Sleep and the gut microbiota in preschool aged children

Sleep plays a significant role in the mental and physical development of children. Emerging evidence in animals and human adults indicates a relationship between sleep and the gut microbiota; however, it is unclear whether the sleep of preschoolers during a key developmental period, associates with features of their gut microbiota. The objective of this study was to assess the relationship between sleep and gut microbiota in preschool aged children (4.37 ±0.48 years, n=143). Sleep measures included total nighttime sleep (TST), sleep efficiency (SE), and wake-time after sleep onset (WASO) assessed using actigraphy. Beta-diversity differences between children with low and high TST (p =0.048) suggest gut microbiota community differences. Particularly, relative abundance of Bifidobacterium was higher in the high TST group and Bacteroides, was higher in children who had higher SE and low WASO (LDA score >2). In contrast, some Lachnospiraceae members including Blautia and Coprococcus 1 were associated with shorter nighttime sleep duration and less efficiency, respectively. We also found a group of faecal metabolites, including specific neuroactive compounds and immunomodulating metabolites were associated with greater sleep efficiency and less time awake at night. Notably, tryptophan and its metabolizing products were higher in children who had higher SE or lower WASO (LDA score >2); concentration of propionate was higher in children with lower WASO (p =0.036). Overall, our results reveal a novel association between sleep and gut microbiota in preschool aged children. Longer nighttime sleep and greater sleep efficiency were associated with specific commensal bacteria that may regulate sleep through modulating neurotransmitter metabolism and the immune system.

Early-life nicotine or cotinine exposure produces long-lasting sleep alterations and downregulation of hippocampal corticosteroid receptors in adult mice

Early-life exposure to environmental toxins like tobacco can permanently re-program body structure and function. Here, we investigated the long-term effects on mouse adult sleep phenotype exerted by early-life exposure to nicotine or to its principal metabolite, cotinine. Moreover, we investigated whether these effects occurred together with a reprogramming of the activity of the hippocampus, a key structure to coordinate the hormonal stress response. Adult male mice born from dams subjected to nicotine (NIC), cotinine (COT) or vehicle (CTRL) treatment in drinking water were implanted with electrodes for sleep recordings. NIC and COT mice spent significantly more time awake than CTRL mice at the transition between the rest (light) and the activity (dark) period. NIC and COT mice showed hippocampal glucocorticoid receptor (GR) downregulation compared to CTRL mice, and NIC mice also showed hippocampal mineralocorticoid receptor downregulation. Hippocampal GR expression significantly and inversely correlated with the amount of wakefulness at the light-to-dark transition, while no changes in DNA methylation were found. We demonstrated that early-life exposure to nicotine (and cotinine) concomitantly entails long-lasting reprogramming of hippocampal activity and sleep phenotype suggesting that the adult sleep phenotype may be modulated by events that occurred during that critical period of life.

Physical activity and sleep differences between osteoarthritis, rheumatoid arthritis and non-arthritic people in China: objective versus self report comparisons

Background Objectively measured differences in physical activity (PA) and sleep have been documented among people with osteoarthritis (OA) and rheumatoid arthritis (RA) compared to non-arthritic controls. However, it is not clear whether OA and RA subgroups also differ on these indexes or the extent to which distinct arthritis subgroups versus controls can be accurately identified on the basis of objective PA and sleep indexes compared to self-report responses on questionnaires. This study addressed these gaps. Methods This case-control study comprised Chinese adults with OA (N = 40) or RA (N = 40) diagnoses based on physician assessments as well as a control group of adults without chronic pain (N = 40). All participants wore a Sensewear Armband (SWA) for consecutive 7 days and completed the International Physical Activity Questionnaire Short Form-Chinese as well as Pittsburgh Sleep Diary to obtain objective and subjective PA and sleep data, respectively. Results There were no differences between the three groups on any self-report indexes of PA or sleep. Conversely, OA and RA subgroups displayed significantly lower PA levels and more sleep problems than controls did on a majority of SWA indexes, though arthritis subgroups were not differentiated from one another on these measures. Logistic regression analyses indicated four non-multicollinear SWA indexes (i.e., steps, active energy expenditure, vigorous activity, time awake after sleep onset) correctly identified the subgroup membership of 75.0–82.5% of participants with RA or OA while classification accuracy results were attenuated for controls. Conclusions Where possible, objective measures should be used to assess PA and sleep of adults with OA and RA while particular self-report PA questionnaires should be used sparingly.

Rest activity rhythms characteristics of breast cancer women following endocrine therapy

Rest-activity rhythm (RAR) disruptions are frequently associated with chemotherapy in breast cancer (BC), but they are less known in BC with endocrine therapy. The aim of this ancillary study was to characterize the RAR and estimated sleep characteristics from actigraphy in BC patients either treated (ET+) or untreated with endocrine therapy (ET-), compared to healthy controls (HC) and using a cross-sectional design. Eighteen ET+, 18 ET- and 16 HC completed questionnaires and wore wrist actigraphs at home for 2 weeks. Parametric and non-parametric RAR, sleep parameters, and quality of life were compared between groups (p<0.05). BC groups presented lower daytime activity than HC according to RAR analysis (mesor and M10 parameters). Compared to HC, ET- had lower inter-daily stability and ET+ had greater sleep complaints. Compared to ET-, ET+ had lower sleep efficiency, more time awake and higher activity levels at night, as assessed with actigraphy. Our results suggest an effect of cancer independent of treatment on RAR in BC, highlighting the need for further investigation of this topic. In contrast, sleep as assessed with actigraphy seems modified only during ET which matches with patients’ sleep complaints. Further longitudinal studies would aid in confirming the latter hypothesis.

Fatigue in Aviation: Safety Risks, Preventive Strategies and Pharmacological Interventions

Fatigue poses an important safety risk to civil and military aviation. In addition to decreasing performance in-flight (chronic) fatigue has negative long-term health effects. Possible causes of fatigue include sleep loss, extended time awake, circadian phase irregularities and work load. Despite regulations limiting flight time and enabling optimal rostering, fatigue cannot be prevented completely. Especially in military operations, where limits may be extended due to operational necessities, it is impossible to rely solely on regulations to prevent fatigue. Fatigue management, consisting of preventive strategies and operational countermeasures, such as pre-flight naps and pharmaceuticals that either promote adequate sleep (hypnotics or chronobiotics) or enhance performance (stimulants), may be required to mitigate fatigue in challenging (military) aviation operations. This review describes the pathophysiology, epidemiology and effects of fatigue and its impact on aviation, as well as several aspects of fatigue management and recommendations for future research in this field.

Sleep during infancy, inhibitory control and working memory in toddlers: findings from the FinnBrain cohort study

Background Sleep difficulties are associated with impaired executive functions (EFs) in school-aged children. However, much less is known about how sleep during infancy relates to EF in infants and toddlers. The aim of this study was to investigate whether parent-reported sleep patterns at 6 and 12 months were associated with their inhibitory control (IC) and working memory (WM) performances at 30 months. Methods This study included children whose parents filled in a sleep questionnaire at 6 or 12 months and who participated in the development assessment at 30 months (initial available sample at 30 months; N = 472). The final sample comprised (a) 359 infants with IC task and sleep questionnaire at 6 months and 322 toddlers at 12 months and (b) 364 infants with WM task and sleep questionnaire at 6 months and 327 toddlers at 12 months. Nighttime, daytime and total sleep duration, frequency of night awakenings, time awake at night, and proportion of daytime sleep were assessed at 6 and 12 months using the Brief Infant Sleep Questionnaire. IC at 30 months was measured using a modified version of the Snack Delay task, and WM was measured at 30 months using the Spin the Pots task. Further, children were divided into three groups (i.e., “poor sleepers”, “intermediate sleepers”, and “good sleepers”) based on percentile cut-offs (i.e., <10th, 10th–90th and > 90th percentiles) to obtain a comprehensive understanding of the direction and nature of the associations between sleep and EF in early childhood. Results Our results showed an inverted U-shaped association between proportion of daytime sleep at 12 months and IC at 30 months, indicating that average proportions of daytime sleep were longitudinally associated with better IC performance. Furthermore, a linear relation between time awake at night at 12 months and WM at 30 months was found, with more time awake at night associating with worse WM. Conclusions Our findings support the hypothesis that sleep disruption in early childhood is associated with the development of later EF and suggest that various sleep difficulties at 12 months distinctively affect WM and IC in toddlers, possibly in a nonlinear manner.

Pre-sleep cognitive arousal exacerbates sleep disturbance in chronic pain: an exploratory daily diary and actigraphy study

Objectives Insomnia is commonly comorbid with chronic pain, and typically leads to worse outcomes. Two factors that could contribute to a cycle of pain and sleeplessness are pre-sleep cognitive arousal (repetitive thought processes) and low mood. This study aimed to examine how pain, sleep disturbance, mood, and pre-sleep cognitive arousal inter-relate, to determine whether low mood or pre-sleep cognitive arousal contribute to a vicious cycle of pain and insomnia. Methods Forty seven chronic pain patients completed twice daily diary measures and actigraphy for one week. Analyses investigated the temporal and directional relationships between pain intensity, sleep quality, time awake after sleep onset, anhedonic and dysphoric mood, and pre-sleep cognitive arousal. Fluctuations in predictor variables were used to predict outcome variables the following morning using mixed-effects modelling. Results For people with chronic pain, an evening with greater pre-sleep cognitive arousal (relative to normal) led to a night of poorer sleep (measured objectively and subjectively), lower mood in the morning, and a greater misperception of sleep (underestimating sleep). A night of poorer sleep quality led to greater pain the following morning. Fluctuations in pain intensity and depression did not have a significant influence on subsequent sleep. Conclusions For people with chronic pain, cognitive arousal may be a key variable exacerbating insomnia, which in turn heightens pain. Future studies could target cognitive arousal to assess effects on sleep and pain outcomes.

296 Sex differences in sleep and wakefulness of police officers working shifts: evidence from a field study

Introduction National reports of work-related injuries found the excess risk of work injury attributed to shift work to be significantly higher among women. The Working Time Society (WTS) concluded that male sex is one of the few factors that is “consistently associated with perceived or actual shift work tolerance”. However, it is unclear if physiological parameters are involved. Laboratory-controlled studies report sex differences in circadian rhythms (body temperature, melatonin). In sleep deprivation protocols, alertness and cognitive performances were affected by sex, menstrual cycle phase and hormonal contraceptives [HC] use. Nevertheless, field studies that compare male and female shift workers are scarce. Methods An observational study including 76 police officers working on patrol: 56 males and 20 females (11 using [HC], 6 not using [non-HC] and 3 with unknown use of hormonal contraception) aged 32.0 ± 5.3 years. Participants were followed throughout a month-long work cycle (1,457 morning, evening, night, or other shifts, plus rest days). They filled out time-stamped questionnaires (Samn-Perelli, KSS, Visual Analogue Scales, ~5/day; sleep and work-related information, ~1–2/day), completed 5-min Psychomotor Vigilance Tasks (PVT, ~2/day), and wore an actigraph to collect activity data. Linear mixed-effects models were used to analyze the effects of group, time awake and time-of-day on fatigue, sleepiness, alertness, mood and PVT measures. Results Self-reported measures and psychomotor performance significantly varied with time awake and time-of-day. Fatigue and sleepiness levels were significantly higher among female compared to male police officers, both with time awake and across the 24-h day. These variations were similar between non-HC females and the other groups. Compared to males, HC females were more fatigued and less alert, both with time awake and across the 24-h day, and sleepier with time awake. Having children at home did not explain these differences. Conclusion The results of this study expand our knowledge on the sex differences in the sleep and circadian physiology and demonstrate a critical effect of HC on women fatigue, sleepiness and alertness when working shifts. Sex and hormonal parameters must be considered in occupational medicine as well as in future laboratory and field studies on shift workers and circadian rhythms. Support (if any) IRSST, FRQS.

690 An Analysis of Objective and Subjective Sleep and Infection Symptoms of Medical Personnel Working through the COVID-19 Pandemic

Introduction There is a well-established connection between sleep and the immune system, and in the midst of a global pandemic, it is vital to understand the relationship between COVID-19 symptomatology and sleep. While our communities practice safety protocols, medical personnel working on the COVID-19 response effort are at high risk for exposure and contraction. This creates an urgent need to better understand whether sleep may contribute to COVID-19 symptom onset, severity, and recovery. This study examined the relationship between subjective and objective sleep during infection. Methods Fifty volunteers (age 35.15±9.97) considered high risk for COVID-19 participated in the study. The sample consisted mostly of medical personnel (93.27%) working through the pandemic. Over six months, participants completed monthly surveys and daily logs via Qualtrics. These surveys included questions about sleep, infection symptoms, COVID-19 tests and diagnoses, and mood. Wrist-worn actigraphy was collected continuously throughout the study. Sleep duration, latency, wake after sleep onset, and efficiency were processed using Philips Actiware 6.0. Actigraphy and survey data were analyzed using SPSS v. 25. Results Sixty-two percent of participants experienced infection symptoms. Those experiencing symptoms were significantly more likely to report having poorer sleep quality t(255.59)=5.78, p=&lt;.001, poorer mood upon waking t(258.03)=6.53, p=&lt;.001, feeling less alert upon waking t(255.61)=4.56, p=&lt;.001, and spending more time awake at night t(2.66.98)=-7.29, p=&lt;.001. Results showed that compared to those asymptomatic, participants with cough t(2164)=2.07, p=.039, diarrhea t(2161)=2.51, p=.012, and headache t(106.18)=7.05, p=&lt;.001 all had significantly less total sleep time, while those with body aches spent significantly more time awake at night t(2164)=2.10, p=.036. Conclusion This preliminary examination of the data broadly suggests that medical personnel experiencing infection symptoms may have difficulty obtaining adequate sleep. Further, specific infection symptoms may share a stronger relationship with key sleep parameters than others. These findings support further testing of the bi-direction relationship between infection symptoms and sleep. Results from this research will contribute to enhancing prevention, detection, and treatment guidance related to future domestic and globally-experienced infections. Support (if any) Support for this study comes from there Military Operational Medicine Research Program of the United States Army Medical Research and Development Command.

076 Bright light during wakefulness improves objective and subjective sleep quality: a forced desynchrony study

Introduction Under real life conditions, increased light exposure during wakefulness seems associated with improved sleep quality, quantified as reduced time awake during bed time, increased time spent in non-REM (NREM) sleep or increased power in the EEG delta band (0.5–4 Hz). The causality of these important relationships and their dependency on circadian clock phase and/or time awake has not been studied in depth. To establish causality of light effects during wake time on subsequent sleep, and to disentangle possible circadian and homeostatic interactions, we employed a forced desynchrony (FD) protocol under dim light (6.5 lux) and bright light (1307 lux) during wakefulness. Methods The protocol consisted of a fast cycling sleep-wake schedule (13h wakefulness – 5h sleep; 4 cycles), followed by 3h recovery sleep in a within subject cross-over design. Individuals (7 men) were equipped with 10 polysomnography electrodes. Subjective sleep quality was measured immediately after wakening. Results Results indicated that circadian variation in delta power was only detected under dim light. Circadian variation in time in rapid eye movement (REM) sleep and wakefulness were uninfluenced by light. Prior light exposure increased accumulation of delta power and time in NREM sleep, while decreasing wakefulness, especially during the circadian wake phase. Subjective sleep quality scores showed that participants were only able to assess light induced improvement of sleep quality correctly when the circadian system promoted wakefulness. Conclusion This study presents significant effects of bright light exposure on sleep architecture, leading to sleep pressure related changes in objective sleep quality. At the end of the scheduled sleep phase after increased light exposure, more delta power and NREM sleep were detected, especially when sleep occurred outside the normal sleep phase. Subjective sleep quality scores showed light-induced improvements coinciding with increased delta power and time spend in NREM sleep, suggesting that light during wakefulness may improve subsequent sleep quality. These findings may have important implications for insomnia treatment and clinical applications of light therapy. Support (if any) This research was funded by the University of Groningen Campus Fryslân (Grant No. 01110939; co-financed by Philips Drachten and Provincie Fryslân). Additional financial support was obtained from a NWO-STW Program Grant “OnTime” (project 12185).