Evaluation of Ki-67, goblet cell and MUC2 mucin RNA expression in dogs with lymphoplasmacytic and granulomatous colitis.

Intestinal mucus barrier disruption may occur with chronic inflammatory enteropathies. The lack of studies evaluating mucus health in dogs with chronic colitis arises from inherent challenges with assessment of the intestinal mucus layer. It is therefore unknown if reduced goblet cell (GBC) numbers and/or mucin 2 (MUC2) expression, which are responsible for mucus production and secretion, correlate with inflammation severity in dogs with granulomatous colitis (GC) or lymphocytic-plasmacytic colitis (LPC). It is undetermined if Ki-67 immunoreactivity, which has been evaluated in dogs with small intestinal inflammation, similarly correlates to histologic severity in GC and LPC. Study objectives included comparing Ki-67 immunoreactivity, GBC population and MUC2 expression in dogs with GC, LPC and non-inflamed colon; and exploring the use of ribonucleic acid (RNAscope®) in-situ hybridization (ISH) to evaluate MUC2 expression in canine colon. Formalin-fixed endoscopic colonic biopsies were obtained from 48 dogs over an eight-year period. A blinded pathologist reviewed all biopsies. Dogs were classified into the GC (n=19), LPC (n=19) or no colitis (NC) (n=10) group based on final histopathological diagnosis. Ki-67 immunohistochemistry, Alcian-Blue/PAS staining to highlight GBCs, and RNAscope® ISH using customized canine MUC2-targeted probes were performed. At least five microscopic fields per dog were selected to measure Ki-67 labelling index (KI67%), GBC staining percentage (GBC%) and MUC2 expression (MUC2%) using image analysis software. Spearman's correlation coefficients were used to determine associations between World Small Animal Veterinary Association histologic score (WHS) and measured variables. Linear regression models were used to compare relationships between WHS with KI67%, GBC%, and MUC2%; and between GBC% and MUC2%. Median WHS was highest in dogs with GC. Median KI67% normalised to WHS was highest in the NC group (6.69%; range, 1.70-23.60%). Median GBC% did not correlate with colonic inflammation overall. Median MUC2% normalised to WHS in the NC group (10.02%; range, 3.05-39.09%) was two- and three-fold higher than in the GC and LPC groups respectively. With increased colonic inflammation, despite minimal changes in GBC% overall, MUC2 expression markedly declined in the LPC group (-27.4%; 95%-CI, -49.8, 5.9%) and mildly declined in the GC and NC groups. Granulomatous colitis and LPC likely involve different pathways regulating MUC2 expression. Decreased MUC2 gene expression is observed in dogs with chronic colitis compared to dogs without colonic signs. Changes in MUC2 expression appear influenced by GBC activity rather than quantity in GC and LPC.

Using natural language processing and patient journey clustering for temporal phenotyping of antimicrobial therapies for cat bite abscesses.

BACKGROUND: Temporal phenotyping of patient journeys, which capture the common sequence patterns of interventions in the treatment of a specific condition, is useful to support understanding of antimicrobial usage in veterinary patients. Identifying and describing these phenotypes can inform antimicrobial stewardship programs designed to fight antimicrobial resistance, a major health crisis affecting both humans and animals, in which veterinarians have an important role to play. OBJECTIVE: This research proposes a framework for extracting temporal phenotypes of patient journeys from clinical practice data through the application of natural language processing (NLP) and unsupervised machine learning (ML) techniques, using cat bite abscesses as a model condition. By constructing temporal phenotypes from key events, the relationship between antimicrobial administration and surgical interventions can be described, and similar treatment patterns can be grouped together to describe outcomes associated with specific antimicrobial selection. METHODS: Cases identified as having a cat bite abscess as a diagnosis were extracted from VetCompass Australia, a database of veterinary clinical records. A classifier was trained and used to label the most clinically relevant event features in each record as chosen by a group of veterinarians. The labeled records were processed into coded character strings, where each letter represents a summary of specific types of treatments performed at a given visit. The sequences of letters representing the cases were clustered based on weighted Levenshtein edit distances with KMeans+ + to identify the main variations of the patient treatment journeys, including the antimicrobials used and their duration of administration. RESULTS: A total of 13,744 records that met the selection criteria was extracted and grouped into 8436 cases. There were 9 clinically distinct event sequence patterns (temporal phenotypes) of patient journeys identified, representing the main sequences in which surgery and antimicrobial interventions are performed. Patients receiving amoxicillin and surgery had the shortest duration of antimicrobial administration (median of 3.4 days) and patients receiving cefovecin with no surgical intervention had the longest antimicrobial treatment duration (median of 27 days). CONCLUSION: Our study demonstrates methods to extract and provide an overview of temporal phenotypes of patient journeys, which can be applied to text-based clinical records for multiple species or clinical conditions. We demonstrate the effectiveness of this approach to derive real-world evidence of treatment impacts using cat bite abscesses as a model condition to describe patterns of antimicrobial therapy prescriptions and their outcomes.

Sensitivity of canine hematological cancers to BH3 mimetics.

BACKGROUND: Inhibition of antiapoptotic B-cell lymphoma 2 (BCL2) proteins by small molecule Bcl-2 homology 3 (BH3) mimetics causes rapid induction of apoptosis of human hematological cancers in vitro and in vivo. OBJECTIVES: Assess in vitro sensitivity of non-neoplastic lymphocytes and primary hematological cancer cells from dogs to venetoclax (VEN) or the dual BCL2/ B-cell lymphoma-extra-large (BCLxL) inhibitor, navitoclax (NAV), and evaluate the association between BCL2 protein expression and VEN sensitivity. ANIMALS: Nine client-owned dogs without cancer and 18 client-owned dogs with hematological cancer. METHODS: Prospective, nonrandomized noncontrolled study. Lymphocytes isolated from peripheral blood, lymph node, or bone marrow from dogs were incubated with BH3 mimetics for 24 hours. Viable cells were counted using flow cytometry and half maximal effective concentration (EC50 ) was calculated. BCL2 protein from whole cell lysates was assessed via immunoblots. RESULTS: Nodal B and T lymphocytes were more sensitive to VEN than circulating lymphocytes (P = .02). Neoplastic T lymphocytes were sensitive to VEN (mean EC50 ± SD = 0.023 ± 0.018 µM), whereas most non-indolent B cell cancers were resistant to killing by VEN (mean EC50 ± SD = 288 ± 700 µM). Unclassified leukemias showed variable sensitivity to VEN (mean EC50 ± SD = 0.49 ± 0.66 µM). Detection of BCL2 protein was not associated with VEN sensitivity. CONCLUSION AND CLINICAL IMPORTANCE: Neoplastic canine T lymphocytes are sensitive to VEN in vitro. Quantification of BCL2 protein alone is insufficient to predict sensitivity to VEN.

Lean body weight-adjusted intravenous iodinated contrast dose for abdominal CT in dogs reduces interpatient enhancement variability while providing diagnostic quality organ enhancement.

Contrast-enhanced computed tomography (CECT) is increasingly used to screen for abdominal pathology in dogs, and the contrast dose used is commonly calculated as a linear function of total body weight (TBW). Body fat is not metabolically active and contributes little to dispersing or diluting contrast medium (CM) in the blood. This prospective, analytic, cross-section design pilot study aimed to establish the feasibility of intravenous CM dosed according to lean body weight (LBW) for abdominal CECT in dogs compared to TBW. We hypothesized that when dosing intravenous CM according to LBW, studies will remain at diagnostic quality, there will be a reduced interindividual contrast enhancement (CE) variability, and there will be less change to heart rate and blood pressure in dogs compared to when administering CM calculated on TBW. Twelve dogs had two CECT studies with contrast doses according to TBW and LBW at least 8 weeks apart. Interindividual organ and vessel CE variability, diagnostic quality of the studies, and changes in physiological status were compared between protocols. The LBW-based protocol provided less variability in the CE of most organs and vessels (except the aorta). When dosed according to LBW, liver enhancement was positively associated with grams of iodine per kg TBW during the portal venous phase (P = 0.046). There was no significant difference in physiological parameters after CM administration between dosing protocols. Our conclusion is that a CM dose based on LBW for abdominal CECT lowers interindividual CE variability and is effective at maintaining studies of diagnostic quality.

A retrospective multi-center study of treatment, outcome, and prognostic factors in 34 dogs with disseminated aspergillosis in Australia.

BACKGROUND: Disseminated aspergillosis (DA) in dogs has a guarded prognosis and there is a lack of a gold standard treatment protocol. OBJECTIVE: To retrospectively assess survival times and factors influencing survival times. ANIMALS: Dogs diagnosed with DA from January 2007 to June 2017. METHODS: Disseminated aspergillosis case data were retrieved from 13 Australian veterinary referral centers, with a diagnosis confirmed with culture or PCR. Factors influencing survival time after diagnosis were quantified using a Cox proportional hazards regression model. RESULTS: Thirty-four dogs met the study inclusion criteria. Twenty-two dogs were treated with antifungal treatment and 12 dogs received no antifungal treatment. Accounting for censoring of dogs that were either still alive on the date of data collection or were loss to follow-up, dogs treated with itraconazole alone (n = 8) had a median survival time (MST) of 63 (95% CI: 20-272) days compared to 830 (95% CI: 267-1259) days for the n = 14 dogs that received multimodal antifungal therapy ( χ 2 test statistic 8.6; df = 1; P < .01). The daily hazard of death (DHOD) for dogs with abnormally high serum creatinine concentration at the time of diagnosis was 7.4 (95% CI: 1.9-29) times that of dogs with serum creatinine within the reference interval. CONCLUSION AND CLINICAL IMPORTANCE: Serum creatinine concentration at the time of diagnosis is a useful prognostic indicator for survival after a diagnosis of DA. The MST for dogs treated with multimodal antifungal therapy is longer than itraconazole alone and warrant further investigation (P < .01).

Identifying the capabilities most important for veterinary employability using a modified Delphi process.

BACKGROUND: In the veterinary profession, employability has been defined as 'a set of personal and professional capabilities that enable a veterinarian to gain employment, contribute meaningfully to the profession, and develop a career pathway that achieves satisfaction and success'. This study was part of a multinational collaborative research project aiming to define the capabilities most important for employability in the veterinary context (www.VetSet2Go.edu.au). METHODS: The project gathered empirical evidence from multiple stakeholders including employees, employers, clients, team members, academics and professional bodies. These perspectives needed to be brought together as a cohesive body of evidence. We used a modified Delphi process, whereby a panel of experts were asked to reach consensus on the capabilities most important for veterinary employability, after considering the evidence from the sub-projects. RESULTS: The Delphi panel reached rapid consensus upon 21 of an initial 47 capabilities, including effective communication with clients and colleagues, teamwork, technical knowledge and skills, resilience and well-being, adaptability, emotional intelligence, workflow management and empathy and compassion. CONCLUSION: Of note for veterinary educators are those attitudinal items identified by this Delphi process as important to employability but potentially underemphasised in existing competency frameworks, such as accepts responsibility, keen to learn, diligence (high standard of care) and self-awareness.

Employability as a Guiding Outcome in Veterinary Education: Findings of the VetSet2Go Project.

This paper presents a mini-review of employability as a guiding outcome in veterinary education-its conceptualisation, utility, core elements and dimensions, and pedagogical approaches-through a summary of the findings of a major international project with the same aims (the VetSet2Go project). Guided by a conception of the successful veterinary professional as one capable of navigating and sustainably balancing the (sometimes competing) needs and expectations of multiple stakeholders, the project integrated multiple sources of evidence to derive an employability framework representing the dimensions and capabilities most important to veterinary professional success. This framework provides a useful complement to those based in narrower views of competency and professionalism. One notable difference is its added emphasis on broad success outcomes of satisfaction and sustainability as well as task-oriented efficacy, thus inserting "the self" as a major stakeholder and bringing attention to resilience and sustainable well-being. The framework contains 18 key capabilities consistently identified as important to employability in the veterinary context, aligned to five broad, overlapping domains: veterinary capabilities (task-oriented work performance), effective relationships (approaches to others), professional commitment (approaches to work and the broader professional "mission"), psychological resources (approaches to self), plus a central process of reflective self-awareness and identity formation. A summary of evidence supporting these is presented, as well as recommendations for situating, developing, and accessing these as learning outcomes within veterinary curricula. Though developed within the specific context of veterinarian transition-to-practise, this framework would be readily adaptable to other professions, particularly in other health disciplines.

Resilience of veterinarians at different career stages: The role of self-efficacy, coping strategies and personal resources for resilience in veterinary practice.

BACKGROUND: The aim of this study was to determine the effect of demographic and psychological factors on resilience in new graduate-, mid- and late-career veterinarians working in Australia. METHOD: An online cross-sectional survey of 800 veterinarians collected demographic and descriptive data in two stages from late 2015 to 2017, such as gender, average hours worked per week, type and region of practice and intention to leave veterinary medicine. Psychological factors were measured utilising the Brief Resilience Scale, the Veterinary Resilience Scale-Personal Resources, the Brief COPE and General Self-Efficacy measures. RESULTS: Using a full-factorial univariate General Linear Model, no significant difference in general resilience was evident between the three career-stage groups (p > 0.05). However, higher self-efficacy, higher personal resources for resilience in veterinary practice, and lower problem-focused, higher emotion-focused and lower dysfunctional coping strategies were related to higher resilience. In the model for mid- and late-career veterinarians, a weak positive relationship existed between higher average hours worked per week and higher resilience, while intention to leave veterinary practice was also related to lower resilience in mid- and late-career veterinarians. CONCLUSION: This study supports the value of personal resources, rather than career stage, gender or region of work, as influential in developing veterinarian resilience.

Hierarchical modelling of immunoglobulin coated bacteria in dogs with chronic enteropathy shows reduction in coating with disease remission but marked inter-individual and treatment-response variability.

Chronic enteropathies are a common problem in dogs, but many aspects of the pathogenesis remain unknown, making the therapeutic approach challenging in some cases. Environmental factors are intimately related to the development and perpetuation of gastrointestinal disease and the gut microbiome has been identified as a contributing factor. Previous studies have identified dysbiosis and reduced bacterial diversity in the gastrointestinal microbiota of dogs with chronic enteropathies. In this case-controlled study, we use flow cytometry and 16S rRNA sequencing to characterise bacteria highly coated with IgA or IgG in faecal samples from dogs with chronic enteropathy and evaluated their correlation with disease and resolution of the clinical signs. IgA and IgG-coated faecal bacterial counts were significantly higher during active disease compared to healthy dogs and decreased with the resolution of the clinical signs. Characterisation of taxa-specific coating of the intestinal microbiota with IgA and IgG showed marked variation between dogs and disease states, and different patterns of immunoglobulin enrichment were observed in dogs with chronic enteropathy, particularly for Erysipelotrichaceae, Clostridicaceae, Enterobacteriaceae, Prevotellaceae and Bacteroidaceae, families. Although, members of these bacterial groups have been associated with strong immunogenic properties and could potentially constitute important biomarkers of disease, their significance and role need to be further investigated.

Longitudinal Survey of Fecal Microbiota in Healthy Dogs Administered a Commercial Probiotic.

The aim of this longitudinal microbiome study was to investigate the effects of a commercially available veterinary synbiotic product (Blackmore's® Paw DigestiCare 60™) on the fecal microbiome of healthy dogs using 16S rRNA gene microbial profiling. Fifteen healthy, privately-owned dogs participated in a 2-week trial administration of the product. Fecal samples were collected at different time points, including baseline (prior to treatment), during administration and after discontinuation of product. Large intra- and inter-individual variation was observed throughout the study, but microbiome composition at higher phylogenetic levels, alpha and beta diversity were not significantly altered after 2 weeks of probiotic administration, suggesting an absence of probiotic impact on microbial diversity. Administration of the synbiotic preparation did, however, result in transient increases in probiotic species from Enterococacceae and Streptococacceae families as well as an increase in Fusobacteria; with the fecal microbiota partially reverting to its baseline state 3-weeks after cessation of probiotic administration.

A comparative analysis of two unrelated outbreaks in Latvia and Australia of acquired idiopathic megaesophagus in dogs fed two brands of commercial dry dog foods: 398 cases (2014-2018).

CASE DESCRIPTION: In Latvia in 2014, acquired idiopathic megaesophagus (AIME) was observed in increased numbers of dogs that consumed varieties of 1 brand of dog food. Within 2 years, 253 dogs were affected. In Australia in November 2017, 6 working dogs that consumed 1 diet of another brand of dog food developed AIME. In total, 145 Australian dogs were affected. CLINICAL FINDINGS: AIME was diagnosed predominantly in large-breed male dogs (> 25 kg [55 lb]). Regurgitation, weight loss, and occasionally signs consistent with aspiration pneumonia (coughing, dyspnea, or fever) were noted. Most Latvian dogs had mild to severe peripheral polyneuropathies as evidenced by laryngeal paralysis, dysphonia, weakness, and histopathologic findings consistent with distal axonopathy. In Australian dogs, peripheral polyneuropathies were not identified, and histopathologic findings suggested that the innervation of the esophagus and pharynx was disrupted locally, although limited samples were available. TREATMENT AND OUTCOME: Investigations in both countries included clinical, epidemiological, neuropathologic, and case-control studies. Strong associations between the dog foods and the presence of AIME were confirmed; however, toxicological analyses did not identify a root cause. In Latvia, the implicated dietary ingredients and formulations were unknown, whereas in Australia, extensive investigations were conducted into the food, its ingredients, the supply chain, and the manufacturing facilities, but a cause was not identified. CLINICAL RELEVANCE: A panel of international multidisciplinary experts concluded that the cause of AIME in both outbreaks was likely multifactorial, with the possibility of individualized sensitivities. Without a sentinel group, the outbreak in Australia may not have been recognized for months to years, as happened in Latvia. A better surveillance system for early identification of pet illnesses, including those associated with pet foods, is needed.

Swiss Primary Teachers' Professional Well-Being During School Closure Due to the COVID-19 Pandemic.

During sudden school closures in spring 2020 due to the COVID-19 pandemic, teachers had to move to distance teaching. This unprecedented situation could be expected to influence teacher well-being and schools as organizations. This article reports a qualitative study that aims at understanding how changes in teachers' professional lives that were related to school closure affected Swiss primary teachers' professional well-being. In semi-structured online-interviews, 21 teachers from 15 schools sampled by snowball method reported their experiences during school closure and distance teaching and how this situation influenced their professional well-being. Results showed that medium to high levels of teacher well-being could accompany a general negative evaluation of the move to distance teaching. Factors such as high work-load, social distancing and feelings of lack of competence and self-efficacy were among the most aversive aspects of distance teaching and associated with deteriorating professional well-being. Among a plethora of factors that supported teachers in maintaining their well-being, contextual work-related aspects such as school resources, collegial support or leadership support along with individual aspects such as resilience, coping strategies, and clear work structures were important. Additionally, it was found that teacher well-being was nourished by positive experiences with the new forms of distance teaching and feelings of professional mastery. Despite methodological limitations (snowball sampling, retrospective interviews), the findings of this study could inform schools and authorities about what is needed to support teacher well-being and might help to develop organizational strategies that aim at preventing harmful declines in teacher well-being during challenging and difficult times such as a pandemic.

Effect of sequentially fed high protein, hydrolyzed protein, and high fiber diets on the fecal microbiota of healthy dogs: a cross-over study.

BACKGROUND: Dietary content and environmental factors can shape the gut microbiota, and consequently, the way the gut microbiota metabolizes fats, carbohydrates, and proteins, affecting overall health of the host. We evaluated the impact of 3 diets (all meat [raw], high-insoluble fiber dry extruded diet and hydrolyzed protein dry extruded diet) on the gut microbiota of healthy dogs in a cross-over sequential study. RESULTS: We showed that diet can have an effect on the gut microbiome in dogs, which was influenced by the order of feeding. High-protein (all meat) diets were characterized by an increase in bacteria belonging to the Fusobacteria and Bacteroidetes phyla, whereas a high-insoluble fiber commercial diet correlated with increases in Firmicutes and Actinobacteria phyla. However, the individual dog's baseline microbiota had the most impact on the magnitude and nature of the changes in response to dietary intervention. CONCLUSION: Our results suggest that the dog fecal microbiota is driven by protein and fiber composition to different degrees in individual animals, and targeted modification of these patterns could be useful in the modulation of the gut microbiota in different diseases.

International multi-stakeholder consensus for the capabilities most important to employability in the veterinary profession.

BACKGROUND: Employability has been defined within the veterinary context as a set of personal and professional capabilities that enable a veterinarian to gain employment, contribute meaningfully to the profession, and develop a career pathway that achieves satisfaction and success. This study explicitly addressed the construct of veterinary employability by exploring the perceptions of multiple stakeholders (recent graduates, employee veterinarians, veterinarian and non-veterinarian employers, para-veterinary staff, academics and policy makers). METHODS: A four-part online survey was distributed internationally via various agencies. Free-text responses, ratings of capabilities and rankings of categories were analysed. RESULTS: The congruence of stakeholder responses was notable, regardless of age and geographical location, with minor differences noted in academics' and para-veterinary staff responses, and gender. The most important capabilities were honesty, ethical behaviour, communicating effectively and collaboratively with clients, knowing when to ask for help, and the willingness to learn. The categories of communication and teamwork ranked highest. CONCLUSION: This study adds granularity to the existing evidence for the importance of communication and teamwork. The relationship between the veterinarian (self) and their work, enabled by engagement, meaning and purpose, and respect for their profession was a key finding, and illustrative of how to achieve personal satisfaction and well-being within the profession.

ACVIM consensus statement on pancreatitis in cats.

BACKGROUND: Pancreatitis in cats, although commonly diagnosed, still presents many diagnostic and management challenges. OBJECTIVE: To summarize the current literature as it relates to etiology, pathogenesis, diagnosis, and management of pancreatitis in cats and to arrive at clinically relevant suggestions for veterinary clinicians that are based on evidence, and where such evidence is lacking, based on consensus of experts in the field. ANIMALS: None. METHODS: A panel of 8 experts in the field (5 internists, 1 radiologist, 1 clinical pathologist, and 1 anatomic pathologist), with support from a librarian, was formed to assess and summarize evidence in the peer reviewed literature and complement it with consensus clinical recommendations. RESULTS: There was little literature on the etiology and pathogenesis of spontaneous pancreatitis in cats, but there was much in the literature about the disease in humans, along with some experimental evidence in cats and nonfeline species. Most evidence was in the area of diagnosis of pancreatitis in cats, which was summarized carefully. In contrast, there was little evidence on the management of pancreatitis in cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Pancreatitis is amenable to antemortem diagnosis by integrating all clinical and diagnostic information available, and recognizing that acute pancreatitis is far easier to diagnose than chronic pancreatitis. Although both forms of pancreatitis can be managed successfully in many cats, management measures are far less clearly defined for chronic pancreatitis.

Development and validation of a contextualised measure of resilience in veterinary practice: the Veterinary Resilience Scale-Personal Resources (VRS-PR).

BACKGROUND: This article reports on the development and validation of a contextualised measure of personal resources for resilience in veterinary practice. METHODS: Exploratory factor analysis and structural equation modelling were used to evaluate data from two surveys of veterinary practitioners. RESULTS: Exploratory factor analysis of the first survey (n=300) revealed six items comprising the Veterinary Resilience Scale-Personal Resources (VRS-PR). These items focused on flexibility, adaptability, optimism, building strengths, enjoying challenges, and maintaining motivation and enthusiasm at work. Structural equation modelling using the second survey (n=744) confirmed the factor structure of the VRS-PR and established convergent validity with an established measure of general resilience, the Brief Resilience Scale. Examination of the mean and standard deviation of the combined survey data enabled scores on the VRS-PR to be provisionally classified into 'low', 'moderate' and 'high' (reported by approximately 13%, 72% and 15% of respondents, respectively). Respondents also reported results spanning 'low', 'moderate' and 'high' classifications for the Brief Resilience Scale (approximately 34%, 57% and 9%, respectively). CONCLUSION: The VRS-PR may be used to evaluate the extent to which respondents draw upon the personal resources captured in the scale and identify areas for improvement.