A new model of experimental diabetic cardiomyopathy using combination of multiple doses of anomer-equilibrated streptozotocin and high fat diet: sex matters.

Diabetes mellitus (DM) leads to a more rapid development of DM cardiomyopathy (dbCM) and progression to heart failure in women than men. Combination of high-fat diet (HFD) and freshly-injected streptozotocin (STZ) has been widely used for DM induction, however emerging data shows that anomer-equilibrated STZ produces an early onset and robust DM model. We designed a novel protocol utilising a combination of multiple doses of anomer-equilibrated STZ injections and HFD to develop a stable murine DM model featuring dbCM analogous to humans.

Delirium prevention in hospices: Opportunities and limitations - A focused ethnography.

Background: Delirium is common and distressing for hospice in-patients. Hospital-based research shows delirium may be prevented by targeting its risk factors. Many preventative strategies address patients' fundamental care needs.

Anatomic and Functional Outcomes of Scleral Buckling Surgery for Advanced Retinopathy of Prematurity: A Systematic Review and Proportional Meta-Analysis.

A significant percentage of patients with retinopathy of prematurity (ROP) who progressed to stages 4 and 5 of ROP will require surgical intervention. Scleral buckling surgery is widely employed for the restoration of retinal detachment in advanced cases of ROP. This systematic review and meta-analysis aim to review the anatomical and visual outcomes following scleral buckling surgery in ROP of stages 4 and 5.

Improving Communication and Teamwork Between Resident Doctor Teams Using a Group Messaging Application: A Quality Improvement Project.

Background Communication and teamwork are essential in medicine. Established standards emphasise the importance of collaboration and access to support. Some departments divide doctors into teams; however, inter-team communication is not always efficient.

Assessing Human Ribosomal DNA Variation and Its Association With Phenotypic Outcomes.

Although genome-scale analyses have provided insights into the connection between genetic variability and complex human phenotypes, much trait variation is still not fully understood. Genetic variation within repetitive elements, such as the multi-copy, multi-locus ribosomal DNA (rDNA), has emerged as a potential contributor to trait variation. Whereas rDNA was long believed to be largely uniform within a species, recent studies have revealed substantial variability in the locus, both within and across individuals.

Combination therapy versus monotherapy: retrospective analysis of antibiotic treatment of enterococcal endocarditis.

Background: Guidelines suggest treating fully penicillin-susceptible Enterococcus faecalis strains causing infective endocarditis with amoxicillin combined with gentamicin or ceftriaxone, but clinical evidence to support this practice is limited and monotherapy cohorts were excluded from studies. We describe antibiotic treatment, complications, and outcomes in patients with Enterococcus faecalis infective endocarditis, specifically comparing monotherapy versus combination therapy.

Methods: Retrospective analysis of prospectively collected cohort of patients with definite or possible infective endocarditis from 2 English centres between 2006 and 2021.

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

Rigour of Development of European Society of Cardiology, American College of Cardiology and American Heart Association guidelines over a 12-year period (2013-2024): a systematic review of guidelines.

Introduction: The ESC and ACC/AHA regularly publish guidelines for the management of cardiovascular disease. By definition, a guideline should follow strict methodological criteria, and have a transparent, traceable and reproducible development process. We aimed to assess the overall strength of the recommendations and rigour of methodological development in ESC and ACC/AHA guidelines.

"Showing the Best Version of Yourself": The Importance of Dynamic Assessment for Trainees Undergoing Workplace-Based Assessments in Postgraduate Training.

Workplace-based assessments (WPBAs) in postgraduate training may not always provide an accurate representation of a trainee's capability to perform a given task, or a true measure of a trainee's overall competence in clinical practice settings. This article describes how trainers can use a theory-driven and evidence-based intervention called dynamic assessment for providing an individual with the best opportunity to demonstrate a more accurate representation of their performance, and ultimately present the best version of themselves when undergoing an observed WPBA, such as a Direct Observation of Procedural Skills (DOPS) or Mini Consultation Evaluation Exercise (MiniCEX). Dynamic assessment simultaneously combines educational support with assessment as the trainee undergoes the WPBA by using focussed questions as prompts to facilitate an individual trainee's essential coordination of their motivational and thinking processes since this is often challenged during assessments.

GM-CSF and IL-21-armed oncolytic vaccinia virus significantly enhances anti-tumor activity and synergizes with anti-PD1 immunotherapy in pancreatic cancer.

Pancreatic cancer is one of the most aggressive cancers and poses significant challenges to current therapies because of its complex immunosuppressive tumor microenvironment (TME). Oncolytic viruses armed with immunoregulatory molecules are promising strategies to overcome limited efficacy and target inaccessible and metastatic tumors. In this study, we constructed a tumor-selective vaccinia virus (VV) with deletions of the TK and A49 genes (VVLΔTKΔA49, VVL-DD) using CRISPR-Cas9-based homologous recombination.

Changes in thoracic erector spinae regional activation during postural adjustments and functional reaching tasks after spinal cord injury.

Many individuals with incomplete spinal cord injury (SCI) exhibit reduced volitional control of trunk muscles, such as impaired voluntary contractions of the erector spinae (ES), due to damage to the neural pathways regulating sensorimotor function. Studies using conventional bipolar electromyography (EMG) showed alterations in the overall, or global, activation of the trunk muscles in people with SCI. However, how activation varied across specific regions within the ES, referred to as regional activation, remains unknown.

Relapsing ANCA-associated vasculitis presenting as a mediastinal mass.

Anti-neutrophil cytoplasmic antibody-associated vasculitides (AAV) represent a heterogeneous multisystem group of disorders typified by necrotising inflammation of smaller blood vessels, classically yielding a pauci-immune, crescentic glomerulonephritis. Without prompt treatment, there is a significant risk of irreversible damage and ensuing renal impairment.Diagnosis is often challenging, exacerbated by the disorder's often vague and insidious presentation.

A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom.

Background: Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload.

Case Presentation: In the early 2000s the United Kingdom created a new occupational role, that of physician assistant.

Self-directed violence and unclear intent presentation within a major trauma system. A multisite analysis.

Background: Determining trauma as an act of Self-directed violence (SDV) or from high risk or unclear behaviours is challenging for trauma clinicians and may be affected by patient sex and mechanism of injury. The aim of this study was to examine the differences in characteristics and outcomes between those who have intentionally directed violence towards themselves with those of unclear intent, within a regional trauma system.

Methods: Data was collected between January 2018 and December 2021 in patients who had been identified as a result of either self-directed violence (SDV) defined as any intentional act that can cause injury to one's self, including death or participated in high-risk behaviours, where the intent was unclear (UI).

NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.

Current models for the study of neuroendocrine tumours (NETs) are severely limited. While (e.g.

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 (IA-2) with Clinical Onset of Type 1 Diabetes.

Increasing evidence shows that pathogenic T cells in type 1 diabetes (T1D) that may have evaded negative selection recognize post-translational modified (PTM) epitopes of self-antigens. We have investigated the profiles of autoantibodies specifically targeting the deamidated epitopes of insulinoma antigen-2 extracellular domain (IA-2ec) to explore their relationship with T1D development. We compared the characteristics of autoantibodies targeting the IA-2ec Q>E epitopes (PTM IA-2ecA) as well as those targeting the IA-2ec unmodified epitopes (IA-2ecA) in participants across different stages of T1D development and in individuals with other types of diabetes and other kinds of autoimmunity.

Circular RNAs in the management of human osteoporosis.

Background: Osteoporosis (OP) is a metabolic bone disease producing reduction in bone mass with consequent bone fragility. Circular ribonucleic acid (CircRNA) is a form of RNA that forms a loop structure rather than a linear one. CircRNA can be used for therapeutic purposes, including molecular targets or to test new therapies.

The Microenvironment in DCIS and Its Role in Disease Progression.

Ductal carcinoma in situ (DCIS) accounts for ~20% of all breast cancer diagnoses but whilst known to be a precursor of invasive breast cancer (IBC), evidence suggests only one in six patients will ever progress. A key challenge is to distinguish between those lesions that will progress and those that will remain indolent. Molecular analyses of neoplastic epithelial cells have not identified consistent differences between lesions that progressed and those that did not, and this has focused attention on the tumour microenvironment (ME).

Mpox: What have we learned and how do we better prepare for the future?

The global outbreak of clade IIb mpox in 2022-2023 changed our understanding of the epidemiology and prevention of mpox, simultaneously highlighting inequities in access to vaccines, diagnostics, and therapeutics. With the recent multinational spread of clade Ib mpox, it is important to revisit these lessons to improve future response. In September 2024, an international mpox symposium was held at Johns Hopkins University to discuss what we have learned and how to better prepare for the future.