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Abstract Background Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Result Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. Conclusion These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract

Summary: Metastasis is one of the defining features of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor prognosis. In this study, the palmitoyl transferase ZDHHC20 was identified in an in vivo short hairpin RNA (shRNA) screen as critical for metastatic outgrowth, with no effect on proliferation and migration in vitro or primary PDAC growth in mice. This phenotype is abrogated in immunocompromised animals and animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumor cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of substrates of this enzyme were identified. These results describe a role for palmitoylation in enabling distant metastasis that could not have been detected using in vitro screening approaches and identify potential effectors through which ZDHHC20 promotes metastasis of PDAC.

AbstractBackground Meerkats (Suricata suricatta) are endemic carnivores of southern Africa and, although currently listed as ‘least concern’ by the International Union for Conservation of Nature (IUCN) red list, there is evidence of a significant decrease in wild populations mainly attributed to effects of climate change. Little is known about diseases associated with mortality in captive meerkats.Aim To characterise macroscopic and microscopic lesions that accounted for the death or euthanasia in a series of captive meerkats.Material and methods Eight captive meerkats submitted for post-mortem examination between 2018 and 2022.Results Three animals died unexpectedly without clinical signs, 2 exhibited neurological signs, 2 collapsed after con-specific fighting and 1 showed gastrointestinal signs. Common pathological findings of this study that may be related to the death of captive meerkats included foreign bodies (trichobezoars or plastic materials) within the alimentary tract, traumatic penetrating injuries or starvation associated with abnormal social behaviours (bullying and con-specific attacks), verminous pneumonia and systemic atherosclerosis. Common incidental findings included pulmonary edema and congestion, cholesterol granulomas, pulmonary adenomas and vertebral spondylosis.Conclusions Non-infectious diseases outreach infectious diseases as causes of mortality in captive meerkats including, foreign bodies within the alimentary tract, con-specific attacks and systemic atherosclerosis, which is described for the first time. These data should raise concern about appropriate husbandry (e.g. environmental enrichment, cleaning of facilities and diet formulation) by zookeepers and emphasise the need for further study of meerkat mortality in both captive and wild populations.

Abstract Background In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. Results Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. Conclusion Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.

Abstract Visceral hemangiosarcomas (HSA) are rare in cats and typically associated with aggressive biologic behavior and poor prognosis. A 4‐year‐old male neutered domestic shorthair cat was presented with a 3‐month history of hematuria and stranguria; ultrasonography identified a large bladder mass. Complete excision was achieved by partial cystectomy. Histopathology and immunohistochemistry for von Willebrand factor confirmed HSA. The cat was treated using adjuvant cyclophosphamide, thalidomide, and meloxicam for 8 months. Abdominal ultrasonography repeated at 2 months and computed tomography repeated at 5 and 19 months after diagnosis showed no evidence of local recurrence or metastasis. The cat was alive at last follow‐up (896 days). Although the cat described in this report experienced a more favorable prognosis compared to other visceral HSA locations, additional cases are needed to further understand the biological behavior of bladder HSAs and guide treatment decisions.

Abstract Background After a strong epidemiological link to diet was established in an outbreak of pancytopenia in cats in spring 2021 in the United Kingdom, 3 dry diets were recalled. Concentrations of the hemato‐ and myelotoxic mycotoxins T‐2, HT‐2 and diacetoxyscirpenol (DAS) greater than the European Commission guidance for dry cat foods were detected in the recalled diets. Objectives To describe clinical and clinicopathological findings in cats diagnosed with suspected diet induced pancytopenia. Animals Fifty cats presenting with pancytopenia after exposure to a recalled diet. Methods Multicenter retrospective case series study. Cats with known exposure to 1 of the recalled diets were included if presented with bi‐ or pancytopenia and underwent bone marrow examination. Results Case fatality rate was 78%. Bone marrow aspirates and biopsy examination results were available in 23 cats; 19 cats had a bone marrow aspirate, and 8 cats had a biopsy core, available for examination. Bone marrow hypo to aplasia—often affecting all cell lines—was the main feature in all 31 available core specimens. A disproportionately pronounced effect on myeloid and megakaryocytic cells was observed in 19 cats. Myelofibrosis or bone marrow necrosis was not a feature. Conclusion and Clinical Importance Mycotoxin induced pancytopenia should be considered as differential diagnosis in otherwise healthy cats presenting with bi‐ or pancytopenia and bone marrow hypo‐ to aplasia.

Abstract A 2‐year‐old male neutered domestic shorthair cat underwent investigations for acute onset of lethargy, hyporexia, and cough. Computed tomography of the thorax identified a large mass‐like lesion in the left cranial lung lobe and bilateral pleural effusion. Thoracotomy and left cranial lung lobectomy were performed. Histopathology of the pulmonary mass was consistent with a localized Toxoplasma gondii pneumonia, confirmed by positive polymerase chain reaction on the affected lung lobe. After adjunctive medical management with a 28‐day course of clindamycin (12.5 mg/kg PO q12h), clinical signs resolved and repeat thoracic radiographs documented no abnormalities. The cat remains clinically well 1 year after surgery.

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Dietary serine and glycine starvation has emerged as a potential therapy for cancer. Here, the authors show that inhibition of PHGDH, which mediates the first step in the serine synthesis pathway, improves the therapeutic efficacy of serine depletion diet in mouse xenograft models.

Coagulase-positive Staphylococci (CoPS) can exist as commensals in humans, companion and food-producing animals, but can cause severe or even lethal diseases. Exchange of these bacteria between humans and animals has been described. Special attention has been focused on Methicillin-Resistant Staphylococcus aureus, but other CoPS can also represent an important threat. In addition to significant antimicrobial resistance, these bacteria may carry a plethora of virulence factors - molecules that allow bacteria to establish on or within a host and increase their ability to cause disease. These virulence factors have been widely described in S. aureus but information about other species of CoPS is scarce. The aim of this paper is to review the recent literature about the virulence factors of non-aureus CoPS of animal origin. Their possible effects on human health are also described. The role and prevalence of different virulence factors including leukocidins, hemolysins, adhesins, enterotoxins, exfoliative and toxic shock syndrome toxins as well as superantigen-like proteins are addressed. The effect of these virulence factors on human health is also described. The possibility of misdiagnosis of species of CoPS has been demonstrated in human clinical samples. Prevalence of zoonotic infections could be higher than thought and medical laboratories should be aware of these other staphylococcal species. In keeping with the ‘One Health’ approach to animal and human disease, medical professionals, veterinarians and health workers should be aware of the risks derived from exposure to these bacteria in people in close contact with animals, including pet owners, farmers and veterinarians themselves.

The purpose of this paper was to do a comparative evaluation of the skull of two species of lizards, the Komodo dragon (Varanus komodoensis) and the Green Iguana (Iguana iguana), by three-dimensional computed tomographic reconstruction. Images provided by this method give excellent anatomic detail of the skull. Therefore, essential differences in the configuration of the orbit and the lateral bones of the neurocranium were visualized in lateral and dorsal reconstructed images. The images obtained by tridimensional computed tomographic reconstruction can be a valuable diagnostic aid for the clinical evaluation of several head disturbances in lizards. Key words: computed tomography; 3D reconstruction; anatomy; skull; lizards PRIMERJAVA LOBANJ KOMODOŠKEGA VARANA (Varanus komodoensis) IN ZELENEGA LEGVANA (Iguana iguana) S POMOČJO TRIDIMENZIONALNE RAČUNALNIŠKE TOMOGRAFSKE REKONSTRUKCIJE Izvleček: Namen prispevka je bil s tridimenzionalno računalniško tomografsko rekonstrukcijo opraviti primerjalno oceno lobanje dveh vrst kuščarjev, komodoškega varana (Varanus komodoensis) in zelenega legvana (Iguana iguana). Slike, pridobljene s to metodo, prikažejo odlične anatomske podrobnosti lobanje. Zato so bile na stranskih in dorzalnih rekonstrukcijah slik vidne bistvene razlike v zgradbi orbitalnega področja in stranskih kosti nevrokranija med obema vrstama kuščarjev. Slike, pridobljene s tridimenzionalno računalniško tomografsko rekonstrukcijo, so lahko dragocena diagnostična pomoč pri klinični oceni večih napak glave pri kuščarjih. Ključne besede: računalniška tomografija; 3D rekonstrukcija; anatomija; lobanja; kuščarji

Abstract Background The cause of low serum vitamin D concentrations in dogs with chronic inflammatory enteropathy (CIE) is not well understood. Objective Improve understanding of pathogenesis of low serum vitamin D concentrations in dogs with CIE by comparing several clinical, clinicopathologic, and histologic variables between CIE dogs with low and normal serum 25‐hydroxyvitamin D concentrations (25[OH]D). Animals Fifteen dogs with CIE and low serum 25[OH]D concentrations; 15 dogs with CIE and normal serum 25(OH)D concentrations. Methods Prospective cohort study. Clinical and clinicopathologic variables were compared between groups. Correlations between serum 25(OH)D concentration and histopathologic variables were assessed. Results Dogs with CIE and low serum 25(OH)D concentrations had higher canine chronic enteropathy clinical activity index scores (P = .003), lower serum α‐tocopherol (P

Abstract Background Lymphatic endothelial cell (LEC) immunohistochemical markers have identified intestinal lymphatic vasculature abnormalities in humans with inflammatory bowel disease, but have not been used to evaluate intestinal lymphatic vasculature in a group of dogs with chronic inflammatory enteropathy (CIE). Objectives To utilize LEC markers to identify and measure intestinal lymphatic vasculature in endoscopic biopsy samples of CIE dogs. To evaluate whether measured lymphatic vasculature variables correlate with serum albumin concentrations. Animals Twenty‐four dogs with CIE; n = 13, serum albumin concentration

A transduced mouse model of SARS-CoV-2 infection was established using Balb/c mice. This was achieved through the adenovirus-vectored delivery of the hACE2 gene, to render the mice transiently susceptible to the virus. The model was characterised in terms of the dissemination of hACE2 receptor expression, the dissemination of three SARS-CoV-2 virus variants in vivo up to 10 days following challenge, the resulting histopathology and the clinical signs induced in the mice. In transduced mice, the infection was short-term, with a rapid loss in body weight starting at day 2 with maximum weight loss at day 4, followed by subsequent recovery until day 10. The induced expression of the hACE2 receptor was evident in the lungs, but, upon challenge, the SARS-CoV-2 virus disseminated beyond the lungs to spleen, liver and kidney, peaking at day 2 post infection. However, by day 10 post infection, the virus was undetectable. The lung histopathology was characterised by bronchial and alveolar inflammation, which was still present at day 10 post infection. Transduced mice had differential responses to viral variants ranking CVR-Glasgow 1 > Victoria-1 > England-2 isolates in terms of body weight loss. The transduced mouse model provides a consistent and manipulatable model of SARS-CoV-2 infection to screen viral variants for their relative virulence and possible interventions.

Merkel cells (MCs) are cutaneous specialized cells with a wide immunohistochemical profile, including low molecular weight cytokeratins and various endocrine and neural markers. Differences in expression of these markers may be a consequence of contradictory results in studies of MCs in normal and damaged canine tissues. The present study aimed to compare five different commercial available antibodies developed against cytokeratins 8 + 18 and 20, neuron-specific enolase, chromogranin A, and synaptophysin on formalin-fixed paraffin-embedded samples of hard palate, cheek skin including sinus hair follicles or vibrissae, nasal planum, and footpads. The antibodies showed great variability with respect to quality and intensity of immunoreactivity to identify MCs. Anti-Cytokeratin 20 antibody is more effective to recognize MCs in the dog skin followed by the antibodies against neuron-specific enolase, cytokeratins 8 and18, chromogranin A, and synaptophysin. There was also a significant difference in intensity of immunoreaction scores between them depending on the location examined. These results represent a necessary basic background for future studies of the role of these cells in normal and damaged canine tissues.

Canine gastric carcinoma (CGC) affects both sexes in relatively equal proportions, with a mean age of nine years, and the highest frequency in Staffordshire bull terriers. The most common histological subtype in 149 CGC cases was the undifferentiated carcinoma. CGCs were associated with increased chronic inflammation parameters and a greater chronic inflammatory score when Helicobacter spp. were present. Understanding the molecular pathways of gastric carcinoma is challenging. All markers showed variable expression for each subtype. Expression of the cell cycle regulator 14-3-3σ was positive in undifferentiated, tubular and papillary carcinomas. This demonstrates that 14-3-3σ could serve as an immunohistochemical marker in routine diagnosis and that mucinous, papillary and signet-ring cell (SRC) carcinomas follow a 14-3-3σ independent pathway. p16, another cell cycle regulator, showed increased expression in mucinous and SRC carcinomas. Expression of the adhesion molecules E-cadherin and CD44 appear context-dependent, with switching within tumor emboli potentially playing an important role in tumor cell survival, during invasion and metastasis. Within neoplastic emboli, acinar structures lacked expression of all markers, suggesting an independent molecular pathway that requires further investigation. These findings demonstrate similarities and differences between dogs and humans, albeit further clinicopathological data and molecular analysis are required.

This study aimed to describe the anatomic features of the normal head of the Komodo dragon (Varanus komodoensis) identified by computed tomography. CT images were obtained in two dragons using a helical CT scanner. All sections were displayed with a bone and soft tissue windows setting. Head reconstructed, and maximum intensity projection images were obtained to enhance bony structures. After CT imaging, the images were compared with other studies and reptile anatomy textbooks to facilitate the interpretation of the CT images. Anatomic details of the head of the Komodo dragon were identified according to the CT density characteristics of the different organic tissues. This information is intended to be a useful initial anatomic reference in interpreting clinical CT imaging studies of the head and associated structures in live Komodo dragons.