Purpose: The purpose of this study was to systematically review and conduct a meta-analysis to examine the impact of comprehensive outpatient cardiac rehabilitation on exercise capacity, functional status, and quality of life in patients with heart failure.
Methods: PubMed, Embase, and CINAHL were searched using keywords and MeSH terms on heart failure and cardiac rehabilitation. Randomized clinical trials published in English using outpatient exercise-based cardiac rehabilitation in patients with heart failure were included.
Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19 patients and 86 controls and perform bulk RNA sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between six distinct neutrophil subtypes.
View Article and Find Full Text PDFAm J Respir Crit Care Med
March 2022
Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation.
View Article and Find Full Text PDFThe introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19.
View Article and Find Full Text PDFMultiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19 patients, 78 COVID-19 acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering.
View Article and Find Full Text PDFBACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants.
View Article and Find Full Text PDFMechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells.
View Article and Find Full Text PDFBackground: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus disease 2019 (COVID-19) in small-scale cohort studies. The mechanisms behind this association remain elusive.
Methods: We evaluated the relationship between SARS-CoV-2 viremia, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants.
COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins.
View Article and Find Full Text PDFMetabolic oligosaccharide engineering (MOE) is a maturing technology capable of modifying cell surface sugars in living cells and animals through the biosynthetic installation of non-natural monosaccharides into the glycocalyx. A particularly robust area of investigation involves the incorporation of azide functional groups onto the cell surface, which can then be further derivatized using "click chemistry." While considerable effort has gone into optimizing the reagents used for the azide ligation reactions, less optimization of the monosaccharide analogs used in the preceding metabolic incorporation steps has been done.
View Article and Find Full Text PDFMetabolic oligosaccharide engineering (MOE) refers to a technique where non-natural monosaccharide analogs are introduced into living biological systems. Once inside a cell, these compounds intercept a targeted biosynthetic glycosylation pathway and in turn are metabolically incorporated into cell-surface-displayed oligosaccharides where they can modulate a host of biological activities or be exploited as "tags" for bio-orthogonal and chemoselective ligation reactions. Undertaking a MOE experiment can be a daunting task based on the growing repertoire of analogs now available and the ever increasing number of metabolic pathways that can be targeted; therefore, a major emphasis of this article is to describe a general approach for analog design and selection and then provide protocols to ensure safe and efficacious analog usage by cells.
View Article and Find Full Text PDFThis report provides a perspective on metabolic glycoengineering methodology developed over the past two decades that allows natural sialic acids to be replaced with chemical variants in living cells and animals. Examples are given demonstrating how this technology provides the glycoscientist with chemical tools that are beginning to reproduce Mother Nature's control over complex biological systems - such as the human brain - through subtle modifications in sialic acid chemistry. Several metabolic substrates (e.
View Article and Find Full Text PDFThis study investigates the breadth of cellular responses engendered by short chain fatty acid (SCFA)-hexosamine hybrid molecules, a class of compounds long used in "metabolic glycoengineering" that are now emerging as drug candidates. First, a "mix and match" strategy showed that different SCFA (n-butyrate and acetate) appended to the same core sugar altered biological activity, complementing previous results [Campbell et al. J.
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