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Concept: Sleep disorder

212

Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

Concepts: Gene, Gene expression, Organism, Sleep, Sleep deprivation, Sleep disorder, Circadian rhythm, Chronotype

194

Traditional screen time (e.g. TV and videogaming) has been linked to sleep problems and poorer developmental outcomes in children. With the advent of portable touchscreen devices, this association may be extending down in age to disrupt the sleep of infants and toddlers, an age when sleep is essential for cognitive development. However, this association has not been demonstrated empirically. This study aims to examine whether frequency of touchscreen use is associated with sleep in infants and toddlers between 6 and 36 months of age. An online survey was administered to 715 parents reporting on child media use (daily exposure to TV and use of touchscreens), sleep patterns (night-time and daytime sleep duration, sleep onset - time to fall asleep, and frequencies of night awakenings). Structural equation models controlling for age, sex, TV exposure and maternal education indicated a significant association between touchscreen use and night-time sleep, daytime sleep and sleep onset. No significant effect was observed for the number of night awakenings. To our knowledge, this is the first report linking the use of touchscreen with sleep problems in infants and toddlers. Future longitudinal studies are needed to clarify the direction of effects and the mechanisms underlying these associations using detailed sleep tracking.

Concepts: Infant, Sleep, Sleep disorder, Circadian rhythm, Narcolepsy, Structural equation modeling, Sleep hygiene

187

A 61-year-old man was referred to our hospital for evaluation of sleep apnea. He snored loudly and had apnea during sleep. During the day, he was sleepy, and when lying down, he could quickly fall asleep. He had a score of 15 on the Epworth Sleepiness Scale, which ranges from 0 to 24, with a score of more than 10 suggestive of excessive daytime somnolence. On physical examination, there were no abnormalities other than obesity (100 kg [220 lb]; body-mass index [the weight in kilograms divided by the square of the height in meters], 31). Overnight polygraphy revealed a score . . .

Concepts: Mass, Sleep, Sleep disorder, Sleep apnea, Sleep medicine, Epworth Sleepiness Scale, Somnolence, Kilogram

169

BACKGROUND: The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. METHODS: We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients' degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients' ESS scores. RESULTS: A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 +/- 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. CONCLUSIONS: The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed.

Concepts: Sleep, Sleep disorder, Parkinson's disease, Sleep apnea, Sleep medicine, Epworth Sleepiness Scale, Excessive daytime sleepiness, Sleep disorders

168

OBJETIVE: To evaluate the effectiveness of adenotonsillectomy for the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS) in children by respiratory polygraphy (RP). MATERIAL AND METHODS: Prospective study was conducted on children referred with clinical suspicion of OSAHS. A clinical history was taken and a general physical and ENT examination was performed on all patients. RP was performed before adenotonsillectomy and six months afterwards. Patients with craniofacial syndromes, neuromuscular disorders, and severe concomitant disease were excluded. RESULTS: We studied 150 children (67. 8% male), with a mean age of 3.74±1.80 years and a BMI of 41.70±31.75. A diagnosis of OSAHS was made if the total number of respiratory events, apneas and hypopneas, divided by the total study time (RDI) was > 4.6, using RP before undergoing adenotonsillectomy. The mean respiratory disturbance index (RDI) was 15.18±11.11, with 58.7% (88) of with severe OSAHS (RDI>10). There was a significant improvement in all clinical and polygraphic variables six months after adenotonsillectomy. The residual OSAHS was 14%. The preoperative RDI was significantly associated with persistent disease (P=.042). CONCLUSIONS: Respiratory polygraphy is useful for monitoring the efficacy of surgical treatment by adenotonsillectomy in children with OSAHS.

Concepts: Pulmonology, Sleep disorder, Sleep apnea, Obstructive sleep apnea, Hypopnea, Abnormal respiration, Apnea, Sleep disorders

148

As the number of freight trains on railway networks increases, so does the potential for vibration exposure in dwellings nearby to freight railway lines. Nocturnal trains in particular are of particular importance since night-time exposure may interfere with sleep. The present work investigates the impact of vibration and noise from night-time freight trains on human sleep. In an experimental polysomnographic laboratory study, 24 young healthy volunteers with normal hearing were exposed to simulated freight pass-bys with vibration amplitudes of 0.7 and 1.4 mm/s either 20 or 36 times during the night. Stronger vibrations were associated with higher probabilities of event-related arousals and awakenings (p < 0.001), and sleep stage changes (p < 0.05). Sleep macrostructure was most affected in high vibration nights with 36 events, with increased wakefulness (p < 0.05), reduced continual slow wave sleep (p < 0.05), earlier awakenings (p < 0.05) and an overall increase in sleep stage changes (p < 0.05). Subjects reported sleep disturbance due to vibration (F(4,92) = 25.9, p < 0.001) and noise (F(4,92) = 25.9, p < 0.001), with the number of trains having an effect only for the 0.7 mm/s condition (p < 0.05). The findings show that combined vibration and noise from railway freight affects the natural rhythm of sleep, but extrapolation of significance for health outcomes should be approached with caution.

Concepts: Sleep, Sleep disorder, Electroencephalography, Wave, Sleep apnea, Polysomnography, Rail transport, Rail tracks

134

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.

Concepts: Sleep, Sleep disorder, Circadian rhythm, Electronics, Delayed sleep phase syndrome, Chronotype, Jet lag, Melatonin

120

We often experience troubled sleep in a novel environment [1]. This is called the first-night effect (FNE) in human sleep research and has been regarded as a typical sleep disturbance [2-4]. Here, we show that the FNE is a manifestation of one hemisphere being more vigilant than the other as a night watch to monitor unfamiliar surroundings during sleep [5, 6]. Using advanced neuroimaging techniques [7, 8] as well as polysomnography, we found that the temporary sleep disturbance in the first sleep experimental session involves regional interhemispheric asymmetry of sleep depth [9]. The interhemispheric asymmetry of sleep depth associated with the FNE was found in the default-mode network (DMN) involved with spontaneous internal thoughts during wakeful rest [10, 11]. The degree of asymmetry was significantly correlated with the sleep-onset latency, which reflects the degree of difficulty of falling asleep and is a critical measure for the FNE. Furthermore, the hemisphere with reduced sleep depth showed enhanced evoked brain response to deviant external stimuli. Deviant external stimuli detected by the less-sleeping hemisphere caused more arousals and faster behavioral responses than those detected by the other hemisphere. None of these asymmetries were evident during subsequent sleep sessions. These lines of evidence are in accord with the hypothesis that troubled sleep in an unfamiliar environment is an act for survival over an unfamiliar and potentially dangerous environment by keeping one hemisphere partially more vigilant than the other hemisphere as a night watch, which wakes the sleeper up when unfamiliar external signals are detected.

Concepts: Neuroimaging, Sleep, Sleep deprivation, Sleep disorder, Sleep apnea, Polysomnography, Sleep medicine, Medial longitudinal fissure

119

Modern lifestyle has profoundly modified human sleep habits. Sleep duration has shortened over recent decades from 8 to 6.5 hours resulting in chronic sleep deprivation. Additionally, irregular sleep, shift work and travelling across time zones lead to disruption of circadian rhythms and asynchrony between the master hypothalamic clock and pacemakers in peripheral tissues. Furthermore, obstructive sleep apnea syndrome (OSA), which affects 4 - 15% of the population, is not only characterized by impaired sleep architecture but also by repetitive hemoglobin desaturations during sleep. Epidemiological studies have identified impaired sleep as an independent risk factor for all cause of-, as well as for cardiovascular, mortality/morbidity. More recently, sleep abnormalities were causally linked to impairments in glucose homeostasis, metabolic syndrome and Type 2 Diabetes Mellitus (T2DM). This review summarized current knowledge on the metabolic alterations associated with the most prevalent sleep disturbances, i.e. short sleep duration, shift work and OSA. We have focused on various endocrine and molecular mechanisms underlying the associations between inadequate sleep quality, quantity and timing with impaired glucose tolerance, insulin resistance and pancreatic β-cell dysfunction. Of these mechanisms, the role of the hypothalamic-pituitary-adrenal axis, circadian pacemakers in peripheral tissues, adipose tissue metabolism, sympathetic nervous system activation, oxidative stress and whole-body inflammation are discussed. Additionally, the impact of intermittent hypoxia and sleep fragmentation (key components of OSA) on intracellular signaling and metabolism in muscle, liver, fat and pancreas are also examined. In summary, this review provides endocrine and molecular explanations for the associations between common sleep disturbances and the pathogenesis of T2DM.

Concepts: Insulin, Diabetes mellitus, Obesity, Sleep, Sleep deprivation, Sleep disorder, Sleep apnea, Obstructive sleep apnea

72

Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1. This gain-of-function CRY1 variant causes reduced expression of key transcriptional targets and lengthens the period of circadian molecular rhythms, providing a mechanistic link to DSPD symptoms. The allele has a frequency of up to 0.6%, and reverse phenotyping of unrelated families corroborates late and/or fragmented sleep patterns in carriers, suggesting that it affects sleep behavior in a sizeable portion of the human population.

Concepts: Gene, Evolution, Sleep disorder, Circadian rhythm, ARNTL, Delayed sleep phase syndrome, Melatonin, Advanced sleep phase syndrome