Protein shapeshifting in necroptotic cell death signaling.

Necroptosis is a mode of programmed cell death executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following its activation by the upstream receptor-interacting protein kinase-3 (RIPK3), subsequent to activation of death, Toll-like, and pathogen receptors. The pathway originates in innate immunity, although interest has surged in therapeutically targeting necroptosis owing to its dysregulation in inflammatory diseases. Here, we explore how protein conformation and higher order assembly of the pathway effectors - Z-DNA-binding protein-1 (ZBP1), RIPK1, RIPK3, and MLKL - can be modulated by post-translational modifications, such as phosphorylation, ubiquitylation, and lipidation, and intermolecular interactions to tune activities and modulate necroptotic signaling flux.

Evaluating the impact of Canadian cannabis legalization on cannabis use outcomes in emerging adults: Comparisons to a US control sample via a natural experiment.

Background: Recreational cannabis legalization marked a significant policy shift in Canada, but has been difficult to evaluate because of the absence of a control group. Although it is unfeasible to evaluate legalization using a randomized controlled trial design, sophisticated statistical techniques can employ quasi-experimental designs using natural experiments. This study evaluates the impact of cannabis legalization in a longitudinal cohort of Canadian emerging adults by comparing changes in cannabis use frequency and related consequences over time to changes in a similar cohort in a United States jurisdiction where no policy change took place.

Understanding Stakeholder Priorities in Dupuytren Disease: A Qualitative Study.

Background: Currently, there is no recommended standard set of outcomes to report in Dupuytren disease treatment studies, nor are there guidelines on how the outcomes themselves should be reported. This study aimed to elicit the most salient issues for patients living with and undergoing treatment for Dupuytren disease, as well as for the hand surgeons, occupational therapists, and physical therapists caring for these patients.

Methods: A qualitative, interpretive description study employing one-on-one semi-structured interviews was conducted.

Orthopaedic Provider Coding Trends After 2021 Changes to the Current Procedural Terminology Evaluation and Management Coding Guidelines: A Retrospective Cohort Study.

Background: The goal of this study was to determine changes in orthopaedic coding practices between December 2020 and January 2021 after training providers on the 2021 Current Procedural Terminology Evaluation and Management (E&M) Centers for Medicare and Medicaid Services guideline changes.

Methods: Outpatient encounters in December 2020, January 2021, December 2021, and January 2023 were grouped by provider and E&M code level. The codes used for established patients were 99211, 99212, 99213, 99214, and 99215, ordered from low to high-complexity visits.

Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses.

Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.