Phenotype-Led Identification of IL-10 Upregulators in Human CD4 T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors.

Therapeutics promoting the endogenous production of IL-10 have the potential to restore homeostasis in inflammatory disorders such as inflammatory bowel disease (IBD). Here we describe the identification of a series of IL-10 upregulators based on a pyrimidyl-piperidine scaffold through a high throughput phenotypic CD4 T-cell multiplex assay. optimization of the initial hit yielded a lead with good potency and an clearance profile, compound 3-7, which additionally demonstrated efficacy in a murine endotoxin challenge PK-PD mechanistic model.

Complete Heart Block in a Patient Declining Pacemaker Implantation: A Discussion on Patient-Centered Care and Shared Decision-Making.

Permanent pacemaker (PPM) implantation is the standard of care in patients with complete heart block (CHB) and second-degree type II atrioventricular (AV) block irrespective of patient symptoms when the conduction abnormality is irreversible. CHB generally constitutes a medical emergency that can be fatal if not urgently treated. This is in contrast to first-degree AV block and second-degree type I AV block, which require PPM implantation only in very special circumstances.

Establishing the African region monitoring vaccine effectiveness (AFRO-MoVE) network for respiratory pathogens.

Population-level vaccination with newly developed vaccines to respond to the COVID-19 pandemic created a need to monitor vaccine effectiveness (VE) in the context of emerging SARS-CoV-2 variants and changing epidemiology. WHO and partners launched the African Region Monitoring Vaccine Effectiveness (AFRO-MoVE) Network in March 2021 to assess the performance of COVID-19 vaccines in real-world conditions in Africa. The Network aimed to facilitate and support comparable COVID-19 vaccine effectiveness studies in the African region, to provide a platform of scientific expertise and infrastructure, encourage the use of robust similar study designs to enable pooling to produce regional VE estimates and to build a sustainable network of hospitals, institutions, and experts to evaluate vaccines against pandemic and endemic respiratory pathogens.

'Mental heAlth and well-being in rUgby pLayers' (MAUL) study: an online survey of diverse cohorts of rugby union players internationally.

Introduction: Mental health and well-being is a relatively under-researched area in rugby, especially outside the elite men's game. Evidence suggests that physical activity and sports benefit mental health and well-being, and rugby provides health-enhancing moderate-to-vigorous physical activity.

Objective: This cross-sectional study used an online approach and engaged national rugby governing bodies to understand adult rugby players' mental health and well-being and increase the diversity of the current evidence base.

Regional Anesthesia With Pectoral Blocks as a Non-inferior Approach for Mastectomy Analgesia: A Quality Improvement Study.

Introduction Breast cancer is one of the most common female malignancies in the United States and often necessitates surgical interventions that carry a substantial risk of postoperative pain. Pectoral nerve blocks have emerged as a simpler alternative for providing regional perioperative analgesia to the chest wall in breast cancer surgery. This retrospective study evaluated the impact of implementing a novel regional anesthesia protocol centering on the use of pectoral nerve blocks for patients undergoing radical mastectomy at a small regional hospital in Spartanburg, South Carolina.