FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.

Introduction: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity.

Open label vancomycin in primary sclerosing cholangitis-inflammatory bowel disease: improved colonic disease activity and associations with changes in host-microbiome-metabolomic signatures.

Background: We conducted a single-arm interventional study, to explore mucosal changes associated with clinical remission under oral vancomycin (OV) treatment, in primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD); NCT05376228.

Method: Fifteen patients with PSC and active colitis (median faecal calprotectin 459µg/g; median total Mayo score 5) were treated with OV (125mg QID) for 4 weeks and followed-up for a further 4 weeks of treatment withdrawal (8 weeks, end-of-study). Colonic biopsies were obtained at baseline and week 4.

Exploring clinician perspectives of systems-based practice: A physician training challenge.

Introduction: Systems-based practice (SBP) has been a competency in US graduate medical education for over 20 years, but it is not well implemented. SBP is loosely defined as physician's responsiveness to the larger system of healthcare. The aim of this study was to describe healthcare professionals' perspectives regarding: (1) their knowledge and beliefs about SBP and (2) their beliefs regarding factors in clinical learning environments (CLE) that facilitate or hinder operationalisation and learning of SBP.

An investigation of sleep problems, gastrointestinal symptoms, comorbid psychopathology and challenging behavior in children and adolescents with Down Syndrome.

Background: Down syndrome (DS) is one of the most common chromosomal abnormalities, and children with DS have increased risks of receiving diagnoses of specific comorbidities.

Aims: This study aimed to assess the frequencies and relationships between sleep problems, gastrointestinal (GI) symptoms, comorbid psychopathology, and challenging behavior.

Methods And Procedures: The Children's Sleep Habits Questionnaire, Gastrointestinal Symptom Inventory, Autism Spectrum Disorder-Comorbid for Children, and Behavior Problems Inventory-Short Form were completed by 123 parents of children and adolescents with DS.

INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS-DERIVED EXTRACELLULAR VESICLES ATTENUATE LPS-INDUCED LUNG INJURY AND ENDOTOXEMIA IN MICE.

Introduction: We hypothesized extracellular vesicles (EVs) from preconditioned human-induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) attenuate LPS-induced acute lung injury (ALI) and endotoxemia. Methods: iMSCs were incubated with cell stimulation cocktail (CSC) and EVs were isolated. iMSC-EVs were characterized by size and EV markers.

Lineage-Specific Mesenchymal Stromal Cells Derived from Human iPSCs Showed Distinct Patterns in Transcriptomic Profile and Extracellular Vesicle Production.

Over the past decades, mesenchymal stromal cells (MSCs) have been extensively investigated as a potential therapeutic cell source for the treatment of various disorders. Differentiation of MSCs from human induced pluripotent stem cells (iMSCs) has provided a scalable approach for the biomanufacturing of MSCs and related biological products. Although iMSCs shared typical MSC markers and functions as primary MSCs (pMSCs), there is a lack of lineage specificity in many iMSC differentiation protocols.

The positive impact of conservation action.

Governments recently adopted new global targets to halt and reverse the loss of biodiversity. It is therefore crucial to understand the outcomes of conservation actions. We conducted a global meta-analysis of 186 studies (including 665 trials) that measured biodiversity over time and compared outcomes under conservation action with a suitable counterfactual of no action.

Educational Podcasts: Effect of Content Delivery Timing on Knowledge Acquisition and Retention.

Purpose: This study examined whether the order of podcast content influenced knowledge acquisition and retention among emergency medicine (EM) resident physicians.

Method: This preplanned secondary analysis of 2 large, multicenter trials included a randomized, crossover trial conducted from November 2019 to June 2020 of 100 residents that compared driving and seated condition for two 30-minute podcasts and a randomized, crossover trial conducted from September 2022 to January 2023 of 95 EM residents that compared exercise with seated condition for the same two 30-minute podcasts. Each podcast contained 6 journal article reviews, with the segments recorded in forward or backward order.

Impact of mental health comorbidity in children and young adults with inflammatory bowel disease: a UK population-based cohort study.

Objective: To evaluate the impact of mental health comorbidity in children and young adults with inflammatory bowel disease (IBD).

Design: Retrospective observational study.

Setting: Representative population, routinely collected primary care data from the UK Optimum Patient Care Research Database (2015-2019).

A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial.

Background: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies.

Methods: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation).

Differences in Emergency Medicine Resident Procedural Reporting by Gender in the United States.

Studies across specialties have demonstrated gender disparities in feedback, learner assessments, and operative cases. However, data are limited on differences in numbers of procedures among residents. To quantify the association between gender and the number of procedures reported among emergency medicine (EM) residents.

Balancing Hemostasis With Thrombosis: A Challenging Case of Pregnancy With a Mechanical Mitral Valve.

A 32-year-old pregnant woman with a mechanical mitral valve was admitted with vaginal bleeding and was found to have placenta previa. During her hospital stay, she developed acute valvular thrombosis. She underwent an emergency cesarean section followed by successful mechanical valve replacement.

LIRAGLUTIDE ALLEVIATES ACUTE LUNG INJURY AND MORTALITY IN PNEUMONIA-INDUCED SEPSIS THROUGH REGULATING SURFACTANT PROTEIN EXPRESSION AND SECRETION.

Glucagon-like peptide 1 (GLP-1) analogs are used to treat type 2 diabetes, and they can regulate insulin secretion, energy homeostasis, inflammation, and immune cell function. This study sought to determine whether the GLP-1 analog liraglutide exerts a beneficial action in an acute lung injury model of pneumonia-induced sepsis. Methods: Wild-type FVB/NJ mice (n = 114) were infected by intratracheal injection with Pseudomonas aeruginosa Xen5 (4 × 10 4 CFU/mouse) or an equal volume (50 μL) of saline (control) with or without a subcutaneous injection of liraglutide (2 mg/kg, 30 min after infection).

A Randomized Trial Assessing the Effect of Exercise on Residents' Podcast Knowledge Acquisition and Retention.

Purpose: Podcasts are commonly used by residents as part of their learning, with many listening concomitantly with other activities (e.g., driving and exercise).

Impact of intestinal microenvironments in obesity and bariatric surgery on shaping macrophages.

Obesity is associated with alterations in tissue composition, systemic cellular metabolism, and low-grade chronic inflammation. Macrophages are heterogenous innate immune cells ubiquitously localized throughout the body and are key components of tissue homeostasis, inflammation, wound healing, and various disease states. Macrophages are highly plastic and can switch their phenotypic polarization and change function in response to their local environments.

Galantamine improves glycemic control and diabetic nephropathy in Lepr mice.

Galantamine, a centrally acting acetylcholinesterase inhibitor, has been shown to attenuate inflammation and insulin resistance in patients with metabolic syndrome. We investigated the effects of galantamine on glycemic control and development of diabetic nephropathy (DN) in Lepr mice. Galantamine significantly reduced food intake, body weight, blood glucose and HbA1c levels.

Children and Young Adults With Inflammatory Bowel Disease Have an Increased Incidence and Risk of Developing Mental Health Conditions: A UK Population-Based Cohort Study.

Background: The burden of mental health conditions in children and young adults with inflammatory bowel disease remains unclear. We assessed this using a primary care database in the United Kingdom.

Methods: A retrospective, observational study compared children and young adults with incident inflammatory bowel disease 5 to 25 years of age (2010-2020) against population control subjects.

An assessment of the simulated performance of basic clinical procedures by junior doctors during the first year of clinical practice.

Background: Upon entering the healthcare system, junior doctors may lack the skills required to care for patients, and feel unprepared for their role, with considerable variation in the level of proficiency in the performance of particular clinical procedures.

Objective: To compare the performance and proficiency (self-report and observed) of the performance of nine basic clinical procedures.

Methods: Seventeen interns were observed performing nine clinical procedures in a simulated setting in June 2021 (Assessment 1) and January 2022 (Assessment 2).

A WNT4- and DKK3-driven canonical to noncanonical Wnt signaling switch controls multiciliogenesis.

Multiciliated cells contain hundreds of cilia whose directional movement powers the mucociliary clearance of the airways, a vital host defense mechanism. Multiciliated cell specification requires canonical Wnt signaling, which then must be turned off. Next, ciliogenesis and polarized ciliary orientation are regulated by noncanonical Wnt/planar cell polarity (Wnt/PCP) signaling.

Breaking Down Silos Between Medical Education and Health Systems: Creating an Integrated Multilevel Data Model to Advance the Systems-Based Practice Competency.

The complexity of improving health in the United States and the rising call for outcomes-based physician training present unique challenges and opportunities for both graduate medical education (GME) and health systems. GME programs have been particularly challenged to implement systems-based practice (SBP) as a core physician competency and educational outcome. Disparate definitions and educational approaches to SBP, as well as limited understanding of the complex interactions between GME trainees, programs, and their health system settings, contribute to current suboptimal educational outcomes elated to SBP.

Notch signaling inactivation by small molecule γ-secretase inhibitors restores the multiciliated cell population in the airway epithelium.

Multiciliated cell loss is a hallmark of airway epithelial remodeling in chronic inflammatory airway diseases including cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease. It disrupts mucociliary clearance, which fuels disease progression. Effective clearance requires an optimal proportion of multiciliated and secretory cells.

Trends in point-of-care ultrasound use among emergency medicine residency programs over a 10-year period.

Background: Point-of-care ultrasound (POCUS) is increasingly utilized in emergency medicine (EM). While residents are required by the Accreditation Council for General Medical Education to complete a minimum of 150 POCUS examinations before graduation, the distribution of examination types is not well-described. This study sought to assess the number and distribution of POCUS examinations completed during EM residency training and evaluate trends over time.