TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia.

Introduction: An association between functional dyspepsia (FD) and wheat-containing foods has been reported in observational studies; however, an adaptive response has not been demonstrated. We examined whether antigens present in wheat could provoke a response from FD duodenal lymphocytes.

Methods: Lamina propria mononuclear cells (LPMCs) were isolated from duodenal biopsies from 50 patients with FD and 23 controls.

The African Liver Tissue Biorepository Consortium: Capacitating Population-Appropriate Drug Metabolism, Pharmacokinetics, and Pharmacogenetics Research in Drug Discovery and Development.

Pharmaceutical companies subject all new molecular entities to a series of in vitro metabolic characterizations that guide the selection and/or design of compounds predicted to have favorable pharmacokinetic properties in humans. Current drug metabolism research is based on liver tissue predominantly obtained from people of European origin, with limited access to tissue from people of African origin. Given the interindividual and interpopulation genomic variability in genes encoding drug-metabolizing enzymes, efficacy and safety of some drugs are poorly predicted for African populations.

Visible-Light-Triggered Photoswitching of Diphosphene Complexes.

Although diphosphene transition metal complexes are known to undergo E to Z isomerization upon irradiation with UV light, their potential for photoswitching has remained poorly explored. In this study, we present diphosphene complexes capable of reversible photoisomerizations through haptotropic rearrangements. The compounds [(2-κ P,κ C)Mo(CO) ][OTf] (3 a[OTf]), [(2-κ P,κ C)Fe(CO)][OTf] (3 b[OTf]), and [(2-κ P)Fe(CO) ][OTf] (4[OTf]) were prepared using the triflate salt [(L )P=P(Dipp)][OTf] (2[OTf) as a precursor (L =4,5-dichloro-1,3-bis(2,6-diisiopropylphenyl)-imidazolin-2-yl; Dipp=2,6-diisiopropylphenyl, OTf=triflate).

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.

Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium.

Highly drug resistant clone of Salmonella Kentucky ST198 in clinical infections and poultry in Zimbabwe.

A highly multidrug-resistant strain of Salmonella enterica serotype Kentucky (S. Kentucky) of sequence type (ST)198 emerged in North Africa and has since spread widely. To investigate the genetic diversity and phylogenetic relationship of S.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively.

Objective: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

A practitioner's guide to geospatial analysis in a neuroimaging context.

Introduction: Health disparities arise from biological-environmental interactions. Neuroimaging cohorts are reaching sufficiently large sample sizes such that analyses could evaluate how the environment affects the brain. We present a practical guide for applying geospatial methods to a neuroimaging cohort.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Multi-ancestry meta-analysis of asthma identifies novel associations and highlights the value of increased power and diversity.

Asthma is a complex disease that varies widely in prevalence across populations. The extent to which genetic variation contributes to these disparities is unclear, as the genetics underlying asthma have been investigated primarily in populations of European descent. As part of the Global Biobank Meta-analysis Initiative, we conducted a large-scale genome-wide association study of asthma (153,763 cases and 1,647,022 controls) via meta-analysis across 22 biobanks spanning multiple ancestries.

Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus.

Introduction: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome.

Methods: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria.

Results: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains.

Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

Background: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries.

Methods: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

Background: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.

Methods: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.

Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness.

Earlier variants of SARS-CoV-2 have been associated with hypercoagulability and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with omicron variants are significantly raised over those of healthy, matched controls, they are raised to levels significantly lower than those seen with more severe variants such as beta and delta.

Work difficulties in people with multiple sclerosis: The role of anxiety, depression and coping.

Background: Symptoms of anxiety and depression affect the daily life of people with multiple sclerosis (MS). This study examined work difficulties and their relationship with anxiety, depression and coping style in people with MS.

Methods: 219 employed people with MS (median age  =  43 years, 79% female) completed questionnaires on anxiety, depression, coping style, demographics and work difficulties, and underwent a neurological examination.

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity.

Site-Level Comprehensiveness of Care Is Associated with Individual Clinical Retention Among Adults Living with HIV in International Epidemiology Databases to Evaluate AIDS, a Global HIV Cohort Collaboration, 2000-2016.

Retention in care (RIC) reduces HIV transmission and associated morbidity and mortality. We examined whether delivery of comprehensive services influenced individual RIC within the International epidemiology Databases to Evaluate AIDS (IeDEA) network. We collected site data through IeDEA assessments 1.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

Background: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited.

Methods: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHADSVASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist.

A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook.

Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies.