A Content Analysis of African Americans' Experience of Engaging in Exercise Intervention in a Community Setting.

Although an increasing number of African Americans 50 years of age and older practice , a mind-body exercise, to manage their health conditions, little is known about their perceptions and experiences of engaging in and learning exercise. This study aimed to explore the subjective perceptions of the health benefits, engagement, adherence, and learning of exercise in African Americans 45-85 years of age as a foundation for promoting this approach for African Americans' physical and psychological health. Fifteen African Americans were enrolled in a 1-h exercise program twice a week for 8 weeks (a total of 16 sessions) in the activity center of a local church.

Simulation of a Compton-based detector for low-dose high-resolution time-of-flight positron emission tomography.

Two major challenges in time-of-flight positron emission tomography (TOF-PET) are low spatial resolution and high radioactive dose to the patient, both of which result from limitations in detection technology rather than fundamental physics. A new type of TOF-PET detector employing low-atomic number (low-Z) scintillation media and large-area, high-resolution photodetectors to record Compton scattering locations in the detector has been proposed as a promising alternative, but the minimum technical requirements for such a system have not yet been established. Here we present a simulation study evaluating the potential of a proposed low-Z detection medium, linear alkylbenzene (LAB) doped with a switchable molecular recorder, for next-generation TOF-PET detection.

Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

Background: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers.

Methods: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH).

Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway.

Background: Since the first description of a BRWD3-associated nonsydromic intellectual disability (ID) disorder in 2007, 21 additional families have been reported in the literature.

Methods: Using exome sequencing (ES) and international data sharing, we identified 14 additional unrelated individuals with pathogenic BRWD3 variants (12 males and 2 females, including one with skewed X-inactivation). We reviewed the 31 previously published cases in the literature with clinical data available, and describe the collective phenotypes of 43 males and 2 females, with 33 different BRWD3 variants.

OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants.

Patients with rare or ultra-rare genetic diseases, which affect 350 million people worldwide, may experience a diagnostic odyssey. High-throughput sequencing leads to an etiological diagnosis in up to 50% of individuals with heterogeneous neurodevelopmental or malformation disorders. There is a growing interest in additional omics technologies in translational research settings to examine the remaining unsolved cases.

Epileptic encephalopathy as a new feature of the sudden infant death with dysgenesis of the testes syndrome caused by TSPYL1 variants.

Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is a rare autosomal recessive disorder associating developmental sex disorder (DSD) in patients with 46,XY karyotype and visceroautonomic dysfunction responsible for sudden infant death. First described in 2004, very few patients have since been reported. We describe here a new patient with SIDDT and epileptic encephalopathy (EE).

Surveillance to achieve malaria elimination in eastern Myanmar: a 7-year observational study.

Background: The collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance.

Methods: This retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021.

Same performance of exome sequencing before and after fetal autopsy for congenital abnormalities: toward a paradigm shift in prenatal diagnosis?

Prenatal exome sequencing could be complex because of limited phenotypical data compared to postnatal/portmortem phenotype in fetuses affected by multiple congenital abnormalities (MCA). Here, we investigated limits of prenatal phenotype for ES interpretation thanks to a blindly reanalysis of postmortem ES data using prenatal data only in fetuses affected by MCA and harboring a (likely)pathogenic variant or a variant of unknown significance (VUS). Prenatal ES identified all causative variant previously reported by postmortem ES (22/24 (92%) and 2/24 (8%) using solo-ES and trio-ES respectively).

Copy number variants calling from WES data through eXome hidden Markov model (XHMM) identifies additional 2.5% pathogenic genomic imbalances smaller than 30 kb undetected by array-CGH.

It has been estimated that Copy Number Variants (CNVs) account for 10%-20% of patients affected by Developmental Disorder (DD)/Intellectual Disability (ID). Although array comparative genomic hybridization (array-CGH) represents the gold-standard for the detection of genomic imbalances, common Agilent array-CGH 4 × 180 kb arrays fail to detect CNVs smaller than 30 kb. Whole Exome sequencing (WES) is becoming the reference application for the detection of gene variants and makes it possible also to infer genomic imbalances at single exon resolution.

GM3 synthase deficiency in non-Amish patients.

Purpose: Biallelic loss-of-function variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD) responsible for Amish infantile epilepsy syndrome. All Amish patients carry the homozygous p.(Arg288Ter) variant arising from a founder effect.

Interest of exome sequencing trio-like strategy based on pooled parental DNA for diagnosis and translational research in rare diseases.

Background: Exome sequencing (ES) has become the most powerful and cost-effective molecular tool for deciphering rare diseases with a diagnostic yield approaching 30%-40% in solo-ES and 50% in trio-ES. We applied an innovative parental DNA pooling method to reduce the parental sequencing cost while maintaining the diagnostic yield of trio-ES.

Methods: We pooled six (Agilent-CRE-v2-100X) or five parental DNA (TWIST-HCE-70X) aiming to detect allelic balance around 8-10% for heterozygous status.

Second-tier trio exome sequencing after negative solo clinical exome sequencing: an efficient strategy to increase diagnostic yield and decipher molecular bases in undiagnosed developmental disorders.

Developmental disorders (DD), characterized by malformations/dysmorphism and/or intellectual disability, affecting around 3% of worldwide population, are mostly linked to genetic anomalies. Despite clinical exome sequencing (cES) centered on genes involved in human genetic disorders, the majority of patients affected by DD remain undiagnosed after solo-cES. Trio-based strategy is expected to facilitate variant selection thanks to rapid parental segregation.

Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests.

With exome/genome sequencing (ES/GS) integrated into the practice of medicine, there is some potential for reporting incidental/secondary findings (IFs/SFs). The issue of IFs/SFs has been studied extensively over the last 4 years. In order to evaluate their implications in care organisation, we retrospectively evaluated, in a cohort of 700 consecutive probands, the frequency and burden of introducing the search for variants in a maximum list of 244 medically actionable genes (genes that predispose carriers to a preventable or treatable disease in childhood/adulthood and genes for genetic counselling issues).

Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function.

The unfolded protein response (UPR) is a highly conserved pathway that allows cells to respond to stress in the endoplasmic reticulum caused by an accumulation of misfolded and unfolded protein. This is of great importance to secretory cells because, in order for proteins to traffic from the endoplasmic reticulum (ER), they need to be folded appropriately. While a wealth of literature has implicated UPR in immune responses, less attention has been given to the role of UPR in T cell development and function.

Treatment of established TH2 cells with 4μ8c, an inhibitor of IRE1α, blocks IL-5 but not IL-4 secretion.

Background: T cell activation induces ER stress and upregulates Inositol Requiring Enzyme 1 alpha (IRE1α), an activator of the unfolded protein response (UPR) pathway. Inhibition of IRE1α RNase activity in activated CD4 splenocytes from naïve mice, via treatment of the cells with the commercially available drug 4μ8c upon activation, results in the reduction of the secretion of proteins IL-5, IL-4, and IL-13. Prior to this work, it was unknown if 4μ8c could inhibit TH2 cytokines in established TH2 cells, cells that are crucial in promoting disease in severe asthma.

Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of prospective annual reanalysis.

PurposeCongenital anomalies and intellectual disability (CA/ID) are a major diagnostic challenge in medical genetics-50% of patients still have no molecular diagnosis after a long and stressful diagnostic "odyssey." Solo clinical whole-exome sequencing (WES) was applied in our genetics center to improve diagnosis in patients with CA/ID.MethodsThis retrospective study examined 416 consecutive tests performed over 3 years to demonstrate the effectiveness of periodically reanalyzing WES data.

Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses.

Background And Objective: Whole-exome sequencing (WES) has now entered medical practice with powerful applications in the diagnosis of rare Mendelian disorders. Although the usefulness and cost-effectiveness of WES have been widely demonstrated, it is essential to reduce the diagnostic turnaround time to make WES a first-line procedure. Since 2011, the automation of laboratory procedures and advances in sequencing chemistry have made it possible to carry out diagnostic whole genome sequencing from the blood sample to molecular diagnosis of suspected genetic disorders within 50 h.