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Children born via cesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. We conducted a meta-analysis of epigenome-wide association studies to examine the associations between delivery mode and blood DNA methylation at birth and its persistence in early childhood. Participants were from 19 pregnancy cohorts (9833 term newborns) and 6 pediatric cohorts (2429 children aged 6 to 10 years). We identified six CpGs in cord blood associated with cesarean delivery (effect size range: 0.4 to 0.7%, P < 1.0 × 10-7): MAP2K2 (cg19423175), LIM2 (cg01500140), CNP (cg13917614), BLM (cg18247172), RASA3 (cg22348356), and RUNX3 (cg20674490), independent of cell proportions and other confounders. In childhood, none of these CpGs were associated with cesarean delivery, and no additional CpGs were identified. Delivery mode was associated with cell proportions at birth but not in childhood. Further research is needed to elucidate cesarean deliverys molecular influence on offspring health.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR

Abstract Background Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation. Methods A total of 4487 mother–newborn pairs from 7 studies were included. Maternal night shift work during pregnancy was ascertained via questionnaires and harmonized into “any” versus “no”. DNA methylation was measured in cord blood using the Illumina Infinium Methylation arrays. Robust linear regression models adjusted for relevant confounders were run in the individual cohorts, and results were meta-analyzed. Results Maternal night shift work during pregnancy ranged from 3.4% to 26.3%. Three CpGs were differentially methylated in relation to maternal night shift work during pregnancy at a false discovery rate adjusted P

Abstract Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific or excessively broad relative to the underlying brain circuitry it seeks to elucidate. To address these concerns, we employ a latent variable approach using bifactor analysis. We examine 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with 6192 participants. A curated subset of 37 maps with a balanced representation of RDoC domains constitute the training set, and the remaining held-out maps form the internal validation set. External validation is conducted using 36 peak coordinate activation maps from Neurosynth, using terms of RDoC constructs as seeds for topic meta-analysis. Here, we show that a bifactor model incorporating a task-general domain and splitting the cognitive systems domain better fits the examined corpus of tfMRI data than the current RDoC framework. We also identify the domain of arousal and regulatory systems as underrepresented. Our data-driven validation supports revising the RDoC framework to reflect underlying brain circuitry more accurately.

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Introduction: Guns were one of the leading causes of death in children and youth aged 0–24 years in the U.S. over the last decade, with large variations by sex, race, region, and income. This paper examines the rates of gun involvement for a group of youth and young adults in the U.S. from ages 10 years to 34 years across major demographic and background factors. Methods: This is a cross-sectional nationally representative survey of participants recruited through an ongoing national research panel. Completed surveys were collected from 5,311 participants from September 2023 to January 2024. Results: Lifetime rates for carrying guns were 26.7%, gun violence victimization rates were 9.5%, and gun violence perpetration rates were 3.3%. High levels of past-year involvement with guns and gun violence were observed, with 13.9% carrying guns, gun violence victimization of 2.5%, and gun violence perpetration of 0.9%. Even more concerning, data indicate that 7.6% of the participants reported carrying a gun before age 18 years, 5.2% experienced gun violence victimization, and 1.8% perpetrated gun violence. Gun carrying and violence were higher by demographics, with a statistically significant difference for all demographic subgroups on at least 1 gun outcome. Conclusions: High levels of exposure to guns and gun violence are experienced among a nationally representative population of young Americans, with rates varying considerably by demographic factors. On the basis of these demographic disparities in gun involvement, more work is needed to address community and other risk and protective factors across different levels of the social ecology, such as structural inequities associated with gun violence.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. There is evidence that specific aberrations in tumour biology contribute to the pathophysiology of this condition. We plan to examine the association between tumour somatic mutations and VTE in an existing cohort of patients with cancer, who were enrolled to the flagship Genomics England 100,000 Genomes Project. Here, we outline an a-priori analysis plan to address this objective, including details on study cohort selection, exposure and outcome definitions, annotation of genetic variants and planned statistical analyses. We will assess the effect of 1) deleterious somatic DNA variants in each gene; 2) tumour mutational burden and 3) tumour mutational signatures on the rate of VTE (outcome) in a pan-cancer cohort. Sensitivity analyses will be performed to examine the robustness of any associations, including adjustment for potentially correlated co-variates: tumour type, stage and systemic anti-cancer therapy. We hope that results from this study may help to identify key genes which are implicated in the development of cancer associated thrombosis, which may shed light on related mechanistic pathways and/or provide data which can be integrated into genetic risk prediction models for these patients.

Parents and carers play a critical role in supporting their children while in hospital. Multiple qualitative studies have explored parental involvement in the care of hospitalised children. Administration of medication to young children can be difficult and cause anxiety and stress for children. Parents are often willing and able to assist, yet little is known about how often parents are given responsibility for medication administration in hospital.We analysed data from a prospective direct observational study of nurses administering medication at a major paediatric referral hospital in Australia. Data from observations of 298 nurses preparing and administering 5137 medication doses to children on nine medical and surgical wards between 07:00 and 22:00 were analysed. Details of drugs administered, whether medications were left for parents/carers to administer, and if nurses observed the administration by parents, were recorded.Parents were at their child’s bedside during 89.7% (n=4610) of observed medication administrations. Parents gave 20.3% (n=1045) of medications. In 14.3% (n=733), medications were left with parents to administer without a nurse present. In 6.1% (n=312) of doses, medications were given to parents, but the administration was observed by a nurse. Parents were most likely to be given medications to administer to young children (1–5 years), and the medications most frequently administered were analgesics and anti-epileptics.Parents/carers are integrally involved in the administration of many medications to children in hospital. The extent of parents’ role and the impact on medication administration efficiency has been largely absent from the healthcare literature. Given that one in five medication doses is administered by parents, hospitals should recognise this contribution and consider if any additional support for parents is required.

AbstractSustainable tourism development can utilize the social capital of society to encourage development. The social networks, norms, and trusts the community has built reflect social capital, which will be important for supporting and responding to sustainable tourism. The village is located in Wonosari District, Malang Regency, which is famous for its tourism village potential, namely Bangelan Village. This tourist village uses the community’s potential and natural resources, plantations, and goat farms as tourist attractions. Thus providing good benefits for the village community. This study has the H1 hypothesis: norms, social networks, and trust have a significant influence on social capital, and the H2 hypothesis: the presence of social capital has a significant influence on sustainable tourism. The sample used for this study was the Bangelan Village community, with SEM-PLS (structural equation modeling) data analysis. The study results show that the H1 and H2 hypotheses have significant and positive values. The findings show that social networks, norms, and trusts can form the social capital of the community and play an important role as a driver of sustainable tourism development in Bangelan Tourism Village.

Purpose: To identify sleep dimensions (characteristics) that co-occur in premenopausal women. The second aim was to examine associations between multiple dimensions of sleep and a set of demographic, lifestyle, and health correlates. The overarching goal was to uncover patterns of poor-sleep correlates that might inform interventions to improve sleep health of women in this age group. Methods: The BioCycle Study included 259 healthy women aged 18–44y recruited between 2005 and 2007 from Western New York. Participants reported sleep data through daily diaries and questionnaires that were used to create five sleep health dimensions (duration, variability, timing, latency, and continuity). We used multivariate analysis – canonical correlation methods – to identify links among dimensions of sleep health and patterns of demographic, psychological, and occupational correlates. Results: Two distinct combinations of sleep dimensions were identified. The first - primarily determined by low variability in nightly sleep duration, low variability in bedtime (timing), greater nocturnal awakening, and less sleep onset latency – was distinguished from the second – primarily determined by sleep duration.The first combination of sleep dimensions was associated with older age and higher parity, fewer depressive symptoms, and higher stress level. The second combination of sleep dimensions was associated with perception of longer sleep duration as optimal, lower parity, not engaging in shift work, older age, lower stress level, higher prevalence of depressive symptoms, and White race. Conclusion: Among premenopausal women, we demonstrated distinct patterns of sleep dimensions that co-occur and vary by demographic, health, and lifestyle correlates. These findings shed light on the correlates of sleep health vulnerabilities among young women.

Low maternal vitamin D concentrations during pregnancy have been associated with a range of offspring health outcomes. DNA methylation is one mechanism by which the maternal vitamin D status during pregnancy could impact offspring’s health in later life. We aimed to evaluate whether maternal vitamin D insufficiency during pregnancy was conditionally associated with DNA methylation in the offspring cord blood. Maternal vitamin D insufficiency (plasma 25-hydroxy vitamin D [Formula: see text] 75 nmol/L) during pregnancy and offspring cord blood DNA methylation, assessed using Illumina Infinium 450k or Illumina EPIC Beadchip, was collected for 3738 mother–child pairs in 7 cohorts as part of the Pregnancy and Childhood Epigenetics (PACE) consortium. Associations between maternal vitamin D and offspring DNA methylation, adjusted for fetal sex, maternal smoking, maternal age, maternal pre-pregnancy or early pregnancy BMI, maternal education, gestational age at measurement of 25(OH)D, parity, and cell type composition, were estimated using robust linear regression in each cohort, and a fixed-effects meta-analysis was conducted. The prevalence of vitamin D insufficiency ranged from 44.3% to 78.5% across cohorts. Across 364,678 CpG sites, none were associated with maternal vitamin D insufficiency at an epigenome-wide significant level after correcting for multiple testing using Bonferroni correction or a less conservative Benjamini–Hochberg False Discovery Rate approach (FDR, p > 0.05). In this epigenome-wide association study, we did not find convincing evidence of a conditional association of vitamin D insufficiency with offspring DNA methylation at any measured CpG site.

One Health is a transdisciplinary approach used to address complex concerns related to human, animal, plant, and ecosystem health. One Health frameworks and operational tools are available to support countries and communities, particularly for the prevention and control of zoonotic diseases and antimicrobial resistance and the protection of food safety. However, One Health has yet to be implemented in a manner that fully considers the complexities and interconnectedness of the diverse influences that have impacts at a larger system level. This lack of consideration can undermine the sustainability of any positive outcomes. To ensure the One Health approach can function effectively within the new global context of converging and escalating health, social, economic, and ecological crises, it must evolve and expand in three overlapping dimensions: (1) Scope: the partners, knowledge, and knowledge systems included, (2) Approach: the techniques, methodologies, and scholarship considered, and (3) Worldview inclusivity: the interweaving of other worldviews together with the mainstream scientific worldview that currently predominates. Diverse partners and knowledge from outside the mainstream health and scientific sectors, including Indigenous peoples and representatives of local communities, and traditionally generated knowledge, must be included. These systems of knowledge can then be braided together with mainstream science to comprise a holistic framework for decision-making. Scholarship and methodologies being applied in other fields and contexts to solve complex challenges and manage uncertainty, such as collaborative governance, social-ecologic systems theory, and complexity science, must be recognized and incorporated. The spectrum of considered worldviews must also expand to authentically integrate the expanded scope and approach into action and sustainable impact. By increasing community and social engagement and by recognizing and entwining different worldviews, the plurality of disciplines, and traditional and scientific ways of knowing to address community concerns in the contexts in which they exist, we can ensure that One Health remains effective and true to its paradigm in our rapidly changing and complex world.