RAC2 gain-of-function variants causing inborn error of immunity drive NLRP3 inflammasome activation.

A growing number of patients presenting severe combined immunodeficiencies attributed to monoallelic RAC2 variants have been identified. The expression of the RHO GTPase RAC2 is restricted to the hematopoietic lineage. RAC2 variants have been described to cause immunodeficiencies associated with high frequency of infection, leukopenia, and autoinflammatory features.

A Stepped-Wedge Cluster-Randomized Trial to Improve Adherence to Evidence-Based Practices for Acute Stroke Management.

Background: There is limited evidence regarding the optimal design and composition of multifaceted quality improvement programs to improve acute stroke care. The researchers aimed to test the effectiveness of a co-designed multifaceted intervention (STELAR: Shared Team Efforts Leading to Adherence Results) directed at hospital clinicians for improving acute stroke care tailored to the local context using feedback of national registry indicator data.

Methods: STELAR was a stepped-wedge cluster trial (partial randomization) using routinely collected Australian Stroke Clinical Registry data from Victorian hospitals segmented in two-month blocks.

PATAS, a First-in-Class Therapeutic Peptide Biologic, Improves Whole-Body Insulin Resistance and Associated Comorbidities In Vivo.

Adipose tissue is a key regulator of whole-body metabolic fitness because of its role in controlling insulin sensitivity. Obesity is associated with hypertrophic adipocytes with impaired glucose absorption, a phenomenon existing in the ultrarare monogenic disorder Alström syndrome consisting of severe insulin resistance. Inactivation of ALMS1 directly inhibits insulin-mediated glucose absorption in the white adipose tissue and induces severe insulin resistance, which leads to type 2 diabetes, accelerated nonalcoholic liver disease, and fibrosis.

Feedback of aggregate patient-reported outcomes (PROs) data to clinicians and hospital end users: findings from an Australian codesign workshop process.

Objectives: Patient-reported outcomes (PROs) are increasingly used to measure the patient's perspective of their outcomes following healthcare interventions. The aim of this study was to determine the preferred formats for reporting service-level PROs data to clinicians, researchers and managers to support greater utility of these data to improve healthcare and patient outcomes.

Setting: Healthcare professionals receiving PRO data feedback at the health service level.

Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice.

Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations.