Cumulative Risk and Cumulative Protection: Relative Contributions to Predicting Substance Use, Antisocial Behaviour and Mental Health Across Development.

Background: Cumulative risk scores predict negative outcomes including antisocial behaviour and mental health. Less work has examined the role of cumulative protection, despite the availability of preventive interventions focused on bolstering protection across domains. Understanding links between cumulative risk and protection measured in childhood and later outcomes can help to guide the timing of prevention programmes.

Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon.

Identification of functional enhancer variants associated with type I diabetes in CD4+ T cells.

Type I diabetes is an autoimmune disease mediated by T-cell destruction of β cells in pancreatic islets. Currently, there is no known cure, and treatment consists of daily insulin injections. Genome-wide association studies and twin studies have indicated a strong genetic heritability for type I diabetes and implicated several genes.

The complex role of Rcor2: Regulates mesenchymal stromal cell differentiation in vitro but is dispensable in vivo.

Recent research has revealed several important pathways of epigenetic regulation leading to transcriptional changes in bone cells. Rest Corepressor 2 (Rcor2) is a coregulator of Lysine-specific histone demethylase 1 (Lsd1), a demethylase linked to osteoblast activity, hematopoietic stem cell differentiation and malignancy of different neoplasms. However, the role of Rcor2 in osteoblast differentiation has not yet been examined in detail.

Acceleration-Based Estimation of Vertical Ground Reaction Forces during Running: A Comparison of Methods across Running Speeds, Surfaces, and Foot Strike Patterns.

Twenty-seven methods of estimating vertical ground reaction force first peak, loading rate, second peak, average, and/or time series from a single wearable accelerometer worn on the shank or approximate center of mass during running were compared. Force estimation errors were quantified for 74 participants across different running surfaces, speeds, and foot strike angles and biases, repeatability coefficients, and limits of agreement were modeled with linear mixed effects to quantify the accuracy, reliability, and precision. Several methods accurately and reliably estimated the first peak and loading rate, however, none could do so precisely (the limits of agreement exceeded ±65% of target values).

Hoof Expansion, Deformation, and Surface Strains Vary with Horseshoe Nail Positions.

Racehorses are susceptible to underrun heel hoof conformation. Racehorses are often shod with nails placed toward the heel. It is unknown if palmar nails restrict or alter hoof deformation in a manner that could promote the development of underrun heel conformation over time with repeated loading.

Testing Cross-Generational Effects of the Raising Healthy Children Intervention on Young Adult Offspring of Intervention Participants.

This study tested whether effects of a preventive intervention delivered in elementary school showed benefits for the young adult offspring of intervention recipients over 20 years later. The Raising Healthy Children (RHC) intervention, trialed in 18 public schools in Seattle, Washington, from 1980-1986 (grades 1-6), sought to build strong bonds to family and school to promote school success and avoidance of substance use and illegal behavior. Four intervention groups were constituted: full, late, parent training only, and control.

Increasing Step Rate Reduces Peak and Cumulative Insole Force in Collegiate Runners.

Purpose: The primary goal of this study was to examine changes in peak insole force and cumulative weighted peak force (CWPF)/km with increased step rate in collegiate runners. The secondary goal was to determine whether sacral acceleration correlates with insole force when increasing step rate.

Methods: Twelve collegiate distance runners ran 1000 m outdoors at 3.

Unsupervised Gait Event Identification with a Single Wearable Accelerometer and/or Gyroscope: A Comparison of Methods across Running Speeds, Surfaces, and Foot Strike Patterns.

We evaluated 18 methods capable of identifying initial contact (IC) and terminal contact (TC) gait events during human running using data from a single wearable sensor on the shank or sacrum. We adapted or created code to automatically execute each method, then applied it to identify gait events from 74 runners across different foot strike angles, surfaces, and speeds. To quantify error, estimated gait events were compared to ground truth events from a time-synchronized force plate.

Effect of the Communities That Care Prevention System on Adolescent Handgun Carrying: A Cluster-Randomized Clinical Trial.

Importance: There is little information on upstream community-based interventions that reduce the prevalence of handgun carrying among adolescents, especially those growing up in rural areas.

Objective: To test whether Communities That Care (CTC), a community-based prevention system focusing on risk and protective factors for behavioral problems early in life, reduces handgun carrying prevalence among adolescents growing up in rural areas.

Design, Setting, And Participants: Community-randomized trial of 24 small towns in 7 states assigned randomly to the CTC or control group with outcomes assessed from 2003 to 2011.

Unique Cell Subpopulations and Disease Progression Markers in Canines with Atopic Dermatitis.

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with unclear molecular and cellular contributions behind the complex etiology. To unravel these differences between healthy control and AD skin we employed single-cell transcriptomics, utilizing the canine AD model for its resemblance to human clinical and molecular phenotypes. In this study, we show that there are overall increases in keratinocytes and T cells and decreases in fibroblast populations in AD dogs.

Is e-cigarette use associated with better health and functioning among smokers approaching midlife?

Introduction: Many adult smokers have tried electronic cigarettes (e-cigarettes) as a less harmful alternative to combustible cigarettes. There is limited evidence, however, for the extent to which switching to e-cigarettes is associated with better health and functioning among nicotine users approaching their 40s-the beginning of midlife-when many health issues become more evident. This study examined the adoption of e-cigarette use ("vaping") among smokers in their 30s, and its association with diverse measures of healthy and successful aging at age 39.

Lysine-Specific Demethylase 1 (LSD1) epigenetically controls osteoblast differentiation.

Epigenetic mechanisms regulate osteogenic lineage differentiation of mesenchymal stromal cells. Histone methylation is controlled by multiple lysine demethylases and is an important step in controlling local chromatin structure and gene expression. Here, we show that the lysine-specific histone demethylase Kdm1A/Lsd1 is abundantly expressed in osteoblasts and that its suppression impairs osteoblast differentiation and bone nodule formation in vitro.

dCas9 fusion to computer-designed PRC2 inhibitor reveals functional TATA box in distal promoter region.

Bifurcation of cellular fates, a critical process in development, requires histone 3 lysine 27 methylation (H3K27me3) marks propagated by the polycomb repressive complex 2 (PRC2). However, precise chromatin loci of functional H3K27me3 marks are not yet known. Here, we identify critical PRC2 functional sites at high resolution.

Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial.

Purpose: Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients.

Parent-focused prevention of adolescent health risk behavior: Study protocol for a multisite cluster-randomized trial implemented in pediatric primary care.

Evidence-based parenting interventions play a crucial role in the sustained reduction of adolescent behavioral health concerns. Guiding Good Choices (GGC) is a 5-session universal anticipatory guidance curriculum for parents of early adolescents that has been shown to reduce substance use, depression symptoms, and delinquent behavior. Although prior research has demonstrated the effectiveness of evidence-based parenting interventions at achieving sustained reductions in adolescent behavioral health concerns, public health impact has been limited by low rates of uptake in community and agency settings.

Sumoylation of the human histone H4 tail inhibits p300-mediated transcription by RNA polymerase II in cellular extracts.

The post-translational modification of histones by the small ubiquitin-like modifier (SUMO) protein has been associated with gene regulation, centromeric localization, and double-strand break repair in eukaryotes. Although sumoylation of histone H4 was specifically associated with gene repression, this could not be proven due to the challenge of site-specifically sumoylating H4 in cells. Biochemical crosstalk between SUMO and other histone modifications, such as H4 acetylation and H3 methylation, that are associated with active genes also remains unclear.

State of the Art in Substance Use Prevention and Early Intervention: Applications to Pediatric Primary Care Settings.

With changes to drug-related policies and increased availability of many drugs, we currently face a public health crisis related to substance use and associated health consequences. Substance use and substance use disorders (SU/SUDs) are complex developmental disorders with etiologies that emerge through the intergenerational transmission of biological, familial, and environmental factors. The family ecosystem both influences and is influenced by SU/SUDs, particularly in children and adolescents.

The role of electronic cigarette use for quitting or reducing combustible cigarette use in the 30s: Longitudinal changes and moderated relationships.

Background: Evidence for use of electronic cigarettes (e-cigs) as a potential aid in quitting or reducing combustible cigarette (c-cig) use is mixed. This study examined the extent to which e-cig initiation among smokers in their 30 s predicted quitting or reducing smoking or nicotine dependence symptoms by age 39, and whether the role of e-cigs in quitting differed by prospectively assessed moderators.

Methods: Data were from the Seattle Social Development Project (SSDP), a panel study of 808 diverse participants with high retention.

Transcriptomes of an Array of Chicken Ovary, Intestinal, and Immune Cells and Tissues.

While the chicken () is the most consumed agricultural animal worldwide, the chicken transcriptome remains understudied. We have characterized the transcriptome of 10 cell and tissue types from the chicken using RNA-seq, spanning intestinal tissues (ileum, jejunum, proximal cecum), immune cells (B cells, bursa, macrophages, monocytes, spleen T cells, thymus), and reproductive tissue (ovary). We detected 17,872 genes and 24,812 transcripts across all cell and tissue types, representing 73% and 63% of the current gene annotation, respectively.

Long-term Impacts and Benefit-Cost Analysis of the Communities That Care Prevention System at Age 23, 12 Years After Baseline.

This study estimated sustained impacts and long-term benefits and costs of the Communities That Care (CTC) prevention system, implemented and evaluated in a longitudinal cluster-randomized trial involving 24 communities in seven states. Analyses utilized reports from a longitudinal panel of 4407 participants, followed since the study's baseline in grade 5, with most recent follow-up 12 years later at age 23. Impacts on lifetime abstinence from primary outcomes of substance use and antisocial behavior were estimated using generalized linear mixed Poisson regression analysis, adjusted for individual and community-level covariates.

In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal γ-globin in β-YAC mice.

Base editors are capable of installing precise genomic alterations without creating double-strand DNA breaks. In this study, we targeted critical motifs regulating γ-globin reactivation with base editors delivered via HDAd5/35++ vectors. Through optimized design, we successfully produced a panel of cytidine and adenine base editor (ABE) vectors targeting the erythroid BCL11A enhancer or recreating naturally occurring hereditary persistence of fetal hemoglobin (HPFH) mutations in the HBG1/2 promoter.