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Purpose: The effect of various sleep traits on the risk of lung cancer differs among pre-existing studies. This study aims to systematically review and synthesise the association between sleep duration and insomnia with the incidence of lung cancer., Methods: PubMed, Embase and The Cochrane Library were searched from inception to 23 April 2023 for observational studies examining the effect of sleep quantity or insomnia on lung cancer incidence. We pooled maximally-adjusted hazard ratios and odds ratios separately using random effects inverse variance weighted models. The risk of bias of observational studies was assessed using the Newcastle-Ottawa Scale., Results: We included 11 observational studies with a pooled cohort of 5,049,141 patients. The mean age of the patients was 49.5 ± 17.7 years, and 51.4% were males. The risk of bias ranged from low-moderate. Individuals who slept for a shorter or longer duration than the reference range of sleep per night showed an increased risk of lung cancer by 11% (HR:1.11; 95%CI:1.00-1.23) and 16% (HR:1.16; 95%CI:1.06-1.27) respectively. Furthermore, individuals with insomnia symptoms had a 9% greater risk of lung cancer than those without symptoms (HR:1.09; 95%CI:1.05-1.13)., Conclusion: This study suggests that insufficient sleep, excessive sleep and insomnia may be associated with an increased risk of lung cancer. Physicians should be mindful of this association and encourage healthy sleep practises among patients. Given the observed heterogeneity among some pre-existing studies, future research with longer periods of follow-up, greater control for covariates and objective testing of sleep parameters may add value to this topic., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To achieve consensus on whether screen-based digital media (1) in general, (2) via prebedtime content, and (3) via prebedtime light impairs sleep health in (a) childhood, (b) adolescence, and (c) adulthood. Furthermore, to address whether employing behavioral strategies and interventions may reduce the potential negative effects of screens on sleep health., Methods: The National Sleep Foundation convened a 16-person multidisciplinary expert panel ("Panel"). Panelists met virtually 5 times throughout 2023, during which they followed a modified Delphi RAND/UCLA Appropriateness Method to reach consensus., Results: The Panel conducted a literature review starting with 2209 articles, narrowed down to 522 relevant empirical articles and 52 relevant review articles. The search was refined to include 35 experimental/intervention studies that examined whether there was a causal link between screen-based digital media and sleep. In addition, panelists reviewed 5 recent relevant systematic review articles. After reviewing the summarized current literature, panelists voted on 10 candidate statements about whether screen use impairs sleep health. The Panel met virtually to discuss the results of the first round of votes, which was then followed by a second round of voting, ultimately achieving consensus on 5 out of the 10 statements., Conclusions: The Panel achieved consensus that (1) in general, screen use impairs sleep health among children and adolescents, (2) the content of screen use before sleep impairs sleep health of children and adolescents, and (3) behavioral strategies and interventions may attenuate the negative effects of screen use on sleep health., Competing Interests: Declaration of conflicts of interest The authors have declared no conflicts of interest., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To investigate whether neurobehavioral impairments are exacerbated during successive cycles of sleep restriction and recovery in young adults, and whether a variable short sleep schedule can mitigate these impairments relative to a stable one., Methods: Fifty-two healthy young adults (25 males, aged: 21-28) were randomly assigned to the stable short sleep group, the variable short sleep group, or the control group in this laboratory-based study. They underwent two baseline nights of 8-hour time-in-bed (TIB), followed by two cycles of "weekday" sleep opportunity manipulation and "weekend" recovery (8-hour TIB). During each manipulation period, the stable short sleep and the control groups received 6- and 8-hour TIBs each night respectively, while the variable short sleep group received 8-hour, 4-hour, 8-hour, 4-hour, and 6-hour TIBs from the first to the fifth night. Neurobehavioral functions were assessed five times each day., Results: The stable short sleep group showed faster vigilance deterioration in the second week of sleep restriction as compared to the first. This effect was not observed in the variable short sleep group. Subjective alertness and practice-based improvement in processing speed were attenuated in both short sleep groups., Conclusions: In young adults, more variable short sleep schedules incorporating days of prophylactic or recovery sleep might mitigate compounding vigilance deficits resulting from recurrent cycles of sleep restriction. However, processing speed and subjective sleepiness were still impaired in both short sleep schedules. Getting sufficient sleep consistently is the only way to ensure optimal neurobehavioral functioning., Clinical Trial: Performance, Mood, and Brain and Metabolic Functions During Different Sleep Schedules (STAVAR), https://www.clinicaltrials.gov/study/NCT04731662, NCT04731662., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine effects of menstrual phase and nighttime light exposure on subjective sleepiness and auditory Psychomotor Vigilance Task performance., Methods: Twenty-nine premenopausal women (12 =Follicular; 17 =Luteal) completed a 6.5-hour nighttime monochromatic light exposure with varying wavelengths (420-620 nm) and irradiances (1.03-14.12 µW/cm 2 ). Subjective sleepiness, reaction time, and attentional lapses were compared between menstrual phases in women with minimal (<33%) or substantial (≥33%) light-induced melatonin suppression., Results: When melatonin was not suppressed, women in the follicular phase had significantly worse reaction time (mean difference=145.1 ms, 95% CI 51.8-238.3, p < .001, Cohen's D=1.9) and lapses (mean difference=12.9 lapses, 95% CI 4.37-21.41, p < .001, Cohen's D=1.7) compared to women in the luteal phase. When melatonin was suppressed, women in the follicular phase had significantly better reaction time (mean difference=152.1 ms, 95% CI 43.88-260.3, p < .001, Cohen's D=1.7) and lapses (mean difference=12.3 lapses, 95% CI 1.14-25.6, p < .01, Cohen's D=1.6) compared to when melatonin was not suppressed, such that their performance was not different (p > .9) from women in the luteal phase. Subjective sleepiness did not differ by menstrual phase (mean difference=0.6, p > .08) or melatonin suppression (mean difference=0.2, p > .4)., Conclusions: Nighttime light exposure sufficient to suppress melatonin can also mitigate neurobehavioral performance deficits associated with the follicular phase. Despite the relatively small sample size, these data suggest that nighttime light may be a valuable strategy to help reduce errors and accidents in female shift workers., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Spatial working memory (SWM) capacity subserves complex cognitive functions, yet it is unclear whether individual diurnal preferences and time-of-day influence SWM in preschool children. The main and interaction effects of chronotype and time-of-day on SWM and SWM differences in preschoolers with different chronotypes within each time-of-day group will be examined., Methods: We studied a subset of typically developing 4.5-year-olds taking part in a birth cohort study (n = 359). The Children's Chronotype Questionnaire categorized children into morning-, intermediate-, and evening-types. Using a computerized neuropsychological test (Cambridge Neuropsychological Test Automated Battery), SWM was determined from the total number of between-search errors (ie, between search-total errors) and Strategy scores. Higher between search-total errors or lower Strategy scores indicated worse SWM. Time-of-day was categorized into late morning (10:00 am to 11:59 am), afternoon (12:00 pm to 3:59 pm), and late afternoon (4:00 pm to 6:30 pm). In a subsample (n = 199), caregiver-reported chronotype was validated using actigraphy-measured sleep midpoint., Results: After controlling for ethnicity, no significant main and interaction effects of chronotype and time-of-day on between search-total errors and Strategy scores were seen (all P > .05). However, evening-types outperformed morning-types (ie, lower mean between search-total errors) in the late afternoon ( P = .013) but not in the late morning and afternoon (all P > .05). Actigraphy data in the subsample confirmed that evening-types had later sleep midpoints during weekdays and weekends ( P < .001)., Conclusions: Since evening-type preschoolers had better SWM in the late afternoon compared to morning-type preschoolers, this gives insights into optimal learning opportunities in early childhood education., Citation: Abdul Jafar NK, Tham EKH, Eng DZH, et al. Chronotype and time-of-day effects on spatial working memory in preschool children. J Clin Sleep Med . 2023;19(10):1717-1726., (© 2023 American Academy of Sleep Medicine.)

Background: Poor sleep quality may elevate cortisol levels and affect prenatal mental health through altered HPA axis functioning. This study aims to examine whether subjective sleep quality during preconception moderates the association between preconception hair cortisol levels and mental health from preconception to pregnancy trimesters., Methods: Women from a prospective cohort study completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale (EPDS), and the State-Trait Anxiety Inventory (STAI) questionnaires during preconception (T0) and at each pregnancy trimesters (T1, T2, and T3). We analyzed 266 of these women who conceived and had fully completed measures at preconception for hair cortisol, sleep quality and either EPDS or STAI-state. Changes in EPDS and STAI-state scores were derived (i.e., T1-T0, T2-T0, T3-T0). Johnson-Neyman technique identified PSQI scores with significant moderation of cortisol on mental health., Results: After adjusting for potential covariates, there was a significant positive correlation between preconception hair cortisol levels and depressive symptom at the second trimester (r s (144) = 0.22, p = 0.008), but not the first and third trimesters (all p s  > 0.05). The positive association between preconception hair cortisol and change in depressive symptoms between third trimester and preconception was significant only among women with poor preconception sleep quality (PSQI ≥ 7)., Limitations: Sleep quality and prenatal mood were derived from self-reported questionnaires, which may be more susceptible to bias., Conclusions: The positive association between preconception hair cortisol and change in prenatal depressive symptoms is significant among women who reported poor sleep quality during preconception. Improving preconception sleep quality can potentially mitigate the association between preconception hair cortisol and depressive symptoms during pregnancy., Competing Interests: Declaration of competing interest Peter D. Gluckman and Yap-Seng Chong is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Michael J. Meaney is supported by the Hope for Depression Research Foundation and the Jacobs Foundation. The remaining authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Study Objectives: School start times impose constraints on sleep-wake timing that may influence academic achievement. We used large university archived datasets to test the hypothesis that larger differences in timing of students' diurnal learning behavior on school days relative to non-school days would be associated with lower grades., Methods: Diurnal learning-directed behavior was examined in 33 645 university students by analyzing their learning management system (LMS) login rhythm. We tested the associations between the phase-difference in students' behavioral rhythm on school days versus non-school days with grade point average, LMS-login phase on non-school days (LMS-login chronotype), and school start time. We also tested the chronotype-dependent effects of school start times on diurnal behavior to determine whether students obtained better course grades when their first class of the day was in synch with their LMS-login chronotype., Results: Students whose LMS-login rhythm was more than 2 hours earlier on school days had significantly lower grades than their peers. The change in LMS-login phase was larger in students with a later LMS-login chronotype and for earlier school start times. Minimal changes in LMS-login phase and higher course grades were observed when students' first class of the day was aligned with their LMS-login chronotype., Conclusions: Our findings demonstrate that school start times have a profound impact on students' diurnal learning behavior with implications for grades. Universities can potentially improve learning by starting school later to minimize differences in diurnal learning behavior between school days and non-school days., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Attending classes and sleeping well are important for students' academic success. Here, we tested whether early morning classes are associated with lower attendance, shorter sleep and poorer academic achievement by analysing university students' digital traces. Wi-Fi connection logs in 23,391 students revealed that lecture attendance was about ten percentage points lower for classes at 08:00 compared with later start times. Diurnal patterns of Learning Management System logins in 39,458 students and actigraphy data in 181 students demonstrated that nocturnal sleep was an hour shorter for early classes because students woke up earlier than usual. Analyses of grades in 33,818 students showed that the number of days per week they had morning classes was negatively correlated with grade point average. These findings suggest concerning associations between early morning classes and learning outcomes., (© 2023. The Author(s).)

Study Objectives: Examine how different trajectories of reported sleep duration associate with early childhood cognition., Methods: Caregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children's Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived-each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively., Results: Compared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory., Conclusions: Longer and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambda max at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambda max was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambda max was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambda max ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.

Study Objectives: We characterized vigilance deterioration with increasing time-on-task (ToT) during recurrent sleep restriction of different extents on simulated weekdays and recovery sleep on weekends, and tested the effectiveness of afternoon napping in ameliorating ToT-related deficits., Methods: In the Need for Sleep studies, 194 adolescents (age = 15-19 years) underwent two baseline nights of 9-h time-in-bed (TIB), followed by two cycles of weekday manipulation nights and weekend recovery nights (9-h TIB). They were allocated 9 h, 8 h, 6.5 h, or 5 h of TIB for nocturnal sleep on weekdays. Three additional groups with 5 h or 6.5 h TIB were given an afternoon nap opportunity (5 h + 1 h, 5 h + 1.5 h, and 6.5 h + 1.5 h). ToT effects were quantified by performance change from the first 2 min to the last 2 min in a 10-min Psychomotor Vigilance Task administered daily., Results: The 9 h and the 8 h groups showed comparable ToT effects that remained at baseline levels throughout the protocol. ToT-related deficits were greater among the 5 h and the 6.5 h groups, increased prominently in the second week of sleep restriction despite partial recuperation during the intervening recovery period and diverged between these two groups from the fifth sleep-restricted night. Daytime napping attenuated ToT effects when nocturnal sleep restriction was severe (i.e. 5-h TIB/night), and held steady at baseline levels for a milder dose of nocturnal sleep restriction when total TIB across 24 h was within the age-specific recommended sleep duration (i.e. 6.5 h + 1.5 h)., Conclusions: Reducing TIB beyond the recommended duration significantly increases ToT-associated vigilance impairment, particularly during recurrent periods of sleep restriction. Daytime napping is effective in ameliorating such decrement., Clinical Trial Registration: NCT02838095, NCT03333512, and NCT04044885., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Study Objectives: The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters., Methods: Twenty healthy adults aged 21-30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested., Results: A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon., Conclusion: The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

The COVID-19 pandemic led to widespread closure of universities. Many universities turned to e-learning to provide educational continuity, but they now face the challenge of how to reopen safely and resume in-class learning. This is difficult to achieve without methods for measuring the impact of school policies on student physical interactions. Here, we show that selectively deploying e-learning for larger classes is highly effective at decreasing campus-wide opportunities for student-to-student contact, while allowing most in-class learning to continue uninterrupted. We conducted a natural experiment at a large university that implemented a series of e-learning interventions during the COVID-19 outbreak. The numbers and locations of 24,000 students on campus were measured over a 17-week period by analysing >24 million student connections to the university Wi-Fi network. We show that daily population size can be manipulated by e-learning in a targeted manner according to class size characteristics. Student mixing showed accelerated growth with population size according to a power law distribution. Therefore, a small e-learning dependent decrease in population size resulted in a large reduction in student clustering behaviour. Our results suggest that converting a small number of classes to e-learning can decrease potential for disease transmission while minimising disruption to university operations. Universities should consider targeted e-learning a viable strategy for providing educational continuity during periods of low community disease transmission., Competing Interests: The authors have declared that no competing interests exist.

Lipids in breastmilk play a critical role in infant growth and development. However, few studies have investigated sources of variability of both high- and low-abundant milk lipids. The objective of our study was to investigate individual and morning-evening differences in the human milk lipidome. In this study, a modified two-phase method (MTBE: Methanol 7:2) was validated for the extraction of lipids from human breastmilk. This method was then applied to samples from a group of 20 healthy women to measure inter- and intra-individual (morning versus evening) variability of the breastmilk lipidome. We report here the levels of 237 lipid species from 13 sub-classes using reversed-phase liquid chromatography mass spectrometry (RP-LCMS) and direct-infusion mass spectrometry (DI-MS). About 85% of lipid species showed stable inter-individual differences across time points. Half of lipid species showed higher concentrations in the evening compared with the morning, with phosphatidylethanolamines (PEs) and triacylglycerols (TAGs) exhibiting the largest changes. In morning and evening samples, the biological variation was greater for diacylglycerols (DAGs) and TAGs compared with phospholipids and sphingolipids, and the variation in DAGs and TAGs was greater in evening samples compared with morning samples. These results demonstrate that variation in the milk lipidome is strongly influenced by individual differences and time of day.

Study Objectives: We compared the basic cognitive functions of adolescents undergoing split (nocturnal sleep + daytime nap) and continuous nocturnal sleep schedules when total sleep opportunity was either below or within the recommended range (i.e. 6.5 or 8 h)., Methods: Adolescent participants (age: 15-19 year) in the 8-h split (n = 24) and continuous (n = 29) sleep groups were compared with 6.5-h split and continuous sleep groups from a previous study (n = 58). These protocols involved two baseline nights (9-h time-in-bed [TIB]), 5 nights of sleep manipulation, 2 recovery nights (9-h TIB), followed by a second cycle of sleep manipulation (3 nights) and recovery (2 nights). Cognitive performance, subjective sleepiness, and mood were evaluated daily; sleep was assessed using polysomnography., Results: Splitting 6.5 h of sleep with a mid-afternoon nap offered a boost to cognitive function compared to continuous nocturnal sleep. However, when total TIB across 24 h increased to 8 h, the split and continuous sleep groups performed comparably in tests evaluating vigilance, working memory, executive function, processing speed, subjective sleepiness, and mood., Conclusions: In adolescents, the effects of split sleep on basic cognitive functions vary by the amount of total sleep obtained. As long as the total sleep opportunity across 24 h is within the recommended range, students may fulfill sleep requirements by adopting a split sleep schedule consisting of a shorter period of nocturnal sleep combined with a mid-afternoon nap, without significant impact on basic cognitive functions., Clinical Trial Registration: NCT04044885., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society.)

Objective: To investigate associations of adolescents' time spent on homework/studying with nocturnal time for sleep and depression symptoms, in a competitive academic environment., Design: Cross-sectional, anonymous survey of sleep habits, school life, and health-related measures., Setting: Eight schools in Singapore., Participants: Total 1225 adolescents aged 13-19 years., Measurements: Self-reported sleep behavior and time use data were collected separately for school days and weekends. Multiple regression models were used to test covariation of time spent on homework/studying with other activities, and associations of homework/studying duration with depression symptoms., Results: Time in bed for sleep and media use were inversely related with homework/studying duration on both school days and weekends, adjusting for time spent on other activities and demographic variables. Face-to-face family time and hanging out with friends were also reciprocally related with homework/studying duration on weekends. Depression scores were higher in adolescents who spent long hours on homework/studying. On school days, this was mediated by reduced time in bed for sleep. On weekends, homework/studying duration associated with depression symptoms, adjusting for time in bed and other covariates. Adolescents who spent ≥5 hours on homework/studying per day on weekends had greater symptoms of anhedonia and anxiety., Conclusions: In a competitive academic setting, adolescents who spent more time on homework/studying spent less time on sleep, media use, and social activities. Independent of effects on sleep, long hours on homework/studying on weekends may be a risk factor for depression. Reducing adolescents' workload outside of class may benefit their sleep, schoolwork-life balance, and mental well-being., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies have identified lifestyle risk factors for perinatal depression, but none have examined the cumulative effect of these risk factors in pregnant women., Methods: We considered the following six factors during pregnancy: poor diet quality (Healthy eating index for Singapore pregnant women 5), physical inactivity (<600 MET-minutes/week), vitamin D insufficiency (<50 nmol/l), smoking before or during pregnancy, and the perceived need for social support. Probable depression was assessed using the Edinburgh postnatal depression scale during pregnancy (>15) and at three months postpartum (≥13). Prevalence risk ratios were calculated with Poisson regressions while adjusting for potential confounders., Results: Of 535 pregnant women, 207 (39%) had zero or one risk factor, 146 (27%) had two, 119 (22%) had three, 48 (9%) had four, and 15 (3%) had ≥5 risk factors at 26-28 weeks' gestation. These six lifestyle habits contributed to 32% of the variance in depressive symptoms during pregnancy. The prevalence of being probably depressed was 6.4 (95% CI 2.1, 19.8; p trend  < 0.001) for expecting women who had ≥4 risk factors compared to women who had ≤1 risk factor. No association was observed between the number of risk factors and depressive symptoms at 3 months postpartum (p trend  = 0.746)., Conclusion: Pregnant women with ≥4 lifestyle risk factors showed a higher prevalence of depression during pregnancy, while no associations were observed for postpartum depression., Clinical Trial Registration: This cohort is registered under the Clinical Trials identifier NCT01174875; http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Shortened sleep has negative consequences on adolescents' well-being. The present study evaluated an interactive school-based sleep education program (SEP) aimed at increasing adolescent sleep duration., Design and Intervention: A cluster-randomized controlled trial with 12 clusters (classes) was used. The intervention group received a SEP and the active control group received a healthy living program (HLP). Both groups underwent a 4-week class-based education program. The SEP students learned about the importance of sleep, the barriers to getting enough sleep, and how to improve their time management to increase their sleep opportunity. The HLP students learned about various health-related topics not including sleep., Participants: A total of 210 students (mean age = 14.04 ± 0.32 years) were randomly assigned to the SEP (n = 102) or the HLP (n = 108) group, with 6 classes per group., Measurements: Sleep (actigraphically measured), sleep knowledge, and time usage were assessed using linear mixed models at three time points: baseline, immediately after intervention, and 1-month follow-up., Results: Sleep knowledge improved at follow-up in the SEP relative to the HLP group (p = .017). Although students were receptive of the program and self-reported the intention to create more time for sleep, no changes in sleep were found following the SEP. Some benefit may have been masked by exam preparations at the follow-up evaluation., Conclusions: Sleep education alone may not be sufficient to change sleep behavior. A combination of sleep education, starting school later, and parental involvement may be needed to encourage and enable changes in adolescent sleep duration., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Women in the luteal phase of the menstrual cycle exhibit better cognitive performance overnight than women in the follicular phase, although the mechanism is unknown. Given the link between core body temperature (CBT) and performance, one potential mechanism is the thermoregulatory role of progesterone (P4), estradiol (E2), and their ratio (P4/E2), which change across the menstrual cycle. We examined the role of P4/E2 in modulating performance during extended wake in premenopausal women. Additionally, we compared the acute effects of nighttime light exposure on performance, CBT, and hormones between the menstrual phases., Methods: Participants were studied during a 50 h constant routine and a 6.5 h monochromatic nighttime light exposure. Participants were 16 healthy, naturally cycling women (eight follicular; eight luteal). Outcome measures included reaction time, attentional failures, self-reported sleepiness, CBT, melatonin, P4, and E2., Results: As compared to women in the luteal phase, women in the follicular phase exhibited worse performance overnight. CBT was significantly associated with performance, P4, and P4/E2 but not with other sex hormones. Sex hormones were not directly related to performance. Light exposure that suppressed melatonin improved performance in the follicular phase (n = 4 per group) to levels observed during the luteal phase and increased CBT but without concomitant changes in P4/E2., Conclusions: Our results underscore the importance of considering menstrual phase when assessing cognitive performance during sleep loss in women and indicate that these changes are driven predominantly by CBT. Furthermore, this study shows that vulnerability to sleep loss during the follicular phase may be resolved by exposure to light., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objectives: The increasing prevalence of advanced maternal age (AMA) coupled with poor sleep quality among pregnant women makes it important to study their association with perinatal outcomes. However, little is known about the interaction of AMA and maternal antenatal sleep on perinatal outcomes. Here, we examined whether associations between AMA and perinatal outcomes are modified by antenatal sleep quality., Participants: Data were collected from 446 women, with a singleton pregnancy and no pregnancy complications, who participated in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study., Measurements: Participants completed the Pittsburgh Sleep Quality Index (PSQI) at 26-28 weeks gestation and had perinatal outcome data collected upon delivery. Interactions between AMA and maternal sleep quality on perinatal outcomes were investigated and where significant, analyses were further stratified by maternal age. All analyses were adjusted for maternal BMI at 26-28 weeks gestation, ethnicity, and maternal education., Results: Neonates of mothers of AMA and poor sleep quality (PSQI score >5) had increased odds of stay in the neonatal intensive care unit (adjusted odds ratio = 3.53, 95% CI: -1.21 to 10.27) and shorter birth length (adjusted mean difference = -1.05 cm, 95% CI: -1.82 to -0.20), as compared with women of AMA and good sleep quality (PSQI score ≤5). In women <35 years, sleep quality did not associate with perinatal outcomes., Conclusion: Poor sleep quality in women of AMA was associated with neonatal health outcomes. Improving maternal antenatal sleep may potentially improve perinatal outcomes in offspring of women of AMA., (Copyright © 2019 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Context: Studies suggest that female reproductive hormones are under circadian regulation, although methodological differences have led to inconsistent findings., Objective: To determine whether circulating levels of reproductive hormones exhibit circadian rhythms., Design: Blood samples were collected across ∼90 consecutive hours, including 2 baseline days under a standard sleep-wake schedule and ∼50 hours of extended wake under constant routine (CR) conditions., Setting: Intensive Physiological Monitoring Unit, Brigham and Women's Hospital., Participants: Seventeen healthy premenopausal women (22.8 ± 2.6 years; nine follicular; eight luteal)., Interventions: Fifty-hour CR., Main Outcome Measures: Plasma estradiol (E2), progesterone (P4), LH, FSH, SHBG, melatonin, and core body temperature., Results: All hormones exhibited significant 24-hour rhythms under both standard sleep-wake and CR conditions during the follicular phase (P < 0.05). In contrast, only FSH and SHBG were significantly rhythmic during the luteal phase. Rhythm acrophases and amplitudes were similar between standard sleep-wake and CR conditions. The acrophase occurred in the morning for P4; in the afternoon for FSH, LH, and SHBG; and during the night for E2., Conclusions: Our results confirm previous reports of ∼24-hour rhythms in many female reproductive hormones in humans under ambulatory conditions but demonstrate that these hormones are under endogenous circadian regulation, defined as persisting in the absence of external time cues. These results may have important implications for the effects of circadian disruption on reproductive function., (Copyright © 2019 Endocrine Society.)

We explored the predictive value of a neurobehavioral performance assessment under rested baseline conditions (evaluated at 8 hours awake following 8 hours of sleep) on neurobehavioral response to moderate sleep loss (evaluated at 20 hours awake two days later) in 151 healthy young participants (18-30 years). We defined each participant's response-to-sleep-loss phenotype based on the number of attentional failures on a 10-min visual psychomotor vigilance task taken at 20 hours awake (resilient: less than 6 attentional failures, n = 26 participants; non-resilient: 6 or more attentional failures, n = 125 participants). We observed that 97% of rested participants with 2 or more attentional failures (n = 73 of 151) and 100% of rested participants with 3 or more attentional failures (n = 57 of 151) were non-resilient after moderate sleep loss. Our approach can accurately identify a significant proportion of individuals who are at high risk for neurobehavioral performance impairment from staying up late with a single neurobehavioral performance assessment conducted during rested conditions. Additional methods are needed to predict the future performance of individuals who are not identified as high risk during baseline.

There are strong individual differences in performance during sleep deprivation. We assessed whether baseline features of Psychomotor Vigilance Test (PVT) performance can be used for classifying participants' relative attentional vulnerability to total sleep deprivation. In a laboratory, healthy adults (n = 160, aged 18-30 years) completed a 10-min PVT every 2 h while being kept awake for ≥24 hours. Participants were categorized as vulnerable (n = 40), intermediate (n = 80), or resilient (n = 40) based on their number of PVT lapses during one night of sleep deprivation. For each baseline PVT (taken 4-14 h after wake-up time), a linear discriminant model with wrapper-based feature selection was used to classify participants' vulnerability to subsequent sleep deprivation. Across models, classification accuracy was about 70% (range 65-76%) using stratified 5-fold cross validation. The models provided about 78% sensitivity and 86% specificity for classifying resilient participants, and about 70% sensitivity and 89% specificity for classifying vulnerable participants. These results suggest features derived from a single 10-min PVT at baseline can provide substantial, but incomplete information about a person's relative attentional vulnerability to total sleep deprivation. In the long term, modeling approaches that incorporate baseline performance characteristics can potentially improve personalized predictions of attentional performance when sleep deprivation cannot be avoided.

Objective: To investigate associations between sleep duration and health-related measures, and factors associated with short sleep, in adolescents in an East Asian society with strong emphasis on academic achievement., Methods: Adolescents aged 13-19 years (n = 2346) from eight schools in Singapore (five local, three international) took part in a cross-sectional survey of sleep habits, school life, and health. Self-rated health, overweight (International Obesity Task Force Criteria), and depression symptoms were compared in adolescents with short (<7 h), moderately short (7 to <8 h), or an appropriate amount of sleep (8-10 h) on school nights., Results: Short sleep on school nights was associated with poorer self-rated health, increased odds of being overweight (adjusted odds ratio [OR adj ] = 2.56, 95% confidence interval = 1.39-4.70), and increased odds of feeling depression symptoms (sadness, irritability, worthlessness, low motivation, difficulty concentrating, anhedonia, anxiety, and thoughts of self-harm/suicide) compared with an appropriate sleep duration (OR adj  = 2.10-4.33, p < 0.05 for each symptom). Barriers to healthy sleep included later preferred sleep timing (a relative indicator of later chronotype), lower parental supervision of bedtime, longer study time, early school start time, and longer travel time. Students at local schools were less likely to have a parent-set bedtime, and spent more time on homework/studying. Later bedtime in local schools attenuated the benefit of later school start time on nocturnal sleep duration., Conclusions: Short sleep may contribute to poorer adolescent health and well-being. Strategies for improving sleep in hard-driving East Asian societies should take into account sociocultural factors that may impede removal of barriers to healthy sleep., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Adequate sleep duration and good sleep quality are considered essential for development, especially during periods of major neurodevelopmental change. Still, relations between parent-reported habitual sleep and emerging cognitive abilities within the first year of life are not well studied. Here, we examined relations between habitual sleep measures and an aspect of cognitive functioning, relational memory, which emerges as early as 6 months of age, as compared to other abilities (ie, recognition memory and attentional orienting), both of which are considered to emerge earlier in development., Participants: Participants were a subset of 267 healthy typically developing 6-month-olds taking part in the Growing Up in Singapore towards Healthy Outcomes cohort study., Measurements: Sleep duration, sleep latency, and number and duration of night awakenings were derived from the Brief Infant Sleep Questionnaire (BISQ). Short sleep was defined as <10 hours per day, categorized as "not recommended" based on the National Sleep Foundation recommendations. Associations between sleep variables and infants' performance on 2 relational memory tests (deferred imitation and relational binding) were examined independently using hierarchical (blockwise entry) linear regression. Associations between sleep and recognition memory and attentional orienting were also explored., Results: Habitual short sleepers had poorer relational memory recall in the deferred imitation task compared with 'typical' sleepers (10-18 hours per day). Shorter sleep latency was related to a greater proportion of correct responses for certain aspects of relational binding. There were no associations between sleep and recognition memory or attention., Conclusions: Our findings suggest that habitual sleep duration and short sleep latency associate with 6-month-olds' relational memory, suggesting a preferential association with memory tasks that are sensitive to development during the second half of the first year., (Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Many adolescents are exposed to sleep restriction on school nights. We assessed how different apportionment of restricted sleep (continuous vs. split sleep) influences neurobehavioral function and glucose levels., Methods: Adolescents, aged 15-19 years, were evaluated in a dormitory setting using a parallel-group design. Following two baseline nights of 9-hour time-in-bed (TIB), participants underwent either 5 nights of continuous 6.5-h TIB (n = 29) or 5-hour nocturnal TIB with a 1.5-hour afternoon nap (n = 29). After two recovery nights of 9-hour TIB, participants were sleep restricted for another three nights. Sleep was assessed using polysomnography (PSG). Cognitive performance and mood were evaluated three times per day. Oral glucose tolerance tests (OGTT) were conducted on mornings after baseline sleep, recovery sleep, and the third day of each sleep restriction cycle., Results: The split sleep group had fewer vigilance lapses, better working memory and executive function, faster processing speed, lower level of subjective sleepiness, and more positive mood, even though PSG-verified total sleep time was less than the continuous sleep group. However, vigilance in both sleep-restricted groups was inferior to adolescents in a prior sample given 9-hour nocturnal TIB. During both cycles of sleep restriction, blood glucose during the OGTT increased by a greater amount in the split sleep schedule compared with persons receiving 6.5-hour continuous sleep., Conclusions: In adolescents, modest multinight sleep restriction had divergent negative effects on cognitive performance and glucose levels depending on how the restricted sleep was apportioned. They are best advised to obtain the recommended amount of nocturnal sleep., Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03333512., (© Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society].)

The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. Rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the 'gold standard' for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.

Chromatic pupillometry is an emerging modality in the assessment of retinal and optic nerve disorders. Herein, we evaluate the effect of low and moderate refractive errors on pupillary responses to blue- and red-light stimuli in a healthy older population. This study included 139 participants (≥50 years) grouped by refractive error: moderate myopes (>-6.0D and ≤-3.0D, n = 24), low myopes (>-3.0D and <-0.5D, n = 30), emmetropes (≥-0.5D and ≤0.5D, n = 31) and hyperopes (>0.5D and <6.0D, n = 54). Participants were exposed to logarithmically ramping-up blue (462 nm) and red (638 nm) light stimuli, designed to sequentially activate rods, cones and intrinsically-photosensitive retinal ganglion cells. Pupil size was assessed monocularly using infra-red pupillography. Baseline pupil diameter correlated inversely with spherical equivalent (R = -0.26, P < 0.01), and positively with axial length (R = 0.37, P < 0.01) and anterior chamber depth (R = 0.43, P < 0.01). Baseline-adjusted pupillary constriction amplitudes to blue light did not differ between groups (P = 0.45), while constriction amplitudes to red light were greater in hyperopes compared to emmetropes (P = 0.04) at moderate to bright light intensities (12.25-14.0 Log photons/cm²/s). Our results demonstrate that low and moderate myopia do not alter pupillary responses to ramping-up blue- and red-light stimuli in healthy older individuals. Conversely, pupillary responses to red light should be interpreted cautiously in hyperopic eyes.

The pupillary light reflex is mediated by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs), which also receive input from rods and cones. Melanopsin-dependent pupillary light responses are short-wavelength sensitive, have a higher threshold of activation, and are much slower to activate and de-activate compared with rod/cone-mediated responses. Given that rod/cone photoreceptors and melanopsin differ in their response properties, light stimuli can be designed to stimulate preferentially each of the different photoreceptor types, providing a read-out of their function. This has given rise to chromatic pupillometry methods that aim to assess the health of outer retinal photoreceptors and ipRGCs by measuring pupillary responses to blue or red light stimuli. Here, we review different types of chromatic pupillometry protocols that have been tested in patients with retinal or optic nerve disease, including approaches that use short-duration light exposures or continuous exposure to light. Across different protocols, patients with outer retinal disease (e.g., retinitis pigmentosa or Leber congenital amaurosis) show reduced or absent pupillary responses to dim blue-light stimuli used to assess rod function, and reduced responses to moderately-bright red-light stimuli used to assess cone function. By comparison, patients with optic nerve disease (e.g., glaucoma or ischemic optic neuropathy, but not mitochondrial disease) show impaired pupillary responses during continuous exposure to bright blue-light stimuli, and a reduced post-illumination pupillary response after light offset, used to assess melanopsin function. These proof-of-concept studies demonstrate that chromatic pupillometry methods can be used to assess damage to rod/cone photoreceptors and ipRGCs. In future studies, it will be important to determine whether chromatic pupillometry methods can be used for screening and early detection of retinal and optic nerve diseases. Such methods may also prove useful for objectively evaluating the degree of recovery to ipRGC function in blind patients who undergo gene therapy or other treatments to restore vision.

Although evidence exists for a daily rhythm in bone metabolism, the contribution of factors such as melatonin levels, the light-dark cycle, and the sleep-wake cycle is difficult to differentiate given their highly correlated time courses. To examine these influences on bone resorption, we collected 48-h sequential urine samples under both ambulatory (8-h sleep:16-h wake) and constant routine (CR) (constant wake, posture, nutrition and dim light) conditions from 20 healthy premenopausal women. Urinary 6-sulphatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked collagen I telopeptide (NTx; bone collagen equivalents nM/h) were assayed and fit by cosinor models to determine significant 24-h rhythms and acrophase. Most participants had significant 24-h aMT6s rhythms during both ambulatory and CR conditions (95 and 85%, respectively), but fewer had significant 24-h NTx rhythms (70 and 70%, respectively). Among individuals with significant rhythms, mean (± SD) aMT6s acrophase times were 3:57 ± 1:50 and 3:43 ± 1:25 h under ambulatory and CR conditions, respectively, and 23:44 ± 5:55 and 3:06 ± 5:15 h, respectively, for NTx. Mean 24-h levels of both aMT6s and NTx were significantly higher during CR compared with ambulatory conditions (p < 0.0001 and p = 0.03, respectively). Menstrual phase (follicular versus luteal) had no impact on aMT6s or NTx timing or 24-h levels. This study confirms an endogenous circadian rhythm in NTx with a night-time peak when measured under CR conditions, but also confirms that environmental factors such as the sleep-wake or light-dark cycles, posture or meal timing affects overall concentrations and peak timing under ambulatory conditions, the significance of which remains unclear.

Purpose: To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease., Design: Cross-sectional study., Participants: Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry., Methods: Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography., Main Outcome Measures: Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis., Results: Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm 2 /s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG., Conclusions: Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To investigate sex differences in the effect of sleep deprivation on performance, accounting for menstrual phase in women., Methods: We examined alertness data from 124 healthy women and men (40 women, 84 men; aged 18-30 years) who maintained wakefulness for at least 30 hr in a laboratory setting using a constant routine protocol. Objective alertness was assessed every 2 hr using a 10 min psychomotor vigilance task. Subjective alertness was assessed every hour via the Karolinska Sleepiness Scale., Results: Women in the follicular phase of the menstrual cycle demonstrated the poorest level of performance. This poor performance was most pronounced at times corresponding to the typical sleep episode, demonstrating a window of vulnerability at night during this menstrual phase. At 24 hr awake, over 60 per cent of their responses were lapses of >500 ms and over one-third of their responses were longer lapses of at least 3 s in duration. Women in the luteal phase, however, were relatively protected from alertness failure, performing similar or better than both follicular-phase women and men., Conclusions: These results have important implications for education and intervention programs for shift workers, specifically during times of vulnerability to attentional failure that increase risk of injury.

Study Objectives: To investigate the short- and longer-term impact of a 45-min delay in school start time on sleep and well-being of adolescents., Methods: The sample consisted of 375 students in grades 7-10 (mean age ± SD: 14.6 ± 1.15 years) from an all-girls' secondary school in Singapore that delayed its start time from 07:30 to 08:15. Self-reports of sleep timing, sleepiness, and well-being (depressive symptoms and mood) were obtained at baseline prior to the delay, and at approximately 1 and 9 months after the delay. Total sleep time (TST) was evaluated via actigraphy., Results: After 1 month, bedtimes on school nights were delayed by 9.0 min, while rise times were delayed by 31.6 min, resulting in an increase in time in bed (TIB) of 23.2 min. After 9 months, the increase in TIB was sustained, and TST increased by 10.0 min relative to baseline. Participants also reported lower levels of subjective sleepiness and improvement in well-being at both follow-ups. Notably, greater increase in sleep duration on school nights was associated with greater improvement in alertness and well-being., Conclusions: Delaying school start time can result in sustained benefits on sleep duration, daytime alertness, and mental well-being even within a culture where trading sleep for academic success is widespread.

Sleep staging is a fundamental but time consuming process in any sleep laboratory. To greatly speed up sleep staging without compromising accuracy, we developed a novel framework for performing real-time automatic sleep stage classification. The client-server architecture adopted here provides an end-to-end solution for anonymizing and efficiently transporting polysomnography data from the client to the server and for receiving sleep stages in an interoperable fashion. The framework intelligently partitions the sleep staging task between the client and server in a way that multiple low-end clients can work with one server, and can be deployed both locally as well as over the cloud. The framework was tested on four datasets comprising ≈1700 polysomnography records (≈12000 hr of recordings) collected from adolescents, young, and old adults, involving healthy persons as well as those with medical conditions. We used two independent validation datasets: one comprising patients from a sleep disorders clinic and the other incorporating patients with Parkinson's disease. Using this system, an entire night's sleep was staged with an accuracy on par with expert human scorers but much faster (≈5 s compared with 30-60 min). To illustrate the utility of such real-time sleep staging, we used it to facilitate the automatic delivery of acoustic stimuli at targeted phase of slow-sleep oscillations to enhance slow-wave sleep.

Many women experience sleep problems during pregnancy. This includes difficulty initiating and maintaining sleep due to physiologic changes that occur as pregnancy progresses, as well as increased symptoms of sleep-disordered breathing (SDB). Growing evidence indicates that sleep deficiency alters glucose metabolism and increases risk of diabetes. Poor sleep may exacerbate the progressive increase in insulin resistance that normally occurs during pregnancy, thus contributing to the development of maternal hyperglycemia. Here, we critically review evidence that exposure to short sleep duration or SDB during pregnancy is associated with gestational diabetes mellitus (GDM). Several studies have found that the frequency of GDM is higher in women exposed to short sleep compared with longer sleep durations. Despite mixed evidence regarding whether symptoms of SDB (e.g., frequent snoring) are associated with GDM after adjusting for BMI or obesity, it has been shown that clinically-diagnosed SDB is prospectively associated with GDM. There are multiple mechanisms that may link sleep deprivation and SDB with insulin resistance, including increased levels of oxidative stress, inflammation, sympathetic activity, and cortisol. Despite emerging evidence that sleep deficiency and SDB are associated with increased risk of GDM, it has yet to be demonstrated that improving sleep in pregnant women (e.g., by extending sleep duration or treating SDB) protects against the development of hyperglycemia. If a causal relationship can be established, behavioral therapies for improving sleep can potentially be used to reduce the risk and burden of GDM.

Dividing attention across two tasks performed simultaneously usually results in impaired performance on one or both tasks. Most studies have found no difference in the dual-task cost of dividing attention in rested and sleep-deprived states. We hypothesized that, for a divided attention task that is highly cognitively-demanding, performance would show greater impairment during exposure to sleep deprivation. A group of 30 healthy males aged 21-30 years was exposed to 40 h of continuous wakefulness in a laboratory setting. Every 2 h, subjects completed a divided attention task comprising 3 blocks in which an auditory Go/No-Go task was 1) performed alone (single task); 2) performed simultaneously with a visual Go/No-Go task (dual task); and 3) performed simultaneously with both a visual Go/No-Go task and a visually-guided motor tracking task (triple task). Performance on all tasks showed substantial deterioration during exposure to sleep deprivation. A significant interaction was observed between task load and time since wake on auditory Go/No-Go task performance, with greater impairment in response times and accuracy during extended wakefulness. Our results suggest that the ability to divide attention between multiple tasks is impaired during exposure to sleep deprivation. These findings have potential implications for occupations that require multi-tasking combined with long work hours and exposure to sleep loss.

Chromatic pupillometry is an emerging method for evaluating ocular health that relies upon the differential stimulation of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it has been investigated in conditions affecting the outer or inner retina, there is a paucity of studies in conditions where the anterior chamber of the eye is affected. Primary angle closure suspects (PACS) are defined as eyes with narrow anterior chamber angles and intact retina. PACS patients are at risk of developing primary angle closure glaucoma and are prophylactically treated by performing laser peripheral iridotomy (LPI). Here we evaluated pupillary responses to monchromatic lights in 18 PACS before and after LPI, and compared the results with those of 36 age-matched controls who had gonioscopically open angles. Dose response curves for pupillary constriction were similar between PACS patients and controls (p = 0.98 for blue and 0.90 for red light) and within subjects pre- and post-LPI (p = 0.58 for blue and 0.20 for red light). Baseline-adjusted pupillary constriction responses to blue and red lights were similar in controls and PACS, and not altered after LPI. Our findings suggest that narrow irido-corneal angles and LPI do not influence pupillary responses in PACS.

Study Objectives: To investigate the temporal evolution of sleep EEG changes in adolescents across two cycles of sleep restriction and recovery simulating an intense school week and to examine the effect of an afternoon nap on nocturnal sleep., Methods: A parallel-group design, quasi-laboratory study was conducted in a student hostel. Fifty-seven adolescents (31 males, age = 15-19 years) were randomly assigned to nap or no nap groups. Participants underwent a 15-day protocol comprising two sleep restriction (5-hour time-in-bed [TIB]) and recovery (9-hour TIB) cycles. The nap group was also provided with a 1-hour nap opportunity at 14:00 following each sleep restriction night. Polysomnography recordings were obtained on nine nights and five nap episodes., Results: Naps reduced homeostatic sleep pressure on sleep restriction nights as evidenced by longer N2 latency and reduced total sleep time (TST), sleep efficiency (SE), and slow wave energy. Sleep debt accumulated in both groups, evidenced by increased TST, greater SE, and reduced wake after sleep onset on recovery compared to baseline nights. Changes were greater in the no nap group. Recovery sleep after the first cycle of sleep restriction did not restore sleep architecture to baseline in either group. SE, rapid eye movement (REM), and non-REM sleep increased, and N2 latency was reduced in the second sleep restriction period., Conclusions: Changes in sleep EEG induced by sleep restriction to 5-hour TIB for five nights were not eliminated after two nights of 9-hour recovery sleep. An afternoon nap helped but residual effects on the sleep EEG suggest that there is no substitute for adequate nocturnal sleep., (© Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].)

With aging, less blue light reaches the retina due to gradual yellowing of the lens. This could result in reduced activation of blue light-sensitive melanopsin-containing retinal ganglion cells, which mediate non-visual light responses (e.g., the pupillary light reflex, melatonin suppression, and circadian resetting). Herein, we tested the hypothesis that older individuals show greater impairment of pupillary responses to blue light relative to red light. Dose-response curves for pupillary constriction to 469-nm blue light and 631-nm red light were compared between young normal adults aged 21-30 years (n = 60) and older adults aged ≥50 years (normal, n = 54; mild cataract, n = 107; severe cataract, n = 18). Irrespective of wavelength, pupillary responses were reduced in older individuals and further attenuated by severe, but not mild, cataract. The reduction in pupillary responses was comparable in response to blue light and red light, suggesting that lens yellowing did not selectively reduce melanopsin-dependent light responses. Compensatory mechanisms likely occur in aging that ensure relative constancy of pupillary responses to blue light despite changes in lens transmission.

PurposeAutosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore.Patients and methodsPreliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene.ResultsAmong 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA.ConclusionWe report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing 'ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.

Study Objectives: To characterize adolescents' neurobehavioral changes during two cycles of restricted and recovery sleep and to examine the effectiveness of afternoon naps in ameliorating neurobehavioral deficits associated with multiple nights of sleep restriction., Methods: Fifty-seven healthy adolescents (aged 15-19 years; 31 males) participated in a parallel group study. They underwent two cycles of sleep restriction (5-hr time in bed [TIB] for five and three nights in the first and the second cycles, respectively; 01:00-06:00) and recovery (9-hr TIB for two nights per cycle; 23:00-08:00) intended to simulate the weekday sleep loss and weekend attempt to "catch up" on sleep. Half of the participants received a 1-hr nap opportunity at 14:00 following each sleep-restricted night, while the other half stayed awake. Sustained attention, sleepiness, speed of processing, executive function, and mood were assessed 3 times each day., Results: Participants who were not allowed to nap showed progressive decline in sustained attention that did not return to baseline after two nights of recovery sleep. Exposure to the second period of sleep restriction increased the rate of vigilance deterioration. Similar patterns were found for other neurobehavioral measures. Napping attenuated but did not eliminate performance decline. These findings contrasted with the stable performance of adolescents, given 9-hr TIB each night in our recent study., Conclusions: Adolescents' neurobehavioral functions may not adapt to successive cycles of sleep curtailment and recovery. In sleep-restricted adolescents, weekend "catch-up sleep," even when combined with napping during weekdays, is inferior to receiving a 9-hr sleep opportunity each night., (© Sleep Research Society 2016. Published by Oxford University Press [on behalf of the Sleep Research Society].)

Photic stimulation of rods, cones and intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) mediates non-visual light responses, including entrainment of circadian rhythms and pupillary light reflex. Unlike visual responses to photic stimulation, the cerebral correlates of non-visual light responses in humans remains elusive. In this study, we used functional magnetic resonance imaging (fMRI) in 14 healthy young participants, to localize cerebral regions which are differentially activated by metameric light that gave rise to different levels of melanopic excitation. Mean blood oxygen-level dependent (BOLD) responses disclosed bilateral activation of the frontal eye fields during exposure to light geared towards melanopsin. Furthermore, multivariate pattern analyses showed distinct bilateral pattern activity in the inferior temporal gyri and the caudate nuclei. Taken together, our findings suggest that melanopsin-based photoreception activates a cerebral network including frontal regions, classically involved in attention and ocular motor responses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objectives: To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population., Methods: A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26-28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75-g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State-Trait Anxiety Inventory score)., Results: In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66)., Conclusions: During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM., (© Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: Adolescents and adults who are evening-types exhibit shorter sleep duration and more sleep problems than individuals with an earlier chronotype. We hypothesized that already at a preschool age, evening-types would exhibit more sleep problems relative to children who are morning or intermediate chronotypes. The aim of this study was to examine the association between chronotype and sleep problems among preschool children., Methods: We studied a subset of typically-developing 4.5-year-olds taking part in the Growing Up in Singapore Towards healthy Outcomes birth cohort study (n = 244). The Children's Chronotype Questionnaire (CCTQ) was used to categorize children into morning-, intermediate-, and evening-types. Sleep problems were measured using the Children's Sleep Habits Questionnaire (CSHQ), with higher scores corresponding to greater sleep problems. The relation between chronotype, sleep-wake timing, and nocturnal sleep time was also evaluated in a subsample of 117 children using actigraphy recordings with parent-reported sleep diaries., Results: After controlling for potential confounders (maternal education, child's sex, birth order, and ethnicity), a significant main effect of chronotype on sleep problems was observed, in which evening-types exhibited greater CSHQ scores compared to morning- and intermediate-types (all p < 0.001). Actigraphy data in the subsample confirmed that evening-types had later bedtimes (p < 0.001) and get-up times (p = 0.02) during weekdays and weekends, but shorter nocturnal sleep time (p = 0.034) only during weekdays, compared to children who had earlier chronotypes., Conclusions: In preschool children, sleep problems were greater in evening-types compared to morning- and intermediate-types, suggesting that chronotype could be a contributing factor to sleep disturbances in early childhood., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Associations among personality, diurnal preference, and circadian phase were investigated using a constant routine laboratory protocol. One hundred and sixty-eight healthy participants aged 18-30 years (Women n = 68) completed either a 30- or 50-hour constant routine under dim-light conditions (<3 lux), during which circadian phase was measured from core body temperature and melatonin. Prior to laboratory admission, self-report measures of personality and diurnal preference were also obtained. The personality trait of Constraint correlated positively with morning diurnal preference and earlier circadian phase, with circadian phase partially mediating the relationship between Constraint and diurnal preference. No other personality variables correlated with circadian phase. Sex was an important covariate in several of the relationships investigated due to lower levels of Constraint and later CBT phase amongst men and was thus controlled for in all relevant analyses. Findings from this highly controlled study are consistent with previous field research in suggesting that earlier circadian phase is associated with the personality trait of Constraint.

The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

Study Objectives: The ability to recall facts is improved when learning takes place at spaced intervals, or when sleep follows shortly after learning. However, many students cram for exams and trade sleep for other activities. The aim of this study was to examine the interaction of study spacing and time in bed (TIB) for sleep on vocabulary learning in adolescents., Methods: In the Need for Sleep Study, which used a parallel-group design, 56 adolescents aged 15-19 years were randomly assigned to a week of either 5 h or 9 h of TIB for sleep each night as part of a 14-day protocol conducted at a boarding school. During the sleep manipulation period, participants studied 40 Graduate Record Examination (GRE)-type English words using digital flashcards. Word pairs were presented over 4 consecutive days (spaced items), or all at once during single study sessions (massed items), with total study time kept constant across conditions. Recall performance was examined 0 h, 24 h, and 120 h after all items were studied., Results: For all retention intervals examined, recall of massed items was impaired by a greater amount in adolescents exposed to sleep restriction. In contrast, cued recall performance on spaced items was similar between sleep groups., Conclusions: Spaced learning conferred strong protection against the effects of sleep restriction on recall performance, whereas students who had insufficient sleep were more likely to forget items studied over short time intervals. These findings in adolescents demonstrate the importance of combining good study habits and good sleep habits to optimize learning outcomes., (© 2016 Associated Professional Sleep Societies, LLC.)

Purpose: To determine the ocular anatomical factors influencing the pupillary light reactions to different wavelengths of light, measured with chromatic pupillometry., Methods: Community-based, cross-sectional study including subjects with normal ocular health (ages 50-79 years). Direct pupillary responses to continuously increasing irradiances (6.8 to 13.8 log photons cm(-2) s(-1)) of red (631 nm) and blue (469 nm) light were measured, using a dedicated infrared pupillometer. All subjects underwent swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) and noncontact partial coherence laser interferometry (Lenstar LS900, Haag-Streit AG, Switzerland). Univariate and multivariable regression analyses were performed to determine the anatomical features influencing pupillographic parameters., Results: Among the 177 included subjects, 167 (94.4 %) were Chinese and 116 (65.5 %) female. The average baseline pupil diameter in darkness (β = -0.080, p < 0.001) and the amplitude of the relative pupillary constriction (β = -0.233, p = 0.006) to blue light decreased with age. The amplitude of pupillary constriction was significantly larger in patients with a thinner iris, in response to stimulation with blue (β = -0.321, p < 0.001) and red light (β = -0.336, p < 0.001). Other ocular parameters (i.e., lens vault, anterior chamber depth width, iris volume, iris curvature, and lens thickness) were not significantly associated with pupillometric outcomes., Conclusions: The amplitude of the pupillary light constriction to chromatic photic stimuli is reduced with increasing age and iris thickness in subjects with normal ocular health, a finding which needs to be integrated into future pupillometric studies.

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)