Using T-Cell Subsets to Better Characterize Immunoresiliency and Immunodeficiency in Patients with Recurrent Infections.

Background/objectives: Common Variable Immunodeficiency Disease (CVID) and other immunodeficiencies can present in subtle and variable ways. Whether or not a genetic lesion can be identified, there are not well understood biomarkers that quantitatively describe how severe a deficiency is. Here we discuss two possible ranking systems, CD4/CD8 T cell ratios and Immune Health Grades, and how such data maybe applicable to some immunodeficiencies.

Neuropsychiatric symptoms in cognitive decline and Alzheimer's disease: biomarker discovery using plasma proteomics.

Background And Objectives: Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer's disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression.

Draft genome of the caprolactam-degrading sp. CAP02 isolated from a landfill.

Here, we report the draft genome sequence of sp. CAP02, which metabolizes caprolactam as a sole source of carbon and nitrogen. This bacterium was isolated from Dane County Landfill Site No.

High-throughput surface epitope immunoaffinity isolation of extracellular vesicles and downstream analysis.

Extracellular vesicles (EVs), including exosomes, have significant potential for diagnostic and therapeutic applications. The lack of standardized methods for efficient and high-throughput isolation and analysis of EVs, however, has limited their widespread use in clinical practice. Surface epitope immunoaffinity (SEI) isolation utilizes affinity ligands, including antibodies, aptamers, or lectins, that target specific surface proteins present on EVs.

Manganese-Mediated Electrochemical Oxidation of Thioethers to Sulfoxides Using Water as the Source of Oxygen Atoms.

Oxygen-atom transfer reactions are a prominent class of synthetic redox reactions that often use high-energy oxygen-atom donor reagents. Electrochemical methods can bypass these reagents by using water as the source of oxygen atoms through pathways involving direct or indirect (mediated) electrolysis. Here, manganese porphyrins and related mediators are shown to be effective molecular electrocatalysts for selective oxidation of thioethers to sulfoxides, without overoxidation to the sulfone.

A broadly-neutralizing antibody against glycoprotein that potentiates the breadth and neutralization potency of other antibodies.

Ebolavirus disease (EVD) is caused by multiple species of . Monoclonal antibodies (mAbs) against the virus glycoprotein (GP) are the only class of therapeutic approved for treatment of EVD caused by (EBOV). Therefore, mAbs targeting multiple species may represent the next generation of EVD therapeutics.

Implementation of a perioperative registry in Ethiopia to enhance surgical quality improvement.

Background: Despite a glaring need and proven efficacy, prospective surgical registries are lacking in low- and middle-income countries. The objective of this study was to design and implement a comprehensive prospective perioperative registry in a low-income country.

Methods: This study was conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia.

Towards cascading genetic risk in Alzheimer's disease.

Alzheimer's disease typically progresses in stages, which have been defined by the presence of disease-specific biomarkers: amyloid (A), tau (T) and neurodegeneration (N). This progression of biomarkers has been condensed into the ATN framework, in which each of the biomarkers can be either positive (+) or negative (-). Over the past decades, genome-wide association studies have implicated ∼90 different loci involved with the development of late-onset Alzheimer's disease.

Single-cell genomics and regulatory networks for 388 human brains.

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.

Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes.

Background: While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance.

Methods: We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension).

Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes.

Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the large-scale production of hiPSC-CMs, implementation of hiPSC-CMs in industry settings, and recent clinical applications of this technology. The key observations are a need for traceable gender and ethnically diverse hiPSC lines, approaches to reduce cost of scale-up, accessible clinical trial datasets, and transparent guidelines surrounding the safety and efficacy of hiPSC-based therapies.

Cardiorespiratory fitness and submaximal exercise dynamics in normal-weight obesity and metabolically healthy obesity.

Purpose: Cardiorespiratory fitness (CRF) is critical for cardiovascular health. Normal-weight obesity (NWO) and metabolically healthy obesity (MHO) may be at increased risk for cardiovascular disease, but a comparison of CRF and submaximal exercise dynamics against rigorously defined low- and high-risk groups is lacking.

Methods: Four groups (N = 40; 10/group) based on body mass index (BMI), body fat %, and metabolic syndrome (MetS) risk factors were recruited: healthy controls (CON; BMI 18.

The efficacy of a verification stage for determining O and the impact of sampling intervals.

It is unknown whether oxygen uptake (V̇O) sampling intervals influence the efficacy of a verification stage following a graded exercise test (GXT). Fifteen females and 14 males (18-25 years) completed a maximal treadmill GXT. After a 5 ​min recovery, the verification stage began at the speed and grade corresponding with the penultimate stage from the GXT.

Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9.

β-Cell function during a high-fat meal in young versus old adults: role of exercise.

The acute effect of exercise on β-cell function during a high-fat meal (HFM) in young adults (YA) versus old adults (OA) is unclear. In this randomized crossover trial, YA ( = 5 M/7 F, 23.3 ± 3.