (scores 0-10) with Pearson's correlation coefficient close to 0.8 for respondents who report hearing the source. At the same level of annoyance, scooters and neighbours are associated with more sleep disturbance, air and road traffic with less. The relation between Annoyance (A) and Sleep Disturbance (SD) is also significantly related to age, the use of sleeping drugs, and living alone. However, the differences in the A-SD relations with respect to source and characteristic are small. Noise-related sleep disturbance is associated more strongly to noise annoyance than it is to noise exposure. For transportation noise both scores are more often equal when the annoyance score is 7 or higher; this change in scoring behaviour could be an indication for a change to severe annoyance. 
24564698	Fatigue is a common and debilitating phenomenon experienced by individuals with traumatic brain injury (TBI) that can negatively influence rate and extent of functional recovery by reducing participation in brain injury rehabilitation services and increasing maladaptive lifestyle practices. The underlying mechanisms of TBI-related fatigue are not entirely understood and focused research on symptom reduction or prevention is limited.The current review of the literature suggests that the aetiology of TBI-related fatigue can be viewed as a multifactorial and complex model impacting physiological systems (i.e. endocrine, skeletal muscle and cardiorespiratory) that can be directly or indirectly influenced by neuropsychological correlates including cognitive and psychological impairment. Distinguishing central from peripheral fatigue is helpful in this regard. Potential therapeutic strategies and pharmacological agents to help alleviate fatigue in this patient population are discussed.	

24560382	Migraine headache is a growing problem for U.S. servicemembers deployed to Iraq and Afghanistan and has been linked to substantial negative socioeconomic consequences. However, there has been no comprehensive examination of the relationship between combat exposure and migraine headache or its stress-related triggers. Analyzing data drawn from the National Longitudinal Study of Adolescent Health, we use exogenous variation in deployment assignment to estimate the effect of combat exposure on migraine headache. We find that those deployed to a combat zone with enemy firefight are at substantially increased risk for migraine headache relative to those deployed to non-combat zones outside the United States or to combat zones without enemy firefight. We find that combat-induced sleep disorders, stress-related psychological problems, and physical injuries in combat explain approximately 40-45 percent of the relationship between combat exposure and migraine headache. 
24560022	Dissociative symptoms may be the by-products of a labile sleep-wake cycle (Koffel and Watson, 2009a). This may help to explain why dissociation overlaps with fantasy proneness and cognitive failures. Using path analysis, we tested to what extent data gathered in a nonclinical, predominantly female sample (N=139) supported two conceptual models. The first model assumes that unusual sleep experiences increase fantasy proneness and cognitive failures, which in turn encourage trait dissociation and reports of trauma. The second model assumes that trauma leads to dissociative experiences both directly and through its influence on sleep. In this cross-sectional design, the data were reasonably well described by both models. Importantly, in both models, unusual sleep experiences serve as antecedents of trait dissociation. Our analysis underlines the importance of unusual sleep experiences and may inspire treatment intervention focusing on sleep normalization. 
24559851	Military personnel who have combat exposures are at increased risk for the service-related disorders of post-traumatic stress disorder (PTSD), depression, sleep disturbances and decreased health related quality of life (HRQOL). Those with a traumatic brain injury (TBI) are at even greater risk. Inflammation is associated with these disorders and may underlie the risk for health declines. We evaluated 110 recently deployed, military personnel presenting with sleep disturbances for service-related disorders (TBI, PTSD, and depression) as well as HRQOL. ANOVA models were used to examine differences among military personnel with two or more service-related disorders (high comorbid group), or one or no disorders (low comorbid group). Logistic regression models were used to determine associations among interleukin-6 (IL-6) to HRQOL and service-related disorders. Approximately one-third of the sample had two or more service-related disorders. HRQOL was lower and IL-6 concentrations were higher in military personnel with PTSD or depression, with the most profound differences in those with more service-related disorders, regardless of sleep disorder. Having symptoms of depression and PTSD resulted in a 3.5-fold risk to be in the lower quartile of HRQOL and the highest quartile of IL-6. In a linear regression model, 41% of the relationship between HRQOL and IL-6 concentrations was mediated by PTSD and depression. Military personnel with PTSD and depression are at high risk for lower HRQOL, and higher IL-6 concentrations. Comprehensive treatment is required to address co-occurring service-related disorders in military personnel to promote health and well-being. 

24555599	The purpose of this study was to determine if there is an association between tentorial length and angle and sleep-wake disturbances in patients with mild traumatic brain injury (TBI).MRI examinations of the brain of 34 consecutive patients with mild TBI with sleep-wake disturbance and 30 patients with mild TBI without sleep-wake disturbance were retrospectively reviewed. The length of the tentorium on a sagittal T1-weighted image (tentorial length) and the angle formed between the tentorium and a line through the foramen magnum (tentorial angle) were measured. Results were correlated with both neuropsychologic testing and any sleep-wake disturbance.	No significant difference existed between patients with and without sleep-wake disturbances in terms of age (p=0.44), sex (p=0.13), Immediate Post-Concussion Assessment Cognitive Test total symptom score (p=0.10), verbal memory score (p=0.32), visual memory score (p=0.31), processing speed (p=0.15), or reaction time (p=0.84). Tentorial length in patients with mild TBI with sleep-wake disturbances was significantly longer than patients with mild TBI without sleep-wake disturbances (p<0.01), and tentorial angle was significantly smaller (p<0.01). Tentorial angle was inversely correlated with length of time to recovery (p=0.002), and tentorial length was directly correlated with length of time to recovery (p<0.001).	Among patients with mild TBI with similar cognitive function and symptom severity, those with sleep-wake disturbances have significantly longer tentorial length with a flatter angle than do patients with mild TBI without sleep symptoms, with length of time to recovery being directly correlated with tentorial length and indirectly correlated with tentorial angle. Direct impact between the tentorium and the pineal gland during mild TBI may lead to pineal gland injury, disruption of melatonin homeostasis, and sleep-wake disturbances.	
24555178	Interventions to improve sleep in fibromyalgia may generalize to improvements in multiple symptom domains. Delta-embedded music, pulsating regularly within the 0.25 Hz to 4 Hz frequency band of brain wave activity, has the potential to induce sleep.To assess the effects of a delta-embedded music program over four weeks for sleep induction in patients with fibromyalgia.	The present unblinded, investigator-led pilot study used a within-subject design. Analysis was based on 20 individuals with fibromyalgia who completed the study, of the 24 recruited into the study. The primary outcome variables were the change from baseline in Fibromyalgia Impact Questionnaire (FIQ) and Jenkins Sleep Scale scores. A patient global impression of change was measured on a seven-point Likert scale. Secondary outcome measures, comprised of items 5, 6 and 7 of the FIQ, were used as indicators of pain, tiredness and being tired on awakening.	The FIQ median score of 76.4 (95% CI 61.3 to 82.1) at baseline improved to 60.3 (95% CI 53.1 to 72.0; P=0.004). The Jenkins Sleep Scale median value of 17.5 (95% CI 15.5 to 18.5) at baseline fell to 12.5&nbsp;(95% CI 8.5 to 14.5; P=0.001) at study completion. The outcomes of the patient global impression of change ratings were mostly positive (P=0.001). Being tired on awakening declined significantly from a median of 9.0 (95% CI 8.0 to 10.0) to 8.0 (95% CI 5.5 to 9.0; P=0.021). However, there was no significant improvement in pain level (baseline median 7.5&nbsp;[95% CI 7.0 to 8.5] versus study completion median 7.0 [95% CI 6.5&nbsp;to 8.0]; P=0.335) or tiredness (baseline median 9.0 [95% CI 8.0 to 9.5] versus study completion median 8.0 [95% CI 6.0 to 8.5]; P=0.061). There were no serious adverse events.	Delta-embedded music is a potential alternative therapy for fibromyalgia.	
24553037	Medical students are a population who are at great risk of having bad sleep practice and hygiene due to demanding clinical and academic activities. Poor sleep practices are a disturbing and destabilizing phenomenon. It affects many people and can affect the quality of work, performance and education of medical students. Determining the sleep practices and behaviors could be useful to establish a systematic mental health curriculum in medical schools.The objectives of this study is to describe sleep practices among undergraduate medical students in a Nigerian University.	Sleep practices were investigated using a convenience sample of medical students from the University of Nigeria Teaching Hospital Ituku Ozalla, Enugu from October 2012 to February 2013.	A total number of participants enrolled were 241 consisting of 150 male and 90 female medical students. However, 222 (response rate: 92.1%) completed and returned the questionnaire. The median number of hours of night sleep on a weekday and weekend were 6 and 7 h respectively. There was a significant correlation between the number of hours of sleep and use of caffeine (Spearman r = -0.148, P < 0.0321). Ninety two (45.3%) had a sleep latency of 10-30 min while 157 (70.7%) woke up 1-2 times/night. Twenty five (11.3%) experience unusual sleep practices such as sleep walking, talking or night terrors.	Medical students in our institution have varying degrees of sleeping practice and behavior and this may affect academic performance.	
24552792	The purpose of this study was to investigate the effect of regular moderate- to high-intensity step aerobics training on the melatonin levels and sleep quality of sleep-impaired postmenopausal women (PMW). PMW with poor sleep (having a score over 5 in the Chinese version of the Pittsburgh sleep quality index [PSQI]) were divided into a training group (TG, n = 10) and an age-, height-, weight-, and PSQI score-matched control group (CG, n = 9). The participants in the TG performed 40-45 minutes of step aerobics exercise 3 times per week for 10 weeks at an intensity of 75-85% of the heart rate reserve, whereas the participants in the CG maintained their regular lifestyle. The fasting blood was analyzed, and the PSQI questionnaire and aerobic fitness test were administered before and after the 10-week program. The results revealed that for the participants in the TG, the PSQI score significantly decreased (TG from 9.40 ± 0.81 to 7.40 ± 0.43; CG from 7.56 ± 0.34 to 7.78 ± 0.68; between-group difference = 2.22, p ≤ 0.05) and the melatonin levels significantly increased (TG from 12.08 ± 4.20 to 44.42 ± 7.03 pg·ml; CG from 11.81 ± 2.03 to 5.5 ± 1.39 pg·ml, between-group difference = 38.65, p ≤ 0.05). In conclusion, a 10-week moderate- to high-intensity step aerobics training program can improve sleep quality and increase the melatonin levels in sleep-impaired PMW. Therefore, regular moderate- to high-intensity step aerobics training is recommended for sleep-impaired PMW.
24552437	The pervasiveness of media use in our society has raised concerns about its potential impact on important lifestyle behaviours, including sleep. Although a number of studies have modelled poor sleep as a negative outcome of media use, a critical assessment of the literature indicates two important gaps: (i) studies have almost exclusively relied on concurrent data, and thus have not been able to assess the direction of effects; and (ii) studies have largely been conducted with children and adolescents. The purpose of the present 3-year longitudinal study, therefore, was to examine whether both sleep duration and sleep problems would be predictors or outcomes of two forms of media use (i.e. television and online social networking) among a sample of emerging adults. Participants were 942 (71.5% female) university students (M = 19.01 years, SD = 0.90) at Time 1. Survey measures, which were assessed for three consecutive years starting in the first year of university, included demographics, sleep duration, sleep problems, television and online social networking use. Results of a cross-lagged model indicated that the association between sleep problems and media use was statistically significant: sleep problems predicted longer time spent watching television and on social networking websites, but not vice versa. Contrary to our hypotheses, sleep duration was not associated with media use. Our findings indicate no negative effects of media use on sleep among emerging adults, but instead suggest that emerging adults appear to seek out media as a means of coping with their sleep problems.
24550652	We investigated the frequency of sleep disturbances and the association between sleep disturbances and glucoregulation in type 2 diabetic patients. The frequency of sleep disturbances in 614 type 2 diabetic patients was investigated using validated sleep questionnaires. There were 381 male and 233 female patients. The mean age was 59.7 ± 11.1 yr; the mean body mass index was 24.9 ± 4.4 kg/m(2); the mean HbA1c was 7.8% ± 1.5%; and the mean duration of diabetes was 10.3 ± 8.4 yr. The questionnaires revealed insomnia in 48.2% of the patients while 8.5% reported excessive daytime sleepiness. A total of 49% of the patients was poor sleepers, while 28.5% had depression. Multivariate logistic regression analysis showed that there was no significant association between HbA1c and other sleep disturbances, such as poor sleep, insomnia, and short duration of sleep. Sleep disturbances were very common in patients with type 2 diabetes mellitus, whereas there was no association between poor or short sleep and glucoregulation. Awareness and identifying sleep complaints in such patients are necessary to improve their quality of daily life. 
24549722	An intricate interplay between circadian and sleep-wake homeostatic processes regulate cognitive performance on specific tasks, and individual differences in circadian preference and sleep pressure may contribute to individual differences in distinct neurocognitive functions. Attentional performance appears to be particularly sensitive to time of day modulations and the effects of sleep deprivation. Consistent with the notion that the neuromodulator, adenosine , plays an important role in regulating sleep pressure, pharmacologic and genetic data in animals and humans demonstrate that differences in adenosinergic tone affect sleepiness, arousal and vigilant attention in rested and sleep-deprived states. Caffeine--the most often consumed stimulant in the world--blocks adenosine receptors and normally attenuates the consequences of sleep deprivation on arousal, vigilance, and attention. Nevertheless, caffeine cannot substitute for sleep, and is virtually ineffective in mitigating the impact of severe sleep loss on higher-order cognitive functions. Thus, the available evidence suggests that adenosinergic mechanisms, in particular adenosine A2A receptor-mediated signal transduction, contribute to waking-induced impairments of attentional processes, whereas additional mechanisms must be involved in higher-order cognitive consequences of sleep deprivation. Future investigations should further clarify the exact types of cognitive processes affected by inappropriate sleep. This research will aid in the quest to better understand the role of different brain systems (e.g., adenosine and adenosine receptors) in regulating sleep, and sleep-related subjective state, and cognitive processes. Furthermore, it will provide more detail on the underlying mechanisms of the detrimental effects of extended wakefulness, as well as lead to the development of effective, evidence-based countermeasures against the health consequences of circadian misalignment and chronic sleep restriction.
24548663	Both sleep-duration and C-reactive protein (CRP) are useful predictors of coronary heart disease (CHD). The increased CRP level is associated with the unusual sleep-duration. However, it is unclear whether CRP impacts the CHD risk prediction of sleep-duration.A total of 3381 individuals from the Framingham Offspring Study, aged 30+, CHD-free, and without missing measurement of CRP and sleep-duration and being followed to the end of 2007 were included in this analysis. Hazards ratio (HR) from the Cox regression models was used to evaluate the strength of association between the sleep-duration, CRP levels, and risk of incident CHD. Compared to sleep-duration 7-8 h (n = 2512) after adjusting for age and gender, the HR (95% CL) of incident CHD were 1.42 (1.15, 1.76, p < 0.005) for sleep-duration ≤6 h (n = 588) and 1.23 (0.90, 1.70, p < 0.2) for sleep-duration ≥9 h (n = 281), respectively. A further adjustment for other covariates including CRP did not change the CHD risk association. When subjects were categorized into 9 groups by sleep-duration (≤6, 7-8, and ≥9 h) and CRP levels (<1, 1-3, and ≥3 mg/L), and compared to those whose sleep-duration was 7-8 h and CRP levels were <1 mg/L, the HRs of CHD were similar for sleep-duration in ≤6 h or ≥9 h categories regardless of their CRP levels. The increased CRP levels, however, did show an increased risk for CHD when sleep-duration was 7-8 h	The levels of CRP do not significantly attenuate the association between sleep duration and incident CHD.	
24548579	This study aimed to determine the association between sleep habits (including bedtime, wake up time, sleep duration, and sleep disorder score) and physical characteristics, physical activity level, and food pattern in overweight and obese versus normal weight children.Case control study.	164 Malaysian boys and girls aged 6-€“12 years.	Anthropometric measurements included weight, height, waist circumference, and body fat percentage. Subjects divided into normal weight (n = 82) and overweight/obese (n = 82) group based on World Health Organization 2007 BMI-for-age criteria and were matched one by one based on ethnicity, gender, and age plus minus one year. Questionnaires related to sleep habits, physical activity, and food frequency were proxy-reported by parents. Sleep disorder score was measured by Children Sleep Habit Questionnaire.	Sleep disorder score and carbohydrate intake (%) to total energy intake were significantly higher in overweight/obese group (p < 0.01 and p < 0.05, respectively). After adjusting for age and gender, sleep disorder score was correlated with BMI (r = 0.275, p < 0.001), weight (r = 0.253, p < 0.001), and WC (r = 0.293, p < 0.001). Based on adjusted odd ratio, children with shortest sleep duration were found to have 4.5 times higher odds of being overweight/obese (odd ratio: 4.536, 95% CI: 1.912-€“8.898) compared to children with normal sleep duration. The odds of being overweight/obese in children with sleep disorder score higher than 48 were 2.17 times more than children with sleep disorder score less than 48.	Children who sleep lees than normal amount, had poor sleep quality, and consumed more carbohydrates were at higher risk of overweight/obesity.	
24548144	The aim was to estimate the prevalence of, and identify independent risk factors for, Advanced (ASPD) and Delayed Sleep Phase Disorder (DSPD) among Māori (indigenous New Zealanders) and non-Māori adults using a self-report questionnaire. The Munich Chronotype Questionnaire was mailed to a stratified sample of 9100 adults (5100 Māori and 4000 non-Māori) aged 20-59 years randomly selected from the electoral rolls (54% response rate). Different definitions for ASPD and DSPD were developed using combinations of symptoms including self-reported bed and rising times, current chronotype, and a desire to change sleep schedule. Logistic regression models were used to model the likelihood of reporting ASPD or DSPD separately after adjusting for ethnicity (Māori versus non-Māori), sex (males versus females), age (in decades), socio-economic deprivation (NZDep2006 deciles) and employment status (unemployed, night work versus employed with no night work). The prevalence of ASPD ranged from 0.25% to 7.13% whereas the prevalence of DSPD was 1.51 to 8.90% depending on the definition used. The prevalence of ASPD was higher among men and increased with age. The prevalence of DSPD was higher among those living in more deprived areas and decreased with age. After controlling for ethnicity, gender, age, socio-economic deprivation and employment status, people with ASPD were more likely to report excessive daytime sleepiness, whereas those with DSPD were more likely to report poor or fair self-rated health. Reporting ASPD and DSPD were associated with self-reported night work. In this large sleep timing survey, we found no differences in the prevalence of self-identified ASPD and DSPD between Maori and non-Maori. This has implications for the development and provision of sleep health services and strategies for managing the significant impact of work patterns on sleep. 

24533916	Sleep disorders are very common in the community and are estimated to affect up to 45% of the world's population. Pharmacists are in a position to give advice and provide appropriate services to individuals who are unable to easily access medical care. The purpose of this study is to develop an intervention to improve the management of sleep disorders in the community. The aims are- (1) to evaluate the effectiveness of a community pharmacy-based intervention in managing sleep disorders, (2) to evaluate the role of actigraph as an objective measure in monitoring certain sleep disorders and (3) to evaluate the extended role of community pharmacists in managing sleep disorders. This intervention is developed to monitor individuals undergoing treatment and overcome the difficulties in validating self-reported feedback.This is a community-based intervention, prospective, controlled trial, with one intervention group and one control group, comparing individuals receiving a structured intervention with those receiving usual care for sleep-related disorders at community pharmacies.	This study will demonstrate the utilisation and efficacy of community pharmacy-based intervention to manage sleep disorders in the community, and will assess the possibility of implementing this intervention into the community pharmacy workflow.	Australian New Zealand Clinical Trial Registry: ACTRN12612000825853.	
24533006	A naturally short sleeper phenotype with a sleep need of less than 6 hours without negative impact on health or performance is rare. We present a case of an acquired short sleeper phenotype after third ventriculostomy. A 59-year-old patient suffering from chronic hydrocephalus reported an average of 7-8 h of nocturnal sleep. After surgical intervention, the patient noted a strikingly reduced sleep need of 4-5 h without consequent fatigue or excessive daytime sleepiness, but with good daytime performance and well-balanced mood. Short sleep per 24 hours was confirmed by actigraphy. Postoperative imaging revealed decreased pressure around the anterior third ventricle. The temporal link between development of a short sleeper phenotype and third ventriculostomy is striking. This might suggest that individual short sleep need is not only determined by genetics but can be also be induced by external factors.
24533003	Temporomandibular pain disorders (TMD) and myofascial pain were linked to increased prevalence of insomnia and obstructive sleep apnea (OSA) on clinical grounds. However, the literature lacks an accurate polysomnographic (PSG) characterization of sleep abnormalities associated with TMD, given that prior studies included small or uncontrolled samples of TMD patients. The present investigation aims to objectively evaluate measures of sleep and respiratory disturbance in a large representative sample of TMD cases in comparison with matched controls.Sleep, respiration, and limb movements were measured using a 2-night attended PSG protocol in 170 women-124 TMD cases with myofascial pain and 46 demographically matched controls. The second night data were compared between the groups using ANCOVAs. In TMD cases, the relationship between pain ratings and sleep parameters was analyzed using multiple regressions.	In comparison to healthy controls, TMD cased evidenced a significant increase in stage N1 sleep (12.2% ± 7.6% vs. 9.2% ± 5.0%, p = 0.03), which was only mild relative to normative values. TMD cases also demonstrated mild but significant elevations in arousals associated with all types of respiratory events (6.0/h ± 6.1 vs. 3.5/h ± 3.3 p = 0.02) and in respiratory effort related arousals (RERAs, 4.3/h ± 4.3 vs. 2.6/h ± 2.7, p = 0.02). Myofascial pain predicted a lower sleep efficiency (p = 0.01), more frequent awakenings (p = 0.04), and higher RERA index (p = 0.04) among TMD cases.	Myofascial pain in TMD is associated with mild elevation in sleep fragmentation and increased frequency of RERA events. Further research is required to evaluate the clinical significance of these findings.	
24533001	Inadequate sleep has negative metabolic consequences that may contribute to obesity. A priori hypotheses posit relationships between sleep characteristics, carbohydrate and lipid metabolism, appetite, fatigue, and obesity in laboratory, clinical, and population settings. There are few reports from primary care; and none that address sleep duration, quality, and stability. This study examines the relationship between three sleep characteristics-duration, quality, or stability-and obesity in our urban hospital affiliated family medicine center in Akron, Ohio.A systematic sampling process yielded 225 representative patients who completed the Pittsburgh Sleep Quality Index, the Berlin Apnea Questionnaire, and the Sleep Timing Questionnaire. Demographic, body mass, hypertension, and insurance data were obtained from the electronic medical record. Associations between self-reported sleep characteristics and obesity were examined via contingency tables and regression models.	Seventy-eight percent (78%) reported poor quality sleep, 59% had elevated Berlin apnea-risk scores, 12% reported restless legs symptoms, and 9% reported a prior diagnosis of sleep apnea; 62% were obese. We found significant (p < 0.05) associations between sleep quality, duration or bedtime stability, and obesity. The association between sleep quality and obesity was negative and linear (69%, 72%, 56%, 43%), while the association between sleep duration and obesity was U-shaped (74%, 53%, 53%, 62%; linear term p = 0.02 and quadratic term p = 0.03). Less stable bedtimes during the week (OR = 2.3, p = 0.008) or on the weekend (OR = 1.8, p = 0.04) were also associated with obesity. The association between sleep quality and obesity was not explained by patient demographics or snoring (ORadj = 2.2; p = 0.008).	This study adds to the sparse literature on the relationship between three self-reported sleep characteristics and obesity in urban primary care settings which typically differ from both general population and specialty outpatient settings.	


24530893	Mathematical modeling has played a significant role in building our understanding of sleep-wake and circadian behavior. Over the past 40 years, phenomenological models, including the two-process model and oscillator models, helped frame experimental results and guide progress in understanding the interaction of homeostatic and circadian influences on sleep and understanding the generation of rapid eye movement sleep cycling. Recent advances in the clarification of the neural anatomy and physiology involved in the regulation of sleep and circadian rhythms have motivated the development of more detailed and physiologically-based mathematical models that extend the approach introduced by the classical reciprocal-interaction model. Using mathematical formalisms developed in the field of computational neuroscience to model neuronal population activity, these models investigate the dynamics of proposed conceptual models of sleep-wake regulatory networks with a focus on generating appropriate sleep and wake state transition patterns as well as simulating disease states and experimental protocols. In this review, we discuss several recent physiologically-based mathematical models of sleep-wake regulatory networks. We identify common features among these models in their network structures, model dynamics and approaches for model validation. We describe how the model analysis technique of fast-slow decomposition, which exploits the naturally occurring multiple timescales of sleep-wake behavior, can be applied to understand model dynamics in these networks. Our purpose in identifying commonalities among these models is to propel understanding of both the mathematical models and their underlying conceptual models, and focus directions for future experimental and theoretical work.
24529826	To assess sleep disturbance and related factors among mid-aged women.This was a cross-sectional study in which 288 women (40-59 years) were requested to complete the Jenkins Sleep Scale (JSS), the 12-item General Health Questionnaire (GHQ-12), the Menopause Rating Scale (MRS) and a general socio-demographic questionnaire containing female and partner data.	Median [interquartile range] age of the whole sample was 47 [8] years. A 62.2% of women were rural residents, 21.2% were postmenopausal, 20.1% were receiving psychotropic drugs, 64.2% had abdominal obesity (waist ≥ 88 cm), and 9.7% reported intimate violence. A 12.8% had an abnormal GHQ-12 score (total score ≥ 3) whereas 14.2% had severe menopause-related symptoms (total MRS score ≥ 17). The prevalence of disturbed sleep (JSS score ≥ 12) was 37.5%. JSS scores displayed significant differences in relation to menopausal status, presence of stress urinary incontinence, use of psychiatric treatment, intimate partner violence, self-perception of healthiness, and partner factors (perception of healthiness, educational level, and regular exercise). Higher JSS scores (disturbed sleep) positively correlated with GHQ-12 and MRS scores, number of co-morbid conditions, body mass index, and female and partner age. Multiple linear regression analysis found that JSS scores correlated positively with somatic MRS scores and with intimate violence, and inversely with partner educational level (r(2)=0.375, p<0.05).	In this mid-aged female sample, disturbed sleep was related to somatic menopause-related symptoms, intimate violence and partner educational level.	
24529544	Using salivary dim light melatonin onset (DLMO) and actigraphy, our study sought to determine if Parkinson disease (PD) patients demonstrate circadian disturbance compared to healthy controls. Additionally, our study investigated if circadian disturbances represent a disease-related process or may be attributed to dopaminergic therapy.Twenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 healthy controls. All participants underwent neurologic assessment and 14 days of actigraphy to establish habitual sleep-onset time (HSO). DLMO time and area under the melatonin curve (AUC) were calculated from salivary melatonin sampling. The phase angle of entrainment was calculated by subtracting DLMO from HSO. Overnight polysomnography (PSG) was performed to determine sleep architecture.	DLMO and HSO were not different across the groups. However, the phase angle of entrainment was more than twice as long in the medicated PD group compared to the unmedicated PD group (U = 35.5; P = .002) and was more than 50% longer than controls (U = 130.0; P = .021). The medicated PD group showed more than double the melatonin AUC compared to the unmedicated group (U = 31; P = 0.001) and controls (U = 87; P = .001). There was no difference in these measures comparing unmedicated PD and controls.	In PD dopaminergic treatment profoundly increases the secretion of melatonin. Our study reported no difference in circadian phase and HSO between groups. However, PD patients treated with dopaminergic therapy unexpectedly showed a delayed sleep onset relative to DLMO, suggesting dopaminergic therapy in PD results in an uncoupling of circadian and sleep regulation.	
24529424	This article reviews literature relating to sleep disturbance and fatigue after traumatic brain injury. It discusses the nature and prevalence of sleep disturbances associated with traumatic brain injury and the measures used to assess them. Potential causes are discussed, including damage to sleep-wake regulating centers, disruption of circadian timing of sleep, and secondary causes, such as pain, depression, and anxiety. The nature and assessment of fatigue are discussed, followed by a review of evidence regarding causes. Evidence is reviewed of the consequences of sleep disturbance and fatigue. Potential treatments of nonpharmacologic and pharmacologic natures are reviewed. 
24529044	The aim of this study was to investigate the sleep disturbance and its correlates in Chinese middle-aged women.A total of 2046 Chinese women 40-60 years of age were recruited in this cross-sectional descriptive study. The subjects were surveyed using the Pittsburgh Sleep Quality Index (PSQI), the modified Kupperman Index (KI), and a general questionnaire to obtain sociodemographic data. Data were analyzed using SPSS 20.0 software.	In this study, the mean (standard deviation) age of the participants was 51.69 (6.54) years and the mean PSQI score was 6.88 (3.20). The prevalence of sleep disturbance was 33.2% (a PSQI global score ≥8). The prevalence of sleep disturbance was higher in women with a menopausal status (from 34.8% in premenopausal women to 40.9% in postmenopausal women, P < .001) and in women with an increased age (from 21.7% in women 40-44 years of age to 41.8% in women 55-60 years of age, P < .001). Vasomotor symptoms (classical menopausal symptoms, VMS) were associated with sleep disturbance. An increase in the severity of menopausal symptoms (higher total KI scores) was observed in women who experienced sleep disturbance. A logistic regression analysis revealed that menopausal status, vasomotor symptoms, modified KI scores, a history of disease, and older age (≥ 50 years) were significant risk factors for sleep disturbance.	Sleep disturbance was highly prevalent in this large sample of middle-aged Chinese women. Therefore, clinicians should pay more attention to sleep problems in middle-aged Chinese women and measures should be taken to improve the quality of sleep in these women.	
24529043	Theoretical and empirical support for the role of dysfunctional beliefs, safety behaviors, and increased sleep effort in the maintenance of insomnia has begun to accumulate. It is not yet known how these factors predict sleep disturbance and fatigue occurring in the context of anxiety and mood disorders. It was hypothesized that these three insomnia-specific cognitive-behavioral factors would be uniquely associated with insomnia and fatigue among patients with emotional disorders after adjusting for current symptoms of anxiety and depression and trait levels of neuroticism and extraversion.Outpatients with a current anxiety or mood disorder (N = 63) completed self-report measures including the Dysfunctional Beliefs About Sleep Scale (DBAS), Sleep-Related Safety Behaviors Questionnaire (SRBQ), Glasgow Sleep Effort Scale (GSES), Pittsburgh Sleep Quality Index (PSQI), NEO Five-Factor Inventory (FFI), and the 21-item Depression Anxiety and Stress Scale (DASS). Multivariate path analysis was used to evaluate study hypotheses.	SRBQ (B = .60, p < .001, 95% CI [.34, .86]) and GSES (B = .31, p < .01, 95% CI [.07, .55]) were both significantly associated with PSQI. There was a significant interaction between SRBQ and DBAS (B = .25, p < .05, 95% CI [.04, .47]) such that the relationship between safety behaviors and fatigue was strongest among individuals with greater levels of dysfunctional beliefs.	Findings are consistent with cognitive behavioral models of insomnia and suggest that sleep-specific factors might be important treatment targets among patients with anxiety and depressive disorders with disturbed sleep.	
24528212	The aim of the study was to compare the frequency and type of sleep disturbances in a group of Malaysian children aged 4 to 18 years with cerebral palsy (CP) with their nearest-age, able-bodied siblings and to identify factors associated with sleep disturbances.The study was a case-control study of 109 children with CP (61 males, 48 females; mean age 9 y, SD 3 y 11 mo, range 4-18 y) and their healthy siblings (56 males, 53 females; mean age 10 y, SD 3 y 9 mo, range 4-18 y). The Sleep Disturbances Scale for Children (SDSC) questionnaire was completed by the main caregiver. In children with CP, multiple regression analysis was be used to determine factors related to higher Total SDSC sleep scores.	Ninety-seven children (89%) had spastic CP, 10 (9%) had dyskinetic CP, and two (2%) had mixed CP. Based on the Gross Motor Function Classification System (GMFSC), 34 patients (31%) were at GMFSC level I or II, 10 patients (9%) at level III, and 65 patients (60%) at level IV or V. Children with CP scored significantly higher than their siblings on Total SDSC and four SDSC subscale scores - difficulty in initiating and maintaining sleep, sleep breathing disorders, sleep-wake transition disorders, and sleep hyperhidrosis. Caregiver sleep duration of less than 7 hours (p=0.02) and caregiver sleep latency of more than 30 minutes (p=0.03) were significantly associated with higher Total SDSC scores. Co-sleeping was not a significant factor.	Sleep disturbances are more common in children with CP than in their siblings. Attention should be given to caregiver sleep when evaluating sleep disturbances in children with CP as this factor was shown to be associated with higher Total SDSC scores.	
24526557	Sleep duration and sleep quality affect patients' general condition and self-reported health status.The aims of this study were:(1) to describe the clinical characteristic of ST-elevation myocardial infarction (STEMI) patients who sleep too little or too much; and(2) to determine whether sleep duration is independently associated with a higher risk of all-cause mortality.	We enrolled into the study 407 consecutive patients admitted with a diagnosis of STEMI. All patients were asked for sleep duration in the first three months after being discharged from the hospital. According to the sleep duration, we divided patients into three groups: A - the reference category defined as 6-8 sleep hours, B - short sleep with < 6 h, and C - long sleep with > 8 h.	The final analysis covered 379 patients (271 males; mean age 59.4 ± 10.61). 36 (9.5%) patients slept less than 6 h, 26 (6.9%) slept more than 8 h per night. The all-cause three-year mortality was 1.9% in the reference category, 13.9% in patients who slept less than 6 h, and 30.8% in patients who slept more than 8 h per night (p < 0.0001). In the multiple logistic regression analysis, short (OR 10.2, 95% CI 2.1-50, p = 0.004) and long sleep duration (OR 33.3, 95% CI 6.8-163.4, p < 0.001) were strong and independent predictors of all-cause mortality.	Too short and especially too long duration of sleep in the first months after myocardial infarction are strong,independent predictors of all-cause mortality.	
24525958	The neurobiological mechanisms of emotional memory processing can be investigated using classical fear conditioning as a model system, and evidence from multiple lines of research suggests that sleep influences consolidation of emotional memory. In rodents, some of this evidence comes from a common finding that sleep deprivation from 0 to 6 h after fear conditioning training impairs processing of conditioned fear memory. Here, we show that during a 6-h session of sleep-wake (S-W) recording, immediately after a session of context-associated fear conditioning training, rats spent more time in wakefulness (W) and less time in slow-wave sleep (SWS) and rapid eye movement (REM) sleep. This context-associated fear conditioning training-induced reduction in SWS lasts for 2 h, and the REM sleep reduction lasts throughout the entire 6-h post-training S-W recording period. Interestingly, these reductions in SWS and REM sleep during this 6-h period did not impair memory consolidation for context-associated fear conditioning. The results of this study show, for the first time, that lesions within the dorsal part of the subcoeruleus nucleus (SubCD), which were unintentionally caused by the implantation of bipolar recording electrodes, impair consolidation of context-associated fear conditioning memory. Together, the results of these experiments suggest that emotional memory processing associated with fear conditioning can be completed successfully within less than a normal amount of sleep, but it requires a structurally and functionally intact SubCD, an area in the brain stem where phasic pontine wave (P-wave) generating cells are located.

24524996	More is now known about the human pharmacology of sleep than a decade ago, but there are still enormous gaps in our understanding and there is still a lack of effective, specific, goal-directed therapeutic agents. Perhaps this is not surprising considering sleep's plurality its patterns and internal structure varying across animal species and humans (changes through life span, variations across cultures and historical differences), not understanding the function or functions of sleep and the risk-aversive regulatory frameworks currently in place. 
24524647	The aim of this study was to determine the frequency and factors associated with fall episodes in advanced cancer patients.We analyzed data that included demographic characteristics, utilization of assistive devices, cancer diagnosis, metastatic site, performance status, medications including hypnotics and opioids, Edmonton Symptom Assessment Scale (ESAS) score, and Memorial Delirium Assessment Scale (MDAS) score in 384 consecutive patients who were newly referred to the Supportive Care Clinic at the MD Anderson Cancer Center from January 1 to December 31, 2009. All patients completed standardized forms to report falls within the last month. Multivariate backward regression analyses were employed to identify factors predictive of falls in advanced cancer.	The mean age of patients was 58 years, and 192 (50%) were male. Mean (SD)/median score for pain was 5 (2.8), 5; fatigue 5.6 (2.6), 6; sleep disturbance 5(2.7), 5; drowsiness 3.7(3), 3; and anorexia 5(3), 5. Some 31 patients (8%) reported fall episodes within the past month, 17 (55%) of whom reported the use of assistive devices. Using assist devices (OR = 5.5, 95% CI: 2.6-11.9, p < 0.0001) and taking zolpidem (OR = 3.39, 95% CI: 1.39-7.7, p = 0.008) were associated with an enhanced chance of falling. Higher MDAS score (4.00 vs. 1.42, p = 0.001) and MDAS positive screening for delirium (21 vs. 3.6%, p < 0.001) were also associated with falls. However, severity on the ESAS at the initial consult was not associated with falls.	We conclude that 31 of 384 patients (8%) with advanced cancer receiving outpatient supportive care reported falls in the previous month. Patients with assistive devices, taking zolpidem, and with a higher MDAS score, and a positive delirium screening reported more frequent falls. Further studies are warranted.	
24524428	We investigated the prevalence of sleep disturbance and psychological distress in lung cancer patients. We also examined the association between sleep disturbance and psychological distress, pain, fatigue, and quality of life in the same population.Fifty lung cancer patients were evaluated. Sleep disturbance was assessed using the Athens Sleep Insomnia Scale (AIS) and psychological distress using the Hospital Anxiety and Depression Scale (HADS). Quality of life (QOL), pain, and fatigue were assessed employing the European Organization of Research and Treatment Quality of Life Questionnaire-Cancer 30 (EORTC QLQ-C30).	We observed that 56% of lung cancer patients had sleep disturbance (AIS score ≥6) and 60% had psychological distress (total HADS score ≥11). Patients with sleep disturbance had a HADS score of 14.6 ± 5.8, a fatigue score of 45.3 ± 22.0, and a pain score of 27.2 ± 26.2. In contrast, patients without sleep disturbance had a lower HADS score of 9.9 ± 8.1 (p < 0.05) and a higher fatigue score of 28.5 ± 18.0 (p < 0.01) and a pain score of 8.7 ± 15.8 (p < 0.01). In addition, we found a lower QOL in patients with sleep disturbance (46.3 ± 20.2) than in those without (65.2 ± 20.7) (p < 0.05). We also observed a significant correlation between the AIS, HADS, fatigue, QOL, and pain scores.	Lung cancer patients suffered from combined symptoms related to sleep. Sleeping pills improved sleep induction but were not sufficient to provide sleep quality and prevent daytime dysfunction. Daytime dysfunction was specifically associated with psychological distress. Additionally, the type of sleep disturbance was related to other patient factors, including whether or not they received chemotherapy.	
24523490	Habitual short sleep duration appears to increase the risk of obesity. The objective of this paper is to investigate the association of habitual sleep duration with objective measures of energy balance. One hundred twelve African-American and 111 non-Hispanic whites aged 21-69 y participated in a cross-sectional study of dietary assessment and biomarkers. Participants reported the mean number of hours per day spent sleeping over the past year. Short sleep duration was defined as ≤6 h/d of sleep. Energy intake (kilocalories) was objectively assessed using the 2-point doubly labeled water technique to determine total energy expenditure, which is approximately equal to energy intake. Physical activity energy expenditure (kilocalories) was estimated as total energy expenditure minus each participant's calculated basal metabolic rate and the thermogenic effect of food. Compared with participants who slept ≤6 h, individuals who slept 8 h were significantly less likely to be obese (OR: 0.33; 95% CI: 0.14, 0.79). However, this association was not linear across 6-9 h of sleep (P-trend = 0.16). There was an inverse association between sleep and energy intake (P-trend = 0.07): compared with ≤6 h/d, adults who reported ≥9 h sleep consumed 178 fewer kcal/d. There was also an inverse association between sleep and physical activity (P-trend = 0.05): compared with ≤6 h/d of sleep, adults who reported 9 h of usual sleep expended 113 fewer kcal/d in physical activity. These data indicate that, compared with longer sleep duration, adults who report habitual short sleep duration have somewhat higher physical activity energy expenditure but considerably higher energy intake. Habitual short sleep duration appears to be 1 of the facets of modern life leading to a mismatch between energy intake and physical activity. 
24523423	Children with attention-deficit/hyperactivity disorder (ADHD) commonly experience behavioural sleep problems, yet these difficulties are not routinely assessed and managed in this group. Presenting with similar symptoms to ADHD itself, sleep problems are complex in children with ADHD and their aetiology is likely to be multifactorial. Common internalising and externalising comorbidities have been associated with sleep problems in children with ADHD; however, this relationship is yet to be fully elucidated. Furthermore, limited longitudinal data exist on sleep problems in children with ADHD, thus their persistence and impact remain unknown. In a diverse sample of children with ADHD, this study aims to: (1) quantify the relationship between sleep problems and internalising and externalising comorbidities; (2) examine sleep problem trajectories and risk factors; and (3) examine the longitudinal associations between sleep problems and child and family functioning over a 12-month period.A prospective cohort study of 400 children with ADHD (150 with no/mild sleep problems, 250 with moderate/severe sleep problems) recruited from paediatric practices across Victoria, Australia. The children's parents and teacher provide data at baseline and 6-month and 12-month post enrolment.	Parent report of child's sleep problem severity (no, mild, moderate, severe); specific sleep domain scores assessed using the Child Sleep Habits Questionnaire; internalising and externalising comorbidities assessed by the Anxiety Disorders Interview Schedule for Children IV/Parent version.	Multiple variable logistic and linear regression models examining the associations between key measures, adjusted for confounders identified a priori.	Ethics approval has been granted. Findings will contribute to our understanding of behavioural sleep problems in children with ADHD. Clinically, they could improve the assessment and management of sleep problems in this group. We will seek to publish in leading paediatric journals, present at conferences and inform Australian paediatricians through the Australian Paediatric Research Network.	
24522288	Poor sleep hygiene including sleeping in the daytime or with the lights on at night is discovered during the assessment of many sleep disorders including sleep apnea. The aim of this study was to investigate whether environmental light affected autonomic control of heart rate, sleep-disordered breathing (SDB), and/or breathing patterning.Seventeen non-obese healthy volunteers without witnessed snoring and apneas were recruited. Studies were performed at home using a type 3 portable monitor combined with actigraphy for sleep-wake timing, using a randomly assigned, crossover between dark, or 1,000 lx of fluorescent lighting environment. The outcomes were low-frequency power divided by high-frequency power (LF/HF ratio) in the analysis of heart rate variability, the apnea-hypopnea index (AHI), and ventilatory pattern variability before and after sleep onset between environments.	The LF/HF ratio and AHI were both significantly higher in light as compared to dark. Before sleep onset, the coefficient of variation (CV) for breath-to-breath tidal volume representing breathing irregularity tended to be higher in light than in dark environment. The CV values for tidal volume after sleep onset were significantly decreased compared with before sleep onset in both sleep environments. Mutual information of the ventilatory pattern was significantly lower before sleep onset than after sleep onset, only in the light environment.	Sleeping in the light has effects like that of a stressor as it is associated with neuroexcitation, SDB, and resting breathing irregularity in healthy volunteers. These findings may be relevant to many sleep disorders associated with poor sleep hygiene.	

24520342	The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD. 
24519731	Sleep problems are prevalent among older adults who are at risk of developing dementia. Until now, there have been relatively few studies investigating subjective sleep quality in these individuals. The first objective of this study was to compare seniors with cognitive impairment no dementia (CIND) and older adults without cognitive impairment (non-CIND) on several subjective sleep measures. The second objective was to verify whether sleep parameters associated with CIND differ between men and women.The population sample consisted of 2287 French-speaking older adults from Québec (Canada) aged between 65 and 96 years. Participants were classified as CIND or non-CIND on the basis of their mini mental state examination score using sex, age, and education-stratified normative data. All participants completed the Pittsburgh Sleep Quality Index, and responses of CIND and non-CIND individuals were compared. A series of confounding variables (age, education, chronic diseases, mood disorders, anxiety disorders, and use of psychotropic drugs) were statistically controlled for. Student's t-tests were performed to compare characteristics of CIND and non-CIND individuals; data from male and female participants were analyzed separately. Moreover, the association between each sleep variable and CIND was measured by odds ratios based on logistic regression.	On the whole, analyses revealed no significant association between subjective sleep parameters and CIND. Moreover, no difference was observed between men and women regarding subjective sleep quality.	Overall, these results suggest that subjective measures of sleep do not allow differentiating cognitively impaired older individuals from those with normal cognition.	


24518285	To investigate the efficacy of fesoterodine vs placebo on nocturia, sleep disturbance, and sleep-related quality of life (QoL) in patients with overactive bladder and nocturia.This posthoc analysis used data from a 12-week, randomized, placebo-controlled trial of fesoterodine 4 and 8 mg per day in Asian adults reporting ≥8 micturitions and ≥1 urgency urinary incontinence episodes per 24 hours at baseline. Patients who reported ≥1 nocturnal micturition/24 h were included in this analysis. Efficacy variables included change from baseline to week 12/end of treatment in nocturnal micturitions/24 h, nocturnal voided volume/micturition, and hours of undisturbed sleep. Sleep-related QoL was assessed using King's Health Questionnaire Sleep/Energy domain. Treatment comparisons were made using analysis of covariance.	Among 555 patients, reductions in nocturnal micturitions with fesoterodine 4 mg (-0.63) and 8 mg (-0.77) were numerically greater vs placebo (-0.56), but differences were not significant (P >.05). When patients with a nocturnal polyuria index >33% were excluded, the decrease in nocturnal micturitions was significantly greater with fesoterodine 8 mg vs placebo (-0.24; P = .031). Increases in nocturnal voided volume/micturition were significantly greater with fesoterodine 4 (38.07 mL; P = .013) and 8 mg (42.05 mL; P <.001) vs placebo (14.89 mL). Hours of undisturbed sleep was significantly longer with fesoterodine 4 mg vs placebo (80 vs 54 minutes; P = .032); improvement in King's Health Questionnaire Sleep/Energy scores was significantly greater with fesoterodine 4 (P = .034) and 8 mg (P = .019) vs placebo.	These results suggest that fesoterodine may reduce nocturnal micturitions and improve sleep quality and QoL in overactive bladder patients with nocturia.	
24517896	New mothers commonly report sleep deprivation and sleep disturbances during the first 3 postpartum months. A better understanding of factors related to postpartum sleep quality is necessary to develop interventions to improve sleep quality in postpartum women.This study explored the impact of specific demographic and obstetric factors on the subjective sleep quality of postpartum women.	We used a cross-sectional, correlational study design. A convenience sample of 202 women in their fourth to sixth postpartum week was recruited from two hospitals in southern Taiwan. A demographic data form and the Postpartum Sleep Quality Scale were used to collect data.	The mean Postpartum Sleep Quality Scale score of participants was 22.82 (SD = 8.16), indicating a mild level of sleep disturbance. We found that better sleep quality correlated positively with a satisfactory childbirth experience and correlated negatively with daily time spent on household work. Pain, discomfort, and fear were the main dimensions associated with unsatisfactory childbirth experiences.	Study results recommend that health professionals should improve current protocols to help women better confront and manage childbirth-related pain, discomfort, and fear. Evidence-based postnatal education for parents should highlight the positive relationship between reduced daily household workloads and sleep quality for new mothers.	
24517139	Many older adults (seniors) experience problems with getting enough sleep. Because of the link between sleep and circadian rhythms, changes in bedtime lead to changes in the amount of sleep obtained. Although primarily determined genetically, chronotype changes with advancing age towards a more morning-type (M-type) orientation. In a 2006 study, we have found a linear relationship, by which the earlier a senior's bedtime, the more sleep she/he will obtain. The aim of this study was to see whether this relationship differs for M-type seniors, as compared to seniors outside the M-type category. Retired seniors (n = 954, 535 M, 410F, 65 years+, mean age 74.4 years) taking part in a telephone interview were divided into M-types and Other types (O-types) using the Composite Scale of Morningness (CSM). The relationship between bedtime and Total Sleep Time (TST), and between rise-time and TST, was tested using linear regression separately for M-types and O-types. For each participant, habitual bedtime, rise-time and total Sleep Time (TST) [after removing time spent in unwanted wakefulness] were obtained using a telephone version of the Sleep Timing Questionnaire (STQ). Both chronotype groups showed a significant linear relationship between bedtime and TST (p < 0.001); with earlier bedtimes leading to more TST (M-type 5.6 min; O-type 4.4 min per 10 min change [slope difference p = 0.05]); and an opposite relationship between rise-time and TST with earlier rise-times leading to less TST (M-type 6.7 min; O-type 4.2 min per 10 min change [slope difference p = 0.001]). M-types retired to bed 56 min earlier (p < 0.001), awoke 93 min earlier (p < 0.001) and obtained 23 min less TST (p < 0.001) than O-types. In conclusion, both chronotypes showed TST to be related in a linear way to bedtime and rise-time; the overall shorter TST in M-types was due to them rising 93 min earlier, but only retiring to bed 56 min earlier than O-types; as well as having a steeper rise-time versus TST relationship. 
24516136	Adult stem cells maintain tissue integrity and function by renewing cellular content of the organism through regulated mitotic divisions. Previous studies showed that stem cell activity is affected by local, systemic, and environmental cues. Here, we explore a role of environmental day-night cycles in modulating cell cycle progression in populations of adult stem cells. Using a classic stem cell system, the Drosophila spermatogonial stem cell niche, we reveal daily rhythms in division frequencies of germ-line and somatic stem cells that act cooperatively to produce male gametes. We also examine whether behavioral sleep-wake cycles, which are driven by the environmental day-night cycles, regulate stem cell function. We find that flies lacking the sleep-promoting factor Sleepless, which maintains normal sleep in Drosophila, have increased germ-line stem cell (GSC) division rates, and this effect is mediated, in part, through a GABAergic signaling pathway. We suggest that alterations in sleep can influence the daily dynamics of GSC divisions. 
24515853	Obstructive sleep apnea and chronic musculoskeletal pain both affect sleep. Sleep architecture of patients suffering from both is largely unknown.This study seeks to define the sleep architecture of patients with chronic musculoskeletal pain and obstructive sleep apnea.	Patients with obstructive sleep apnea diagnosed by sleep study during the past 3 years were included. Patients with clinical documentation of chronic musculoskeletal pain constituted cases, while others were classified as controls.	Demographics, clinical factors affecting sleep, medications affecting sleep, Epworth sleepiness scores, and polysomnographic parameters; total sleep time, sleep efficiency, sleep stages, rapid eye movement (REM) sleep onset, apnea-hypopnea index, arousal index, and periodic leg movements were recorded.	There were 393 subjects: 200 cases (obstructive sleep apnea and chronic musculoskeletal pain) and 193 controls (obstructive sleep apnea alone). There was significant difference in total sleep time (274.5 ± 62.5 vs. 302.2 ± 60.1 min, p = 0.0001), sleep efficiency (73.54 ± 15.8 vs. 78.76 ± 14.3%, p = 0.0003), and REM sleep onset (148.18 ± 80.5 vs. 124.8 ± 70.9 min, p = 0.006). Subgroup analysis within the obstructive sleep apnea with chronic musculoskeletal pain group revealed that subjects had better total sleep time and sleep efficiency if they were on REM sleep affecting medications (suppressants and stimulants). Those on REM sleep suppressants slept 25.7 min longer and had 6.4% more efficient sleep than those not on REM suppressants (p = 0.0034 and p = 0.0037).	Patients with obstructive sleep apnea and chronic musculoskeletal pain sleep not only significantly less but also with inferior sleep quality. Their REM sleep is also less in duration and its onset is delayed. Despite low TST and SE, these patients may not exhibit sleepiness.	
24513042	A series of fused cyclopropyl-4,5-dihydropyridazin-3-one (3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one) phenoxypiperidine analogs was designed and synthesized, leading to the identification of (1R,6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one (R,S-4a) as a second-generation pyridazin-3-one H3R antagonist. Compound R,S-4a was a potent H3R functional antagonist in vivo in the rat dipsogenia model, demonstrated potent wake activity in the rat EEG/EMG model, and enhanced short-term memory in the rat social recognition memory model at doses as low as 0.03-0.3 mg/kg po.
24512957	Many people in our society experience curtailment and disruption of sleep due to work responsibilities, care-giving, or life style choice. Delineating the health effect of acute and chronic disruptions in sleep is essential to raising awareness of and creating interventions to manage these prevalent concerns. To provide a platform for studying the health impact and underlying pathophysiologic mechanisms associated with inadequate sleep, we developed and characterized an approach to creating chronic disruption of sleep in laboratory mice. We used this method to evaluate how 3 durations of sleep fragmentation (SF) affect sleep recuperation and blood and lung analyte concentrations in male C57BL/6J mice. Mice housed in environmentally controlled chambers were exposed to automated SF for periods of 6, 12, or 24 h or for 12 h daily during the light (somnolent) phase for 4 sequential days. Sleep time, slow-wave amplitude, or bout lengths were significantly higher when uninterrupted sleep was permitted after each of the 3 SF durations. However, mice did not recover all of the lost slow-wave sleep during the subsequent 12- to 24-h period and maintained a net loss of sleep. Light-phase SF was associated with significant changes in serum and lung levels of some inflammatory substances, but these changes were not consistent or sustained. The data indicate that acute light-phase SF can result in a sustained sleep debt in mice and may disrupt the inflammatory steady-state in serum and lung. 

24512361	This study examined the relationship between dysmenorrhea and insomnia, as well as variability in sleep across the menstrual cycle. Participants were 89 women, ages 18 to 24 (M = 18.63, SD = 0.93), who completed daily surveys for five weeks. On the second day of menses, they completed a questionnaire regarding dysmenorrhea. Participants having insomnia rated their dysmenorrhea as being more severe and causing more interference with daily activities than did participants without insomnia. Insomnia severity was directly associated with dysmenorrhea severity and interference. Sleep onset latency was longer and sleep efficiency was lower in participants with severe dysmenorrhea than in those with mild dysmenorrhea. Further, participants with mild dysmenorrhea reported significantly better sleep quality than did those having moderate or severe dysmenorrhea. Additionally, wake time after sleep onset was shortest and number of awakenings was lowest around the time of ovulation. Future research should examine whether treating dysmenorrhea or insomnia alone results in improvements in the other condition. 
24512086	Sleep disorders (SDs) are common in cirrhotics and are often associated with hepatic encephalopathy. SDs negatively affect patients' daily activities and work efficiency. For this reason, early diagnosis is important. The methods used for diagnosis of SDs are not practical and need longer periods of application and evaluation. In this study, we aimed to investigate sleep disorders and related clinical parameters in cirrhosis and also wanted to investigate the using of Sleep Timing and Sleep Quality Screening questionnaire (STSQS), a simple form with a short application time, for diagnosis of SDs and its correlation with Pittsburg Sleep Quality Index (PSQI) form.Cirrhotic patients and age-matched healthy volunteers were enrolled. Patients were excluded from this study if they had neuropsychiatric disease or used excessive alcohol or drugs known to affect sleep. Both groups completed validated Turkish form of PSQI and STSQS. SD was defined as PSQI score (0-21) of >5 or STSQS ≥5.	One hundred and thirty-one cirrhotic patients and 18 healthy volunteers were enrolled. SDs in cirrhotics and control group were detected 56.5% and 27.8% by PSQI, 49.6% and 16.7% by STSQS respectively. SDs are the most frequent in the Child C patients, and the least frequent in the Child A patients (P > 0.05). No correlation was found between the MELD score and SDs. SDs were more common in cirrhotic patients with hypoalbuminaemia and low haemoglobin levels. In addition, the patients with decompensated cirrhosis had more frequently SDs than the patients with compensated cirrhosis. In the patient group, sleep latency and total sleep time, sleep parameters were correlated with SDs. STSQS had statistical significant correlation with PSQI for diagnosis of SDs.	SDs are common in cirrhotics and STSQS could be an appropriate and practical method for diagnosis of SDS in these patients. We can use it in cirrhotic patients at outpatient clinics.	
24511653	There is a well-established correlation between sleep disturbances and attention deficit hyperactivity disorder (ADHD). A large number of pediatric patients diagnosed with ADHD have sleep problems, while patients with sleep disturbances often display behavioral patterns that resemble some features of ADHD. Despite these observations, the relationship between sleep problems and ADHD is not yet fully understood. It is often difficult to pinpoint which of the disorders is the primary and which a byproduct of the other. A complicating factor is that stimulant medication such as methylphenidate, a drug of choice for ADHD, may adversely affect sleep quality in ADHD patients. However, there have also been reports that it may actually improve sleep quality. This review examines the latest trends in the contemporary literature on this clinical dilemma.
24509897	Fibromyalgia (FM) is recognized as a common condition, characterized by widespread pain and associated with sleep disturbances and poor-quality sleep. The Pittsburgh Sleep Questionnaire Index (PSQI) is one of the most recommended instruments to measure sleep quality and sleep disorders. The purpose of our study was to translate the questionnaire into Spanish and to assess the psychometric properties of the Spanish version of the PSQI. A total of 138 women with FM belonging to a FM association (AFIXA, Andalusia, Spain) completed the study. Internal consistency and test-retest reliability were analyzed. Factorial analysis was performed for the PSQI components. Convergent validity of the PSQI was evaluated using Spearman's rank correlation coefficient with the Spanish versions of the Fibromyalgia Impact Questionnaire (FIQ) and the health survey short form-36 (SF-36). In our analysis, the Spanish version of the PSQI has shown a good internal consistency of the total score, with a Cronbach's alpha of 0.805, and an acceptable test-retest reliability, with a Spearman's correlation coefficient of 0.773 (p < 0.001), for the total score. A two-factor structure was generated by exploratory factor analysis, with a Cronbach's alpha of 0.866 for factor 1 and of 0.712 for factor 2. In convergent validity analysis, the PSQI total score showed a significant correlation (p < 0.01) with the FIQ total score and with the mental and physical health summaries scores of the SF-36. Our results show that the Spanish version of the PSQI provides a reliable instrument, with a good convergent validity for measuring sleep quality among Spanish FM patients.

24509148	The aim of the study was to investigate depressive mood in association with sociodemographic, behavioral, self-perceived health, and coronary artery disease (CAD) risk factors and sleep complaints among 35-74-year-old citizens of Palanga. MATERIAL AND METHODS. A representative sample of randomly selected 1602 persons, 600 men and 1002 women, was studied. Depressive mood was assessed by the WHO-5 Well-being Index. Sleep complaints, self-perceived health, and behavioral factors were evaluated by the Basic Nordic Sleep Quality questionnaire and questionnaires on self-perceived health and health behavior. Risk factors for CAD were assessed according to WHO recommendations. RESULTS. The highest prevalence of depressive mood (34.7%) was identified in the age group of 45-54 years in the men and in the age group of 55-64 years in the women (30.0%). The highest odds ratios demonstrating a strong association between depressive mood and health behavior were established for the use of antidepressants (OR=26.0) in the men and for the use of sedatives (OR=3.09) in the women. The highest odds ratios demonstrating an association between depressive mood and self-perceived health were established for chronic pyelonephritis (OR=3.13) in the men and diabetic foot pain (OR=4.46) in the women. The highest odds ratios reflecting an association between depressive mood and sleep quality were established for the inability to work due to disturbed sleep (OR=1.93) in the men and self-perceived sleep quality (OR=1.55) in the women. CONCLUSIONS. Depressive mood, which was significantly associated with risky health behavior, poor self-perceived health, and disturbed sleep, was observed more often in the women than the men; however, significant associations between depressive mood and risk factors for CAD were not established. 
24509118	This study hypothesized that the sleep-wake cycle is the major determinant factor affecting blood pressure (BP) dipping in rats and that the sympathovagal imbalance during quiet sleep is associated with the degree of BP fall.Polysomnographic recording was performed by telemetry on freely moving Wistar-Kyoto rats over 24  h. Active waking and quiet sleep stages were scored using electroencephalogram and electromyogram. BP dipping was assessed as the percentage decline in SBP from dark active waking to light quiet sleep. About 38% of the rats were classified as dippers (>10% dip) and 62% as nondippers (<10% dip).	Among the dipper rats, as compared to dark active waking, the R-R interval and high-frequency power of heart rate variability (a cardiac vagal index) were increased, whereas low-frequency power of blood pressure variability [(BLF), a vascular sympathetic index)] was decreased in light quiet sleep. The sleep-wake cycle rather than the light-dark cycle played the major role in determining BP dipping. The light-dark change in R-R interval, BLF during dark active waking, and baroreflex sensitivity indices during quiet sleep were significantly lower among nondipper rats than among dipper rats. Correlation analysis revealed that BLF during dark active waking as well as high-frequency power of heart rate variability and baroreflex sensitivity indices during light quiet sleep were correlated with the BP dipping percentage.	This study confirms that the sleep-wake cycle is more important than the light-dark cycle in determining BP dipping. Moreover, lower baroreflex control and parasympathetic activity during quiet sleep as well as lower sympathetic activity during active waking are associated with reduced BP dipping.	
24508153	The endocannabinoid system is a modulatory system that has been strongly associated with the regulation of functions as learning and memory, pain perception and sensory physiology in many areas of the central nervous system. However, although a role in sensory processing has been demonstrated at the level of the thalamus, the influence of the endocannabinoid system on thalamic rhythms and oscillations has been less studied, despite the fact that such activities are significant characteristics of the thalamic state. The present work aimed to characterize the role of anandamide (AEA) - one of the endogenous CB1 receptor agonists - and AM251 - a CB1 antagonist - in the modulation of burst firing and oscillatory activity present in the dLGN of the anesthetized rat. Administration of AEA (0.5mg/kg iv) increased the number of bursts in the majority of the cells tested and induced the appearance of a slow delta-like (1.5Hz) oscillatory activity. These effects were CB1-mediated, as demonstrated by the complete antagonism during the co-application of AM251 (0.5mg/kg iv). Thus, by demonstrating that the AEA-mediated activation of CB1 receptors increases spontaneous bursting and oscillatory activity in the thalamus our study infers that endocannabinoids could have a role in processes controlling the sleep-wake cycle and level of arousal. 
24508049	The aim of our study was to evaluate the importance of sleep recordings and stimulus-related evoked potentials (EPs) in patients with prolonged disorders of consciousness (DOCs) by correlating neurophysiologic variables with clinical evaluation obtained using specific standardized scales.There were 27 vegetative state (VS) and 5 minimally conscious state (MCS) patients who were evaluated from a clinical and neurophysiologic perspective. Clinical evaluation included the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), and Glasgow Coma Scale (GCS). Neurophysiologic evaluation included 24-h polysomnography (PSG), somatosensory EPs (SEPs), brainstem auditory EPs (BAEPs), and visual EPs (VEPs).	Patients with preservation of each single sleep element (sleep-wake cycle, sleep spindles, K-complexes, and rapid eye movement [REM] sleep) always showed better clinical scores compared to those who did not have preservation. Statistical significance was only achieved for REM sleep. In 7 patients PSG showed the presence of all considered sleep elements, and they had a CRS-R score of 8.29±1.38. In contrast, 25 patients who lacked one or more of the sleep elements had a CRS-R score of 4.84±1.46 (P<.05). Our multivariate analysis clarified that concurrent presence of sleep spindles and REM sleep were associated with a much higher CRS-R score (positive interaction, P<.0001). On the other hand, no significant associations were found between EPs and CRS-R scores.	PSG recordings have proved to be a reliable tool in the neurophysiologic assessment of patients with prolonged DOCs, correlating more adequately than EPs with the clinical evaluation and the level of consciousness. The main contribution to higher clinical scores was determined by the concomitant presence of REM sleep and sleep spindles. PSG recordings may be considered inexpensive, noninvasive, and easy-to-perform examinations to provide supplementary information in patients with prolonged DOCs.	
24506941	The circadian abnormality of delayed sleep phase has been suggested to characterise a subgroup of depressed young adults with different risk factors and course of illness. We aim to assess the prevalence and factors, particularly substance use, associated with such delay in a large help-seeking cohort of young people with mental health problems.From a consecutively recruited sample of 802 help-seeking young people, 305 (38%) had at least moderate depressive symptoms (QIDS-C16 >10), sleep data and did not have a chronic severe mental illness. Demographic and clinical characteristics were evaluated through self report and clinical interview. Delayed sleep phase was defined as a sleep onset between the hours of 02:00 a.m. - 06:00 a.m. and the characteristics of this group were compared to normal phase sleepers.	Delayed sleep onset was reported amongst 18% (n = 56/305) of the depressed group compared to 11% of the non-depressed young people. Amongst the depressed group, delayed sleep onset was associated with tobacco, alcohol and cannabis misuse and short sleep duration (x̅: 5.8 hrs vs. x̅: 7.8 hrs). There were no differences in demographic factors, personality traits or symptoms. Tobacco smoking was very common: In logistic regression analyses only tobacco use (OR 2.28, 95% CI: 1.04 - 5.01) was associated with delayed sleep onset. There was no interaction with age.	Delayed sleep onset was twice as common in depressed young people as the general population and young people with other mental health problems, and is a potential marker for a subgroup of mood disorders. Those with delayed sleep onset were not more severely depressed but had short sleep duration, a risk for chronic psychological ill health, and higher levels of tobacco use. Nicotine use was common in this group, has biological evidence as a sleep disrupter, and requires specifically addressing in this population.	
24506342	Agomelatine has demonstrated antidepressant efficacy in randomized, controlled trials. This non-interventional study VIVALDI evaluated agomelatine treatment under practice conditions.Psychiatrists documented the treatment of 3,317 patients over 12 weeks. According to the treatment condition three subgroups were selected: Agomelatine in treatment-naïve patients as mono-therapy (A), in pretreated patients as add-on-therapy (B), and in pretreated patients switched to agomelatine (C). Effect on depressive symptoms was evaluated via svMADRS and CGI. Daytime functioning and sleep-wake rhythm were assessed by a patient-questionnaire.	The svMADRS decreased from values > 30 at baseline to 12.8 (total population), 10.3 (A), 15.1 (B), and 13.5 (C). 76.1%, 55.7%, and 62.5% of patients were responders in subgroups A, B, and C, respectively, 65.8% in the total population. Remission was achieved in 66.5% (A), 44.7% (B), and 50.9% (C) of patients. After 12 weeks, subjective sleep quality and daytime functioning improved in the majority of patients. Adverse drug reactions (ADR/serious ADR) were reported for 6.0%/0% (A), 11.0%/0.2% (B), and 12.6%/0.3% (C) of patients. Overall, 25.8% of patients discontinued treatment prematurely, 5.2% due to ADR.	Agomelatine improved depressive symptoms, daytime functioning, and sleep-wake rhythm, and demonstrated good tolerability also in pretreated patients and combination therapy under routine practice.	
24504123	Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III), yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7-10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice. 
24503473	Sleep patterns have been linked to various health outcomes, but sleep patterns in the British population have not been extensively reported. We aimed to describe the sleep characteristics reported by the European Prospective Investigation of Cancer (EPIC)-Norfolk participants, with a particular emphasis on the comparison of measures of sleep quantity.From 2006 to 2007, a total of 8480 participants aged 45-90 years reported sleep timing, nighttime sleep duration, and sleep difficulties. Time in bed (TIB) was calculated from the difference between rise time and bedtime, and sleep proportion was defined as the ratio of sleep duration and TIB.	On average, the reported TIB was more than 1.5h longer than sleep durations. Compared to men, women spent 15 min longer in bed, but they slept for 11 min less and reported more sleep difficulties. In multivariate analysis sleep duration and TIB varied with socioeconomic factors, but sleep proportion was consistently lower among women, nonworkers, and older individuals, as well as those who were widowed, separated, or divorced; those who reported sleep difficulties and more frequently used sleep medication; and those who had lower education, poorer general health, or a major depressive disorder (MDD).	Self-reported sleep duration and TIB have different meanings and implications for health. Sleep proportion may be a useful indicator of sleep patterns in the general population.	
24503446	Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail.The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS.	We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients' urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases.	Sleep-wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN.	AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS.	
24501808	Not all smoking addicts can succeed in quitting smoking with willpower only. These people may use nicotine replacement therapy (patches, gums, lozenges, sublingual tablets, inhalers), medicines (bupropion, varenicline and cytisine) and psychological aid. Each drug, besides its therapeutic effect, creates the risk of adverse reactions which number and severity is not always accepted by the patient. The aim of the study was to analyze adverse effects of bupropion, varenicline and cytisine formulations reported by patients. From July 2011 to June 2013 Regional Centre for Monitoring Adverse Drug Reactions (Department of Clinical Pharmacology, Department of Cardiology, Poznan University of Medical Sciences) recorded 32 suspected adverse reactions to the use of drugs for the treatment of nicotine addiction (12 after the preparation of cytisine and varenicline, 8 after preparations of bupropion). High determination caused that none of the patients withdrew from the therapy because of adverse effects.
24501437	We investigated a generally unappreciated feature of the sleep disorder narcolepsy, in which patients mistake the memory of a dream for a real experience and form sustained delusions about significant events.We interviewed patients with narcolepsy and healthy controls to establish the prevalence of this complaint and identify its predictors.	Academic medical centers in Boston, Massachusetts and Leiden, The Netherlands.	Patients (n = 46) with a diagnosis of narcolepsy with cataplexy, and age-matched healthy healthy controls (n = 41).	N/A.	"Dream delusions" were surprisingly common in narcolepsy and were often striking in their severity. As opposed to fleeting hypnagogic and hypnopompic hallucinations of the sleep/wake transition, dream delusions were false memories induced by the experience of a vivid dream, which led to false beliefs that could persist for days or weeks.	The delusional confusion of dreamed events with reality is a prominent feature of narcolepsy, and suggests the possibility of source memory deficits in this disorder that have not yet been fully characterized.	

24500032	Nocturnal symptoms are frequent in Parkinson disease (PD) and consist of nocturnal sleep disorders such as REM sleep behavior disorder (RBD) and restless legs syndrome. There is an increasing need for reliable, early, pre-motor diagnosis of PD, since motor symptoms occur when there is already significant neuronal loss. Recent prospective studies have shown that over 80% of idiopathic RBD patients over time converted to PD and related synucleinopathies. RBD patients have autonomic, visual, and olfactory dysfunction as well as neuroimaging abnormalities similar to those seen in PD. Studies have shown that neuroimaging abnormalities and visual and olfactory dysfunction can help predict which RBD patients will likely convert to a neurodegenerative diagnosis within a short follow-up period. These factors make RBD an ideal population for prediction to PD conversion, allowing future testing and eventual use of neuroprotective strategies.
24499130	To evaluate the effectiveness of Koru, a mindfulness training program for college students and other emerging adults.Ninety students (66% female, 62% white, 71% graduate students) participated between Fall 2012 and Spring 2013.	Randomized controlled trial. It was hypothesized that Koru, compared with a wait-list control group, would reduce perceived stress and sleep problems, and increase mindfulness, self-compassion, and gratitude.	As hypothesized, results showed significant Group (Koru, Wait-List)×Time (Pre, Post) interactions for improvements in perceived stress (F[1, 76.40]=4.50, p=.037, d=.45), sleep problems (F [1, 79.49]=4.71, p=.033, d=.52), mindfulness (F [1, 79.09]=26.80, p<.001, d=95), and self-compassion (F[1, 74.77]=18.08, p<.001, d=.75). All significant effects were replicated in the wait-list group. Significant correlations were observed among changes in perceived stress, sleep problems, mindfulness, and self-compassion.	Results support the effectiveness of the Koru program for emerging adults in the university setting.	
24499013	Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by long-standing clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (a) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep; (b) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning; and (c) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on posttraumatic stress disorder and major depression. 
24497659	Mexican immigrants to the United States report longer sleep duration and fewer sleep complaints than their US-born counterparts. To investigate whether this effect extends to other immigrant groups, we examined whether the prevalence of self-reported sleep complaints is higher among US-born Hispanic/Latina, Chinese, and Japanese immigrant women compared to their first-generation immigrant ethnic counterparts as well as to US-born whites. We examined whether these associations persisted after adjusting for sociodemographic and health characteristics and whether acculturation mediated the effects.Cross-sectional observational study.	Multisite study in Oakland, CA; Los Angeles, CA; and Newark, NJ.	Hispanic/Latina (n = 196), Chinese (n = 228), Japanese (n = 271) and non-Hispanic white (n = 485) women (mean age = 46 y, range 42-52 y) participating in the Study of Women's Health Across the Nation (SWAN); 410 or 59.0% of the nonwhites were first-generation immigrants.	None.	Questionnaires were used to assess sleep complaints, race/ethnicity, immigrant status, language acculturation (use of English language), and sociodemographic and health variables. Approximately 25% of first-generation immigrant women reported sleep complaints compared to 37% of those who were US-born nonwhites and 42% of US-born whites. Multivariable adjusted logistic regression analyses showed that US-born nonwhites had higher odds of reporting any sleep complaints (odds ratio = 2.1, 95% confidence interval [CI] 1.5-3.0), compared to first-generation immigrants. Women with higher levels of language acculturation had greater odds of reporting any sleep complaint compared to those with less language acculturation. Adjustment for language acculturation mediated 40.4% (95% CI 28.5-69.8) of the association between immigrant status and any sleep complaint. When results were stratified by race/ethnicity, significant mediation effects of acculturation were only found for Hispanic/Latina and Japanese women, but not for Chinese women.	US-born Hispanic/Latina, Chinese, and Japanese immigrants were more likely to report sleep complaints than their first-generation ethnic counterparts, a finding largely explained by language acculturation and unmeasured factors associated with language acculturation.	
24497657	We examined associations between pubertal maturation and sleep in early adolescence, at age 12 y, and continuity and change in actigraphy-based sleep and parent-reported sleep disorders from age 8 to 12 y. We also explored longitudinal associations between actigraph estimates of sleep and sleep disorders.A cohort study of children born in 1998 and tested at ages 8 y (standard deviation [SD] = 0.3) and 12 y (SD = 0.5).	A total of 348 children participated in cross-sectional analyses. We had longitudinal actigraphy data for 188 children and repeated parent reports of sleep disorders for 229 children.	At age 8 y, participants wore actigraphs for 7.1 nights (SD = 1.2, range 3-14) on average and at age 12 y for 8.4 nights (SD = 1.7, range 3-11). Sleep disorders were parent-rated based on the Sleep Disturbance Scale for Children. Pubertal maturity was self-reported at age 12 y using the continuous Pubertal Development Scale and the picture-assisted categorical Tanner scales.	Significant mean-level changes toward shorter but higher quality sleep occurred over time. Sleep variables had low to high rank-order stability over time. Sleep disorders were highly stable from age 8 to 12 y. Actigraphy-based sleep and parent-rated sleep disorders showed no association either in cross-section or longitudinally. Pubertal maturation was not associated with worse sleep.	Sleep in early adolescence can be anticipated from childhood sleep patterns and disorders, but is not associated with pubertal maturity. Although sleep duration becomes shorter, sleep quality may improve during early adolescence. Parent-rated sleep disorders are distinct from actigraph estimates of sleep.	
24497628	Evidence suggests that pain interferes with sleep in youth with developmental disabilities. This study examined the relationship between pain and sleep problems in a sample of youth with parent-reported autism spectrum disorder (N = 62). Mothers reported on standardized measures of pain and sleep problems. Youth demonstrated atypically high levels of both observed pain and sleep problems. Pain predicted overall sleep disturbance and three specific sleep problems: sleep duration, parasomnias, and sleep-disordered breathing. These specific sleep problems were predicted by specific modalities of nonverbal pain communication (e.g. sleep duration problems were predicted by social communication of pain). Effects were consistent across probing of relevant moderators. These findings suggest that comprehensive assessment of both pain and sleep problems may provide important information for medical and behavioral treatment planning for youth with autism spectrum disorder. 
24496489	Sleep problems often co-occur with psychopathological conditions and affective dysregulation. Individuals with mood disorders have significantly higher rates of sleep disturbances than healthy individuals, and among those with mood disorders, sleep problems are associated with lower rates of remission and response to treatment. Sleep disruption may itself be a risk factor for various forms of psychopathology, as experimental sleep deprivation has been found to lead to increased affective, cognitive, and somatic symptoms within healthy volunteers. However, little is known about the relationship between recurring sleep complaints in a naturalistic environment and symptoms of psychopathology among healthy individuals. In the present study, 49 healthy adults (21 males and 28 females) reported sleep quality and completed the Personality Assessment Inventory, a standardized self-report assessment of symptoms of psychopathology. Consistent with prior published findings during total sleep deprivation, individuals endorsing self-reported naturally occurring sleep problems showed higher scores on scales measuring somatic complaints, anxiety, and depression. Furthermore, the reported frequency of sleep disturbance was closely linked with the severity of self-reported symptoms. While causal directionality cannot be inferred, these findings support the notion that sleep and emotional functioning are closely linked. 
24495406	There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances (SD) in patients with Alzheimer disease (AD). We tested the efficacy and safety of trazodone to treat SD in patients with AD.We conducted a double-blind, randomized and controlled trial during periods of 7-9 days at baseline and 2 weeks of treatment.	Geriatric medical center of the university's general hospital.	Individuals with probable AD and SD. The complete analysis comprised 30 patients assigned to either the active treatment group (N = 15) or the placebo group (N = 15).	Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks.	Patients were evaluated using actigraphy and structured scales before and after intervention.	Compared with the placebo group, trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment. Neither trazodone nor placebo induced significant daytime sleepiness or naps. The treatments with trazodone or placebo did not show any effects either on cognition (Mini-Mental State Examination, forward/backward digit span task, letter-number sequencing, arithmetic, digit symbol-coding, and symbol search) or functionality (Katz index). There were no differences in frequency or severity rating of adverse events between the groups.	This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD.	
24495222	Ambulatory monitoring is of major clinical interest in the diagnosis of obstructive sleep apnoea syndrome. We compared a novel non-contact biomotion sensor, which provides an estimate of both sleep time and sleep-disordered breathing, with wrist actigraphy in the assessment of total sleep time in adult humans suspected of obstructive sleep apnoea syndrome. Both systems were simultaneously evaluated against polysomnography in 103 patients undergoing assessment for obstructive sleep apnoea syndrome in a hospital-based sleep laboratory (84 male, aged 55 ± 14 years and apnoea-hypopnoea index 21 ± 23). The biomotion sensor demonstrated similar accuracy to wrist actigraphy for sleep/wake determination (77.3%: biomotion; 76.5%: actigraphy), and the biomotion sensor demonstrated higher specificity (52%: biomotion; 34%: actigraphy) and lower sensitivity (86%: biomotion; 94%: actigraphy). Notably, total sleep time estimation by the biomotion sensor was superior to actigraphy (average overestimate of 10 versus 57 min), especially at a higher apnoea-hypopnoea index. In post hoc analyses, we assessed the improved apnoea-hypopnoea index accuracy gained by combining respiratory measurements from polysomnography for total recording time (equivalent to respiratory polygraphy) with total sleep time derived from actigraphy or the biomotion sensor. Here, the number of misclassifications of obstructive sleep apnoea severity compared with full polysomnography was reduced from 10/103 (for total respiratory recording time alone) to 7/103 and 4/103 (for actigraphy and biomotion sensor total sleep time estimate, respectively). We conclude that the biomotion sensor provides a viable alternative to actigraphy for sleep estimation in the assessment of obstructive sleep apnoea syndrome. As a non-contact device, it is suited to longitudinal assessment of sleep, which could also be combined with polygraphy in ambulatory studies.
24492883	A physiologically based mathematical model of sleep-wake cycles is used to examine the effects of shift rotation interval (RI) (i.e., the number of days spent on each shift) on sleepiness and circadian dynamics on forward rotating 3-shift schedules. The effects of the schedule start time on the mean shift sleepiness are also demonstrated but are weak compared to the effects of RI. The dynamics are studied for a parameter set adjusted to match a most common natural sleep pattern (i.e., sleep between 0000 and 0800) and for common light conditions (i.e., 350 lux of shift lighting, 200 lux of daylight, 100 lux of artificial lighting during nighttime, and 0 lux during sleep). Mean shift sleepiness on a rotating schedule is found to increase with RI, reach maximum at intermediate RI=6 d, and then decrease. Complete entrainment to shifts within the schedules is not achieved at RI≤10 d. However, circadian oscillations synchronize to the rotation cycles, with RI=1,2 d and RI≥6 d demonstrating regular periodic changes of the circadian rhythm. At rapid rotation, circadian phase stays within a small 4-h interval, whereas slow rotation leads to around-the-clock transitions of the circadian phase with constantly delayed sleep times. Schedules with RI=3-5 d are not able to entrain the circadian rhythms, even in the absence of external circadian disturbances like social commitments and days off. To understand the circadian dynamics on the rotating shift schedules, a shift response map is developed, showing the direction of circadian change (i.e., delay or advance) depending on the relation between the shift start time and actual circadian phase. The map predicts that the un-entrained dynamics come from multiple transitions between advance and delay behavior on the shifts in the schedules. These are primarily caused by the imbalance between the amount of delay and advance on the different shift types within the schedule. Finally, it is argued that shift response maps can aid in the development of shift schedules with desired circadian characteristics. 
24491348	Sleep disturbances, including insomnia and sleep-disordered breathing, are a common complaint in people with heart failure and impair well-being. Exercise training (ET) improves quality of life in stable heart failure patients. ET also improves sleep quality in healthy older patients, but there are no previous intervention studies in heart failure patients.The aim of this study was to examine the impact of ET on sleep quality in patients recently discharged from hospital with heart failure.	This was a sub-study of a multisite randomised controlled trial. Participants with a heart failure hospitalisation were randomised within six weeks of discharge to a 12-week disease management programme including exercise advice (n=52) or to the same programme with twice weekly structured ET (n=54). ET consisted of two one-hour supervised aerobic and resistance training sessions, prescribed and advanced by an exercise specialist. The primary outcome was change in Pittsburgh Sleep Quality Index (PSQI) between randomisation and week 12.	At randomisation, 45% of participants reported poor sleep (PSQI≥5). PSQI global score improved significantly more in the ET group than the control group (-1.5±3.7 vs 0.4±3.8, p=0.03). Improved sleep quality correlated with improved exercise capacity and reduced depressive symptoms, but not with changes in body mass index or resting heart rate.	Twelve weeks of twice-weekly supervised ET improved sleep quality in patients recently discharged from hospital with heart failure.	
24491141	Sleep problems are common in attention-deficit/hyperactivity disorder (ADHD) to the extent that they mimic or exacerbate daytime symptoms expression. In this review, we advocate the need for a better understanding of sleep alterations in youths with ADHD and their impact on neurobehavioral functions including learning, memory and emotional regulation. An in-depth exploration of existing data showed that although extensively studied, the actual nature of sleep problems in ADHD and their effects on daytime behavior are still less well understood. Important issues, among which developmental changes in sleep architecture and role of subtle sleep electroencephalogram signatures, are generally neglected. Future research of sleep effects on behavior in ADHD would benefit from considering developmental aspects and links between brain activation patterns during sleep and wake. 
24491008	To translate and validate the Pittsburgh Sleep Quality Index (PSQI), a standardized self-administered questionnaire for the assessment of subjective sleep quality into the Urdu language.Validation study.	Mayo Hospital, Lahore, from March to April 2012.	The PSQI was translated into Urdu following standard guidelines. The final Urdu version (PSQI-U) was administered to 200 healthy volunteers comprising medical students, nursing staff and doctors. Inter-item correlation was assessed by calculating Cronbach alpha. Correlation of component scores with global score was assessed by calculating Spearman correlation coefficient. Correlation between global PSQI-U scores at baseline with global scores for each PSQI-U and PSQI-E at 4-week interval was evaluated by calculating Spearman correlation coefficient. Moreover, scores on individual items of the scale at baseline were compared with respective scores after 4-week by t-test.	One hundred and eighty five (185) participants completed the PSQI-U at baseline. The Cronbach alpha for PSQI-U was 0.56. Scores on individual components of the PSQI-U and composite scores were all highly correlated with each other (all p-values < 0.01). Composite scores for PSQI-U at baseline and PSQI-E at 4-week interval were also highly correlated with each other (Spearman correlation coefficient 0.74, p-value < 0.01) indicating good linguistic interchangeability. Composite scores for PSQI-U at baseline and at 4-week interval were positively correlated with each other (Spearman correlation coefficient 0.70, p < 0.01) indicating good test-retest reliability.	The PSQI-U is a valid and reliable instrument for the assessment of sleep quality. It shows good linguistic interchangeability and test-retest reliability in comparison to the original English version when applied to individuals who speak the Urdu language. The PSQI-U can be a tool either for clinical management or research.