Desmoplakin Cardiomyopathy in Pediatric Patients: A Distinct, Underrecognized Cohort of Arrhythmogenic Cardiomyopathy.

Background: cardiomyopathy is a distinct subset of arrhythmogenic cardiomyopathy, reported primarily in adults, that has predominantly left ventricular involvement and features of myocarditis. Clinical characteristics, risk stratification, and management of pediatric patients with variants are not well known. We sought to identify phenotypic features and prognosis of pediatric patients with pathogenic or likely pathogenic variants.

Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis.

The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA-atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors.

Analysis of the Associations of Measurements of Body Composition and Inflammatory Factors with Cardiovascular Disease and Its Comorbidities in a Community-Based Study.

The associations of cardiovascular disease (CVD) with comorbidities and biochemical and body composition measurements are repeatedly described but have not been studied simultaneously. In the present cross-sectional study, information on CVD and comorbidities [type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HDL)], body composition, levels of soluble markers, and other measures were collected from 1079 individuals. When we examined the association of each comorbidity and CVD, controlling for other comorbidities, we observed a clear pattern of the comorbidity-related specific associations with tested covariates.

Genetic Variants and Persistent Impairment Following Mild Traumatic Brain Injury: A Systematic Review.

Objective: The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction persisting 30 days or more following mild traumatic brain injury (mTBI).

Summary Of Review: A search of PubMed and Embase from inception through June 2022 identified 42 studies that associated genetic variants with the presence of symptoms or cognitive dysfunction 30 days or more following mTBI. Risk of bias was assessed for each publication using the Newcastle Ottawa Scale (NOS).

Relationships between Circulating Biomarkers and Body Composition Parameters in Patients with Metabolic Syndrome: A Community-Based Study.

Metabolic syndrome (MetS) is a complex disease involving multiple physiological, biochemical, and metabolic abnormalities. The search for reliable biomarkers may help to better elucidate its pathogenesis and develop new preventive and therapeutic strategies. In the present population-based study, we looked for biomarkers of MetS among obesity- and inflammation-related circulating factors and body composition parameters in 1079 individuals (with age range between 18 and 80) belonging to an ethnically homogeneous population.

Bayesian network modeling of patterns of antibiotic cross-resistance by bacterial sample source.

Background: Antimicrobial resistance is a major healthcare burden, aggravated when it extends to multiple drugs. While cross-resistance is well-studied experimentally, it is not the case in clinical settings, and especially not while considering confounding. Here, we estimated patterns of cross-resistance from clinical samples, while controlling for multiple clinical confounders and stratifying by sample sources.

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.

Exploring potential shared genetic influences between rheumatoid arthritis and blood lipid levels.

Background And Aims: The association between rheumatoid arthritis (RA) and blood lipid levels has often been described as paradoxical, despite the strong association between RA and cardiovascular disease (CVD) risk. We aimed to clarify the genetic architecture that would explain the relationship between RA and blood-lipid levels, while considering inflammation as measured by C-reactive protein (CRP).

Methods: Genome-wide association study (GWAS) summary statistics were collected from the CHARGE Consortium and Global Lipids Genetics Consortium.

Insights into the pleiotropic relationships between chronic back pain and inflammation-related musculoskeletal conditions: rheumatoid arthritis and osteoporotic abnormalities.

The ageing process includes the development of debilitating musculoskeletal (MSK) conditions, including chronic back pain (CBP), rheumatoid arthritis (RA), and osteoporosis (OP). The mechanisms involved in the genetic-epidemiological relationships between these MSK phenotypes are controversial and limited and thus require clarification, in particular, between CBP and the other MSK phenotypes. A cross-sectional statistical analysis was conducted using Europeans from the UK Biobank data collection, including 73,794 CBP, 4883 RA, and 7153 OP cases as well as 242,216 calcaneus bone mineral density scores.

Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders.

The pre-mRNA-processing factor 8, encoded by PRPF8, is a scaffolding component of a spliceosome complex involved in the removal of introns from mRNA precursors. Previously, heterozygous pathogenic variants in PRPF8 have been associated with autosomal dominant retinitis pigmentosa. More recently, PRPF8 was suggested as a candidate gene for autism spectrum disorder due to the enrichment of sequence variants in this gene in individuals with neurodevelopmental disorders.

Genetic and environmental correlational structure among metabolic syndrome endophenotypes.

Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood.

Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways.

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank.

Deciphering the Causal Relationships Between Low Back Pain Complications, Metabolic Factors, and Comorbidities.

Purpose: Low back pain (LBP) is one of the major disabling health conditions in aging societies presenting significant cost burdens to health and social care systems. Its complications and associated disability are often accompanied by mental disorders, metabolic comorbidities, changed body composition, and inflammation. However, their mutual relationships in LBP-associated disability remain unclear.

Deviation from baseline mutation burden provides powerful and robust rare-variants association test for complex diseases.

Identifying rare variants that contribute to complex diseases is challenging because of the low statistical power in current tests comparing cases with controls. Here, we propose a novel and powerful rare variants association test based on the deviation of the observed mutation burden of a gene in cases from a baseline predicted by a weighted recursive truncated negative-binomial regression (RUNNER) on genomic features available from public data. Simulation studies show that RUNNER is substantially more powerful than state-of-the-art rare variant association tests and has reasonable type 1 error rates even for stratified populations or in small samples.

Shared Genetic Architecture Between Rheumatoid Arthritis and Varying Osteoporotic Phenotypes.

Rheumatoid arthritis (RA) and low bone mineral density (BMD), an indicator of osteoporosis (OP), appear epidemiologically associated. Shared genetic factors may explain this association. This study aimed to investigate the presence of pleiotropy to clarify the potential genetic association between RA and OP.

Abnormal Microarray, Clinical Outcomes, and Surgical Risk Scores in Young Children with Cardiac Disease.

The clinical implications of abnormal chromosomal microarray (CMA) remain unclear for children less than 1 year of age with critical heart disease. Our objective was to determine whether abnormal CMA was related to surgical severity scores or to pre-determined clinical outcomes, including cardiac arrest. Retrospective review of children under 1 year of age admitted to a pediatric cardiac intensive care unit from December, 2014 to September, 2017.

A random forest-based framework for genotyping and accuracy assessment of copy number variations.

Detection of copy number variations (CNVs) is essential for uncovering genetic factors underlying human diseases. However, CNV detection by current methods is prone to error, and precisely identifying CNVs from paired-end whole genome sequencing (WGS) data is still challenging. Here, we present a framework, CNV-JACG, for udging the ccuracy of NVs and enotyping using paired-end WGS data.

Primary nasal Kaposi Sarcoma in well-controlled HIV-positive patient with normal CD4 count associated with long-term nasal steroid use.

Kaposi sarcoma (KS) is an angioproliferative disease that is caused by human herpesvirus 8. The epidemic form of KS is associated with acquired immunodeficiency syndrome (AIDS) and is common in HIV-positive patients with CD4 counts less than 200 cells/mm. We present the case of a 63-year-old man with well-controlled HIV and normal CD4 count developing atypical nasal KS associated with intranasal steroid use.