Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.

All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.

The duper mutation reveals previously unsuspected functions of Cryptochrome 1 in circadian entrainment and heart disease.

The Cryptochrome 1 (Cry1)-deficient duper mutant hamster has a short free-running period in constant darkness (τDD) and shows large phase shifts in response to brief light pulses. We tested whether this measure of the lability of the circadian phase is a general characteristic of Cry1-null animals and whether it indicates resistance to jet lag. Upon advance of the light:dark (LD) cycle, both duper hamsters and Cry1-/- mice re-entrained locomotor rhythms three times as fast as wild types. However, accelerated re-entrainment was dissociated from the amplified phase-response curve (PRC): unlike duper hamsters, Cry1-/- mice show no amplification of the phase response to 15' light pulses. Neither the amplified acute shifts nor the increased rate of re-entrainment in duper mutants is due to acceleration of the circadian clock: when mutants drank heavy water to lengthen the period, these aspects of the phenotype persisted. In light of the health consequences of circadian misalignment, we examined effects of duper and phase shifts on a hamster model of heart disease previously shown to be aggravated by repeated phase shifts. The mutation shortened the lifespan of cardiomyopathic hamsters relative to wild types, but this effect was eliminated when mutants experienced 8-h phase shifts every second week, to which they rapidly re-entrained. Our results reveal previously unsuspected roles of Cry1 in phase shifting and longevity in the face of heart disease. The duper mutant offers new opportunities to understand the basis of circadian disruption and jet lag.

The effects of social jetlag and sleep variability on sleepiness in a population-based study: The mediating role of sleep debt.

Sleepiness is a multicausal condition, and previous research has highlighted associations between this symptom and the circadian timing system, specifically concerning social jetlag and sleep variability. Recent inquiries have shown that the effects of social jetlag on sleepiness can be confounded with the consequences of sleep debt. In light of the current evidence, we aimed to assess the effects of social jetlag and sleep variability on sleepiness and the potential mediating role of sleep debt. We used data from the EPISONO study, a cross-sectional population-based study with a sample size of 1042 participants, representative of the city of Sao Paulo, Brazil. Participants completed the UNIFESP Sleep Questionnaire (self-reported bedtime and get-up time) and the Epworth Sleepiness Scale (subjective daytime sleepiness). Subsequently, sleep-corrected mid-sleep time (chronotype), total sleep time, social jetlag (absolute difference between the mid-sleep time on workdays and mid-sleep time on free days), sleep variability (standard deviation of mid-sleep time), and sleep debt (difference between total sleep time on workdays and free days) were calculated. Generalised linear models were used to test whether social jetlag and sleep variability affected sleepiness. Mediation models were used to determine if any observed significant effects were mediated by sleep debt. The prevalence of social jetlag was 23% for >1 h and 12% for >2 h. The mean sleep variability was 41 ± 30 min. Social jetlag had a significant effect on the Epworth Sleepiness Scale scores. This association was no longer statistically significant after controlling for age, sex, body mass index, work schedule, and chronotype. A significant indirect effect of social jetlag on sleep debt and subsequently on the Epworth Sleepiness Scale scores was found. No effect of sleep variability on sleepiness could be identified. In conclusion, the association between social jetlag and sleepiness was mediated by sleep debt but was not independent of demographic, work, and chronotype variables. This study provides new evidence on the importance of circadian misalignment and sleep debt for sleep health on a population level.

Disruption of circadian rhythms promotes alcohol use: a systematic review.

This systematic review investigates the bidirectional relationship between alcohol consumption and disrupted circadian rhythms. The goal of this study was to identify (i) the types of circadian rhythm disruptors (i.e. social jet lag, extreme chronotypes, and night shift work) associated with altered alcohol use and (ii) whether sex differences in the consequences of circadian disruption exist. We conducted a search of PubMed, Embase, and PsycINFO exclusively on human research. We identified 177 articles that met the inclusion criteria. Our analyses revealed that social jet lag and the extreme chronotype referred to as eveningness were consistently associated with increased alcohol consumption. Relationships between night shift work and alcohol consumption were variable; half of articles reported no effect of night shift work on alcohol consumption. Both sexes were included as participants in the majority of the chronotype and social jet lag papers, with no sex difference apparent in alcohol consumption. The night shift research, however, contained fewer studies that included both sexes. Not all forms of circadian disruption are associated with comparable patterns of alcohol use. The most at-risk individuals for increased alcohol consumption are those with social jet lag or those of an eveningness chronotype. Direct testing of the associations in this review should be conducted to evaluate the relationships among circadian disruption, alcohol intake, and sex differences to provide insight into temporal risk factors associated with development of alcohol use disorder.

Mismatch of Biological and Social Time in Cocaine-Addicted Men.

INTRODUCTION: Chronotype describes a person's preferential activity pattern during a 24-hour period, which may not be in line with their social lifestyle. A mismatch between biological and social time is known as "social jetlag," which has negative effects on wellbeing. Cocaine influences a person's activity levels, but very little is known about possible changes in chronotype of patients with cocaine use disorder (CUD). Here, we aimed to shed light on self-reported changes in chronotype in patients with CUD and the clinical implications. METHODS: A total of 90 men from the local community were recruited; about half of the sample met the criteria for CUD, while the other half were healthy without a personal history of substance use disorder. Participants completed the Munich Chronotype Questionnaire along with questionnaires about mental health, daily fatigue, and drug/alcohol use. RESULTS: Half of the CUD patients fell into the category of late chronotype - a significantly larger proportion than their healthy peers. Late "night owls" tended to have started using cocaine at an earlier age than other chronotypes; a finding that was not observed with tobacco, cannabis, or alcohol. Drug use severity in CUD patients did not differ across chronotypes. CUD patients (52%) did not have a preferred time of day to use cocaine. The mismatch between social and biological time was significantly greater in CUD patients and unrelated to drug use or mental health status. CONCLUSION: CUD appears to be associated with disruptions in chronotype which are, contrary to a widely held view, not reflected by using patterns or addiction severity.

Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/- ) or SCN lesioning and/or melanopsin-based phototransduction (Opn4-/- ), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light-dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.

Associations of multiple sleep dimensions with overall and abdominal obesity among children and adolescents: a population-based cross-sectional study.

BACKGROUND: The relationship of insufficient sleep with the increased risk of obesity has been reported, but less is known about other sleep dimensions in the sleep-obesity associations. OBJECTIVES: To assess the associations of multiple sleep dimensions with overall and abdominal obesity among Chinese students. METHODS: This was a cross-sectional study involving 10,686 Han students aged 9-18 from Chinese National Survey on Students' Constitution and Health (CNSSCH). We collected sex, age, regions, parental educational levels, physical activity duration and sleep-related information by questionnaire survey, and also conducted anthropometric measurements including height, weight and waist circumference (WC). Unadjusted and adjusted binary logistic regression models were used to estimate the associations of sleep-related dimensions with obesity-related indicators. RESULTS: Short sleep duration was associated with higher body mass index (BMI), larger WC and higher waist-to-height ratio (WHtR) in 9-12 and 16-18 age groups, whereas prolonged sleep duration on weekday was associated with higher BMI in 13-15 age group. Non-habitual midday napping and midday napping ≤0.5 h/d (vs 0.5 to 1 h/d) increased the risk of higher BMI in 13-15 age group, and the former was also associated with larger WC in 9-12 age group. Late bedtime was associated with larger WC and higher WHtR in 9-12 age group and with higher BMI and WHtR in 13-15 age group. Students aged 9-12 with social jet lag ≥2 h were found to have greater BMI after adjustment (Odds Ratio: 1.421; 95% confidence interval: 1.066-1.894). CONCLUSIONS: Short or overlong sleep duration, late bedtime and great social jet lag were associated with higher prevalence of overall or abdominal obesity, while moderate midday napping can effectively decrease the risk. Those findings may assist in developing preventive strategies to combat obesity epidemic.

Association of social jetlag and eating patterns with sleep quality and daytime sleepiness in Japanese high school students.

A high prevalence of excessive daytime sleepiness and poor sleep quality has been reported in adolescents, but the effects of social jetlag on sleep quality and daytime sleepiness are unclear. Therefore, we assessed the association of sleep and eating patterns with daytime sleepiness and sleep quality among a total of 756 Japanese high school students. Participants completed the Pittsburgh Sleep Quality Index to evaluate sleep quality, the Pediatric Daytime Sleepiness Scale to evaluate daytime sleepiness, and an 8-day sleep diary. Data on average sleep duration, social jetlag, midsleep on free days sleep corrected, and the differences in the first and last meal timing between school days and non-school days were obtained from participants' sleep diaries. The results reveal that social jetlag is associated with differences in the first meal timing between school days and non-school days, and that social jetlag of more than 2 hr is associated with extremely poor sleep quality and excessive daytime sleepiness in Japanese high school students. Our findings suggest that reducing social jetlag to within a 2-hr window is important to prevent poor sleep quality and excessive daytime sleepiness for this population.

Later school start time is associated with longer school day sleep duration and less social jetlag among Norwegian high school students: Results from a large-scale, cross-sectional study.

The present study explored the associations between school start time and sleep habits among older adolescents, and whether these associations depended on circadian preference. The sample comprised 4010 high school students aged 16-17 years who completed a web-based survey on habitual school start time, sleep, and health. The survey included the Munich ChronoType Questionnaire, and the short version of the Horne-Östberg Morningness-Eveningness Questionnaire. Students were categorised according to habitual school start time (before 08:00 hours, 08:00 hours, 08:15 hours, 08:30 hours or after 08:30 hours) and circadian preference (morning, intermediate or evening). Data were analysed using two-way analyses of variance (school start time × circadian preference) and linear regression analyses. Results showed an overall effect of school start time on school day sleep duration (main effect, p < 0.001), with the latest school starters having the longest, and the earliest school starters having the shortest sleep duration (7:03 hr versus 6:16 hr; Tukey HSD p < 0.001). Similarly, later school starters generally reported shorter social jetlag and later school day wake-up times than earlier starting students (both main effect p < 0.001). Circadian preference did not modify these associations (interaction effects p > 0.05). In the crude regression analysis, 15 min later school start was associated with 7.2 min more sleep (p < 0.001). School start time remained a significant predictor of school day sleep duration when adjusted for sex, parental educational level and circadian preference (p < 0.001). Results suggest that school start time is a significant predictor of school day sleep duration among adolescents.

The association between social jetlag and parameters of metabolic syndrome and type 2 diabetes: a systematic review and meta-analysis.

This study aims to determine the association between social jetlag and parameters of metabolic syndrome and type 2 diabetes (T2D) in a systematic review and meta-analysis. A systematic literature search was conducted in PubMed/Embase/Scopus until May 2022. Included studies described an association between social jetlag and parameters of the metabolic syndrome and/or T2D, were available full text and written in English or Dutch. Data extraction and quality assessment were performed on pre-piloted forms independently by two reviewers. Results were meta-analysed using random-effects analysis. A total of 6,290 titles/abstracts were screened, 176 papers were read full-text, 68 studies were included. Three studies were rated as low quality, 27 were moderate, and 38 were high quality. High quality studies showed that having social jetlag compared to no social jetlag was significantly associated with higher body mass index in 20 studies (0.49 kg/m2 , 95% confidence interval [CI] 0.21-0.77; I2  = 100%), higher waist circumference in seven studies (1.11 cm, 95% CI 0.42-1.80; I2  = 25%), higher systolic blood pressure in 10 studies (0.37 mmHg, 95% CI 0.00-0.74; I2  = 94%) and higher glycated haemoglobin in 12 studies (0.42%, 95% CI 0.12- 0.72; I2  = 100%). No statistically significant associations were found for obesity, abdominal obesity, high- and low-density lipoprotein levels, cholesterol, triglycerides, diastolic blood pressure, hypertension, fasting glucose, homeostatic model assessment for insulin resistance, metabolic syndrome or T2D. Sensitivity analyses did not reduce heterogeneity. Despite substantial heterogeneity, social jetlag is associated with certain parameters of the metabolic syndrome and T2D, but not with prevalent metabolic syndrome or T2D. These findings should be interpreted with caution as the level of evidence is low and mostly based on cross-sectional data. Longitudinal studies are needed to further assess the direction of causality.

Influence of social jetlag on daytime sleepiness in obstructive sleep apnea.

Social jetlag is the discrepancy between socially determined sleep timing on workdays and biologically determined sleep timing on days free of social obligation. Poor circadian timing of sleep may worsen sleep quality and increase daytime sleepiness in obstructive sleep apnea (OSA). We analysed de-identified data from 2,061 participants (75.2% male, mean [SD] age 48.6 [13.4] years) who completed Sleep Apnea Global Interdisciplinary Consortium (SAGIC) research questionnaires and underwent polysomnography at 11 international sleep clinic sites. Social jetlag was calculated as the absolute difference in the midpoints of sleep between weekdays and weekends. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Linear regression analyses were performed to estimate the association between social jetlag and daytime sleepiness, with consideration of age, sex, body mass index, ethnicity, insomnia, alcohol consumption, and habitual sleep duration as confounders. Of the participants, 61.5% had <1 h of social jetlag, 27.5% had 1 to <2 h, and 11.1% had ≥2 h. Compared to those with <1 h of social jetlag, those with ≥2 h of social jetlag had 2.07 points higher ESS (95% confidence interval [CI] 0.77-3.38, p = 0.002), and those with 1 to <2 h of social jetlag had 0.80 points higher ESS (95% CI 0.04-1.55, p = 0.04) after adjustment for potential confounding. Interaction with OSA severity was observed; social jetlag appeared to have the greatest effect on daytime sleepiness in mild OSA. As social jetlag exacerbates daytime sleepiness in OSA, improving sleep timing may be a simple but novel therapeutic target for reducing the impact of OSA.

The relationship between pain and sleep in pediatric sickle cell disease.

BACKGROUND: Pain and sleep disturbances are prevalent complications experienced by pediatric patients with sickle cell disease (SCD). This study aims to identify associations between pain and sleep, and to characterize sleep chronotype and social jetlag in children and adolescent patients with SCD. METHODS: We performed a cross-sectional survey of 105 pediatric patients with SCD aged 8-17 years using PROMIS (Patient Reported Outcomes Measurement System) pain interference, sleep disturbance, and sleep-related impairment item banks. The µMCTQ (Ultra-short Munich Chronotype Questionnaire) assessed chronotype and social jetlag. Analyses were performed to assess associations between PROMIS measures, sleep patterns, and clinical variables. RESULTS: Female participants reported higher T-scores for sleep-related impairment than males (females: 56.7 ± 10 vs. males 50.2 ± 9.4, p = .0009). Patients with one or more emergency department (ED) visits for pain in the last 12 months reported greater sleep disturbance (55.0 ± 8.5 vs. 50.7 ± 10, p = .046) and sleep-related impairment (57.1 ± 9.3 vs. 52.1 ± 10.2, p = .03) than patients without any ED visits for pain in the last 12 months. Pain interference was significantly associated with both sleep disturbance (r = .49, p < .0001) and sleep-related impairment (r = .46, p < .0001). The average mid-sleep time was 4:14 ± 1:44 a.m. and the average social jetlag (hh:mm) was 2:32 ± 1:35. CONCLUSION: Our study demonstrates that pain interference is associated with both sleep disturbance and sleep-related impairment. PROMIS measures can identify patients that suffer from pain and sleep disturbances and highlights the need to conduct longitudinal prospective studies to define the directionality of pain and sleep in SCD.

Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort.

PURPOSE: In this study, we explore the relationship between social jetlag (SJL), a parameter of circadian misalignment, and gut microbial composition, diet and cardiometabolic health in the ZOE PREDICT 1 cohort (NCT03479866). METHODS: We assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures (n = 1002). We used self-reported habitual sleep (n = 934) to calculate SJL (difference in mid-sleep time point of ≥ 1.5 h on week versus weekend days). We tested group differences (SJL vs no-SJL) in cardiometabolic markers and diet (ANCOVA) adjusting for sex, age, BMI, ethnicity, and socio-economic status. We performed comparisons of gut microbial composition using machine learning and association analyses on the species level genome bins present in at least 20% of the samples. RESULTS: The SJL group (16%, n = 145) had a greater proportion of males (39% vs 25%), shorter sleepers (average sleep < 7 h; 5% vs 3%), and were younger (38.4 ± 11.3y vs 46.8 ± 11.7y) compared to the no-SJL group. SJL was associated with a higher relative abundance of 9 gut bacteria and lower abundance of 8 gut bacteria (q < 0.2 and absolute Cohen's effect size > 0.2), in part mediated by diet. SJL was associated with unfavourable diet quality (less healthful Plant-based Diet Index), higher intakes of potatoes and sugar-sweetened beverages, and lower intakes of fruits, and nuts, and slightly higher markers of inflammation (GlycA and IL-6) compared with no-SJL (P < 0.05 adjusted for covariates); rendered non-significant after multiple testing adjustments. CONCLUSIONS: Novel associations between SJL and a more disadvantageous gut microbiome in a cohort of predominantly adequate sleepers highlight the potential implications of SJL for health.

Chronobiological changes due to school closures during the COVID-19 pandemic among adolescents in the DOrtmund Nutritional and Anthropometric Longitudinally Designed cohort study.

Due to the lockdown of schools as one of the COVID-19 control measures, adolescents have had the opportunity to re-organise their daily lives; e.g. some of them have adapted their bedtimes to the new situation during the lockdown in favour of their own chronotype. Hence, we investigated differences in chronobiological characteristics (e.g., the midpoint of sleep, sleep duration or social jetlag (SJL); i.e., a discrepancy between biological and social timing) before and during the pandemic lockdown to examine potential changes. We asked participants from the ongoing open cohort Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study to fill out the Munich Chronotype Questionnaire during the COVID-19 lockdown and received the information of participants (n = 66) during the pandemic. A reference group matched for age, season, and sex was randomly selected from the DONALD study to assess participants' chronobiological characteristics prior to (n = 132) the pandemic. Analyses of covariance were applied to examine differences between the two groups reflecting the situation before and during the COVID-19 pandemic. Participants were aged 9-18 years (52% males). In the current examination, average sleep duration across the week was higher among adolescents during the pandemic (ß = 00:30; p = 0.0006) and social jetlag was significantly lower (ß = -00:39; p < 0.0001). CONCLUSION: Our results showed that the COVID-19 lockdown enabled adolescents to adapt their sleeping habits according to their naturally late chronotype, which led to a significant reduction in SJL. These observations are likely to be explained by the effect of school closure. WHAT IS KNOWN: • Under 'normal conditions' without pandemic lockdowns, adolescents accumulate a lack of sleep due to social obligations such as school starts, resulting in social jetlag. • A late chronotype or exposure to social jetlag is a known risk factor for the development of chronic diseases. WHAT IS NEW: • The COVID-19 lockdown represents a 'natural experiment' that enables adolescents to adhere to their internal biological clock. Without the usual social obligations, social jetlag can be significantly reduced.

Chronotype is associated with eating behaviors, physical activity and overweight in school-aged children.

BACKGROUND: A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children. METHODS: Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight. RESULTS: Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity. CONCLUSIONS: This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.

A developmental perspective on sleep consistency: Preschool age through emerging adulthood.

OBJECTIVE/BACKGROUND: Beyond sleep duration, the regularity of sleep patterns (e.g., sleep consistency), including variability in sleep timing (e.g., bedtime, wake time) and duration, is a critical marker of sleep health. Sleep consistency is captured using a variety of methods within the literature (e.g., sleep intraindividual variability, social jetlag), but most of the research focuses on adolescents. METHODS: Drawing on a developmental perspective, this narrative review highlights how normative changes at the individual (e.g., biological, cognitive, and social) and contextual (e.g., home, school, sociocultural) levels may contribute to inconsistent sleep patterns across development. RESULTS AND CONCLUSIONS: This review emphasizes how inconsistent sleep may increase across pivotal transitions throughout development (e.g., elimination of naps, puberty, summertime, entering college). Finally, recommendations for measuring sleep consistency and areas to address in future research are discussed.

A National Survey of U.S. Adolescent Sleep Duration, Timing, and Social Jetlag During the COVID-19 Pandemic.

OBJECTIVES: To assess changes in duration, timing, and social jetlag in adolescent sleep during the COVID-19 pandemic and evaluate the impact of mood, physical activity, and social interactions on sleep. STUDY DESIGN: An online survey queried adolescents' sleep before (through retrospective report) and during the initial phase of COVID-19 in May 2020. Adolescents (N = 3,494), 13-19 years old, in the United States (U.S.) answered questions about their current and retrospective (prior to COVID-19) sleep, chronotype, mood, and physical and social activities. Linear regression models were fit for time in bed, reported bed and wake times, and social jetlag during COVID-19, accounting for pre-COVID-19 values. RESULTS: Total reported time in bed (a proxy for sleep duration) increased on weekdays by an average of 1.3 ± 1.8 hours (p < .001) during COVID-19, compared to retrospective report of time in bed prior to COVID-19. During COVID-19, 81.3% of adolescents reported spending 8 hours or more in bed on weekdays compared to only 53.5% prior to COVID-19. On weekdays, bedtimes were delayed on average by 2.5 hours and wake times by 3.8 hours during COVID-19 compared to prior to COVID-19. On weekends, bedtimes were delayed on average by 1.6 hours and waketimes by 1.5 hours (all p's < 0.001). Social jetlag of >2 hours decreased to 6.3% during COVID-19 compared to 52.1% prior to COVID-19. Anxiety and depression symptoms and a decline in physical activity during COVID-19 were associated with delayed bed and wake times during COVID-19. CONCLUSIONS: During COVID-19, adolescents reported spending more time in bed, with most adolescents reporting 8 hours of sleep opportunity and more consistent sleep schedules. As schools return to in-person learning, additional research should examine how sleep schedules may change due to school start times and what lessons can be learned from changes that occurred during COVID-19 that promote favorable adolescent sleep.

Uncovering the Novel Role of NR1D1 in Regulating BNIP3-Mediated Mitophagy in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic, incurable condition characterized by mucosal inflammation and intestinal epithelial cell (IEC) damage. The circadian clock gene NR1D1, implicated in UC and the critical mitophagy process for epithelial repair, needs further exploration regarding its role in mitophagy regulation in UC. METHODS: We created a jet lag mouse model and induced colitis with dextran sulfate sodium (DSS), investigating NR1D1's role. Intestinal-specific Nr1d1 knockout mice were also generated. RNA sequencing, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays helped ascertain NR1D1's regulatory effect on BNIP3 expression. The mitochondrial state in IECs was assessed through transmission electron microscopy, while confocal microscopy evaluated mitophagy-associated protein expression in colon tissue and CCD841 cells. Cell apoptosis and reactive oxygen species (ROS) were measured via flow cytometry. RESULTS: We observed reduced NR1D1 expression in the IECs of UC patients, accentuated under jet lag and DSS exposure in mice. NR1D1 ablation led to disrupted immune homeostasis and declined mitophagy in IECs. NR1D1, usually a transcriptional repressor, was a positive regulator of BNIP3 expression, leading to impaired mitophagy, cellular inflammation, and apoptosis. Administering the NR1D1 agonist SR9009 ameliorated colitis symptoms, primarily by rectifying defective mitophagy. CONCLUSIONS: Our results suggest that NR1D1 bridges the circadian clock and UC, controlling BNIP3-mediated mitophagy and representing a potential therapeutic target. Its agonist, SR9009, shows promise in UC symptom alleviation.

Gradual Advance of Sleep-Wake Schedules Before an Eastward Flight and Phase Adjustment After Flight in Elite Cross-Country Mountain Bikers: Effects on Sleep and Performance.

ABSTRACT: Garbellotto, L, Petit, E, Brunet, E, Guirronnet, S, Clolus, Y, Gillet, V, Bourdin, H, and Mougin, F. Gradual advance of sleep-wake schedules before an eastward flight and phase adjustment after flight in elite cross-country mountain bikers: effects on sleep and performance. J Strength Cond Res 37(4): 872-880, 2023-Strategies, for alleviating jet lag, specifically targeted to competitive athletes have never been studied, in ecological conditions. This study aimed to assess the effects of a phase advance before a 7-hour eastward flight followed by a strategy of resynchronization at destination on sleep and physical performance in professional mountain bikers. Six athletes participated in this study divided into 4 periods: (i) baseline (usual sleep-wake rhythm); (ii) phase advance (advance sleep-wake schedules of 3 hours for 6 days); (iii) travel (flight: Paris-Tokyo); and (iv) phase adjustment (resynchronization of sleep-wake schedules). Melatonin pills and light therapy were administrated during the phase advance and phase adjustment. Sleep was recorded by polysomnography and actigraphy, core body temperature (CBT) rhythm was assessed by ingestible capsules, and physical performances were tested by the Wingate and 5-minute maximal exercise tests. Results showed that bedtime was advanced by 2.9 hours at the end of the phase advance ( p ≤ 0.01) with a batyphase of CBT advanced by 2.5 hours ( p = 0.07). Bedtime was similar at destination compared with baseline. Total sleep time and sleep composition were unchanged at the end of the phase advance or at destination, compared with baseline. Physical performances were maintained after phase advance and at destination. The phase advance enabled to preshift part of the time zones without disturbing sleep and physical performances and contributed to preserving them once at destination. A phase advance before eastward travel represents an effective strategy to counter harmful effects of jet lag.

High School Students' Social Jetlag, Lifelong Competency, and Academic Stress During the COVID-19 Pandemic: A Cross-Sectional Study.

With the prolongation of non-ordinary situations such as school closures due to the coronavirus disease 2019 (COVID-19) pandemic, high school students have experienced irregular sleep-wake cycles and elevated academic stress resulting from reduced academic achievement and widened gaps in academic performance. This cross-sectional study aimed to investigate the associations among chronotype, social jetlag, lifelong learning competency, and academic stress in high school students during the COVID-19 pandemic. Data were collected through an online survey from May-June 2021. The mean social jetlag was found to be 2 h and 9 min, and multiple regression analysis revealed that social jetlag and lifelong competency affected academic stress. Thus, measures to minimize social jetlag and improve lifelong learning competencies should be implemented to reduce academic stress among high school students. School nurses should identify students with severe social jetlag and provide guidance and interventions to promote sleep hygiene and regular lifestyles.