A minimally invasive swine model of chronic kidney disease-associated heart failure.

Chronic kidney disease (CKD) is on the rise, and over 50% of patients die from cardiac causes. Patients develop heart failure due to unelucidated reno-cardiac interactions, termed type 4 cardiorenal syndrome (CRS4). The aim of this study is to establish and characterize a reliable model of CRS4 in swine with marked cardiac diastolic dysfunction.

AAV delivery strategy with mechanical support for safe and efficacious cardiac gene transfer in swine.

Adeno-associated virus-based gene therapy is a promising avenue in heart failure treatment, but has shown limited cardiac virus uptake in humans, requiring new approaches for clinical translation. Using a Yorkshire swine ischemic heart failure model, we demonstrate significant improvement in gene uptake with temporary coronary occlusions assisted by mechanical circulatory support. We first show that mechanical support during coronary artery occlusions prevents hemodynamic deterioration (n = 5 female).

A functional microbiome catalogue crowdsourced from North American rivers.

Predicting elemental cycles and maintaining water quality under increasing anthropogenic influence requires knowledge of the spatial drivers of river microbiomes. However, understanding of the core microbial processes governing river biogeochemistry is hindered by a lack of genome-resolved functional insights and sampling across multiple rivers. Here we used a community science effort to accelerate the sampling, sequencing and genome-resolved analyses of river microbiomes to create the Genome Resolved Open Watersheds database (GROWdb).

Towards harmonized laboratory methodologies in veterinary clinical bacteriology: outcomes of a European survey.

Introduction: Veterinary clinical microbiology laboratories play a key role in antimicrobial stewardship, surveillance of antimicrobial resistance and prevention of healthcare associated-infections. However, there is a shortage of international harmonized guidelines covering all steps of veterinary bacterial culture from sample receipt to reporting.

Methods: In order to gain insights, the European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT) designed an online survey focused on the practices and interpretive criteria used for bacterial culture and identification (C&ID), and antimicrobial susceptibility testing (AST) of animal bacterial pathogens.

Megakaryocyte maturation involves activation of the adaptive unfolded protein response.

Endoplasmic reticulum stress triggers the unfolded protein response (UPR) to promote cell survival or apoptosis. Transient endoplasmic reticulum stress activation has been reported to trigger megakaryocyte production, and UPR activation has been reported as a feature of megakaryocytic cancers. However, the role of UPR signaling in megakaryocyte biology is not fully understood.

Temporal trends and factors associated with vaccination uptake in dogs and cats from 2016 to 2022 in the United Kingdom.

Background: Vaccination of dogs and cats is considered a mainstay of preventive health, providing benefit to individual animals and the population. This study aimed to assess temporal trends in vaccination and factors associated with vaccination uptake in a large veterinary visiting population of UK cats and dogs.

Methods: The electronic health records (EHRs) of 712,266 dogs and 306,888 cats (voluntarily contributed by 201 veterinary practices) were used to determine the proportion that had record of any type of veterinary vaccination either within one-year or within three-years of attending a participating veterinary practice.

European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) guidelines for antimicrobial use in canine acute diarrhoea.

Acute diarrhoea is a common presentation in dogs, and a common reason for antimicrobial prescription and nutraceutical use. This evidence-based guideline provides recommendations for antimicrobial and probiotic treatment of canine acute diarrhoea (CAD). A multidisciplinary panel developed the recommendations by adhering to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Influencing attitudes towards antimicrobial use and resistance in companion animals-the impact on pet owners of a short animation in a randomized controlled trial.

Objectives: Antimicrobial resistance (AMR) is a vital One Health issue; the rational use of antimicrobials is essential to preserve their efficacy. Veterinarians cite pressure from pet owners as a contributor to antimicrobial prescription. Engaging pet owners in antimicrobial stewardship could reduce this pressure.

Real-World Gait Detection Using a Wrist-Worn Inertial Sensor: Validation Study.

Background: Wrist-worn inertial sensors are used in digital health for evaluating mobility in real-world environments. Preceding the estimation of spatiotemporal gait parameters within long-term recordings, gait detection is an important step to identify regions of interest where gait occurs, which requires robust algorithms due to the complexity of arm movements. While algorithms exist for other sensor positions, a comparative validation of algorithms applied to the wrist position on real-world data sets across different disease populations is missing.

Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.

Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia-activated prodrugs (HAPs).

Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking.

We report a new class of carboplatin-TFO hybrid that incorporates a bifunctional alkyne-amine nucleobase monomer called AP-C3-dT that enables dual 'click' platinum(ii) drug conjugation and thiazole orange fluorophore coupling. Thiazole orange enhances the binding of Pt(ii)-TFO hybrids and provides an intrinsic method for monitoring triplex formation. These hybrid constructs possess increased stabilisation and crosslinking properties in comparison to earlier Pt(ii)-TFOs, and demonstrate sequence-specific binding at neutral pH.

Risk factors for tick attachment in companion animals in Great Britain: a spatiotemporal analysis covering 2014-2021.

Background: Ticks are an important driver of veterinary health care, causing irritation and sometimes infection to their hosts. We explored epidemiological and geo-referenced data from > 7 million electronic health records (EHRs) from cats and dogs collected by the Small Animal Veterinary Surveillance Network (SAVSNET) in Great Britain (GB) between 2014 and 2021 to assess the factors affecting tick attachment in an individual and at a spatiotemporal level.

Methods: EHRs in which ticks were mentioned were identified by text mining; domain experts confirmed those with ticks on the animal.

A mixed-methods approach utilising electronic health records to examine antimicrobial prescription surrounding gastrointestinal clinical presentations in dogs and cats.

Introduction: Systemically-administered antimicrobials are often prescribed in canine and feline gastrointestinal clinical presentations. Responsible use of antimicrobials, particularly those considered Highest Priority Critically Important Antimicrobials (HPCIAs) is vital to tackle antimicrobial resistance. Although practice-level prescription guidance is available, further strategies based on a greater understanding of antimicrobial prescription at the population-level are needed.

Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines.

Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines.

Analysis of the molecular determinants for furin cleavage of the spike protein S1/S2 site in defined strains of the prototype coronavirus murine hepatitis virus (MHV).

We analyzed the spike protein S1/S2 cleavage of selected strains of a prototype coronavirus, mouse hepatitis virus (MHV) by the cellular protease furin, in order to understand the structural requirements underlying the sequence selectivity of the scissile segment. The probability of cleavage of selected MHV strains was first evaluated from furin cleavage scores predicted by the ProP computer software, and then cleavage was measured experimentally with a fluorogenic peptide cleavage assay consisting of S1/S2 peptide mimics and purified furin. We found that in vitro cleavability varied across MHV strains in line with predicted results-but with the notable exception of MHV-A59, which was not cleaved despite a high score predicted for its sequence.

A multinational survey of companion animal veterinary clinicians: How can antimicrobial stewardship guidelines be optimised for the target stakeholder?

Antimicrobial stewardship initiatives are widely regarded as a cornerstone for ameliorating the global health impact of antimicrobial resistance. Within companion animal health, such efforts have largely focused on development and dissemination of antimicrobial stewardship guidelines (ASGs). However, there have been few attempts to understand veterinarian attitudes towards and knowledge of ASGs or to determine how awareness regarding ASGs might best be increased.

Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces.

The intersection of human, animal, and ecosystem health at One Health interfaces is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focused on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group's discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges.

Uptake of Genetic Research Results and Patient-Reported Outcomes With Return of Results Incorporating Web-Based Predisclosure Education.

Purpose: We developed a web-based education intervention as an alternative to predisclosure education with a genetic counselor (GC) to reduce participant burden and provider costs with return of genetic research results.

Methods: Women at three sites who participated in 11 gene discovery research studies were contacted to consider receiving cancer genetic research results. Participants could complete predisclosure education through web education or with a GC.

A functional microbiome catalog crowdsourced from North American rivers.

Predicting elemental cycles and maintaining water quality under increasing anthropogenic influence requires understanding the spatial drivers of river microbiomes. However, the unifying microbial processes governing river biogeochemistry are hindered by a lack of genome-resolved functional insights and sampling across multiple rivers. Here we employed a community science effort to accelerate the sampling, sequencing, and genome-resolved analyses of river microbiomes to create the Genome Resolved Open Watersheds database (GROWdb).