Sleep tight! Adolescent sleep quality across three distinct sleep ecologies

Background and objectivesGood sleep quality, associated with few arousals, no daytime sleepiness and self-satisfaction with one’s sleep, is pivotal for adolescent growth, maturation, cognition and overall health. This article aims to identify what ecological factors impact adolescent sleep quality across three distinct sleep ecologies representing a gradient of dense urbanity to small, rural environments with scarce artificial lighting and no Internet.MethodologyWe analyze variation of sleep efficiency, a quantitative measure of sleep quality—defined as the ratio of total time spent asleep to total time dedicated to sleep—in two agricultural indigenous populations and one post-industrial group in Mexico (Campeche = 44, Puebla = 51, Mexico City = 50, respectively). Data collection included actigraphy, sleep diaries, questionnaires, interviews and ethnographic observations. We fit linear models to examine sleep efficiency variation within and between groups.ResultsWe found that sleep efficiency varied significantly across sites, being highest in Mexico City (88%) and lowest in Campeche (75%). We found that variation in sleep efficiency was significantly associated with nightly exposure to light and social sleep practices.Conclusions and implicationsOur findings point toward contextual cost-benefits of sleep disruption in adolescence. We highlight the need to prioritize research on adolescent sleep quality across distinct developmental ecologies and its impact on health to improve adolescent wellbeing through evidence-based health practices

Sleep deprivation among adolescents in urban and indigenous-rural Mexican communities

Comparing the nature of adolescent sleep across urban and more isolated, rural settings through an ecological, cross-cultural perspective represents one way to inform sleep nuances and broaden our understanding of human development, wellbeing and evolution. Here we tested the Social Jetlag Hypothesis, according to which contemporary, urban lifestyles and technological advances are associated with sleep insufficiency in adolescents. We documented the adolescent sleep duration (11–16 years old; X̅ = 13.7 ± 1.21; n = 145) in two small agricultural, indigenous and one densely urban context in Mexico to investigate whether adolescents in socio-ecologically distinct locations experience sleep deprivation. Sleep data was assembled with actigraphy, sleep diaries and standardized questionnaires. We employed multilevel models to analyze how distinct biological and socio-cultural factors (i.e., pubertal maturation, chronotype, napping, gender, working/schooling, access to screen-based devices, exposure to light, and social sleep practices) shape adolescent sleep duration. Results suggest that the prevalence of adolescent short sleep quotas is similar in rural, more traditional environments compared to highly urbanized societies, and highlight the influence of social activities on the expression of human sleep. This study challenges current assumptions about natural sleep and how adolescents slept before contemporary technological changes occurred

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results: Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions: SRD5A1/5α reductase-1 responds epigenetically to the environment and its down-regulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment, and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs

Population variation in ovarian function

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30638/1/0000280.pd

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome