Effect of pulmonary rehabilitation duration on exercise capacity and health-related quality of life in people with chronic obstructive pulmonary disease (PuRe Duration Trial): A randomized controlled equivalence trial.

Background And Objective: There is no strong evidence on the optimal duration of pulmonary rehabilitation (PR) programmes. The aim of the study was to determine whether an 8-week PR programme was equivalent to a 12-week PR programme in improving endurance exercise capacity in people with chronic obstructive pulmonary disease (COPD).

Methods: Participants with COPD were randomized to either an 8-week (8-wk Group) or 12-week (12-wk Group), twice weekly, supervised PR programme consisting of endurance and strength training and individualized self-management education.

Patterns of physical activity of people with COPD during participation in a pulmonary rehabilitation program.

Introduction: Very few studies have examined patterns of physical activity (PA) during a pulmonary rehabilitation (PR) program in people with COPD.

Aims: To compare the patterns of PA in: 1) the week before commencing PR (pre-PR) with a week during PR (PR week); 2) PR days and non-PR days during a PR week; 3) pre-PR and the week following PR completion (post-PR).

Methods: This was a multicenter, prospective cohort study.

Effect of a 4-Week Telerehabilitation Program for People With Post-COVID Syndrome on Physical Function and Symptoms: Protocol for a Randomized Controlled Trial.

Objective: COVID-19 has led to significant morbidity and mortality globally. Post-COVID sequelae can persist beyond the acute and subacute phases of infection, often termed post-COVID syndrome (PCS). There is limited evidence on the appropriate rehabilitation for people with PCS.

Changes in Exercise Capacity and Health-Related Quality of Life at Four and Eight Weeks of a Pulmonary Rehabilitation Program in People with COPD.

Pulmonary Rehabilitation (PR) is a key intervention in the management of people with chronic obstructive pulmonary disease (COPD), though few studies have assessed where changes in outcomes occur during a PR program. The aim of this study was to determine the changes in exercise capacity and health-related quality of life at four and eight weeks during a twice-weekly supervised PR program in people with COPD. Fifty participants with COPD were recruited and attended PR twice-weekly for eight weeks.

Identification and Mechanistic Characterization of a Peptide Inhibitor of Glycogen Synthase Kinase (GSK3β) Derived from the Disrupted in Schizophrenia 1 (DISC1) Protein.

Glycogen synthase kinase 3-beta (GSK3β) is a critical regulator of several cellular pathways involved in neurodevelopment and neuroplasticity and as such is a potential focus for the discovery of new neurotherapeutics toward the treatment of neuropsychiatric and neurodegenerative diseases. The majority of efforts to develop inhibitors of GSK3β have been focused on developing small molecule inhibitors that compete with adenosine triphosphate (ATP) through direct interaction with the ATP binding site. This strategy has presented selectivity challenges due to the evolutionary conservation of this domain within the kinome.

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo.

There is a paucity of efficacious new compounds to treat neuropsychiatric disorders. We present a novel approach to neuropsychiatric drug discovery based on high-content characterization of druggable signaling network responses at the single-cell level in patient-derived lymphocytes ex vivo. Primary T lymphocytes showed functional responses encompassing neuropsychiatric medications and central nervous system ligands at established (e.

Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide Selectivity and Their Functional Effects.

The mood stabilizer lithium, the first-line treatment for bipolar disorder, is hypothesized to exert its effects through direct inhibition of glycogen synthase kinase 3 (GSK3) and indirectly by increasing GSK3's inhibitory serine phosphorylation. GSK3 comprises two highly similar paralogs, GSK3α and GSK3β, which are key regulatory kinases in the canonical Wnt pathway. GSK3 stands as a nodal target within this pathway and is an attractive therapeutic target for multiple indications.

Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the prevalence of HCC, there is no effective, systemic treatment. The transcription factor LSF is a promising protein target for chemotherapy; it is highly expressed in HCC patient samples and cell lines, and promotes oncogenesis in rodent xenograft models of HCC.

Disc1 regulates both β-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis.

Disc1 is a schizophrenia risk gene that engages multiple signaling pathways during neurogenesis and brain development. Using the zebrafish as a tool, we analyze the function of zebrafish Disc1 (zDisc1) at the earliest stages of brain and body development. We define a "tool" as a biological system that gives insight into mechanisms underlying a human disorder, although the system does not phenocopy the disorder.

Enantioselective addition of boronates to acyl imines catalyzed by chiral biphenols.

On the big screen: A chiral biphenol catalyst screening protocol was developed for the rapid identification of enantioselective nucleophilic boronate reactions with acyl imines (see scheme). The approach successfully identified a unique catalyst for the reaction of aryl, vinyl, and alkynyl boronates. Mechanistic studies demonstrate boronate ligand exchange with the catalyst is necessary for activation towards nucleophilic addition.