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The evaluation of student and faculty opinions on curricular changes in veterinary medical education is an essential part of the quality assurance process. This study investigates if the perceived educational value of a newly introduced module (veterinary pathobiology) in the earlier stages of a veterinary curriculum changes as students progress into the later phases of their training. Data were collected by anonymous questionnaire from two sequential final year student cohorts in 2021 and 2022. These students had previously been surveyed on their views of the new integrated pathobiology module immediately after taking it in their third year. Within 2 years, student satisfaction with the module's learning objectives increased significantly. Final year students had much clearer appreciation of how this pedagogical innovation enhanced their learning and that this was particularly true of the case-based learning approach adopted. While faculty teaching these students in their final year clinical pathobiology rotation expressed the view that overall, student performance was no different when compared to previous years, this somewhat disappointing finding needed to be viewed in the context of the intervening COVID-19 pandemic where face-to-face teaching of students over many months had been severely curtailed as had student attendance of their extramural studies. This study confirms a positive effect of an integrated curricular intervention in veterinary undergraduate education and highlights the necessity of student evaluation at multiple time points as their perception of the value of such changes appears to be linked to their experience and expectations.

Stranded seals are often infected with a broad range of parasites, although whether they are the cause of significant morbidity or an incidental finding is usually unclear. In this study we used stable isotope ratio analysis, a method frequently used to investigate food webs, to explore the extent to which common seal parasites feed directly on host tissue and fluids or absorb host-derived metabolites, which in turn may give an indication of their potential impact on the host's health. The trophic discrimination factor Δ 15 N for the nasal mite, Halarachne halichoeri , was mostly positive, ranging between −0.015 and 3.2‰ ( n = 6), while for the Acanthocephalan worm, Corynosoma strumosum and the anisakid nematode, Pseudoterranova decipiens , Δ 15 N ranged between −4.2 and −2.0‰ ( n = 7), and between −6.7 and −0.8‰ ( n = 5) respectively. In the case of the lungworm, Otostrongylus circumlitus , Δ 15 N measured between −5.6 and 0‰ for worms collected in the stomach ( n = 5), between −1.1 and 0.2‰ for worms collected from the heart ( n = 3), between −0.7 and 1.9‰ for worms situated in the lungs ( n = 4). Based on Δ 15 N, parasites could be clearly divided into those that were on a higher trophic level than their host suggesting a predator–prey-like relationship, and those that were not. It is hypothesized that Δ 15 N may be indicative of the clinical significance of parasite–host associations.

In the past 20 years in Switzerland, dogs with suspect acute leptospirosis frequently showed severe glomerular changes that had not been previously reported. These features were characterized by abundant extravasated erythrocytes and fewer neutrophils accompanied by marked fibrin exudation into the urinary space that was interpreted as an exudative glomerulonephritis (GN). This retrospective study describes this significant glomerular pathological change and investigates the association with leptospirosis. Tissues from 50 dogs with exudative GN, retrieved from 2 pathology archives in Switzerland were reviewed using hematoxylin and eosin, periodic acid-Schiff, phosphotungstic acid-hematoxylin, and Warthin and Starry stains. Clinical and postmortem data were collected for each case. Immunohistochemistry (IHC) and/or polymerase chain reactions were used as confirmatory tests for leptospirosis. While all 50 cases had clinical and pathological features supporting a diagnosis of leptospirosis, 37 cases were confirmed for the disease. Using a LipL32 antibody in addition to the OMV2177 antibody raised against the lipopolysaccharide of Leptospira interrogans serovar Copenhageni increased the detection rate of Leptospira by IHC in exudative GN from 24% to 62%. Signalment, seasonality, clinical signs, blood results, and pathological changes in dogs with exudative GN were similar to those reported for dogs without GN and confirmed infection by Leptospira spp.. Exudative GN was common among Swiss dogs with leptospirosis where it caused acute severe disease. Leptospirosis should be considered as a cause of this new pathologic feature by the pathologist. The pathogenesis remains unclear, but involvement of a geographic-specific serovar with unique virulence factors is suspected and warrants further investigation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Closed-loop adaptive deep brain stimulation (aDBS) continuously adjusts stimulation parameters, with the potential to improve efficacy and reduce side effects of deep brain stimulation (DBS) for Parkinson's disease (PD). Rodent models can provide an effective platform for testing aDBS algorithms and establishing efficacy before clinical investigation. In this study, we compare two aDBS algorithms, on-off and proportional modulation of DBS amplitude, with conventional DBS in hemiparkinsonian rats., Materials and Methods: DBS of the subthalamic nucleus (STN) was delivered wirelessly in freely moving male and female hemiparkinsonian (N = 7) and sham (N = 3) Wistar rats. On-off and proportional aDBS, based on STN local field potential beta power, were compared with conventional DBS and three control stimulation algorithms. Behavior was assessed during cylinder tests (CT) and stepping tests (ST). Successful model creation was confirmed via apomorphine-induced rotation test and Tyrosine Hydroxylase-immunocytochemistry. Electrode location was histologically confirmed. Data were analyzed using linear mixed models., Results: Contralateral paw use in parkinsonian rats was reduced to 20% and 25% in CT and ST, respectively. Conventional, on-off, and proportional aDBS significantly improved motor function, restoring contralateral paw use to approximately 45% in both tests. No improvement in motor behavior was observed with either randomly applied on-off or low-amplitude continuous stimulation. Relative STN beta power was suppressed during DBS. Relative power in the alpha and gamma bands decreased and increased, respectively. Therapeutically effective adaptive DBS used approximately 40% less energy than did conventional DBS., Conclusions: Adaptive DBS, using both on-off and proportional control schemes, is as effective as conventional DBS in reducing motor symptoms of PD in parkinsonian rats. Both aDBS algorithms yield substantial reductions in stimulation power. These findings support using hemiparkinsonian rats as a viable model for testing aDBS based on beta power and provide a path to investigate more complex closed-loop algorithms in freely behaving animals., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This is the first report of Besnoitia bennetti in donkeys in Ireland. B. bennetti, an apicomplexan protozoan parasite specific to equids, is an emerging pathogen in Europe. This parasite forms chronic intracytoplasmic cysts in cells of the mesenchymal lineage, mainly fibroblasts, in the skin, sclera and mucosa. Clinical signs in affected equine hosts vary from mild to severe debilitating disease. Little is known of the phylogeny, epidemiology or transmission of B. bennetti infection in donkeys, mules or horses., Case Presentation: Two cases of besnoitiosis in donkeys are presented. Both donkeys were born and raised in theSouthwest of Ireland. The first case was a 2.5-year-old donkey that had a suspect sarcoid removed, while the second case,a 2-year-old donkey, had a biopsy of nodular dermatitis of the muzzle. Diagnosis was made by histopathology and the parasite species, B. bennetti, was confirmed by PCR followed by sequencing and microsatellite analysis. Both donkeys had high antibody titres against Besnoitia spp. Small (0.5 mm) scleral, conjunctival and dermal cysts over the muzzle were subsequently observed in both animals. Treatment with trimethoprim sulfadiazine for 30 days did not lead to clinical resolution. The findings are compared to the cases of besnoitiosis in donkeys reported in the past 10 years throughout Europe., Conclusions: Besnoitiosis should be considered as a differential diagnosis for chronic skin disease particularly in cases of cutaneous masses, non-pruritic dermatitis, and dermatitis that is not responsive to treatment in donkeys and other equids. Future studies are needed to investigate the prevalence of the disease in Irish donkeys, the spread of the disease and the potential impact on the health and welfare of the donkeys., (© 2024. The Author(s).)

Accelerated by the COVID-19 pandemic, online teaching has become widely established in higher education in recent years. However, little is known about the influence of the online environment on collaborative student activities, which are an integral part of veterinary education. This study explored engagement, collaboration, and communication among fourth-year veterinary students working in groups on online case-based learning (CBL) activities. Data were collected by questionnaire (93/135) and anonymous peer assessment (98/135) at the end of the trimester. While most students (67%) enjoyed group work and 75% considered it of benefit to their learning, the results indicated that the students' interaction was mainly limited to task management and collating individual answers on shared documents. Rather than meeting online, students communicated by chat and messenger apps. Agreement of roles, rules, and the group contract were largely treated as box-ticking exercises. Conflict was the only factor that affected group work satisfaction and was largely avoided rather than addressed. Interestingly lack of student engagement in group work was not related to overall academic performance and had no impact on their end-of-term exam results. This study highlights high student satisfaction and engagement with online group CBL activities even when collaboration and communication were limited. Achieving higher levels of collaborative learning involving co-regulation of learning and metacognitive processing of learning content may require more specific, formal training in relevant skill sets from an early stage of the veterinary curriculum.

Centrosome amplification (CA) is a prominent feature of human cancers linked to tumorigenesis in vivo. Here, we report mechanistic contributions of CA induction alone to tumour architecture and extracellular matrix (ECM) remodelling. CA induction in non-tumorigenic breast cells MCF10A causes cell migration and invasion, with underlying disruption of epithelial cell-cell junction integrity and dysregulation of expression and subcellular localisation of cell junction proteins. CA also elevates expression of integrin β-3, its binding partner fibronectin-1 and matrix metalloproteinase enzymes, promoting cell-ECM attachment, ECM degradation, and a migratory and invasive cell phenotype. Using a chicken embryo xenograft model for in vivo validation, we show that CA-induced (+CA) MCF10A cells invade into the chick mesodermal layer, with inflammatory cell infiltration and marked focal reactions between chorioallantoic membrane and cell graft. We also demonstrate a key role of small GTPase Rap-1 signalling through inhibition using GGTI-298, which blocked various CA-induced effects. These insights reveal that in normal cells, CA induction alone (without additional oncogenic alterations) is sufficient to confer early pro-tumorigenic changes within days, acting through Rap-1-dependent signalling to alter cell-cell contacts and ECM disruption., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Formalin-Fixed Paraffin Embedded (FFPE) biopsies would provide a critical mass of cases to allow investigation of canine liver disease, however their use is often limited by challenges typically associated with transcriptomic analysis. This study evaluates the capability of NanoString® to measure the expression of a broad panel of genes in FFPE liver samples. RNA was isolated from matched histopathologically normal liver samples using FFPE (n = 6) and snap frozen in liquid nitrogen (n = 6) and measured using a custom NanoString® panel. Out of the 40 targets on the panel, 27 and 23 targets were above threshold for non-diseased snap frozen and FFPE tissue respectively. The binding density and total counts were significantly reduced in the FFPE samples relative to the snap frozen samples (p = 0.005, p = 0.01, respectively), confirming a reduction in sensitivity. The concordance between the snap frozen and FFPE samples was high, with correlations (R) ranging between 0.88 and 0.99 between the paired samples. An additional 14 immune-related targets, undetectable the non-diseased FFPE liver, were above threshold when the technique was applied to a series of diseased samples, further supporting their inclusion on this panel. This use of NanoString® based analysis opens up huge opportunity for retrospective evaluation of gene signatures in larger caseloads through harnessing the capacity of archived FFPE samples This information used alongside clinical and histological data will not only afford a way to explore disease etiopathogenesis, it may also offer insight into sub-types of liver disease in dogs, which cannot be discerned using more traditional diagnostic methods., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5.7 ± 3.6 years; mean ± SD). Predominant clinical signs were altered mental state, central vestibular dysfunction, and cerebellar incoordination. Twelve gliomas, all high grade, were the most common tumors observed: oligodendrogliomas (n = 6), astrocytomas (n = 4), and undefined gliomas (n = 2). The oligodendrogliomas were located in the brainstem and extended into the ventricles, whereas all astrocytomas were located in the forebrain. Isocitrate dehydrogenase 1 gene mutation as described in humans was not detected. The 5 meningiomas exhibited microcystic, chordoid, atypical, papillary, and anaplastic subtypes. Metastatic carcinomas (n = 4) were the only secondary tumor type present, and these were located at the level of the medulla with infiltration of cranial nerves and in one case leptomeningeal carcinomatosis. In addition, 2 medulloblastomas and 1 choroid plexus carcinoma were diagnosed. Immunohistochemistry for vimentin and pancytokeratin was particularly useful to distinguish meningiomas and choroid plexus carcinoma (positive for vimentin only) from mestastatic carcinomas (positive for cytokeratin only) as all showed a papillary growth pattern. Overall, the morphological features were comparable with other species and the human and canine classifications could be applied.

In collaboration with the American College of Veterinary Pathologists.

A 2.5-year-old cat presented with progressive ataxia and lethargy. Magnetic resonance imaging (MRI) showed enlargement of the cerebellum and herniation of cerebellar vermis. Postmortem examination confirmed the MRI findings, and histopathology showed numerous large dysplastic neurons populating and displacing the Purkinje cell layer and extending into the molecular and granular layers of the cerebellum. The lesion was diagnosed as dysplastic gangliocytoma of the cerebellum. In humans, this tumor is often associated with Cowden syndrome, a genetic disorder characterized by multiple hamartomas and an increased risk of developing certain neoplasms, known to be linked to a germline mutation of the phosphatase and tensin homolog ( PTEN ) gene. Reduction in PTEN nuclear and cytoplasmic immunohistochemical labeling of dysplastic neurons in this case suggested a possible PTEN mutation involved in the tumorigenesis. This report provides a detailed pathology description of the tumor and the use of neuronal and PTEN markers which will help guide pathologists presented with this rare condition in the future.

The School of Veterinary Medicine, University College Dublin, Ireland, restructured the teaching of general pathology, parasitology, and microbiology in third year in 2018 as part of the development of an outcome-based curriculum. A new integrated teaching module was created, called Veterinary Pathobiology, which encompassed the three paraclinical subjects, worth 20 ECTS credits. Subject integration was driven and supported by case-based learning (CBL) activities, and practical classes, which were aimed at facilitating the understanding of basic disease processes, infectious agents, and the application of diagnostic tests. The disciplines maintained their identities within lectures which were aligned by content. The restructuring led to a reduction of contact hours by 20% and of assessment time by 40%. The examinations included integrated questions with an emphasis on the material students had covered in their CBL. Despite positive outcomes, which included equivalent examination scores and positive written feedback by students on teaching and learning, understanding, assessment, relevance, CBL, group work, and generic skills, the average scores for overall student satisfaction dropped dramatically in the second academic year of implementation. This followed the introduction of new regulations by the University relating to student progression, which was capped at "carrying" 10 ECTS credits, thus preventing students that failed the new module from progressing. Other criticisms of the new module by students included too little communication on the changes implemented in its first iteration and a workload perceived to be too heavy. Further restructuring is therefore necessary. This study highlights the process/pitfalls of integration/curricular innovation.

Breast ductal carcinoma in situ (DCIS) is clinically challenging, featuring high diagnosis rates and few targeted therapies. Expression/signaling from junctional adhesion molecule-A (JAM-A) has been linked to poor prognosis in invasive breast cancers, but its role in DCIS is unknown. Since progression from DCIS to invasive cancer has been linked with overexpression of the human epidermal growth factor receptor-2 (HER2), and JAM-A regulates HER2 expression, we evaluated JAM-A as a therapeutic target in DCIS. JAM-A expression was immunohistochemically assessed in patient DCIS tissues. A novel JAM-A antagonist (JBS2) was designed and tested alone/in combination with the HER2 kinase inhibitor lapatinib, using SUM-225 cells in vitro and in vivo as validated DCIS models. Murine tumors were proteomically analyzed. JAM-A expression was moderate/high in 96% of DCIS patient tissues, versus 23% of normal adjacent tissues. JBS2 bound to recombinant JAM-A, inhibiting cell viability in SUM-225 cells and a primary DCIS culture in vitro and in a chick embryo xenograft model. JBS2 reduced tumor progression in in vivo models of SUM-225 cells engrafted into mammary fat pads or directly injected into the mammary ducts of NOD-SCID mice. Preliminary proteomic analysis revealed alterations in angiogenic and apoptotic pathways. High JAM-A expression in aggressive DCIS lesions and their sensitivity to treatment by a novel JAM-A antagonist support the viability of testing JAM-A as a novel therapeutic target in DCIS.

A critical challenge for the successful development of RNA interference-based therapeutics therapeutics has been the enhancement of their in vivo metabolic stability. In therapeutically relevant, fully chemically modified small interfering RNAs (siRNAs), modification of the two terminal phosphodiester linkages in each strand of the siRNA duplex with phosphorothioate (PS) is generally sufficient to protect against exonuclease degradation in vivo. Since PS linkages are chiral, we systematically studied the properties of siRNAs containing single chiral PS linkages at each strand terminus. We report an efficient and simple method to introduce chiral PS linkages and demonstrate that Rp diastereomers at the 5' end and Sp diastereomers at the 3' end of the antisense siRNA strand improved pharmacokinetic and pharmacodynamic properties in a mouse model. In silico modeling studies provide mechanistic insights into how the Rp isomer at the 5' end and Sp isomer at the 3' end of the antisense siRNA enhance Argonaute 2 (Ago2) loading and metabolic stability of siRNAs in a concerted manner., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)