Exit Interviews Exploring Patients' Experience of Change in Crohn's Disease Symptoms During the Mirikizumab Phase 3 Clinical Trial In Adult Patients With Moderately-to-Severely Crohn's Disease.

Background: Exit interviews with patients who completed the Phase 3 VIVID-1 mirikizumab clinical trial for moderately-to-severely active Crohn's disease explored the content validity of bowel urgency, stool frequency, and abdominal pain patient-reported outcome measures and perceptions of meaningful within-patient change and remission in these key Crohn's disease symptoms.

Methodology: Cognitive debriefing explored patient understanding of the bowel urgency numeric rating scale (Urgency NRS), Crohn's Disease Activity Index: Stool Frequency (CDAI-SF) and Abdominal Pain (CDAI-AP), and patient global rating/impression of severity/change (PGRS/PGIC). Perceptions of meaningful change and remission were explored qualitatively.

An IL-6 promoter variant (-174 G/C) augments IL-6 production and alters skeletal muscle transcription in response to exercise in mice.

Interleukin-6 (IL-6) is produced and secreted by skeletal muscle cells during exercise and plays an important role in mediating metabolic responses to exercise. The promoter region of the IL-6 gene contains a common genetic variant (-174 G/C, rs1800795), which may alter responses to exercise training. To isolate the impact of this gene variant on exercise-induced IL-6 expression and skeletal muscle transcription responses following exercise, we generated knock-in mice with a GG or variant CC genotype for the murine homolog of rs1800795.

Mechanical loading reveals an intrinsic cardiomyocyte stiffness contribution to diastolic dysfunction in murine cardiometabolic disease.

Cardiometabolic syndromes including diabetes and obesity are associated with occurrence of heart failure with diastolic dysfunction. There are no specific treatments for diastolic dysfunction, and therapies to manage symptoms have limited efficacy. Understanding of the cardiomyocyte origins of diastolic dysfunction is an important priority to identify new therapeutics.

Methods for detection of cardiac glycogen-autophagy.

Glycogen-autophagy ('glycophagy') is a selective autophagy process involved in delivering glycogen to the lysosome for bulk degradation. Glycophagy protein intermediaries include STBD1 as a glycogen tagging receptor, delivering the glycogen cargo into the forming phagosome by partnering with the Atg8 homolog, GABARAPL1. Glycophagy is emerging as a key process of energy metabolism and development of reliable tools for assessment of glycophagy activity is an important priority.

Comparison of gene-by-gene and genome-wide short nucleotide sequence-based approaches to define the global population structure of .

Defining the population structure of a pathogen is a key part of epidemiology, as genomically related isolates are likely to share key clinical features such as antimicrobial resistance profiles and invasiveness. Multiple different methods are currently used to cluster together closely related genomes, potentially leading to inconsistency between studies. Here, we use a global dataset of 26 306  genomes to compare four clustering methods: gene-by-gene seven-locus MLST, core genome MLST (cgMLST)-based hierarchical clustering (HierCC) assignments, life identification number (LIN) barcoding and k-mer-based PopPUNK clustering (known as GPSCs in this species).

Mechanical loading reveals an intrinsic cardiomyocyte stiffness contribution to diastolic dysfunction in murine cardiometabolic disease.

Cardiometabolic syndromes including diabetes and obesity are associated with occurrence of heart failure with diastolic dysfunction. There are no specific treatments for diastolic dysfunction, and therapies to manage symptoms have limited efficacy. Understanding of the cardiomyocyte origins of diastolic dysfunction is an important priority to identify new therapeutics.

Myocardial glycophagy flux dysregulation and glycogen accumulation characterize diabetic cardiomyopathy.

Diabetic heart disease morbidity and mortality is escalating. No specific therapeutics exist and mechanistic understanding of diabetic cardiomyopathy etiology is lacking. While lipid accumulation is a recognized cardiomyocyte phenotype of diabetes, less is known about glycolytic fuel handling and storage.

Using behavioral science to increase core outcome set use in trials.

Objectives: Core outcome sets (COS) are agreed sets of outcomes for use in clinical trials, which can increase standardization and reduce heterogeneity of outcomes in research. Using a COS, or not, is a behavior that can potentially be increased using behavioral strategies. The aim of this study was to identify behavioral intervention components to potentially increase use of COS in trials.

The cardiomyocyte origins of diastolic dysfunction: cellular components of myocardial "stiffness".

The impaired ability of the heart to relax and stretch to accommodate venous return is generally understood to represent a state of "diastolic dysfunction" and often described using the all-purpose noun "stiffness." Despite the now common qualitative usage of this term in fields of cardiac patho/physiology, the specific quantitative concept of stiffness as a molecular and biophysical entity with real practical interpretation in healthy and diseased hearts is sometimes obscure. The focus of this review is to characterize the concept of cardiomyocyte stiffness and to develop interpretation of "stiffness" attributes at the cellular and molecular levels.

Using behavioural science to enhance use of core outcome sets in trials: protocol.

Background: Core outcome sets (COS) represent agreed-upon sets of outcomes, which are the minimum that should be measured and reported in all trials in specific health areas. Use of COS can reduce outcome heterogeneity, selective outcome reporting, and research waste, and can facilitate evidence syntheses. Despite benefits of using COS, current use of COS in trials is low.

Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.

Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients.

Evidence of virulence and antimicrobial resistance in serotype 16F lineages.

Introduction: Due to the emergence of non-vaccine serotypes in vaccinated populations, remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA).

Aim: To characterise lineages and antimicrobial resistance in 16F isolates obtained from South Africa and placed the local findings in a global context.

Enhanced Stress Resilience Training for UK Surgical Trainees; Effect and Evolution Evaluated.

Introduction: Core Surgical Training (CST) programs are associated with high burnout. This study aimed to assess the influence of Enhanced Stress Resilience Training (ESRT) over a 2-year period in a single UK Statutory Education Body.

Method: CSTs participated in 5-weeks of formal ESRT to address work stressors.

Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology.

Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies.

A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia.

Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries.

Reminding Peer Reviewers of Reporting Guideline Items to Improve Completeness in Published Articles: Primary Results of 2 Randomized Trials.

Importance: Numerous studies have shown that adherence to reporting guidelines is suboptimal.

Objective: To evaluate whether asking peer reviewers to check if specific reporting guideline items were adequately reported would improve adherence to reporting guidelines in published articles.

Design, Setting, And Participants: Two parallel-group, superiority randomized trials were performed using manuscripts submitted to 7 biomedical journals (5 from the BMJ Publishing Group and 2 from the Public Library of Science) as the unit of randomization, with peer reviewers allocated to the intervention or control group.

Accuracy of diagnostic tests in cardiac injury after blunt chest trauma: a systematic review and meta-analysis.

Introduction: The diagnosis of cardiac contusion, caused by blunt chest trauma, remains a challenge due to the non-specific symptoms it causes and the lack of ideal tests to diagnose myocardial damage. A cardiac contusion can be life-threatening if not diagnosed and treated promptly. Several diagnostic tests have been used to evaluate the risk of cardiac complications, but the challenge of identifying patients with contusions nevertheless remains.

A retrospective cohort study of differential attainment, COVID and chaos: taking the difference out of a terrible trinity.

Background: This study aimed to evaluate core surgical training (CST) differential attainment related to coronavirus disease 2019 (COVID-19), gender and ethnicity. The hypothesis was that COVID-19 adversely influenced CST outcomes.

Methods: A retrospective cohort study of 271 anonymised CST records was undertaken at a UK Statutory Education Body.

Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy.

Anthracyclines such as doxorubicin are widely used chemotherapy drugs. A common side effect of anthracycline therapy is cardiotoxicity, which can compromise heart function and lead to dilated cardiomyopathy and heart failure. Dexrazoxane and heart failure medications (i.

Differential attainment in higher surgical training: scoping pan-specialty spectra.

Introduction: This study aimed to evaluate differential attainment during higher surgical training (HST; all specialties) related to three ethnic cohorts: White UK (WUKG), Black and Minority Ethnic UK Graduates (BMEUKG), and International Medical Graduates (IMG).

Method: Anonymised records of 266 HSTs (126 WUKG, 65 BMEUKG, 75 IMG; 7 years) in a single UK Statutory Education Body were examined. Primary effect measures were Annual Record of Competency Progression Outcome (ARCPO) and Fellowship of the Royal College of Surgeons (FRCS) pass.

Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice.

Diminished insulin and insulin-like growth factor-1 signaling extends the lifespan of invertebrates; however, whether it is a feasible longevity target in mammals is less clear. Clinically utilized therapeutics that target this pathway, such as small-molecule inhibitors of phosphoinositide 3-kinase p110α (PI3Ki), provide a translatable approach to studying the impact of these pathways on aging. Here, we provide evidence that dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females.

Prognostic significance of drivers at work and learning styles in surgical training.

Purpose Of The Study: Drivers at work (DW) and Learning Styles (LS) refer to contentious theories that aim to account for differential career development yet seldom feature in assessment. This study aimed to quantify the influence of core surgical trainees' (CST) DW and LS on career progress.

Study Design: DW questionnaires and Kolb LS inventories were distributed to 168 CSTs during five consecutive induction boot camps in a single-statutory education body.