Explore the vast range of titles available.

Abstract Background Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium-to-aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. Hypothesis/Objectives A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. Animals One hundred twenty-seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. Methods Randomized double-blinded controlled multicenter clinical trial. Results The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end-diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%-13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%-12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). Conclusions and Clinical Importance Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.

Chronic wounds are painful and debilitating to patients, pose a clinical challenge to physicians, and impose financial burden on the health-care system. New treatment options are therefore highly sought after. Ultrasound debridement is a promising technology that functions to disperse bacterial biofilms and stimulate wound healing. In this review, we focus on low-frequency ultrasound (20-60 kHz) and summarize the findings of 25 recent studies examining ultrasound efficacy. Ultrasound debridement appears to be most effective when used 3 times a week and has the potential to decrease exudate and slough, decrease patient pain, disperse biofilms, and increase healing in wounds of various etiology. Although current studies are generally of smaller size, the results are promising and we recommend the testing of low-frequency ultrasound therapy in clinical practice on a larger scale.

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition.

IntroductionIndividuals with end-stage kidney disease (ESKD), whether receiving dialysis or conservative care, experience high symptom burden and limited life expectancy, indicating substantial palliative care needs. Integrating palliative care into kidney care is vital for comprehensive ESKD management, but access remains uneven across sociodemographic groups. Identifying and addressing these disparities is key to ensuring equitable care and improving patient outcomes. This study aims to explore sociodemographic factors associated with specialist palliative care utilisation among people with ESKD.Methods and analysisThis study protocol outlines a scoping review of peer-reviewed and grey literature using an established methodological framework by the Joanna Briggs Institute (JBI), and reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Relevant literature will be identified through a multi-database (Ovid MEDLINE, Embase, CINAHL, PsycINFO) and grey literature search strategy designed alongside a health sciences librarian. To be included, articles must involve individuals with ESKD and report on how sociodemographic factors influence access to and utilisation of specialist palliative care services. Results of the search will be screened independently by two reviewers and data from included studies will be extracted independently and in duplicate. A narrative and thematic analysis will be conducted to identify key themes related to sociodemographic influences on specialist palliative care access and utilisation among individuals with ESKD, with particular attention to differences between kidney care modalities (dialysis vs conservative care) and the extent to which intersectionality of sociodemographic factors has been examined.Ethics and disseminationEthics approval is not required for this scoping review. Findings will be submitted for publication in a peer-reviewed journal. Results will identify patient-related factors influencing access to specialist palliative care in ESKD and remaining gaps in the literature, informing future research and policy to support equitable care.

SummaryA post-menopausal Caucasian woman sustained an atypical femoral fracture (AFF) after 5-years continuous denosumab for osteoporosis without prior bisphosphonate exposure. This is only the fifth case reported of AFF in a bisphosphonate-naïve patient receiving denosumab for osteoporosis. Although rare, physicians should consider AFF in patients taking denosumab even without prior bisphosphonate exposure.IntroductionDenosumab has demonstrated overwhelmingly favourable skeletal benefit/risk profile in managing post-menopausal osteoporosis with up to 10-year exposure in the extension of the pivotal FREEDOM randomised placebo-controlled trial. Four previous cases of atypical femoral fracture have been reported in bisphosphonate-naïve patients receiving denosumab for osteoporosis.MethodsWe present an 85-year-old Caucasian post-menopausal woman without prior fragility fracture who sustained unilateral atypical femoral fracture after 5-years continuous subcutaneous denosumab for osteoporosis. She had no prior bisphosphonate or glucocorticoid exposure and had known chronic kidney disease.ResultsX-ray scan demonstrated complete, non-comminuted left proximal femoral shaft fracture meeting radiographic criteria for an atypical femoral fracture. Computed tomography (CT) scan lower limbs revealed unusual side-by-side appearance of proximal and distal fragments of left proximal femur. DXA BMD was artefactually elevated at lumbar spine (1.504 g/cm2, T-score + 2.5) and low-normal at right femoral neck (0.856 g/cm2, T-score -1.0). Serum biochemistry showed renal impairment at baseline (eGFR 30 mL/min/1.73m2). Low-normal serum C telopeptide of type 1 collagen (CTX) (230 ng/L) indicated therapeutic suppression of bone resorption.ConclusionThe patient underwent intramedullary nailing of the femur and denosumab was ceased. This is only the fifth case reported of atypical femoral fracture in a bisphosphonate-naïve patient receiving denosumab for osteoporosis. Although rare, physicians should maintain a high index of suspicion for atypical femoral fracture in a patient taking denosumab even without prior bisphosphonate exposure.

There are no ideal non-invasive tests for assessing the severity of liver fibrosis in people with metabolic dysfunction-associated steatotic liver disease (MASLD) and class 3 obesity, where body habitus often makes imaging technically challenging. This study aimed to assess the applicability and diagnostic performance of two-dimensional shear wave elastography (2D-SWE), alongside several serum-based liver fibrosis scoring methods, in individuals with class 3 obesity. A cross-sectional study was conducted in patients aged ≥18 years and with a body mass index (BMI) ≥ 40 kg/m2 who were participants in a publicly funded multidisciplinary weight management program in South Western Sydney. The 2D-SWE was performed using the ElastQ Imaging (EQI) procedure with the Phillips EPIQ Elite series ultrasound. An EQI Median value of ≥6.43 kPa was taken as a cutoff score for significant fibrosis, and the scan was considered valid when the liver EQI IQR/Med value was <30%. The Fibrosis-4 (FIB-4) index, AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and circulating fibroblast activation protein index (FAP index) were calculated from fasting blood samples. The participants (n = 116; 67.2% female) were aged 47.2 ± 12.9 years, with BMI 54.5 ± 11.0 kg/m2. EQI Median values were obtained for 97.4% (113/116) of the 2D-SWE scans, and 91.4% (106/116) of the scans were considered valid. The EQI Median values exhibited a moderately positive correlation with the FIB-4 index (r = 0.438; p < 0.001) and a weakly positive correlation with the APRI (r = 0.388; p < 0.001), NFS (r = 0.210; p = 0.036) and FAP index (r = 0.226; p = 0.020). All liver fibrosis scores were positively correlated with one another. Among those referred for a liver biopsy based on the 2D-SWE and serum scores, half (11/22) underwent liver biopsy, and their 2D-SWE scores exhibited 72.7% accuracy (sensitivity: 71.4%; specificity: 75%) in detecting significant fibrosis. Our results show that 2D-SWE is a feasible, non-invasive test to assess liver fibrosis among people with class 3 obesity. Further research is needed to assess how 2D-SWE can be used alongside existing serum-based risk scores to reliably detect significant fibrosis, which would potentially reduce the need for invasive liver biopsy.

Abstract Disclosure: R. Chang: None. R. Pandher: None. D. Hibbs: None. J. Du: None. K. McGrath: None. A. Heather: None. V. Jayadev: None. D.J. Handelsman: None. Objective Androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations create a spectrum of clinical presentations based on residual AR function. The mildest impairment of this condition is known as mild AIS (MAIS), whose undefined molecular mechanism and subtle clinical features leave it little understood and underdiagnosed. Methods and Result The clinical features of this mutation are discussed along with response to high dose testosterone in three cases of MAIS across a six-generation family pedigree with a missense AR exon 8 mutation (nucleotide aga --> gga, p. R872G arginine to glycine). All three cases of MAIS displayed consistent gynaecomastia and micropenis but variable fertility. High dose testosterone treatment for 3 years in one young man caused increased virilisation and height growth but was ineffective for micropenis. Genetic counselling allowed for effective prediction of MAIS risks in progeny for carrier and non-carrier sisters. This AR mutation, previously shown to display increased ligand dissociation rate from the mutated AR in binding assays, was shown by in silico structural modelling to demonstrate weakened closure energy of the “lid” of the ligand binding pocket allowing for easier ligand dissociation from binding site. An in vitro yeast-based androgen bioassay demonstrated unimpaired androgen bioactivity. Conclusion: The molecular mechanism of the p. R8729G mutation in exon 8 of the AR ligand binding domain demonstrated increased ligand dissociation from its binding site due to weakened closure of the binding pocket “lid” but without impact on androgen bioactivity. This novel molecular mechanism may be present in other cases of MAIS. Discrepancy between MAIS genotype and phenotype in those carrying the same AR mutation is known and may be present within our cohort. Presentation: Monday, July 14, 2025

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition.

In the summer of 2017, heavy ozone pollution swamped most of the North China Plain (NCP), with the maximum regional average of daily maximum 8 h ozone concentration (MDA8) reaching almost 120 ppbv. In light of the continuing reduction of anthropogenic emissions in China, the underlying mechanisms for the occurrences of these regional extreme ozone episodes are elucidated from two perspectives: meteorology and biogenic emissions. The significant positive correlation between MDA8 ozone and temperature, which is amplified during heat waves concomitant with stagnant air and no precipitation, supports the crucial role of meteorology in driving high ozone concentrations. We also find that biogenic emissions are enhanced due to factors previously not considered. During the heavy ozone pollution episodes in June 2017, biogenic emissions driven by high vapor pressure deficit (VPD), land cover change and urban landscape yield an extra mean MDA8 ozone of 3.08, 2.79 and 4.74 ppbv, respectively, over the NCP, which together contribute as much to MDA8 ozone as biogenic emissions simulated using the land cover of 2003 and ignoring VPD and urban landscape. In Beijing, the biogenic emission increase due to urban landscape has a comparable effect on MDA8 ozone to the combined effect of high VPD and land cover change between 2003 and 2016. In light of the large effect of urban landscape on biogenic emission and the subsequent ozone formation, the types of trees may be cautiously selected to take into account of the biogenic volatile organic compound (BVOC) emission during the afforestation of cities. This study highlights the vital contributions of heat waves, land cover change and urbanization to the occurrence of extreme ozone episodes, with significant implications for ozone pollution control in a future when heat wave frequency and intensity are projected to increase under global warming.