Microglial AKAP8L: a key mediator in diabetes-associated cognitive impairment via autophagy inhibition and neuroinflammation triggering.

Background: Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI.

Methods: We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo.

Protocol update for a multi-centre randomised controlled trial of exercise rehabilitation for people with pulmonary hypertension: the SPHERe trial.

Background: The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020.

Cost-effectiveness of a new multi-lumen infusion device to reduce central-venous-line-associated bloodstream infections in neonates.

Background: A new medical device was developed for multi-infusion in neonatal intensive care units (NICUs) with the aim of addressing issues related to drug incompatibilities and central-line-associated bloodstream infections (CLABSIs).

Aim: To assess the cost-effectiveness of implementing this new perfusion system in an NICU setting.

Methods: This single-centre, observational study was conducted in all infants admitted to the NICU within 3 days of birth, and who required a central venous line, to evaluate the cost and effectiveness before (2019) and after (2020) implementation of the new perfusion system.

CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD.

Graft-versus-host disease (GVHD) remains a major challenge after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and further understanding of its immunopathology is crucial for developing new treatments. CD70 interacts with CD27 and is upregulated transiently on T cells after recent T-cell receptor (TCR) engagement. Here, we investigated the functional and clinical significance of CD70 expression on T cells during the early posttransplantation period.

Volumetric measurement of terminal ileal Crohn's disease by magnetic resonance enterography: a feasibility study.

Objectives: Magnetic resonance enterography (MRE) interpretation of Crohn's disease (CD) is subjective and uses 2D analysis. We evaluated the feasibility of volumetric measurement of terminal ileal CD on MRE compared to endoscopy and sMARIA, and the responsiveness of volumetric changes to biologics.

Methods: CD patients with MRE and contemporaneous CD endoscopic index of severity-scored ileocolonoscopy were included.

When should lockdown be implemented? Devising cost-effective strategies for managing epidemics amid vaccine uncertainty.

During an infectious disease outbreak, public health policy makers are tasked with strategically implementing interventions whilst balancing competing objectives. To provide a quantitative framework that can be used to guide these decisions, it is helpful to devise a clear and specific objective function that can be evaluated to determine the optimal outbreak response. In this study, we have developed a mathematical modelling framework representing outbreaks of a novel emerging pathogen for which non-pharmaceutical interventions (NPIs) are imposed or removed based on thresholds for hospital occupancy.

Photo-Cross-linked Gelatin Methacryloyl Hydrogels Enable the Growth of Primary Human Endometrial Stromal Cells and Epithelial Gland Organoids.

three-dimensional (3D) models are better able to replicate the complexity of real organs and tissues than 2D monolayer models. The human endometrium, the inner lining of the uterus, undergoes complex changes during the menstrual cycle and pregnancy. These changes occur in response to steroid hormone fluctuations and elicit crosstalk between the epithelial and stromal cell compartments, and dysregulations are associated with a variety of pregnancy disorders.

Practitioner Review: Continuity of mental health care from childhood to adulthood for youths with ADHD - who, how and when?

Many youths with attention-deficit/hyperactivity disorder (ADHD) experience significant long-term impairment and may develop concurrent mental and somatic health difficulties as adults. This is associated with burden and costs for the individual and society which could be prevented through continued support in youth. Yet, only few young people transition to adult mental health services for ongoing care in different countries worldwide.

Acute frailty services: results of a national day of care survey.

Introduction: Older people living with frailty are at high risk of emergency hospital admission and often have complex care needs which may not be adequately met by conventional models of acute care. This has driven the introduction of adaptations to acute care pathways designed to improve outcomes in this patient group. The identification of differences in the organisational approach to frailty may highlight opportunities for quality improvement.

Glucose influences endometrial receptivity to embryo implantation through O-GlcNAcylation-mediated regulation of the cytoskeleton.

Phenotypic changes to endometrial epithelial cells underpin receptivity to embryo implantation at the onset of pregnancy but the effect of hyperglycemia on these processes remains poorly understood. Here, we show that physiological levels of glucose (5 mM) abolished receptivity in the endometrial epithelial cell line, Ishikawa. However, embryo attachment was supported by 17 mM glucose as a result of glucose flux through the hexosamine biosynthetic pathway (HBP) and modulation of cell function via protein O-GlcNAcylation.

Investigating grey matter volumetric trajectories through the lifespan at the individual level.

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14-23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV).

Tailored leadership training in emergency medicine: qualitative exploration of the impact of the EMLeaders programme on consultants and trainees in England.

Background: Emergency medicine (EM) consultants are expected to provide leadership to facilitate optimal clinical results, effective teamwork and learning. To foster leadership skills, the Emergency Medicine Leadership Programme (EMLeaders) was launched in 2018 by the Royal College of Emergency Medicine (RCEM), Health Education England and National Health Service England. A mixed-methods evaluation of EMLeaders was commissioned to assess the impact at the strategic, team and individual levels.

Core Set of Patient-Reported Outcome Measures for Measuring Quality of Life in Clinical Obesity Care.

Purpose: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care.

Materials And Methods: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022.

Ambulatory Management of Bite Injuries to the Hand: A Safe and Cost-Effective Option.

Introduction Animal or human hand bites are a common presentation to the emergency department. If hand bites are not treated adequately, they can give rise to significant local and systemic complications, potentially leading to functional deficits that impact patients' lives. Traditionally, hand bites require hospital admission for the administration of intravenous antibiotics and, in some cases, surgical intervention.

The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included.

Teaching team competencies within resuscitation training: A systematic review.

Objectives: To evaluate the effectiveness of life support training with specific emphasis on team competencies on clinical and educational outcomes.

Methods: This systematic review was prospectively registered (PROSPERO CRD42023473154) and followed the PICOST (population, intervention, comparison, outcome, study design, timeframe) format. All randomized controlled trials and non-randomized studies evaluating learners undertaking life support training with specific emphasis on team competencies in any setting (actual and simulated resuscitations) were included.

Consistently lower volumes across thalamus nuclei in very premature-born adults.

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years.

Advances in the management of parathyroid carcinoma.

Parathyroid carcinoma (PCA) is a rare malignancy accounting for approximately 1% of all patients with primary hyperparathyroidism. It is characterised by excessive parathyroid hormone (PTH) production. This manuscript reviews recent advances in the management of parathyroid carcinoma, focusing on molecular insights, diagnostic modalities, surgical innovations, adjuvant therapies, and emerging targeted treatments.

Randomized 20-year infancy-onset dietary intervention, life-long cardiovascular risk factors and retinal microvasculature.

Background And Aims: Retinal microvasculature characteristics predict cardiovascular morbidity and mortality. This study investigated associations of lifelong cardiovascular risk factors and effects of dietary intervention on retinal microvasculature in young adulthood.

Methods: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project study.

A low molecular weight dextran sulphate, ILB®, for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial.

Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics.

The cost-effectiveness of mental health interventions amongst prison populations: a systematic review (research letter to the editor).

The link between imprisonment and adverse mental health is well established and linked to both recidivism and prison misconduct, with negative consequences for prisoners, the prison system and society. To help minimise these impacts, appropriate mental health interventions are required. However, owing to finite resources to deliver healthcare in prisons, interventions must be both clinically and cost-effective.