There is a need to understand how the ongoing COVID-19 pandemic has affected the mental and behavioral health of young adults in the U.S.
 
  This study used quantitative and qualitative survey data to identify young adults at highest risk for psychological distress during the U.S. outbreak of COVID-19 and to further understand how the pandemic has impacted their stress, mood, and substance use.
 
  Participants were 670 young adult cohort members (ages 21-29) of the population-based longitudinal study EAT 2010-2018 who participated in the C-EAT study (COVID-19 Eating and Activity over Time).
 
  Among the sample, 84% (n=561) reported pandemic-related changes to their mood or stress and 33% (n=221) reported changes to their substance use. Linear regression analyses identified several meaningful risk factors for higher psychological distress during the pandemic, including female gender, White race, higher pre-pandemic depressive symptoms and perceived stress, and lower pre-pandemic stress management ability. A thematic analysis further identified five major themes related to changes in stress and mood following the COVID-19 outbreak describing specific emotional reactions, stress related to the direct impact of the pandemic as well as interpersonal connectedness and economic factors, and strategies for managing stress. In addition, two major themes were identified related to substance use during the pandemic detailing specific changes in and motivations for substance use.
 
  These findings underscore the need to develop effective, scalable, and rapidly deployable public health resources that target the stressors commonly experienced among young adults to improve their psychological wellbeing during this pandemic.
 These findings underscore the need to develop effective, scalable, and rapidly deployable public health resources that target the stressors commonly experienced among young adults to improve their psychological wellbeing during this pandemic.The 21st century has seen the proliferation of technologies and sources of information on issues of all kinds, including sexuality. Amid debates about the role of social media and the internet in mediating sexuality, questions about credible, reliable and objective sources of information have also arisen, particularly in relation to young people's knowledge-seeking. Drawing on theorisations of sexual citizenship, Foucault's notion of the 'episteme', and the work of science and technology studies scholar John Law, this article examines a 'collateral reality' produced by contemporary demands on young people to source, assess and act on sexual health information. Using interviews with 37 young people living in Australia, the analysis identifies a range of approaches to sexual health-seeking practices, key dynamics in the construction of reliability and fact, and the extent and nature of the accommodations young people report making to navigate incomplete and unreliable information. With the contemporary self incn their own, and who in turn feel more included.The complexities of gene expression pose challenges for the clinical interpretation of splicing variants.  https://www.selleckchem.com/products/epz-5676.html  To better understand splicing variants and their contribution to hereditary disease, we evaluated their prevalence, clinical classifications, and associations with diseases, inheritance, and functional characteristics in a 689,321-person clinical cohort and two large public datasets. In the clinical cohort, splicing variants represented 13% of all variants classified as pathogenic (P), likely pathogenic (LP), or variants of uncertain significance (VUSs). Most splicing variants were outside essential splice sites and were classified as VUSs. Among all individuals tested, 5.4% had a splicing VUS. If RNA analysis were to contribute supporting evidence to variant interpretation, we estimated that splicing VUSs would be reclassified in 1.7% of individuals in our cohort. This would result in a clinically significant result (i.e., P/LP) in 0.1% of individuals overall because most reclassifications would change VUSs to likely benign. In ClinVar, splicing VUSs were 4.8% of reported variants and could benefit from RNA analysis. In the Genome Aggregation Database (gnomAD), splicing variants comprised 9.4% of variants in protein-coding genes; most were rare, precluding unambiguous classification as benign. Splicing variants were depleted in genes associated with dominant inheritance and haploinsufficiency, although some genes had rare variants at essential splice sites or had common splicing variants that were most likely compatible with normal gene function. Overall, we describe the contribution of splicing variants to hereditary disease, the potential utility of RNA analysis for reclassifying splicing VUSs, and how natural variation may confound clinical interpretation of splicing variants.The DNA damage-binding protein 1 (DDB1) is part of the CUL4-DDB1 ubiquitin E3 ligase complex (CRL4), which is essential for DNA repair, chromatin remodeling, DNA replication, and signal transduction. Loss-of-function variants in genes encoding the complex components CUL4 and PHIP have been reported to cause syndromic intellectual disability with hypotonia and obesity, but no phenotype has been reported in association with DDB1 variants. Here, we report eight unrelated individuals, identified through Matchmaker Exchange, with de novo monoallelic variants in DDB1, including one recurrent variant in four individuals. The affected individuals have a consistent phenotype of hypotonia, mild to moderate intellectual disability, and similar facies, including horizontal or slightly bowed eyebrows, deep-set eyes, full cheeks, a short nose, and large, fleshy and forward-facing earlobes, demonstrated in the composite face generated from the cohort. Digital anomalies, including brachydactyly and syndactyly, were common. Three older individuals have obesity. We show that cells derived from affected individuals have altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage. Overall, our study adds to the growing family of neurodevelopmental phenotypes mediated by disruption of the CRL4 ubiquitin ligase pathway and begins to delineate the phenotypic and molecular effects of DDB1 misregulation.