Bi-allelic MED16 variants cause a MEDopathy with intellectual disability, motor delay, and craniofacial, cardiac, and limb malformations.

The Mediator complex regulates protein-coding gene transcription by coordinating the interaction of upstream enhancers with the basal transcription machinery at the promoter. Pathogenic variants in Mediator subunits typically lead to neurodevelopmental or neurodegenerative disorders with variable clinical presentations, designated as MEDopathies. Here, we report the identification of 25 individuals from 18 families with bi-allelic MED16 variants who have a multiple congenital anomalies (MCAs)-intellectual disability syndrome.

Caries Trajectories From Childhood to Adulthood Associated With Mental Disorders in Midlife.

Unlabelled: Oral and mental health are integral to overall health and well-being. Primary dentition caries is associated with poorer oral and general health and faster aging by midlife, but it remains unclear whether these associations also hold for mental health.

Objectives: To investigate whether primary dentition caries, caries experienced in adolescence and adulthood, and caries trajectories across the life course are associated with mental disorders in the fifth decade of life in two New Zealand birth cohorts.

A qualitative exploration of illness-related experiences, emotions, and coping among adults with postural orthostatic tachycardia syndrome (POTS).

Postural orthostatic tachycardia syndrome (POTS) is a relatively common, burdensome condition of the autonomic nervous system characterized by orthostatic intolerance. This paper presents a subset of findings from a qualitative study investigating the lived experience and perspectives of adults with POTS. Twenty-nine individuals participated in a series of focus groups.

VIEWER: an extensible visual analytics framework for enhancing mental healthcare.

Objective: A proof-of-concept study aimed at designing and implementing Visual & Interactive Engagement With Electronic Records (VIEWER), a versatile toolkit for visual analytics of clinical data, and systematically evaluating its effectiveness across various clinical applications while gathering feedback for iterative improvements.

Materials And Methods: VIEWER is an open-source and extensible toolkit that employs natural language processing and interactive visualization techniques to facilitate the rapid design, development, and deployment of clinical information retrieval, analysis, and visualization at the point of care. Through an iterative and collaborative participatory design approach, VIEWER was designed and implemented in one of the United Kingdom's largest National Health Services mental health Trusts, where its clinical utility and effectiveness were assessed using both quantitative and qualitative methods.

Crossing the streams: improving data quality and integration across the One Health genomics continuum with data standards and implementation strategies.

The Canadian Genomics Research and Development Initiative for Antimicrobial Resistance (GRDI-AMR) uses a genomics-based approach to understand how health care, food production and the environment contribute to the development of antimicrobial resistance. Integrating genomics contextual data streams across the One Health continuum is challenging because of the diversity in data scope, content and structure. To better enable data harmonization for analyses, a contextual data standard was developed.

Cohort profile: working age adults accessing secondary mental health services in South London (UK) and benefits - a data linkage of electronic mental health records and benefits data.

Introduction: In the UK, mental disorders are one of the most common reasons for claiming a benefit relating to unemployment, income, sickness and disability. Limited information exists regarding the demographic characteristics and psychiatric profiles of working age individuals claiming benefits in London. Until recently, detailed data on both mental disorders and benefit receipt were unavailable.

UK Foot and Ankle Thromboembolism (UK-FATE).

Aims: Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture.

Neurodevelopmental Disorder Caused by Deletion of , a lncRNA Gene.

encodes a human long noncoding RNA (lncRNA) adjacent to , a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here, we report our findings in three unrelated children with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - a phenotype that is distinct from the phenotypes of patients with haploinsufficiency.

Implications of child poverty reduction targets for public health and health inequalities in England: a modelling study between 2024 and 2033.

Background: We investigated the potential impacts of child poverty (CP) reduction scenarios on population health and health inequalities in England between 2024 and 2033.

Methods: We combined aggregate local authority-level data with published and newly created estimates on the association between CP and the rate per 100 000 of infant mortality, children (aged <16) looked after, child (aged <16) hospitalisations for nutritional anaemia and child (aged <16) all-cause emergency hospital admissions. We modelled relative, absolute (per 100 000) and total (per total population) annual changes for these outcomes under three CP reduction scenarios between 2024 and 2033- (15% reduction), (25% reduction) and (35% reduction)-compared with a baseline CP scenario (15% increase).

Activation of IPR in atrial cardiomyocytes leads to generation of cytosolic cAMP.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Excessive stimulation of the inositol (1,4,5)-trisphosphate (IP) signaling pathway has been linked to AF through abnormal calcium handling. However, little is known about the mechanisms involved in this process.

The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence.

Use of an Opt-Out vs Opt-In Strategy Increases Use of Residency Mental Health Services.

Residents report high levels of distress but low utilization of mental health services. Prior research has shown several barriers that prevent residents from opting into available mental health services. To determine the impact of a mental health initiative centered around an opt-out versus an opt-in approach to help-seeking, on the use of psychotherapy.

Ecotourism and mangrove conservation in Southeast Asia: Current trends and perspectives.

Mangroves in Southeast Asia provide numerous supporting, provisioning, regulating, and cultural services that are crucial to the environment and local livelihoods since they support biodiversity conservation and climate change resilience. However, Southeast Asia mangroves face deforestation threats from the expansion of commercial aquaculture, agriculture, and urban development, along with climate change-related natural processes. Ecotourism has gained prominence as a financial incentive tool to support mangrove conservation and restoration.

Chamber-specific contractile responses of atrial and ventricular hiPSC-cardiomyocytes to GPCR and ion channel targeting compounds: A microphysiological system for cardiac drug development.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) have found utility for conducting in vitro drug screening and disease modelling to gain crucial insights into pharmacology or disease phenotype. However, diseases such as atrial fibrillation, affecting >33 M people worldwide, demonstrate the need for cardiac subtype-specific cells. Here, we sought to investigate the base characteristics and pharmacological differences between commercially available chamber-specific atrial or ventricular hiPSC-CMs seeded onto ultra-thin, flexible PDMS membranes to simultaneously measure contractility in a 96 multi-well format.

Are changes in malocclusion associated with adulthood psychosocial well-being?

Introduction: The purpose of this study was to investigate the longitudinal psychosocial effects of changes in malocclusion from adolescence to adulthood on oral health-related quality of life (OHRQOL), self-rated dental appearance, and overall life satisfaction.

Methods: The Dunedin Multidisciplinary Health and Development Study is a longitudinal birth cohort study of 1037 children born at Queen Mary Hospital, Dunedin, New Zealand, between April 1, 1972 and March 31, 1973. Data on their health and development, including dental examinations, has since been collected periodically.

AMPK regulates phagophore-to-autophagosome maturation.

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation.

Is Austerity Responsible for the Stalled Mortality Trends Across Many High-Income Countries? A Systematic Review.

This article systematically reviews evidence evaluating whether macroeconomic austerity policies impact mortality, reviewing high-income country data compiled through systematic searches of nine databases and gray literature using pre-specified methods (PROSPERO registration: CRD42020226609). Eligible studies were quantitatively assessed to determine austerity's impact on mortality. Two reviewers independently assessed eligibility and risk of bias using ROBINS-I.

Genomic Analysis and Surveillance of Respiratory Syncytial Virus Using Wastewater-Based Epidemiology.

Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical surveillance and the lack of predictable seasonal dynamics limit the public health response. Wastewater-based epidemiology (WBE) has recently been used globally as a key metric in determining prevalence of severe acute respiratory syndrome coronavirus 2 in the community, but its application to other respiratory viruses is limited.

"I lost my first tooth here": Syrian former refugees' experiences of oral healthcare in Dunedin, New Zealand.

Aim: Oral health conditions are highly prevalent among former refugees; however, little is known about their experiences of accessing dental care. We aimed to explore Syrian former refugees' experiences of oral healthcare in New Zealand.

Method: Thirty-nine Syrian former refugees resettled in Dunedin, New Zealand participated in nine focus group discussions.

The effect of dietary interventions or patterns on the cardiometabolic health of individuals treated with androgen deprivation therapy for prostate cancer: A systematic review.

Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or management of cardiovascular disease for these individuals are lacking. This review synthesizes the evidence on the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk in prostate cancer survivors receiving androgen deprivation therapy.