Midpoint Of Sleep Research Articles

Assessment of MTNR1B Type 2 Diabetes Genetic Risk Modification by Shift Work and Morningness-Eveningness Preference in the UK Biobank

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.

Effect of maternal sleep in late pregnancy on leptin and lipid levels in umbilical cord blood

ObjectivesTo study the impact of maternal sleep in late pregnancy on birth weight (BW) and leptin and lipid levels in umbilical cord blood. Study designA total of 277 healthy and singleton pregnancy women were recruited for participation in the Shanghai Sleep Birth Cohort Study (SSBC) during their 36–38 weeks of pregnancy, from May 2012 to July 2013. Maternal night sleep time (NST), sleep efficiency (SE), sleep onset latency (SOL) and the percentage of wake after sleep onset (WASO) in NST and midpoint of sleep (MSF) were measured by actigraphy for seven consecutive days. The leptin and lipid levels were determined in cord blood samples collected from the umbilical vein immediately after delivery. Birth information (birth weight, gender, delivery type, etc.) was extracted from medical records. A multivariable linear regression model was applied to examine the effect of maternal sleep in late pregnancy on newborn leptin and lipid levels in umbilical cord blood. ResultsA total of 177 women and their infants were included in the analysis. Maternal mean NST was 7.03 ± 1.10 h in late pregnancy, and 48% had a shorter sleep time (NST < 7 h). The average maternal SE was 72.54% ± 9.66%. The mean percentage WASO/NST was 21.62% ± 9.98%; the average MSF was about 3:34 (0:53); and the SOL was 46.78 ± 36.00 min. After adjustment for confounders, both maternal NST and SE were found to be significantly associated with triglyceride levels (β = −0.219, p = 0.006; β = −0.224, p = 0.006) in umbilical cord blood; and maternal NST was also observed to have positive association with newborn leptin levels (β = 0.146, p = 0.047). However, we did not find significant association between other maternal sleep parameters in late pregnancy and leptin and lipid levels and birth weight. ConclusionsShort sleep duration and poor sleep quality during late pregnancy were associated with newborn leptin and lipid levels, and efforts on improving maternal sleep during late pregnancy should be advocated for children's health.

Higher Rates of Sleep Disturbance Among Offspring of Parents With Recurrent Depression Compared to Offspring of Nondepressed Parents.

Youth who have a parent with recurrent depression are at high risk for mental health problems. There is a need to identify transdiagnostic and clinically actionable mechanisms that explain higher rates of psychopathology among high-risk youth. The present study sought to examine whether offspring of depressed parents exhibit greater parent- and self-reported sleep disturbance, shorter sleep duration, and later sleep midpoint compared to youth without any parental psychopathology. Participants included 82 youth, including 41 youth (ages 9-13; mean age = 11.07 years; 46% female) deemed to be at high-risk based on having a parent with a recurrent depression history, and 41 (mean age = 11.16 years; 49% female) at low-risk based on having parents without any history of psychopathology. Youth and their parents completed measures of youth sleep disturbance, and youth completed measures of sleep duration and midpoint using a daily sleep diary for 9 days. Offspring of parents with depression exhibited more sleep disturbance (e.g., problematic nighttime behaviors and daytime sleepiness) than low-risk youth as reported by both parents and youth. For parent-reported sleep disturbance, there were also sex differences. High-risk girls had more sleep disturbance than high-risk boys or low-risk girls. There were no group differences for daily sleep duration and midpoint. Sleep disturbance may be an important area for assessment among offspring of parents with depression. Our findings highlight one potential transdiagnostic risk factor that may emerge among high-risk youth, and sex-specific differences in sleep disturbance, which have implications for prevention and intervention.

The erythrocyte membrane stability is associated with sleep time and social jetlag in shift workers.

The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile.

Chronotype, Social Jet Lag, and Cardiometabolic Risk Factors in Early Adolescence

Inadequate sleep duration and quality increase the risk of obesity. Sleep timing, while less studied, is important in adolescents because increasing evening preferences (chronotypes), early school start times, and irregular sleep schedules may cause circadian misalignment. To investigate associations of chronotype and social jet lag with adiposity and cardiometabolic risk in young adolescents. Starting in 1999, Project Viva recruited pregnant women from eastern Massachusetts. Mother-child in-person visits occurred throughout childhood. From January 23, 2012, to October 16, 2016, 804 adolescents aged 12 to 17 years completed 5 days or more of wrist actigraphy, questionnaires, and anthropometric measurements. A cross-sectional analysis using these data was conducted from April 31, 2018, to May 1, 2019. Chronotype, measured via a continuous scale with higher scores indicating greater evening preferences, and social jet lag, measured as the continuous difference in actigraphy sleep midpoint in hours from midnight on weekends vs weekdays, with higher values representing more delayed sleep timing on weekends. Adiposity, measured via anthropometry and dual-energy x-ray absorptiometry. For a subset of 479 adolescents with blood samples, cardiometabolic risk scores were computed as the mean of 5 sex- and cohort-specific z scores for waist circumference, systolic blood pressure, inversely scaled high-density lipoprotein cholesterol, and log-transformed triglycerides and homeostatic model of insulin resistance. Among the 804 adolescents in the study, 418 were girls and 386 were boys, with a mean (SD) age of 13.2 (0.9) years. In multivariable models adjusted for age, puberty, season, and sociodemographics, associations of chronotype and social jet lag with adiposity varied by sex. For girls, greater evening preference was associated with a 0.58-cm (95% CI, 0.12-1.03 cm; P = .04 for interaction) higher waist circumference and 0.16 kg/m2 (95% CI, 0.01-0.31 kg/m2; P = .03 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry; each hour of social jet lag was associated with a 1.19-cm (95% CI, 0.04-2.35 cm; P = .21 for interaction) higher waist circumference and 0.45 kg/m2 (95% CI, 0.09-0.82 kg/m2; P = .01 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry. Associations of social jet lag and evening chronotypes persisted for many measures of adiposity after adjustment for sleep duration and other lifestyle behaviors. By contrast, no associations were observed in boys. There were no associations with the cardiometabolic risk score for either sex, although statistical power was low for this outcome. Evening chronotypes and social jet lag were associated with greater adiposity in adolescent girls but not adolescent boys. Interventions aimed at improving sleep schedules may be useful for obesity prevention, especially in girls.

Later sleep timing is associated with an increased risk of preterm birth in nulliparous women

Although uterine contractions have a diurnal periodicity and increase in frequency during hours of darkness, data on the relationship between sleep duration and sleep timing patterns and preterm birth are limited. We sought to examine the relationship of self-reported sleep duration and timing in pregnancy with preterm birth. In the prospective Nulliparous Pregnancy Outcome Study: Monitoring Mothers-to-be cohort, women completed a survey of sleep patterns at 6-13 weeks gestation (visit 1) and again at 22-29 weeks gestation (visit 3). Additionally, at 16-21 weeks gestation (visit 2), a subgroup completed a weeklong actigraphy recording of their sleep. Weekly averages of self-reported sleep duration and sleep midpoint were calculated. A priori, sleep duration of <7 hours was defined as "short," and sleep midpoint after 5 am was defined as "late." The relationships among these sleep characteristics and all preterm birth and spontaneous preterm birth at <37 weeks gestation were examined in univariate analyses. Multivariable logistic regressions that controlled for age and body mass index alone (model 1) and with additional covariates (race, smoking, insurance, and employment schedule) following a backward elimination process (model 2) were performed. Of the 10,038 women who were enrolled, sleep survey data were available on 7524 women at visit 1 and 7668 women at visit 3. The rate of short sleep duration was 17.1% at visit 1 and 20.7% at visit 3. The proportion with a late sleep midpoint was 11.6% at visit 1 and 12.2% at visit 3. There was no significant relationship between self-reported short sleep and preterm birth across all visits. However, self-reported late sleep midpoint (>5 am) was associated with preterm birth . Women with a late sleep midpoint (>5 am) in early pregnancy had a preterm birth rate of 9.5%, compared with 6.9% for women with sleep midpoint ≤5 am (P=.005). Similarly, women with a late sleep midpoint had a higher rate of spontaneous preterm birth (6.2% vs 4.4%; P=.019). Comparable results were observed for women with a late sleep midpoint at visit 3 (all preterm birth 8.9% vs 6.6%; P=.009; spontaneous preterm birth 5.9% vs 4.3%; P=.023). All adjusted analyses on self-reported sleep midpoint (models 1 and 2) maintained statistical significance (P<.05), except for visit 1, model 2 for spontaneous preterm birth (P=.07). The visit 2 objective data from the smaller subgroup (n=782) demonstrated similar trends in preterm birth rates by sleep midpoint status. Self-reported late sleep midpoint in both early and late pregnancy, but not short sleep duration, is associated with an increased rate of preterm birth.

An epidemiological study of sleep−wake timings in school children from 4 to 11 years old: insights on the sleep phase shift and implications for the school starting times' debate

ObjectiveIt has been assumed that during adolescence there is a strong shift toward eveningness chronotype, whereas children's sleep is relatively stable. Several studies have focused on the conflict between school start times and adolescents' circadian rhythms; however, fewer studies have been conducted in younger children. The aim of this study was to examine sleep durations, schedules, and sleep phase shift in preschool- and school-aged children. MethodsData for sleep patterns on school days and free days (ie, days when children's sleep−wake patterns were free from any influence of individual or family activities) was obtained by means of questionnaires (Children ChronoType Questionnaire) for 3155 Portuguese children 4–11 years of age. ResultsAs children grew older and school grade level increases, we found later bedtimes and sleep onsets on both school days and free days; and later wake times only on free days. By contrast, wake times were progressively earlier, imposed by school start times. There was a progressive reduction in the amount of sleep on school nights as grade level increased. Greater social jetlag, later midpoint of sleep, and higher restriction−extension patterns were found across age groups. ConclusionThe displacement of bed and wake times for later hours on free days starts at an early age. Changing early school start times could adjust social demands to the biological rhythm of children.

Using big data to explore worldwide trends in objective sleep in the transition to adulthood

BackgroundDevelopment induces changes in sleep, and its duration has been reported to change as a function of aging. Additionally, sleep timing is a marker of pubertal maturation, where during adolescence, the circadian rhythm shifts later. Typically, this is manifested in a later sleep onset in the evening and later awakening in the morning. These changes across development seem to be universal around the world but are unlikely to persist into adulthood. MethodsThis study utilized accelerometer data from 17,355 participants aged 16–30 years (56% female) measured by validated Polar wearables over a 14-day period. We compared sleep duration, chronotype (sleep midpoint) and weekend catch-up (ie, social jetlag) sleep across ages and regions over 242,948 nights. ResultsThe data indicate a decline in sleep duration as well as a dramatic shift in sleep onset times throughout adolescence. This continues well into early adulthood and stabilizes nearer age 30. Differences in sleep duration across ages were significant, and ranged from 7:53 h at age 16 to 7:29 h at age 30 in the sample. Additionally, there was a clear difference between females and males throughout adolescence and young adulthood: girls had longer sleep duration and earlier timed sleep in the current study. Differences in sleep were found between regions across the world, and across European areas. ConclusionsBoth sleep duration and sleep timing go through a clear developmental pattern, particularly in early adulthood. Females had an earlier sleep midpoint and obtained more sleep. Regional differences in sleep occurred across the world.

Behavioral Predictors of Weight Regain in Postmenopausal Women: Exploratory Results From the Breast Cancer and Exercise Trial in Alberta.

ObjectiveThis secondary analysis assessed associations between changes in energy balance and sleep behaviors and the risk of weight regain following exercise‐induced weight loss.MethodsOf 400 participants initially randomized in the Breast Cancer and Exercise Trial in Alberta (BETA), 227 lost weight following the moderate‐ to vigorous‐intensity exercise intervention (−4.2 ± 3.6 kg) and were included in this analysis. Self‐reported energy intake (EI), sleep duration, quality and timing, and objective measurements of physical activity (PA) and sedentary time were collected at the end of the intervention and the end of follow‐up. Linear regression models assessed associations between changes in these behaviors and risk of weight regain during follow‐up.ResultsParticipants regained 43% of the weight lost during follow‐up. Reductions in moderate to vigorous PA (β = −1.00; 95% CI = −1.74 to −0.25 h/d; P = 0.01) and steps per day (β = −0.0003; 95% CI = −0.0005 to −0.0001 steps/d; P = 0.004); increases in sedentary time (β = 0.54; 95% CI = 0.67 to 1.02 h/d; P = 0.03), EI (β = 0.001; 95% CI = 0.0003 to 0.002 kcal; P = 0.01), and fat intake (β = 0.004; 95% CI = 0.001 to 0.006 kcal; P = 0.002); and delayed sleep timing midpoint (β = 0.02; 95% CI = 0.004 to 0.03 min; P = 0.01) were associated with weight regain during follow‐up.ConclusionsThese exploratory results suggest that reductions in moderate to vigorous PA; increases in EI, fat intake, and sedentary time; and delayed sleep timing midpoint were significantly associated with risk of weight regain.

Social Jet-Lag in Tertiary Students Following a Modern Curriculum with Few Time-Tabled Contact Hours: A Pilot Study.

Social jet-lag (SJL) impairs academic performance, specifically for late chronotypes faced with early start times. Most modern tertiary educational systems have fewer time-tabled contact hours and consequently fewer early starts, which may limit SJL. We performed a pilot study of SJL in a convenience sample of students from Maastricht University, where problem-based learning (PBL) is implemented throughout the curricula. PBL is a modern curriculum, with only few contact hours and student-driven learning, comprising substantial amounts of self-study. Fifty-two students kept a detailed sleep diary for one week, and completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Participants were divided into early and late sleepers based on a ranking of their reported sleeping times, combined with a single question on their self-reported chronotype. Late sleepers (for brevity: “Owls”; n = 22) had later midpoint-sleep (5:14 ± 0:11 on weekdays; 5:50 ± 0:07 on weekend days) than early sleepers (for brevity: “Larks”; n = 11, 3:21 ± 0:05 on weekdays; 3:41 ± 0:06 on weekend days, F = 10.8, p = 0.003). The difference between the midpoint of sleep on weekdays and weekend days was comparable for Larks and Owls (F = 1.5; p = 0.22). SJL (0:53 ± 0:06, T = 1.4; p = 0.16), total sleep duration (7:58 ± 0:08; p = 0.07), and PSQI score (4.7 ± 0.3, U = 137; p = 0.56) were comparable for Larks and Owls. Average ESS score was higher in Larks (10.7 ± 0.96) than in Owls (7.0 ± 0.72; U = 52; p = 0.007). Within this pilot study of students engaged in a problem-based learning curriculum, Owls have no selective disadvantage compared to Larks concerning sleep.

A survey on social jetlag in Japan: a nationwide, cross-sectional internet survey

Misalignment between an individual’s circadian phase and his/her environment due to social imposition is called social jetlag (SJL). SJL has emerged as a public health concern, as it contributes to an unhealthy lifestyle and adverse health outcomes. This study aimed to elucidate the percentage of SJL in a large Japanese population using the Japanese version of the Munich ChronoType Questionnaire (MCTQ). A total of 10,000 participants responded to a web-based cross-sectional survey, and the final sample comprised 3708 participants (60.1% male; average age 45.1 [SD 13.4] years). SJL was measured by subtracting each participant’s midpoint of sleep on workdays from their midpoint of sleep on free days. The average [SD] absolute SJL (SJLabs) value was 0.91 [0.89] hours, and the percentage of participants with SLJabs of more than 1 h was 40.1%. Our data also showed that SJLabs becomes progressively smaller with advancing age. A considerable number of participants of our Japanese population showed differences in sleep behavior between workdays and free days. Young people in particular commonly oversleep on free days to compensate for the sleep debt accumulated over the workweek because of their late chronotype.

A Comparison of Physical Activity Behaviors and Sleep in Female NCAA Division-I Athletes versus Controls

Physical activity behaviors and sleep patterns influence health in the general population but have not been evaluated in collegiate student athletes. For these individuals the demands of academics and athletics alter these parameters but have not been fully characterized or compared to students who are not collegiate athletes. PURPOSE: This study compared physical activity (PA) behaviors and sleep patterns of female NCAA D I student-athletes (Athletes) to recreationally active female students (Controls). METHODS: Across three consecutive semesters, subjects were recruited for one to three weeks of monitoring. Sleep was monitored with Actiwatches. PA was monitored using ActivPals. Forty-five females were recruited from the University of Colorado, Boulder. Athletes were recruited from the Golf (n=6) and Tennis teams (n=8). Controls were recruited from the general student body (n=31). Subjects were instructed to wear devices at all times except during competitions. Travel days and days with less than 90% waking wear time were removed from analysis. Time spent in Sedentary (SED), Low Intensity (LIT) and Moderate-Vigorous Physical Activity (MVPA) are presented as percent of waking day. RESULTS: Mean days recorded per individual was: Controls 15.1; golf 10.2; and tennis 15. Compared to Controls, Athletes had higher daily step counts (12,040 ± 6498 vs 8,992 ± 5240, p<.01), less SED (63.5±15.0 vs 71.4±13.3, p<.05), higher LIT (26.4 ± 12.9 vs 21±10.8, p<.05)) and higher MVPA (9.7 ± 3 vs 7.6 ± 3.3, p<.01). For both groups, weekends had higher LIT (+3.0%, p<.01), decreased MVPA (-.75%, p<.05), and a trend toward decreased SED (-2.3%, p=.0563) compared to weekdays. There were no differences in PA between Golf and Tennis. Sleep was not significantly different in Athletes versus Controls, including duration of sleep (07:04 ± 00:49 vs 7:32 ± 00:42, p=.6) and sleep midpoint. Yet, midpoint was significantly later on weekends vs. weekdays in both groups (04:35 ± 01:01 vs 04:03 ± 00:55, p<.01) CONCLUSION: Female Athletes had higher physical activity demands than Controls. Yet both groups, on average, slept only slightly more than the American Academy of Sleep Medicine recommended 7-hours. This may negatively impact overall health. Research is needed on how these sleep and activity behaviors influence academic and athletic outcomes.

Adolescent Beverage Intake in Relation to Actigraphy-assessed Sleep Duration, Timing, and Fragmentation (P18-100-19)

ObjectivesTo examine whether usual beverage intake was associated with sleep timing, duration, and fragmentation among adolescents. MethodsThe study population included 528 Mexico City adolescents enrolled in a longitudinal study. Beverage intake over the last week was assessed with a food frequency questionnaire. The following beverage groups were analyzed: milk, sweetened milk, regular soda, coffee/tea, 100% fruit juice, commercial fruit juice with sugar, fruit drink/flavored water with sugar, and plain water. Sleep timing, duration, and fragmentation were assessed with 7-day actigraphy. Overall and sex-stratified linear regression was conducted with sleep characteristics as separate outcomes and quantiles of energy-adjusted beverage intake as exposures, accounting for sex, age, maternal education, physical activity, and smoking. ResultsThe mean age (SD) was 14.4 (2.1) years; 48% were male. The most commonly consumed drinks were water, milk, soda, and fruit juice with added sugar (energy-adjusted mean = 666 (557) mL per day, 360 (278) mL per day, 225 (251) mL per day and 203 (263) mL per day, respectively). In overall regression analysis, soda was associated with later sleep timing; those in the 4th (highest) quartile of soda consumption had a 19 minute later weekday sleep timing than those in the lowest quartile [95% CI 1, 37]. Among boys, milk and water consumption were each associated with longer weekday sleep duration (25 [1, 48] and 26 [4, 47] more minutes, respectively in the 4th compared to the 1st quartile); and higher 100% fruit juice consumption was related to earlier weekday sleep timing (−22 [−28, 1] minutes in the 1st compared to the last quantile; P trend = 0.03). Among girls, soda was associated with higher sleep fragmentation (1.6 [0.4, 2.8] % in the 4th compared to the 1st), and coffee/tea consumption was related to shorter weekend sleep duration (−23 [−44, −2] minutes in the 4th compared to the 1st). ConclusionsHigher soda intake was associated with later sleep midpoint in boys and girls, while other beverages were associated with sleep in a sex-specific manner. Among girls, adverse associations with sleep were observed for caffeinated drinks only, while boys with higher consumption of water, milk, and natural juice had evidence of healthier sleep. Funding SourcesNIH/NIEHS, EPA.

Validation of the Mobile App-Recorded Circadian Rhythm by a Digital Footprint.

BackgroundModern smartphone use is pervasive and could be an accessible method of evaluating the circadian rhythm and social jet lag via a mobile app.ObjectiveThis study aimed to validate the app-recorded sleep time with daily self-reports by examining the consistency of total sleep time (TST), as well as the timing of sleep onset and wake time, and to validate the app-recorded circadian rhythm with the corresponding 30-day self-reported midpoint of sleep and the consistency of social jetlag.MethodsThe mobile app, Rhythm, recorded parameters and these parameters were hypothesized to be used to infer a relative long-term pattern of the circadian rhythm. In total, 28 volunteers downloaded the app, and 30 days of automatically recorded data along with self-reported sleep measures were collected.ResultsNo significant difference was noted between app-recorded and self-reported midpoint of sleep time and between app-recorded and self-reported social jetlag. The overall correlation coefficient of app-recorded and self-reported midpoint of sleep time was .87.ConclusionsThe circadian rhythm for 1 month, daily TST, and timing of sleep onset could be automatically calculated by the app and algorithm.

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke

BackgroundThe time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging.MethodsWe conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline.ResultsAfter 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P=0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P=0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days.ConclusionsAmong the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.)

0027 Adolescent Sleep Timing And Dietary Patterns In Relation To Dna Methylation Of Core Clock Genes

Abstract Introduction Mistimed sleep/wake and eating patterns put adult shift workers at increased risk for chronic disease, and epigenetic modification of core clock genes has been proposed as a mechanism. Although not as extreme as shift workers, adolescents often have delayed sleep timing. Our aim was to assess whether sleep midpoints in adolescents are associated with DNA methylation of circadian genes. A secondary aim was to examine associations between dietary patterns and circadian gene methylation. Methods The study population included 142 Mexican youth (average age 14.0 (SD=2.0) years, 49% male) enrolled in a cohort study. Average sleep midpoint (between bed time and wake time) over 7 days was estimated with actigraphy. Diet was assessed with a semi-quantitative food frequency questionnaire, and three dietary patterns were derived from principal components analysis (a vegetable-based pattern, a meat and starch-based pattern, and a breakfast pattern). DNA methylation was quantified in blood leukocytes with the Infinium MethylatinEPIC BeadChip. We selected 166 loci (CpG sites) within CpG islands of core ‘clock’ genes known to regulate circadian rhythms (CLOCK, BMAL, PER1, PER2, PER3, CRY1, CRYI2, RORA, RORB, REV-VERBA, REV-VERBB). Linear regression was used to analyze associations between sleep midpoint or dietary patterns and logit-transformed percent methylation at the 166 CpG sites. All models were adjusted for sex and age. Results The average midpoint was 3:41 AM (SD=1 hr 15 min); average bed time was 11:29 PM (SD=68 min) and average wake time was 7:53 AM (SD=97 min). Sleep midpoint was positively associated with DNA methylation of CpG sites from the genes REV-VERBA and RORB at the Bonferroni-corrected significance level of p&amp;lt;0.005. The breakfast dietary pattern (rich in eggs, milk, and bread) was inversely associated with DNA methylation at RORA (P=0.003). Conclusion Sleep timing and dietary habits are associated with DNA methylation of core clock genes in adolescents. Epigenetic modification of clock genes could in part underlie relationships between sleep, diet, and metabolic health among adolescents. Support (If Any) Dr. Jansen is supported by the NIH/NHLBI grant 5T32HL110952-05.

The association of sleep with metabolic pathways and metabolites: evidence from the Dietary Approaches to Stop Hypertension (DASH)-sodium feeding study.

Sleep is increasingly being viewed as an issue of public health concern, yet few epidemiologic studies have explored associations between sleep habits and metabolomic profile. To assess the association between sleep and blood metabolites. We examined the association between sleep and 891 fasting plasma metabolites in a subgroup of 106 participants from the Dietary Approaches to Stop Hypertension (DASH)-Sodium feeding trial (1997-1999). We produced two sleep variables to analyze, sleep midpoint (median time between bedtime and waketime) and sleep duration, as well as bedtime and wake time. Metabolites were measured using liquid and gas chromatography, coupled with mass spectrometry. We assessed associations between sleep variables and log transformed metabolites using linear mixed-effects models. We combined the resulting p-values using Fisher's method to calculate associations between sleep and 38 metabolic pathways. Sixteen pathways were associated (p < 0.05) with midpoint. Only the γ-glutamyl amino acid metabolism pathway reached Bonferroni-corrected threshold (0.0013). Eighty-three metabolites were associated with midpoint (FDR < 0.20). Similar associations were found for wake time. Neither bed time nor duration were strongly associated. The top metabolites (pathways given in brackets) associated with sleep were erythrulose (advanced glycation end-product) (positive association) and several γ-glutamyl pathway metabolites, including CMPF (fatty acid, dicarboxylate), isovalerate (valine, leucine and isoleucine and fatty acid metabolism) and HWESASXX (polypeptide) (inverse association). Within our study, several metabolites that have previously been linked to inflammation and oxidative stress (processes involved in diseases such as cardiovascular disease and cancer) were found to be associated with sleep.

Associations between Sleep and Dietary Patterns among Low-Income Children Attending Preschool

BackgroundSleep disturbances and low-quality diets are prevalent among children in low-income settings, yet the nature of their relationship remains unclear. In particular, whether aspects other than sleep duration, including timing and quality, are associated with dietary patterns has rarely been examined, especially among preschool-aged children. ObjectiveTo evaluate whether nightly and total sleep duration, sleep timing, differences in timing and duration from weekdays to weekends, and sleep quality were related to dietary patterns. DesignA cross-sectional analysis of children attending preschool. Parents completed questionnaires about children’s sleep habits as well as a semiquantitative food frequency questionnaire. Participants/settingThree hundred fifty-four English-speaking children (49.9% boys) with no serious medical conditions aged 3 to 5 years who were enrolled in Head Start in Michigan (2009-2011) with complete information on sleep and diet. Main outcome measuresDietary pattern scores derived from food frequency questionnaire. Statistical analyses performedPrincipal component analysis was used to identify dietary patterns. Separate linear regression models with dietary pattern scores as the dependent variable and continuous sleep measures as independent variables were used to evaluate associations between sleep and diet, adjusting for sex, age, parent education level, and sleep hygiene. ResultsThree dietary patterns were identified: Vegetables, Healthy Proteins, and Sides; Breads and Spreads; and Processed and Fried. Longer average weekend sleep duration and a greater difference in weekend-to-weekday sleep duration was related to lower Vegetables, Healthy Proteins, and Sides pattern scores. Later sleep midpoint during weekdays was related to lower Vegetables, Healthy Proteins, and Sides pattern scores, whereas later sleep midpoint on the weekend was associated with higher Processed and Fried pattern scores. Similarly, a larger weekend–weekday midpoint difference was associated with higher Processed and Fried pattern scores. ConclusionsLater sleep timing and differences in sleep duration and timing from weekends to weekdays were related to less-optimal dietary pattern scores in young children.

Sex Moderates Relationships Among School Night Sleep Duration, Social Jetlag, and Depressive Symptoms in Adolescents

Social jetlag, a misalignment between sleep timing on the weekend and during the work week, is associated with depressive symptoms among adults across both sexes. A previous study found that later sleep timing was associated with depressive symptoms in women but not men. To date, however, no research has investigated whether the association between social jetlag and depression varies by sex among adolescents. The current study assessed self-reported sleep, depressive symptoms, and demographic information from 3058 adolescents (48% female, mean [SD] age 15.59 [0.77] years) from the age 15 wave of the Fragile Families and Child Wellbeing Study (FFCWS). Social jetlag was calculated as the absolute value of the midpoint of sleep on the weekend minus the midpoint of sleep during the school week. Depressive symptoms were measured through a modified 5-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). We assessed whether the associations among sleep duration on school nights, social jetlag, and depressive symptoms were similar between male and female adolescents using multiple linear regression. In fully adjusted models, sex moderated the association between school night total sleep time and depressive symptoms ( p < 0.001) and between social jetlag and depressive symptoms ( p = 0.037). In females, but not in males, school night total sleep time was negatively associated with depressive symptoms ( p < 0.001), whereas social jetlag ( p < 0.001) was positively and independently associated with depressive symptoms. The results indicate the importance of regular sleep timing across the week and adequate sleep duration for the maintenance of optimal emotional health among female adolescents.

Sleep Timing in Patients with Precocious and Delayed Pubertal Development.

Previous studies have reported a shift in the timing of sleep during adolescence toward a later time. To date, it is unclear whether hormonal changes during puberty might contribute to this change in sleeping behavior. We systematically assessed pubertal development and sleep timing in a cross-sectional case-control study in girls with precocious (n = 42) and boys with delayed pubertal development (n = 19). We used the Munich ChronoType Questionnaire and the Children’s ChronoType Questionnaire to assess sleep timing in patients and age- and sex-matched controls (n = 309) and used the midpoint of sleep on free days, corrected for potential sleep debt accumulated during the school week, as a marker for sleep timing. Compared to the controls, girls with central precocious puberty showed a delay in sleep timing of 54 min, and girls with premature pubarche slept on average 30 min later. Male adolescents with delayed pubertal development showed an average sleep midpoint that was 40 min earlier compared to the control group. The results of this pilot study suggest an association between pubertal onset and shifts in sleep timing, which is a novel finding in human sleep behavior. Prospective studies in larger cohorts will be needed to examine the robustness and generalizability of the findings.