A Square Peg in A Round Hole: Social Experiences of Living with Diabetes in Canada in 2024.

Introduction: Diabetes self-management often occurs in social contexts, around others without diabetes. International consensus identifies the pervasive presence of social stigma towards those with diabetes, negatively impacting health, well-being, social and professional lives. We aimed to determine the social experiences of Canadian adults living with type 1(T2D) or type 2 (T2D) diabetes.

A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial.

New tuberculosis treatments are needed to address drug resistance, lengthy treatment duration and adverse reactions of available agents. GSK3036656 (ganfeborole) is a first-in-class benzoxaborole inhibiting the Mycobacterium tuberculosis leucyl-tRNA synthetase. Here, in this phase 2a, single-center, open-label, randomized trial, we assessed early bactericidal activity (primary objective) and safety and pharmacokinetics (secondary objectives) of ganfeborole in participants with untreated, rifampicin-susceptible pulmonary tuberculosis.

Discovery of a Series of Pyrazinone RORγ Antagonists and Identification of the Clinical Candidate BI 730357.

The interleukin (IL)-23/T helper (Th)17 axis plays a critical role in autoimmune diseases, and there is an increasing number of biologic therapies that target IL-23 and IL-17. The transcription factor retinoic acid receptor-related orphan nuclear receptor γt (RORγt) is important for the activation and differentiation of Th17 cells and thus is an attractive pharmacologic target for the treatment of Th17-mediated diseases. A novel series of pyrazinone RORγ antagonists was discovered through hybridization of two distinct screening hits and scaffold hopping.

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

Background: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax.

Discovery and optimization of pyrazole amides as antagonists of CCR1.

A HTS screen for CCR1 antagonists afforded a novel sub-micromolar hit 5 containing a pyrazole core. In this report the design, optimization, and SAR of novel CCR1 antagonists based on a pyrazole core motif is presented. Optimization led to the advanced candidate compounds (S)-16q and (S)-16r with 250-fold improved CCR1 potency, excellent off-target selectivity and attractive drug-like properties.

Enhancing community-based rehabilitation for stroke survivors: creating a discharge link.

Background And Objective: Intensive poststroke rehabilitation is critical to maximizing outcomes, improving inpatient flow, and decreasing long-term costs. This regional initiative investigated the impact of improving access to timely intensive home-based stroke rehabilitation follow-up care on hospital length of stay (LOS) and readmission rates. The enhanced service was made available across the region's rural geography to new stroke survivors transitioning home who were unable to access outpatient care.