Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

The moderating effect of recent positive and negative life events on the impact of early life stress on mental wellbeing and distress.

Early life stress (ELS) significantly influences mental health in later stages of life. Yet it is unclear whether recent life events lessen or intensify the effects of ELS on present wellbeing and distress. We addressed this question in 1064 healthy community adults with a normative range of wellbeing and distress.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

An umbrella review of health outcomes following traumatic brain injury.

While numerous reviews have assessed the association between traumatic brain injury (TBI) and various mental and physical health outcomes, a comprehensive evaluation of the scope, validity, and quality of evidence is lacking. Here we present an umbrella review of a wide range of health outcomes following TBI and outline outcome risks across subpopulations. On 17 May 2023, we searched Embase, Medline, Global Health, PsycINFO, and Cochrane Database of Systematic Reviews for systematic reviews and meta-analyses.

Chromosomal rearrangements and instability caused by the LINE-1 retrotransposon.

LINE-1 (L1) retrotransposition is widespread in many cancers, especially those with a high burden of chromosomal rearrangements. However, whether and to what degree L1 activity directly impacts genome integrity is unclear. Here, we apply whole-genome sequencing to experimental models of L1 expression to comprehensively define the spectrum of genomic changes caused by L1.

Single-use versus multiple-use endotracheal suction catheters flushed with chlorhexidine in mechanically ventilated ICU patients: A study protocol of a feasibility randomized controlled trial with an embedded qualitative study.

Background: Endotracheal suction catheters are often used multiple times during endotracheal suctioning procedures in resource-limited intensive care units (ICU). The impact of this practice on mechanically ventilated patients' outcomes remains unclear.

Aim: The aim of this feasibility randomized controlled trial (fRCT) is to assess the feasibility and acceptability of single-use versus multiple-use endotracheal suction catheters flushed with chlorhexidine in mechanically ventilated ICU patients.

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.

Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum.

The public health significance of prior homelessness: findings on multimorbidity and mental health from a nationally representative survey.

Aims: The associations of prior homelessness with current health are unknown. Using nationally representative data collected in private households in England, this study aimed to examine Common Mental Disorders (CMDs), physical health, alcohol/substance dependence, and multimorbidities in people who formerly experienced homelessness compared to people who never experienced homelessness.

Methods: This cross-sectional study utilised data from the 2007 and 2014 Adult Psychiatric Morbidity Surveys.

Deferiprone in Alzheimer Disease: A Randomized Clinical Trial.

Importance: Interventions that substantially slow neurodegeneration are needed to address the growing burden of Alzheimer disease (AD) to societies worldwide. Elevated brain iron observed in AD has been associated with accelerated cognitive decline and may be a tractable drug target.

Objective: To investigate whether the brain-permeable iron chelator deferiprone slows cognitive decline in people with AD.

Causal relationships between diseases mined from the literature improve the use of polygenic risk scores.

Motivation: Identifying causal relations between diseases allows for the study of shared pathways, biological mechanisms, and inter-disease risks. Such causal relations can facilitate the identification of potential disease precursors and candidates for drug re-purposing. However, computational methods often lack access to these causal relations.

Feasibility, acceptability, and preliminary efficacy of a self-directed online psychosocial intervention for women with metastatic breast cancer: Finding My Way-Advanced.

Purpose: Few digital interventions target patients with advanced cancer. Hence, we feasibility-tested Finding My Way-Advanced (FMW-A), a self-guided program for women with metastatic breast cancer.

Methods: A single-site randomised controlled pilot trial was conducted.

Diel metatranscriptomes capture cyanobacteria-dominated Lake Erie community response to episodic events.

Here, we report on the raw and coassembled metatranscriptomes of 39 Lake Erie surface (1.0 m) water samples collected over a 2-day diel period encompassing episodic weather and bloom events. Preliminary taxonomic annotations and read mappings revealed that spp.

Antibiotic prescribing intensity and community UTI resistance: a cross-sectional ecological study.

Background: Antibiotic overuse is associated with antimicrobial resistance (AMR). It is unclear whether community AMR is driven by overall antibiotic use or by high levels of repeated (intense) use by individual patients.

Aim: To determine the association between high antibiotic prescribing intensity (all antibiotic prescriptions; any indication), and rates of UTI resistance among patients within small communities.

Talking about diseases; developing a model of patient and public-prioritised disease phenotypes.

Deep phenotyping describes the use of standardised terminologies to create comprehensive phenotypic descriptions of biomedical phenomena. These characterisations facilitate secondary analysis, evidence synthesis, and practitioner awareness, thereby guiding patient care. The vast majority of this knowledge is derived from sources that describe an academic understanding of disease, including academic literature and experimental databases.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

Introduction: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations.

Methods: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.

The experiences of physiotherapists delivering pain science education via an interpreter: a mixed-methods online survey.

Objective: To explore physiotherapist's experiences of delivering Pain Science Education (PSE) via an interpreter to people with persistent pain.

Method: A cross-sectional online survey study of UK Physiotherapists. The study protocol was registered on the Open Science Framework Registry.