Search

Summary Adequate sleep timed appropriately during the circadian night is important for numerous biological processes and systems. New evidence suggests that both sleep timing and duration may be important for optimal bone health as well. This review examines the diurnal variation of bone turnover markers (BTMs) and the importance of circadian clock genes in regulating bone mass. In addition, this review explores the evidence for a link between shift work (and its associated disturbances in sleep duration/quality and circadian alignment) and alterations in bone metabolism and bone health. Finally, we review how commonly used medications and over-the-counter substances (e.g. caffeine, melatonin) complicate the relationship between sleep and circadian disorders and bone health.

Introduction U.S. adolescents have high rates of insufficient sleep. School closures and stay-at-home orders were implemented to mitigate disease spread during the Coronavirus 2019 (COVID-19) pandemic. Without the restriction of imposed early school start times, we hypothesized that adolescents would have longer, later, and less variable sleep compared to pre-COVID-19. We further hypothesized these changes would be associated with increased and later light exposure. Methods High school students age 14–19 years with Results Participants (N=16) were 16.5 ±1.2-years-old at Pre-COVID-19, 70.6% female, 68.8% White, and 25.1% Hispanic. Youth were participating in online learning due to in-person school closures and only 2 participants (14.3%) had a set start time, while the remainder reported learning per their own schedule. Youth obtained approximately one hour more weekday sleep per night during the COVID-19 week compared to Pre-COVID-19 (p Conclusion An unintended effect of the switch to online learning may have been affording adolescents the opportunity to obtain longer and more regular sleep. Understanding the impact of these changed sleep behaviors on daytime functioning, academic performance, and health outcomes is particularly urgent as schools plan for the remainder of the academic year and eventual return to in-person learning. Support (if any) K23DK117021 to SLS

Introduction Insufficient sleep is associated with a down-regulation of genes involved in glycolysis, in conjunction with an upregulation of genes involved in lipid metabolism in skeletal muscle. However, whether changes in RNA are associated with impairments in insulin sensitivity is unclear. We therefore tested the hypothesis that insufficient sleep will induce alterations in skeletal muscle RNA that correlate with changes in insulin sensitivity. Methods As part of an ongoing study, sixteen sedentary, healthy, lean adults (24.9±3.4y; 22.6±1.7kg/m2; 6F; mean±SD) participated in a controlled 6-day in-laboratory protocol with 9h in bed (habitual sleep) followed by 4 nights of 5h in bed (insufficient sleep), achieved by delaying bedtime by 4 hours. For one week prior to the study, participants maintained a 9h sleep schedule based on their habitual bed and wake times. Participants consumed energy-balanced diets 3 days prior to and throughout the laboratory protocol. Whole body insulin sensitivity was assessed using glucose infusion rate from a hyperinsulinemic euglycemic clamp before and after 4 nights of insufficient sleep. Skeletal muscle biopsies of the vastus lateralis were taken immediately before each clamp. In a subset of subjects (n=12), RNA sequencing was performed (Novogene Co., Ltd). Generalized linear model likelihood ratio tests were completed using the DESeq2/EdgeR R packages with a false discovery rate (FDR) cut-off of 5%. P-values were adjusted for multiple comparisons using the Benjamini-Hochberg method and a corrected p-value of 0.05 and log2 fold-change of 0 were set as the threshold for statistical significance. Results Insulin sensitivity was impaired by 6% following insufficient sleep (10.1±1.4 vs 9.1±1.1mg/kg/min, p Conclusion Preliminary findings suggest insufficient sleep alters skeletal muscle RNA. Changes in these aforementioned pathways may contribute to metabolic dysregulation during insufficient sleep. Support (if any) NIH K01DK110138, R03 DK118309, UL1 TR002535, and GCRC RR-00036

Introduction In adults, exposure to light at night delays the timing of the circadian clock in a dose-dependent manner with intensity. Although children’s melatonin levels are highly suppressed by evening bright light, the sensitivity of young children’s circadian timing to evening light is unknown. This research aimed to establish an illuminance response curve for phase delay in preschool children as a result of exposure to varying light intensities in the hour before bedtime. Methods Healthy children (n=36, 3.0 – 4.9 years, 39% males), participated in a 10-day protocol. For 7 days, children followed a strict parent-selected sleep schedule. On Days 8-10, an in-home dim-light assessment was performed. On Day 8, dim light melatonin onset (DLMO) was measured through saliva samples collected in 20-30-min intervals throughout the evening until 1-h past habitual bedtime. On Day 9, children were exposed to a white light stimulus (semi-randomly assigned from 5lx to 5000lx) for 1-h before their habitual bedtime, and saliva was collected before, during, and after the exposure. On Day 10, children provided saliva samples in the evening for 2.5-h past bedtime for a final DLMO assessment. Phase angle of entrainment (habitual bedtime – DLMObaseline) and circadian phase delay (DLMOfinal – DLMObaseline) were computed. Results Final DLMO (Day 10) shifted between -8 and 123 minutes (M = 56.1 +/- 33.6 min; negative value = phase advance, positive value = phase delay) compared with DLMO at baseline (Day 8). Raw phase shift did not demonstrate a dose-dependent relationship with light intensity. Rather, we observed a robust phase delay across all intensities. Conclusion These data suggest preschoolers’ circadian clocks are immensely sensitive to a large range of light intensities, which may be mechanistically influenced by less mature ophthalmologic features (e.g. clearer lenses, larger pupils). With young children’s ever-growing use of light-emitting devices and evening exposure to artificial lighting, as well as the prevalence of behavioral sleep problems, these findings may inform recommendations for parents on the effects of evening light exposure on sleep timing in early childhood. Support (if any) This research was supported with funds from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01-HD087707).

Introduction Disturbed gut microbiome diversity has been associated with poor health outcomes and various disease states. We investigated the impact of combined sleep restriction (3h time in bed [TIB] sleep opportunities per day) and circadian misalignment (daytime sleep and nighttime wakefulness) on gut microbiome alpha diversity in healthy young individuals in a controlled laboratory setting. Methods Twenty healthy adults (8 female), mean age (±SD) 25.65(±4.2) completed a 39-day protocol consisting of two laboratory visits lasting 4 days each. Two weeks of ambulatory monitoring prior to laboratory visits confirmed ~8h habitual sleep duration per night. Participants consumed energy-balanced diets, identical within participants, 2 days before and during the laboratory visits. The laboratory visits consisted of sleep opportunities as follows: night 1 (8h TIB), night 2 (3h TIB), day 3 (3h TIB) and day 4 (3h TIB). Fecal microbiome samples were obtained at baseline between day 1 and 2, and during sleep and circadian disruption (between day 3 and 4). Alpha diversity measures were calculated using Pielou’s evenness, Faith’s phylogenetic diversity and number of observed OTUs. Results Linear mixed models with subject as a random factor and visit as a fixed factor were performed to assess whether any alpha diversity measures changed during sleep and circadian disruption compared to baseline. Alpha diversity did not change significantly between baseline and sleep and circadian disruption (all p > 0.57). Additionally, intraclass correlation coefficients (ICCs) were calculated at baseline and during sleep and circadian disruption to determine if alpha diversity measures showed trait-like stability at both time points. ICCs were substantial to almost perfect (ICC 0.64–0.84) at baseline and substantial (ICC 0.70–0.80) during sleep and circadian disruption. Conclusion Four days of combined sleep restriction and circadian misalignment does not appear to alter alpha diversity of gut microbiota species in healthy adults. Further, substantial to almost perfect intraclass correlation coefficients suggest alpha diversity of the human microbiome is stable during combined sleep and circadian perturbation and that examination at the level of microbiota community composition and functional outcomes are needed. Support (if any) Office of Naval Research MURI (N00014- 15-1-2809), NIH/NCATS (UL1TR002535), NIH T32 HL149646, CU Undergraduate Research Opportunities.

BACKGROUND: Prior data demonstrated three weeks of sleep restriction and concurrent circadian disruption uncoupled bone turnover markers (BTMs), indicating decreased bone formation and no change or increased bone resorption. The effect of insufficient sleep with or without ad libitum weekend recovery sleep on BTMs is unknown. METHODS: BTMs were measured in stored serum from 20 healthy adults randomized to one of three study groups consisting of a control group (N = 3 men; 9 h/night) or one of two nocturnal sleep restriction groups in an inpatient laboratory environment. One Sleep Restriction group (“SR”; N = 9; 4 women) had 5h sleep opportunity per night for nine nights. The other sleep restriction group had an opportunity for ad libitum Weekend Recovery sleep (“WR”; N = 8; 4 women) after four nights of 5h sleep opportunity per night. Food intake was energy balanced at baseline and ad libitum thereafter. Fasted morning BTM levels and hourly 24h melatonin levels were obtained on study days 3 (baseline), 5 (after 1 night of sleep restriction for WR and SR), and 11 (after a sleep restricted workweek with weekend recovery sleep in WR or 7 nights of sleep restriction in SR). Linear mixed-effects modeling was used to examine the effect of study duration (e.g., change over time), study condition, age, and sex on BTMs. Pearson correlations were used to determine associations between changes in BTMs and changes in weight and morning circadian misalignment (i.e., duration of high melatonin levels after wake time). RESULTS: There was no significant difference between the three study groups in change over time (p ≥ 0.4 for interaction between assigned group and time for all BTMs), adjusted for age and sex. There was no significant change in N-terminal propeptide of procollagen type I (P1NP), osteocalcin, or C-telopeptide of type I collagen (CTX) from baseline to day 11 (all p ≥ 0.3). In women

Summary Sleep inertia is affected by circadian phase, with worse performance upon awakening from sleep during the biological night than biological day. Visual search/selective visual attention performance is known to be sensitive to sleep inertia and circadian phase. Individual differences exist in the circadian timing of habitual wake time, which may contribute to individual differences in sleep inertia. Because later chronotypes awaken at an earlier circadian phase, we hypothesized that later chronotypes would have worse visual search performance during sleep inertia than earlier chronotypes if awakened at habitual wake time. We analysed performance from 18 healthy participants [five females (22.1 ± 3.7 years; mean ± SD)] at ~1, 10, 20, 30, 40 and 60 min following electroencephalogram-verified awakening from an 8 h in-laboratory sleep opportunity. Cognitive throughput and reaction times of correct responses were impaired by sleep inertia and took ~10–30 min to improve after awakening. Regardless whether chronotype was defined by dim light melatonin onset or mid-sleep clock hour on free days, derived from the Munich ChronoType Questionnaire, the duration of sleep inertia for cognitive throughput and reaction times was longer for later chronotypes (n = 7) compared with earlier chronotypes (n = 7). Specifically, performance for earlier chronotypes showed significant improvement within ~10–20 min after awakening, whereas performance for later chronotypes took ~30 min or longer to show significant improvement (P

Introduction Easily measuring individual circadian timing is increasingly important to inform personalized chronotherapy, screen for circadian disorders and circadian misalignment, and advance circadian research. Findings from multiple studies show that transcriptomics is a viable method to estimate dim-light melatonin onset (DLMO), but no published omics-based findings have predicted dim-light melatonin offset (DLMOff), and only one known study has used metabolomics to predict DLMO. Here, we developed and tested a plasma metabolomics-based biomarker of circadian phase using DLMO and DLMOff as phase markers. Methods Sixteen (8M/8F) healthy participants aged 22.4 ± 4.8y (mean ± SD) completed an in-laboratory study with 3 baseline days (9h sleep opportunity/night), followed by a randomized cross-over protocol with 9h sleep and 5h sleep conditions, each lasting 5 days. Blood was collected every 4h on the final 24h of each condition for untargeted metabolomics analyses. DLMO and DLMOff were determined during the final 24h of each condition. Samples from all conditions were randomly split into training (68%) and test (32%) datasets. DLMO and DLMOff models were developed using partial least squares regression in the training dataset and validated in the test dataset. Results When validating with the test dataset, R2 for the DLMO model was 0.60, median absolute error (MdAE) was 2.2 ± 2.8h (± interquartile range), and 44% of samples had MdAE under 2h. R2 for the DLMOff model was 0.62, MdAE was 1.8 ± 2.6, and 51% of samples had MdAE under 2h. The DLMOff model predicted baseline samples, under conditions of 9h sleep and controlled food intake, with an R2 of 0.91 and MdAE 1.1 ± 1.1h. Conclusion These findings show promise for metabolomics-based biomarkers of circadian phase and highlight the need for biomarker efforts to predict multiple circadian phase markers. Additional analyses with an independent validation dataset will help advance these initial findings. Support NIH-R01HL085705, NIH-R01HL109706, NIH-R01HL132150, NIH-K01HL145099, NIH-F32DK111161, and NIH-UL1TR000154; and Sleep Research Society Foundation 011-JP-16

Introduction Insufficient sleep impairs insulin sensitivity; however, the mechanism(s) by which this occurs are unknown. We previously reported an elevation in plasma free fatty acid concentration during insufficient sleep, suggesting dysregulated lipid metabolism. Lipid accumulation in muscle—specifically certain species of diacylglycerol (DAG)—is associated with impaired insulin sensitivity. We therefore tested the hypothesis that insufficient sleep leads to skeletal muscle DAG accumulation. Methods As part of an ongoing study, thirteen sedentary, healthy, lean adults (25.8±3.2y; 22.7±1.9kg/m2; 3F; mean±SD) participated in a controlled 6-day in-laboratory protocol with 9h in bed (habitual sleep) followed by 4 nights of 5h in bed (insufficient sleep), achieved by delaying bedtime by 4 hours. For one week prior to the study, participants maintained a 9h sleep schedule. Participants consumed energy balanced diets 3 days prior to and throughout the laboratory protocol. Insulin sensitivity was assessed using a hyperinsulinemic euglycemic clamp before and after insufficient sleep. Skeletal muscle biopsies of the vastus lateralis were taken immediately before each clamp. In a subset of subjects (n=10), quantitative lipidomic analyses using LC/MS/MS were performed on biopsied muscle tissue. Results Insulin sensitivity was impaired following insufficient sleep (10.7±1.5 vs 9.6±1.2 mg/kg/min, p Conclusion Preliminary findings suggest that skeletal muscle lipid accumulation of diacylglycerol species during insufficient sleep may be a contributing mechanism by which insufficient sleep dysregulates metabolic physiology. Support NIH K01DK110138, R03 DK118309, UL1 TR002535, and GCRC RR-00036

Introduction There are numerous potential benefits of developing objective biomarkers of insufficient sleep including providing screening and diagnostic tools, increasing our understanding of poor sleep health, and supporting sleep-based countermeasures. We analyzed plasma metabolites in humans during two separate occasions of experimental sleep restriction to identify stable biomarkers of insufficient sleep, and assessed the association of these biomarkers with cognitive performance. Methods 12 healthy adults (6M/6F), aged 24±5y (mean±SD), completed two 18-day protocols separated by 10 days. For each 18-day protocol, participants maintained habitual 9h sleep schedules for two weeks at home, and then completed 4-day laboratory visits with sleep opportunities of: 9h on night 1, 5h on nights 2 and 3, and recovery sleep on night 4. Energy balanced diets were provided 2 days before and throughout laboratory visits. Blood was collected every 2h during scheduled wakefulness on days 1–2 (baseline) and days 3–4 (insufficient sleep), and was analyzed by untargeted liquid chromatography/mass-spectrometry. Sustained attention was assessed every 2 h during scheduled wakefulness with the Psychomotor Vigilance Test (PVT). Results After filtering, we detected 6,822 metabolites. Elastic-net regression identified 21 metabolites consistently altered by insufficient sleep in both 18-day protocols. We developed a logistic regression-based biomarker fingerprint of insufficient sleep using 11 of these 21 metabolites with consistent responses to insufficient sleep. This biomarker fingerprint has 74.4% accuracy and 0.822 (0.782–0.858; 95%CI) area under the receiver operator curve. Median reaction time was slower (P Conclusion We identified a plasma metabolomics-based biomarker of insufficient sleep with “good” performance. However, this biomarker only accounts for ~6% of reduced PVT performance during insufficient sleep. Our findings suggest that specific biomarkers for insufficient sleep versus cognitive deficits associated with insufficient sleep may be required. Support This work was supported by NIH R01HL132150, NIH K01HL145099, NIH F32DK111161, NIH/NCATS Colorado CTSA Grant UL1TR002535, Sleep Research Society Foundation 011-JP-16, and the University of Colorado Boulder Undergraduate Research Opportunities Grant.

Study ObjectiveIdentify small molecule biomarkers of insufficient sleep using untargeted plasma metabolomics in humans undergoing experimental insufficient sleep.MethodsWe conducted a crossover laboratory study where 16 normal-weight participants (eight men; age 22 ± 5 years; body mass index < 25 kg/m2) completed three baseline days (9 hours sleep opportunity per night) followed by 5-day insufficient (5 hours sleep opportunity per night) and adequate (9 hours sleep opportunity per night) sleep conditions. Energy balanced diets were provided during baseline, with ad libitum energy intake provided during the insufficient and adequate sleep conditions. Untargeted plasma metabolomics analyses were performed using blood samples collected every 4 hours across the final 24 hours of each condition. Biomarker models were developed using logistic regression and linear support vector machine (SVM) algorithms.ResultsThe top-performing biomarker model was developed by linear SVM modeling, consisted of 65 compounds, and discriminated insufficient versus adequate sleep with 74% overall accuracy and a Matthew’s Correlation Coefficient of 0.39. The compounds in the top-performing biomarker model were associated with ATP Binding Cassette Transporters in Lipid Homeostasis, Phospholipid Metabolic Process, Plasma Lipoprotein Remodeling, and sphingolipid metabolism.ConclusionWe identified potential metabolomics-based biomarkers of insufficient sleep in humans. Although our current biomarkers require further development and validation using independent cohorts, they have potential to advance our understanding of the negative consequences of insufficient sleep, improve diagnosis of poor sleep health, and could eventually help identify targets for countermeasures designed to mitigate the negative health consequences of insufficient sleep.

It has been established in recent years that the gut microbiome plays a role in health and disease, potentially via alterations in metabolites that influence host physiology. Although sleep disruption and gut dysbiosis have been associated with many of the same diseases, studies investigating the gut microbiome in the context of sleep disruption have yielded inconsistent results, and have not assessed the fecal metabolome. We exposed mice to five days of sleep disruption followed by four days of ad libitum recovery sleep, and assessed the fecal microbiome and fecal metabolome at multiple timepoints using 16S rRNA gene amplicons and untargeted LC-MS/MS mass spectrometry. We found global shifts in both the microbiome and metabolome in the sleep-disrupted group on the second day of recovery sleep, when most sleep parameters had recovered to baseline levels. We observed an increase in the Firmicutes:Bacteroidetes ratio, along with decreases in the genus Lactobacillus, phylum Actinobacteria, and genus Bifidobacterium in sleep-disrupted mice compared to control mice. The latter two taxa remained low at the fourth day post-sleep disruption. We also identified multiple classes of fecal metabolites that were differentially abundant in sleep-disrupted mice, some of which are physiologically relevant and commonly influenced by the microbiome. This included bile acids, and inference of microbial functional gene content suggested reduced levels of the microbial bile salt hydrolase gene in sleep-disrupted mice. Overall, this study adds to the evidence base linking disrupted sleep to the gut microbiome and expands it to the fecal metabolome, identifying sleep disruption-sensitive bacterial taxa and classes of metabolites that may serve as therapeutic targets to improve health after poor sleep.

The human metabolome has remained largely unknown, with most studies annotating ~10% of features. In nucleic acid sequencing, annotating transcripts by source has proven essential for understanding gene function. Here we generalize this concept to stool, plasma, urine and other human metabolomes, discovering that food-based annotations increase the interpreted fraction of molecular features 7-fold, providing a general framework for expanding the interpretability of human metabolomic “dark matter.”

We studied the dynamics of melatonin suppression and changes in cortisol levels in humans in response to light exposure at night using high-frequency blood sampling. Twenty-one young healthy participants were randomized to receive either intermittent bright (~9,500 lux) light (IBL), continuous bright light (CBL) or continuous dim (~1 lux) light (VDL) for 6.5 h during the biological night (n = 7 per condition). Melatonin suppression occurred rapidly within the first 5 min and continued until the end of each IBL stimuli (t1/2 = ~13 min). Melatonin recovery occurred more slowly between IBL stimuli (half-maximal recovery rate of ~46 min). Mean melatonin suppression (~40%) and recovery (~50%) were similar across IBL stimuli. Suppression dynamics under CBL were also rapid (t1/2 = ~18 min), with no recovery until the light exposure ended. There was a significant linear increase of cortisol levels between the start and end of each IBL stimulus. Under CBL conditions cortisol showed trimodal changes with an initial linear activating phase, followed by an exponential inhibitory phase, and a final exponential recovery phase. These results show that light exposure at night affects circadian driven hormones differently and that outcomes are influenced by the duration and pattern of light exposure.

Study Objectives To determine how sleepiness and sleep deprivation drive the motivation to engage in different behaviors. Methods We studied the sleepiness of 123 participants who had been randomized to sleep deprivation or normal sleep, and their willingness to engage in a range of everyday behaviors. Results Self-reported sleepiness was a strong predictor of the motivation to engage in sleep-preparatory behaviors such as shutting one’s eyes (OR = 2.78, 95% CI: 2.19–3.52 for each step up on the Karolinska Sleepiness Scale) and resting (OR = 3.20, CI: 2.46–4.16). Sleepiness was also related to the desire to be cared for by a loved one (OR = 1.49, CI: 1.22–1.82), and preparedness to utilize monetary and energy resources to get to sleep. Conversely, increased sleepiness was associated with a decreased motivation for social and physical activities (e.g. be with friends OR = 0.71, CI: 0.61–0.82; exercise OR = 0.65, CI: 0.56–0.76). Sleep deprivation had similar effects as sleepiness on these behaviors. Neither sleepiness nor sleep deprivation had strong associations with hunger, thirst, or food preferences. Conclusions Our findings indicate that sleepiness is a dynamic motivational drive that promotes sleep-preparatory behaviors and competes with other drives and desired outcomes. Consequently, sleepiness may be a central mechanism by which impaired alertness, for example, due to insufficient sleep, contributes to poor quality of life and adverse health. We propose that sleepiness helps organize behaviors toward the specific goal of assuring sufficient sleep, in competition with other needs and incentives. A theoretical framework on sleepiness and its behavioral consequences are likely to improve our understanding of several disease mechanisms.

Summary There is evidence that the spring Daylight Saving Time (DST) transition acutely increases motor vehicle accident (MVA) risk (“DST effect”), which has been partly attributed to sleep deprivation and circadian misalignment [ 1 , 2 , 3 , 4 , 5 , 6 ]. Because spring DST also shifts clock time 1 h later, mornings are darker and evenings brighter, changing illumination conditions for peak traffic density. This daytime-dependent illumination change (“time of day effect”) is hypothesized to result in DST-associated afternoon and evening accident risk reductions [ 2 , 5 , 7 ]. Furthermore, sunrise and local photoperiod timing depend on position in time zone. The sun rises at an earlier clock time in the eastern regions of a given time zone than in the western regions, which is thought to induce higher levels of circadian misalignment in the west than in the east (“time zone effect”) [ 8 , 9 ]. This study evaluated the acute consequences of the DST transition on MVAs in a chronobiological context, quantifying DST, time of day, and time zone effects. We used large US registry data, including 732,835 fatal MVAs recorded across all states (1996–2017), and observed that spring DST significantly increased fatal MVA risk by 6%, which was more pronounced in the morning and in locations further west within a time zone. DST-associated MVA risk increased even in the afternoon hours, despite longer daylight hours. The MVA risk increase waned in the week subsequent to DST, and there were no effects of the fall-back transition to Standard Time (ST) on MVA risk, further supporting the hypothesis that DST-transition-associated, preventable circadian misalignment and sleep deprivation might underlie MVA risk increases.

Study Objectives Estimate the genetic and environmental influences on the relationship between onset of regular cannabis use and young adult insomnia. Methods In a population-based twin cohort of 1882 twins (56% female, mean age = 22.99, SD = 2.97) we explored the genetic/environmental etiology of the relationship between onset of regular cannabis use and insomnia-related outcomes via multivariate twin models. Results Controlling for sex, current depression symptoms, and prior diagnosis of an anxiety or depression disorder, adult twins who reported early onset for regular cannabis use (age 17 or younger) were more likely to have insomnia (β = 0.07, p = 0.024) and insomnia with short sleep on weekdays (β = 0.08, p = 0.003) as young adults. We found significant genetic contributions for the onset of regular cannabis use (a2 = 76%, p < 0.001), insomnia (a2 = 44%, p < 0.001), and insomnia with short sleep on weekdays (a2 = 37%, p < 0.001). We found significant genetic correlations between onset of regular use and both insomnia (rA = 0.20, p = 0.047) and insomnia with short sleep on weekdays (rA = 0.25, p = 0.008) but no significant environmental associations between these traits. Conclusions We found common genetic liabilities for early onset of regular cannabis use and insomnia, implying pleiotropic influences of genes on both traits.

OBJECTIVE/BACKGROUND: Rates of overweight/obesity and insufficient/delayed sleep are high among adolescents and are also unique risk factors for mood/behavior difficulties. This study aimed to evaluate relationships between sleep/circadian health and mood/behavior in a cohort of adolescents with overweight/obesity. PARTICIPANTS: Twenty-two adolescents (16.4±1.1 years) with overweight/obesity attending high school completed in the study. METHODS: Participants completed one week of home sleep monitoring (actigraphy), questionnaires assessing chronotype (diurnal preference; Morningness/Eveningness Scale for Children) and mood/behavior (Strengths & Difficulties Questionnaire), and had in-laboratory salivary melatonin sampling on a Thursday or Friday during the academic year. RESULTS: Linear regressions revealed later weekday bedtime and shorter weekday time in bed and sleep duration were associated with worse mood/behavior scores. Shorter duration of melatonin secretion and greater “eveningness” were also associated with worse mood/behavior scores. CONCLUSIONS: Short and late sleep, shorter melatonin secretion, and eveningness chronotype are associated with worse mood/behavior symptoms in a cohort of adolescents with overweight/obesity. Clinicians should assess for both sleep and mood/behavior symptoms and further research is needed to evaluate the impact of improved sleep on mood/behavior in adolescents with overweight/obesity.

Local and national governments around the world are currently considering the elimination of the annual switch to and from Daylight Saving Time (DST). As an international organization of scientists dedicated to studying circadian and other biological rhythms, the Society for Research on Biological Rhythms (SRBR) engaged experts in the field to write a Position Paper on the consequences of choosing to live on DST or Standard Time (ST). The authors take the position that, based on comparisons of large populations living in DST or ST or on western versus eastern edges of time zones, the advantages of permanent ST outweigh switching to DST annually or permanently. Four peer reviewers provided expert critiques of the initial submission, and the SRBR Executive Board approved the revised manuscript as a Position Paper to help educate the public in their evaluation of current legislative actions to end DST.

Demands of modern society force many work operations into the night when the internal circadian timekeeping system is promoting sleep. The combination of disturbed daytime sleep and circadian misalignment, which is common in overnight shift work, decreases cognitive performance, yet how performance may differ across multiple consecutive nights of shift work is not fully understood. Therefore, the primary aim of this study was to use a simulated night-shift protocol to examine the cognitive performance and ratings of sleepiness and clear-headedness across the hours of a typical daytime shift, a first night shift with an afternoon nap and extended wakefulness, and 2 subsequent overnight shifts. We tested the hypothesis that cognitive performance would be worse on the first night shift as compared with the baseline and subsequent nighttime shifts and that performance during nighttime shifts would be reduced as compared with the baseline daytime shift. Fifteen healthy adults (6 men) were studied in the 6-day in-laboratory protocol. Results showed that working during the night increased subjective sleepiness and decreased clear-headedness and performance on the Psychomotor Vigilance Task (i.e., slower median, fastest and slowest reaction times, and increased attentional lapses), Stroop color word task (decreased number of correct responses and slower median reaction time), and calculation addition performance task (decreased number attempted and correct). Furthermore, we observed limited evidence of sleepiness, clear-headedness, or performance adaptation across subsequent nights of simulated night work. Our findings demonstrate that night-shift work, regardless of whether it is the first night shift with a nap and extended wakefulness or subsequent night shifts, decreases performance and clear-headedness as compared with the day shift.

Insufficient sleep induces insulin resistance and is associated with an increased risk for developing obesity and cardiometabolic diseases, implicating sleep loss as a metabolic stressor. Fibroblas...

Introduction: While the Accreditation Council for Graduate Medical Education limited first year resident-physicians to 16 consecutive work hours from 2011 to 2017, resident-physicians in their second year or higher were permitted to work up to 28 h consecutively. This paper describes the Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS) study, a clustered-randomized crossover clinical trial designed to evaluate the effectiveness of eliminating traditional shifts of 24 h or longer for second year or higher resident-physicians in pediatric intensive care units (PICUs). Methods: ROSTERS was a multi-center non-blinded trial in 6 PICUs at US academic medical centers. The primary aim was to compare patient safety between the extended duration work roster (EDWR), which included shifts �24 h, and a rapidly cycling work roster (RCWR), where shifts were limited to a maximum of 16 h. Information on potential medical errors was gathered and used for classification by centrally trained physician reviewers who were blinded to the study arm. Secondary aims were to assess the relationship of the study arm to resident-physician sleep duration, work hours and neurobehavioral performance. Results: The study involved 6577 patients with a total of 38,821 patient days (n = 18,749 EDWR, n = 20,072 RCWR). There were 413 resident-physician rotations included in the study (n = 203 EDWR, n = 210 RCWR). Resident-physician questionnaire data were over 95% complete. Conclusions: Results from data collected in the ROSTERS study will be evaluated for the impact of resident-physician schedule roster on patient safety outcomes in PICUs, and will allow for examination of a number of secondary outcome measures. ClinicalTrials.gov Identifier: NCT02134847 © 2019 Elsevier Inc.

Introduction Circadian amplitude measures the strength or robustness of a rhythm and changes in amplitude may have implications for health. Large individual differences in melatonin amplitude are recognized. Here we aimed to determine the strength of relationships between melatonin and the core body (CBT) and distal-proximal skin temperature gradient (DPG) amplitudes during a constant routine protocol. Additionally, we determined the best fitting harmonic model for the DPG circadian rhythm. Methods 17 young healthy adults [13 males (22.3±3.9yr;mean±SD)] completed a 28-hr constant routine protocol after maintaining 8h habitual sleep schedules for one week at home. Endogenous circadian amplitudes of melatonin and CBT were fit with standard three- and dual-harmonic linear regression models, respectively. The DPG amplitude was analyzed with both dual and three-harmonic regression models to determine which model produced the best fit. Results The DPG was best fit by a three-harmonic regression model with significantly lower standard deviation and higher signal-to-noise ratio compared to the 2-harmonic model (both p0.10). Conclusion While it is common for melatonin and body temperature circadian phase estimates to be used interchangeably, non-significant findings for associations between circadian amplitudes of melatonin, CBT and DPG indicate that these markers may not provide similar information about circadian amplitude. Further, research is needed to explore possible associations between individual differences in melatonin, CBT and DPG amplitudes with other physiological and behavioral outcomes to determine which measure(s) of circadian amplitude may be functionally relevant. Support (if any) NIH R01 HL081761

Introduction Individual differences in cognition during sleep restriction and circadian misalignment have been shown to be trait-like. Here we explored the consistency of individual differences in cardiovascular responses to the cold pressor test (CPT) measured by changes in the distal-proximal skin temperature gradient (DPG) using the contralateral hand to that immersed in the ice water bath, which reflects a reflex cutaneous vasoconstriction. Methods Eighteen healthy participants (8 females) mean (±SD) age 25.28 (±4.3), underwent two identical in-laboratory combined sleep restriction and circadian misalignment protocols preceded by an 8h baseline in-laboratory sleep opportunity. The participants were given a 3h sleep opportunity on night 2 and a 3h sleep opportunity on days 3 and 4 followed by recovery sleep. The CPT occurred the morning after the baseline sleep opportunity and the morning before recovery sleep. Participants maintained a seated posture beginning 30 min prior to the CPT and skin temperature was assessed starting 15 min before until 45 min after the CPT. DPG (proximal=subclavicular; distal=hand palmar) data were averaged into 3 min bins. Changes in DPG from pre-CPT and 5 min post-CPT were assessed as the primary outcome using mixed-model ANOVAs. Intra-class correlation coefficients (ICC) were calculated to measure consistency of individual differences for DPG responses. Results Mixed-model ANOVA revealed significant effects of time and combined sleep restriction and circadian misalignment on DPG during the CPT (both p Conclusion Findings support that combined sleep restriction and circadian misalignment is associated with sympathetic activation and that individual differences in the DPG response to cold pressor stress are consistent. Support (if any) Office of Naval Research MURI grant N00014-15-1-2809, NIH/NCATS Colorado CTSA Grant UL1TR002535

Weight gain, obesity and diabetes have reached alarming levels in the developed world. Traditional risk factors such as over-eating, poor nutritional choices and lack of exercise cannot fully account for the high prevalence of metabolic disease. This review paper examines the scientific evidence on two novel risk factors that contribute to dys-regulated metabolic physiology: sleep disruption and circadian misalignment. Specifically, fundamental relationships between energy metabolism and sleep and circadian rhythms and the impact of sleep and circadian disruption on metabolic physiology are examined. Millions of individuals worldwide do not obtain sufficient sleep for healthy metabolic function, and many participate in shift work and social activities at times when the internal physiological clock is promoting sleep. These behaviours predispose an individual for poor metabolic health by promoting excess caloric intake in response to reduced sleep, food intake at internal biological times when metabolic physiology is not prepared, decreased energy expenditure when wakefulness and sleep are initiated at incorrect internal biological times, and disrupted glucose metabolism during short sleep and circadian misalignment. In addition to the traditional risk factors of poor diet and exercise, disturbed sleep and circadian rhythms represent modifiable risk factors for prevention and treatment of metabolic disease and for promotion of healthy metabolism.

Light exposure and sleep timing are two factors that influence inter-individual variability in the timing of the human circadian clock. The aim of this study was to quantify the degree to which evening light exposure predicts variance in circadian timing over and above bedtime alone in preschool children. Participants were 21 children ages 4.5–5.0 years (4.7±0.2 years; 9 females). Children followed their typical sleep schedules for 4 days during which time they wore a wrist actigraph to assess sleep timing and a pendant light meter to measure minute-by-minute illuminance levels in lux. On the 5th day, children participated in an in-home dim-light melatonin onset (DLMO) assessment. Light exposure in the 2 h before bedtime was averaged and aggregated across the 4 nights preceding the DLMO assessment. Mean DLMO and bedtime were 19:22±01:04 and 20:07±00:46, respectively. Average evening light exposure was 710.1±1418.2 lux. Children with later bedtimes (lights-off time) had more delayed melatonin onset times ( r =0.61, p =0.002). Evening light exposure was not independently associated with DLMO ( r =0.32, p =0.08); however, a partial correlation between evening light exposure and DLMO when controlling for bedtime yielded a positive correlation ( r =0.46, p =0.02). Bedtime explained 37.3% of the variance in the timing of DLMO, and evening light exposure accounted for an additional 13.3% of the variance. These findings represent an important step in understanding factors that influence circadian phase in preschool-age children and have implications for understanding a modifiable pathway that may underlie late sleep timing and the development of evening settling problems in early childhood.

Epidemiological findings suggest short sleep duration is associated with overweight and obesity across the lifespan. In adults, experimental sleep loss increases caloric intake more than total daily energy needs, thus leading to weight gain. To date, little is known about the relationship between sleep restriction and dietary intake in preschool children. Healthy children (n = 10; 41.2 ± 5.4 months; 5 females) followed a strict sleep schedule for 5 days before each experimental condition: 1 day of baseline sleep (nap and scheduled bedtime/wake time) and 1 day of sleep restriction (no-nap and ~2.3 h bedtime delay). Standardized parent-report dietary intake measures were obtained on baseline, sleep restriction and sleep recovery (ad libitum sleep opportunity in the 24-h following sleep restriction) days. As designed, children slept ~3 h less on the sleep restriction than the baseline day (P

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.

AB We have previously shown that motor-driven (passive) stationary cycling elevates energy expenditure (EE). Purpose: This study aimed to quantify how acute passive cycling affects glucose and insulin responses to an oral glucose tolerance test (OGTT) and basic cognition compared with sitting and moderate-intensity active cycling. Methods: Twenty-four physically inactive healthy males completed three trials in randomized order involving 30-min conditions of sitting, passive cycling, and moderate-intensity cycling. During each condition, EE was measured, and participants performed cognitive tests. After each condition, a 2-h OGTT was performed. Results: EE was significantly higher during the cycling conditions compared with sitting (1.36 +/- 0.58 and 6.50 +/- 1.73 kcal[middle dot]min-1 greater than sitting for passive and moderate-intensity, respectively). A significant correlation was found between body fat percentage and postsitting OGTT 2-h postplasma glucose (r2 = 0.30, P < 0.05); thus, participants were divided into lean (n = 11) and nonlean (n = 13) groups. In the nonlean group, compared with sitting, passive cycling lowered 2-h postplasma glucose (7.7 +/- 1.3 vs 6.9 +/- 1.6 mmol[middle dot]L-1, respectively, P < 0.05), and the Matsuda whole-body insulin sensitivity index (WBISI) was higher (2.74 +/- 0.86 vs 3.36 +/- 1.08, P < 0.05). In addition, passive and moderate-intensity cycling had similar beneficial effects on 2-h postplasma glucose and WBISI. Cognitive performance did not significantly differ between the sitting and passive cycling conditions. Conclusions: Two-hour postplasma glucose was lower and WBISI after acute passive cycling was higher in nonlean participants. Given that and the increase in EE without changes in cognitive performance, we propose passive cycling as a promising intervention to counteract some of the deleterious effects of prolonged sitting in the workplace. (C) 2016 American College of Sports Medicine

The hygiene or "Old Friends" hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory circuits and suppress inappropriate inflammation. Such diseases include but are not limited to allergies and asthma; we and others have proposed that the markedly reduced exposure to these Old Friends in modern urban societies may also increase vulnerability to neurodevelopmental disorders and stress-related psychiatric disorders, such as anxiety and affective disorders, where data are emerging in support of inflammation as a risk factor. Here, we review recent advances in our understanding of the potential for Old Friends, including environmental microbial inputs, to modify risk for inflammatory disease, with a focus on neurodevelopmental and psychiatric conditions. We highlight potential mechanisms, involving bacterially derived metabolites, bacterial antigens, and helminthic antigens, through which these inputs promote immunoregulation. Though findings are encouraging, significant human subjects' research is required to evaluate the potential impact of Old Friends, including environmental microbial inputs, on biological signatures and clinically meaningful mental health prevention and intervention outcomes.

New Findings What is the central question of this study? Is haemoglobin mass (Hbmass) decreased following 4 days of head-down tilt bed rest (HDTBR), and does increased red blood cell (RBC) destruction mediate this adaptation? What is the main finding and its importance? Haemoglobin mass was increased immediately following HDTBR, before decreasing below baseline 5 days after return to normal living conditions. The transient increase in Hbmass might be the result of decreased RBC destruction, but it is also possible that spleen contraction after HDTBR contributed to this adaptation. Our data suggest that the decreased Hbmass 5 days following HDTBR resulted from decreased RBC production, not increased RBC destruction. Rapid decreases in haemoglobin mass (Hbmass) have been reported in healthy humans following spaceflight and descent from high altitude. It has been proposed that a selective increase in the destruction of young red blood cells (RBCs) mediates these decreases, but conclusive evidence demonstrating neocytolysis in humans is lacking. Based on the proposed triggers and time course of adaptation during spaceflight, we hypothesized that Hbmass would be reduced after 4 days of −6 deg head-down tilt bed rest (HDTBR) and that this would be associated with evidence for increased RBC destruction. We assessed Hbmass in seven healthy, recreationally active men before (PRE), 5 h after (POST) and 5 days after (POST5) 4 days of HDTBR. The concentration of erythropoietin decreased from 7.1 ± 1.8 mIU ml−1 at PRE to 5.2 ± 2.8 mIU ml−1 at POST (mean ± SD; P = 0.028). Contrary to our hypothesis, Hbmass was increased from 817 ± 135 g at PRE to 849 ± 141 g at POST (P = 0.014) before decreasing below PRE to 789 ± 139 g at POST5 (P = 0.027). From PRE to POST, the concentration of haptoglobin increased from 0.54 ± 0.32 to 0.68 ± 0.28 g l−1 (P = 0.013) and the concentration of bilirubin decreased from 0.50 ± 0.24 to 0.32 ± 0.11 mg dl−1 (P = 0.054), suggesting that decreased RBC destruction might have contributed to the increased Hbmass. However, it is possible that spleen contraction following HDTBR also played a role in the increase in Hbmass at POST, but as the transient increase in Hbmass was unexpected, we did not collect data that would provide direct evidence for or against spleen contraction. From PRE to POST5, the concentration of soluble transferrin receptor decreased from 20.7 ± 3.9 to 17.1 ± 3.3 nmol l−1 (P = 0.018) but the concentrations of ferritin, haptoglobin and bilirubin were not significantly altered, suggesting that the decrease in Hbmass was mediated by decreased RBC production rather than increased RBC destruction. Peak oxygen uptake decreased by 0.31 ± 0.16 l min−1 from PRE to POST (P = 2 × 10−4) but was not significantly altered at POST5 compared with PRE. Overall, these findings indicate that 4 days of HDTBR does not increase RBC destruction and that re-examination of the time course and mechanisms of Hbmass alterations following short-term spaceflight and simulated microgravity is warranted.

Methodological limitations preclude determination of the association between sleep duration and bone mineral density (BMD) from existing literature. This was the first study to use objective sleep duration to determine its association with BMD. Nocturnal sleep duration, assessed objectively (actigraphy) or subjectively (questionnaire), was not independently associated with BMD in postmenopausal women. Both long and short self-reported sleep durations are associated with low bone mineral density (BMD) in men and women. The association between sleep duration measured by actigraphy and BMD in postmenopausal women is unknown. The Study of Osteoporotic Fractures (SOF) ancillary sleep study was used to determine the association between sleep duration and BMD at the total hip and femoral neck in postmenopausal women ≥ 75 years old. Sleep duration was assessed by wrist actigraphy (average 4 nights) and questionnaire. BMD was compared between postmenopausal women with short (

Potential effects of shift work on health are probably related to the misalignment between the light-dark cycle and the human activity-rest cycle. Light exposure at night mediates these effects, including social misalignment and leads to an inversion of activity and rest, which, in turn, is linked to changes in behaviours. This article reviews the epidemiological evidence on the association between shift work and health, and possible mechanisms underlying this association. First, evidence from findings of the meta-analyses and systematic reviews published in the last 10 yr is presented. In addition, it reports the larger single-occupation studies and recent large population-based studies of the general workforce. Koch's postulates were used to evaluate the evidence related to the development of disease as a result of exposure to shift work. Finally, we discussed limitations of the multiple pathways that link shift work with specific disorders and the methodological challenges facing shift work research. We concluded that the clearest indications of shift work being the cause of a disease are given when there is a substantial body of evidence from high quality field studies showing an association and there is good evidence from laboratory studies supporting a causal explanation of the link.

Introduction Timing of food intake has emerged as a novel risk factor for weight gain and obesity. Higher evening food intake, especially during insufficient sleep, is associated with weight gain. We aimed to explore initial changes in evening food intake and the respiratory quotient (RQ) during insufficient sleep and subsequent weight gain. We also explored sex differences. Methods 28 healthy adults (14F) aged 26.3±4.5y completed a 14–16 daylong laboratory protocol. In their home environment participants maintained one week of ~9h/night sleep schedules and consumed energy balanced diets for 3 days prior to completing the laboratory protocol. The laboratory protocol consisted of 3 baseline days of 9h/night scheduled sleep with energy balanced diets followed by 10 days of 5h/night scheduled sleep with ad-libitum food intake, with (n=14) and without (n=14) weekend recovery sleep. RQ was assessed on days 3 and 5 in a whole room calorimeter. Evening (dinner and after-dinner snacks) energy intake and body weight were assessed daily. Results A significant sex by condition effect was observed for evening food intake such that men and women were similar at baseline, but men ate more than women during insufficient sleep, when controlling for body mass (p Conclusion Findings suggest that rapid changes in evening food intake during insufficient sleep contributes to subsequent weight gain during sustained insufficient sleep, especially in men. Support NIH HL109706, DK111161, TR001082, DK048520, Sleep Research Society Foundation grant 011-JP-16 and Office of Naval Research MURI (N00014-15-1-2809).

Introduction Jet lag can significantly impact an athlete’s health and performance. However, the effect of ultra long-haul travel (> 12h flying time) westward across nine time zones on the sleep of female collegiate athletes is limited. We therefore studied the sleep behavior of NCAA Division I female volleyball players on an exhibition tour to China. Methods For this observational study, eleven females were recruited from a NCAA Division I Volleyball team. During the Tour, sleep behavior was monitored using wrist actigraphy (Actiwatch Spectrum, Phillips) before (5 days) outbound travel (PRE-FLIGHT), during air travel to (1) & from (2) China (FLIGHT-DAY 1 & 2) and during the athletes’ tour while in China (TOUR-DAY 1–8). Athletes were instructed to wear the actigraphs at all times, except during competition. Standard parameters were collected from the actigraph including sleep durations and sleep efficiency and expressed as mean ± sd. Results Sleep duration and sleep efficiency were similar for PRE-FLIGHT days (~8.3 hrs ± 1.5, 90.6 ± 3.2%). Sleep duration and efficiency were significantly lower on FLIGHT-DAY 1 & 2 compared to TOUR-DAY and PRE-FLIGHT, but were not significantly different from each other (~5.2 ± 2.4h, 80.5 ± 8.8%). Sleep duration during TOUR-DAY 1–7 followed a quadratic relationship, peaking on TOUR-DAY 1 and reaching a nadir on TOUR-DAY 5, before increasing again through TOUR-DAY 7 (p Conclusion During travel female collegiate volleyball players showed sleep disturbance. Implementation of sleep interventions for jet lag are warranted for athletes traveling across multiple time zones. Support PAC-12 Student-Athlete Health and Wellbeing Initiative, Grant #1554240

Introduction Sleep is critical to cognitive and physiologic function. It is likely being a female collegiate student athlete places unique demands upon sleep behavior. Therefore, we aimed to study the sleep behavior of female collegiate athletes versus a female collegiate control group. Methods Full time female students from the University of Colorado Boulder (Altitude = 1,624 m) were recruited from NCAA Division I athletic teams: Cross Country (XC, n=10), Lacrosse (LAX, n =17), Soccer (SOC, n=15), Golf (GOLF, n=6), Tennis (TENN, n=9). 31 female full-time students were recruited as Controls (CONT). Sleep was monitored with wrist actigraphy (Spectrum Actiwatch, Phillips) for a minimum of one week. Subjects were instructed to wear actigraphs at all times except during competition. Outcome variables included nightly sleep duration, total 24h sleep duration, sleep efficiency, sleep midpoint, social jet lag (SJL) and nap duration/frequency. Results On weekdays, XC, LAX and SOC had greater nightly sleep durations ~8.5h compared to TENN, GOLF and CONT (p Conclusion Variations in sleep behavior exists between collegiate student athletes based upon varsity sport with some sports being similar to controls and others being significantly different. Additional research is needed to determine the significance of these findings to academic and athletic performance. Support PAC-12 Student-Athlete Health and Wellbeing Initiative, Grant #1554240

Introduction The human circadian clock evolved in the presence of the natural light-dark solar cycle. Exposure to artificial light at night suppresses endogenous melatonin levels and delays the timing of the circadian clock. The advent of tunable LED (light emitting diode) technology presents an opportunity to develop and implement circadian based practices for healthy lighting. Here we determined the influence of a simulated sunset with tunable LED technology on evening melatonin levels. Methods Nine healthy adults (3 females, 24.0 ± 5.3 years) completed a 15-day crossover study comparing typical artificial indoor lighting versus a simulated sunset using tunable LEDs (Acuity Brands-Rubik). After 1 week maintaining an ~8h sleep schedule, participants arrived at the laboratory 6h prior to habitual bedtime. Typical electrical indoor home lighting was Results Melatonin levels were initially similar between conditions but were significantly higher (p Conclusion These preliminary findings suggest that simulating a sunset transition with tunable LED technology prior to habitual bedtime in the evening has potential to benefit circadian health. Support This work was supported in part by NIH R01 HL135598 and NASA Award 80NSSC17K0569.

Study ObjectivesWe compared resident physician work hours and sleep in a multicenter clustered-randomized crossover clinical trial that randomized resident physicians to an Extended Duration Work Roster (EDWR) with extended-duration (≥24 hr) shifts or a Rapidly Cycling Work Roster (RCWR), in which scheduled shift lengths were limited to 16 or fewer consecutive hours.MethodsThree hundred two resident physicians were enrolled and completed 370 1 month pediatric intensive care unit rotations in six US academic medical centers. Sleep was objectively estimated with wrist-worn actigraphs. Work hours and subjective sleep data were collected via daily electronic diary.ResultsResident physicians worked fewer total hours per week during the RCWR compared with the EDWR (61.9 ± 4.8 versus 68.4 ± 7.4, respectively; p < 0.0001). During the RCWR, 73% of work hours occurred within shifts of ≤16 consecutive hours. In contrast, during the EDWR, 38% of work hours occurred on shifts of ≤16 consecutive hours. Resident physicians obtained significantly more sleep per week on the RCWR (52.9 ± 6.0 hr) compared with the EDWR (49.1 ± 5.8 hr, p < 0.0001). The percentage of 24 hr intervals with less than 4 hr of actigraphically measured sleep was 9% on the RCWR and 25% on the EDWR (p < 0.0001).ConclusionsRCWRs were effective in reducing weekly work hours and the occurrence of >16 consecutive hour shifts, and improving sleep duration of resident physicians. Although inclusion of the six operational healthcare sites increases the generalizability of these findings, there was heterogeneity in schedule implementation. Additional research is needed to optimize scheduling practices allowing for sufficient sleep prior to all work shifts.Clinical Trial: Multicenter Clinical Trial of Limiting Resident Work Hours on ICU Patient Safety (ROSTERS), https://clinicaltrials.gov/ct2/show/NCT02134847

Summary People commonly increase sleep duration on the weekend to recover from sleep loss incurred during the workweek. Whether ad libitum weekend recovery sleep prevents metabolic dysregulation caused by recurrent insufficient sleep is unknown. Here, we assessed sleep, circadian timing, energy intake, weight gain, and insulin sensitivity during sustained insufficient sleep (9 nights) and during recurrent insufficient sleep following ad libitum weekend recovery sleep. Healthy, young adults were randomly assigned to one of three groups: (1) control (CON; 9-h sleep opportunities, n = 8), (2) sleep restriction without weekend recovery sleep (SR; 5-h sleep opportunities, n = 14), and (3) sleep restriction with weekend recovery sleep (WR; insufficient sleep for 5-day workweek, then 2 days of weekend recovery, then 2 nights of insufficient sleep, n = 14). For SR and WR groups, insufficient sleep increased after-dinner energy intake and body weight versus baseline. During ad libitum weekend recovery sleep, participants cumulatively slept ∼1.1 h more than baseline, and after-dinner energy intake decreased versus insufficient sleep. However, during recurrent insufficient sleep following the weekend, the circadian phase was delayed, and after-dinner energy intake and body weight increased versus baseline. In SR, whole-body insulin sensitivity decreased ∼13% during insufficient sleep versus baseline, and in WR, whole-body, hepatic, and muscle insulin sensitivity decreased ∼9%–27% during recurrent insufficient sleep versus baseline. Furthermore, during the weekend, total sleep duration was lower in women versus men, and energy intake decreased to baseline levels in women but not in men. Our findings suggest that weekend recovery sleep is not an effective strategy to prevent metabolic dysregulation associated with recurrent insufficient sleep.

Study Objectives Determine stability of individual differences in executive function, cognitive processing speed, selective visual attention, and maintenance of wakefulness during simulated sustained operations with combined sleep restriction and circadian misalignment. Methods Twenty healthy adults (eight female), aged 25.7 (±4.2 SD), body mass index (BMI) 22.3 (±2.1) kg/m2 completed an 18-day protocol twice. Participants maintained habitual self-selected 8-hour sleep schedules for 2 weeks at home prior to a 4-day laboratory visit that included one sleep opportunity per day: 8 hours on night 1, 3 hours on night 2, and 3 hours on mornings 3 and 4. After 3 days of unscheduled sleep at home, participants repeated the entire protocol. Stability and task dependency of individual differences in performance were quantified by intra-class correlation coefficients (ICC) and Kendall’s Tau, respectively. Results Performance on Stroop, Visual Search, and the Maintenance of Wakefulness Test were highly consistent within individuals during combined sleep restriction and circadian misalignment. Individual differences were trait-like as indicated by ICCs (0.54–0.96) classified according to standard criteria as moderate to almost perfect. Individual differences on other performance tasks commonly reported in sleep studies showed fair to almost perfect ICCs (0.22–0.94). Kendall’s rank correlations showed that individual vulnerability to sleep restriction and circadian misalignment varied by task and by metric within a task. Conclusions Consistent vulnerability of higher-order cognition and maintenance of wakefulness to combined sleep restriction and circadian misalignment has implications for the development of precision countermeasure strategies for workers performing safety-critical tasks, e.g. military, police, health care workers and emergency responders.

Study Objectives To evaluate the associations between sedentary time, total (total-PA), light (light-PA), moderate (MOD-PA), and vigorous (VIG-PA) physical activity with indices of sleep in postmenopausal women. Methods Baseline self-reported data from the Women’s Health Initiative Observational Study (n = 75 074) were used in this cross-sectional analysis. Total-PA, light-PA, MOD-PA, and VIG-PA were categorized by metabolic equivalents of the activity (MET-hour [hr]/week [wk]) and were estimated using validated questionnaires. Sedentary time was categorized by hr/day and was estimated via questionnaire. Logistic regression was used to examine the associations between these variables and short sleep (≤6 hr/night), long sleep (≥10 hr/night), poor sleep quality, and insomnia symptoms after adjustment for age, race, socioeconomic status, body mass index, health status, depressive symptoms, smoking status, alcohol use, hormone therapy, and comorbidities. Results Higher sedentary time (>11 hr/day) was associated with higher odds of short sleep (odds ratio [OR] = 1.80, 95% confidence interval [CI]: 1.72–1.88), poor sleep quality (OR = 1.85, 95% CI: 1.74–1.97), and insomnia symptoms (OR = 1.56, 95% CI: 1.49–1.64). Light-PA (>0 MET-hr/wk) was associated with lower odds of short sleep (OR = 0.96, 95% CI: 0.92–1.00), and higher amounts of total-PA (OR = 0.90, 95% CI: 0.84–0.97), light-PA (OR = 0.94, 95% CI: 0.89–1.00), and MOD-PA (OR = 0.91, 95% CI: 0.86–0.97) were associated with lower odds of poor sleep quality. Conclusions Our findings suggest that higher levels of light and moderate intensity physical activity are associated with better sleep quality, whereas higher amounts of sedentary time are associated with short sleep and lower quality sleep. Future studies should investigate the directionality of these associations and potential causal pathways.

Despite the omnipresence of artificial and natural light exposure, there exists little guidance in the United States and elsewhere on light exposure in terms of timing, intensity, spectrum, and other light characteristics known to affect human health, performance, and well-being; in parallel, there is little information regarding the quantity and characteristics of light exposure that people receive. To address this, the National Center on Sleep Disorders Research, in the Division of Lung Diseases, National Heart, Lung, and Blood Institute, held a workshop in August 2016 on circadian health and light. Workshop participants discussed scientific research advances on the effects of light on human physiology, identified remaining knowledge gaps in these research areas, and articulated opportunities to use appropriate lighting to protect and improve circadian-dependent health. Based on this workshop, participants put forth the following strategic intent, objectives, and strategies to guide discovery, measurement, education, and implementation of the appropriate use of light to achieve, promote, and maintain circadian health in modern society.

Daytime light exposure has been reported to impact or have no influence on energy metabolism in humans. Further, whether inter-individual differences in wake, sleep, 24 h energy expenditure, and RQ during circadian entrainment and circadian misalignment are stable across repeated 24 h assessments is largely unknown. We present data from two studies: Study 1 of 15 participants (7 females) exposed to three light exposure conditions: continuous typical room ~100 lx warm white light, continuous ~750 lx warm white light, and alternating hourly ~750 lx warm white and blue-enriched white light on three separate days in a randomized order; and Study 2 of 14 participants (8 females) during circadian misalignment induced by a simulated night shift protocol. Participants were healthy, free of medical disorders, medications, and illicit drugs. Participants maintained a consistent 8 h per night sleep schedule for one week as an outpatient prior to the study verified by wrist actigraphy, sleep diaries, and call-ins to a time stamped recorder. Participants consumed an outpatient energy balance research diet for three days prior to the study. The inpatient protocol for both studies consisted of an initial sleep disorder screening night. For study 1, this was followed by three standard days with 16 h scheduled wakefulness and 8 h scheduled nighttime sleep. For Study 2, it was followed by 16 h scheduled wake and 8 h scheduled sleep at habitual bedtime followed by three night shifts with 8 h scheduled daytime sleep. Energy expenditure was measured using whole-room indirect calorimetry. Constant posture bedrest conditions were maintained to control for energy expenditure associated with activity and the baseline energy balance diet was continued with the same exact meals across days to control for thermic effects of food. No significant impact of light exposure was observed on metabolic outcomes in response to daytime light exposure. Inter-individual variability in energy expenditure was systematic and ranged from substantial to almost perfect consistency during both nighttime sleep and circadian misalignment. Findings show robust and stable trait-like individual differences in whole body 24 h, waking, and sleep energy expenditure, 24 h respiratory quotient—an index of a fat and carbohydrate oxidation—during repeated assessments under entrained conditions, and also in 24 h and sleep energy expenditure during repeated days of circadian misalignment. Keywords: Shift work, Biological day, Biological night

Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.