SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts.

Previous studies highlight the potential for sodium-glucose cotransporter type 2 (SGLT2) inhibitors (SGLT2i) to exert cardioprotective effects in heart failure by increasing plasma ketones and shifting myocardial fuel utilization toward ketone oxidation. However, SGLT2i have multiple in vivo effects and the differential impact of SGLT2i treatment and ketone supplementation on cardiac metabolism remains unclear. Here, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology combined with infusions of [13C6]glucose or [13C4]βOHB, we demonstrate that acute SGLT2 inhibition with dapagliflozin shifts relative rates of myocardial mitochondrial metabolism toward ketone oxidation, decreasing pyruvate oxidation with little effect on fatty acid oxidation in awake rats.

A family-centric, comprehensive nurse-led home oxygen programme for neonatal chronic lung disease: home oxygen policy evaluation (HOPE) study.

Objectives: Considerable variation and little objective evidence exists to guide the use of supplemental oxygen therapy in infants with neonatal chronic lung disease (nCLD) after hospital discharge. We developed a new policy utilizing regular oximetry downloads to help determine commencement and titration of low flow oxygen. The aim of this policy is to improve safety and uniformity in practice and potentially lead to improvements in outcomes including the number of infants being discharged on home oxygen therapy (HOT) and length of stay (LOS).

Factor 3 regulates airway engraftment by human bronchial basal cells.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene editing and transplantation of CFTR-gene corrected airway basal cells has the potential to cure CF lung disease. Although mouse studies established that cell transplantation was feasible, the engraftment rate was typically low and frequently less than the estimated therapeutic threshold. The purpose of this study was to identify genes and culture conditions that regulate the therapeutic potential of human bronchial basal cells.

Computed tomography of the equine caudal spine and pelvis. Pathological findings in 56 clinical cases (2018-2023).

Background: Computed tomography (CT) of the axial skeleton is increasing across many equine hospitals. CT of the pelvis and caudal spine in a large group of clinical cases has not been reported previously.

Objective: To describe the pathological lesions identified in the caudal spine/pelvis in horses and ponies undergoing CT spine of this region.

DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-Length cDNA in Airway Stem Cells.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator () gene. Although many people with CF (pwCF) are treated using CFTR modulators, some are non-responsive due to their genotype or other uncharacterized reasons. Autologous airway stem cell therapies, in which the cDNA has been replaced, may enable a durable therapy for all pwCF.

Outcome of tenoscopically guided palmar/plantar annular ligament desmotomy for the treatment of palmar/plantar annular ligament constriction without concurrent intrathecal soft-tissue injury in a UK horse population.

Objective: To determine the outcome of tenoscopically guided palmar/plantar annular ligament (PAL) desmotomy to treat PAL constriction without concurrent intrathecal soft-tissue injury, notably of the digital flexor tendons and manica flexoria.

Study Design: Retrospective multicenter cohort study.

Animals: Sixty-five horses.

Review of the clinical diagnosis of sacroiliac dysfunction in horses - Challenges and limitations.

Sacroiliac dysfunction (SID) is a condition seen in horses associated with poor performance that affects hind limb gait and impulsion. The condition comprises pain and dysfunction but there lacks clarity around the aetiopathogenesis and whether SID encompasses abnormal joint pathology, abnormal joint movement, abnormal regional biomechanical function, joint laxity and pain, or various combinations of these that may vary over time. Clinical assessment remains challenging for equine clinicians due to the deep location of the sacroiliac joint (SIJ) and surrounding structures which limits access for palpation, diagnostic imaging and joint-specific injection.

Single-Stranded DNA with Internal Base Modifications Mediates Highly Efficient Gene Insertion in Primary Cells.

Single-stranded DNA (ssDNA) templates along with Cas9 have been used for gene insertion but suffer from low efficiency. Here, we show that ssDNA with chemical modifications in 10-17% of internal bases (eDNA) is compatible with the homologous recombination machinery. Moreover, eDNA templates improve gene insertion by 2-3 fold compared to unmodified and end-modified ssDNA in airway basal stem cells (ABCs), hematopoietic stem and progenitor cells (HSPCs), T-cells and endothelial cells.

Airway disease decreases the therapeutic potential of epithelial stem cells.

Backgorund: Tissue-engineered tracheal grafts (TETG) can be recellularized by the host or pre-seeded with host-derived cells. However, the impact of airway disease on the recellularization process is unknown.

Methods: In this study, we determined if airway disease alters the regenerative potential of the human tracheobronchial epithelium (hTBE) obtained by brushing the tracheal mucosa during clinically-indicated bronchoscopy from 48 pediatric and six adult patients.

Use of physical examination, electrocardiography, radiography, and biomarkers to predict echocardiographic stage B2 myxomatous mitral valve disease in preclinical Cavalier King Charles Spaniels.

Introduction: Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD). Dogs with stage B2 MMVD benefit from medication.

Objectives: To develop (1) breed-specific cut-offs for individual screening tests and (2) predictive models utilizing physical examination (PE), ECG, radiograph, and blood-based biomarker variables in combination for identification of echocardiographic stage B2 MMVD in preclinical CKCS.

Successful total hip arthroplasty in a miniature horse.

Objective: To describe the surgical treatment, postoperative management, and outcome of a miniature horse undergoing total hip arthroplasty (THA).

Study Design: Case report.

Animals: A 4-year-old miniature horse stallion weighing 85 kg.

Development of a joint set of database parameters for the EU-ROP and Fight Childhood Blindness! ROP Registries.

Background/aims: The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes.

Methods: A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice.

Machine learning algorithms for predicting outcomes of traumatic brain injury: A systematic review and meta-analysis.

Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The use of machine learning (ML) has emerged as a key advancement in TBI management. This study aimed to identify ML models with demonstrated effectiveness in predicting TBI outcomes.

Galectin-3 as a novel biomarker in cats with hypertrophic cardiomyopathy.

Introduction/objectives: Galectin-3 (Gal-3) is a circulating biomarker of fibrosis. In humans, increased Gal-3 is predictive of myocardial fibrosis and adverse cardiac events. The aim of this study was to evaluate the potential for Gal-3 as a cardiac biomarker in cats with hypertrophic cardiomyopathy (HCM).

Language outcomes at 4 years of linguistically diverse children born very preterm: an Australian retrospective single-centre study.

Background: Very preterm children are at increased risk of language delays. Concerns have been raised about the utility of standardised English language tools to diagnose language delay in linguistically diverse children. Our study investigated the incidence of language delay at 4 years in linguistically diverse very preterm children.

Regeneration of tracheal neotissue in partially decellularized scaffolds.

Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decellularized tracheal grafts (PDTG) by removing the cells of the epithelium and lamina propria while preserving donor cartilage.