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The clinical, imaging and histopathologic findings in this case are similar to those reported in humans with calcification of the ligamentum flavum, and in dogs with calcinosis circumscripta. A 4-year-6-month old, male neutered domestic rabbit presented with a 3-week history of progressive pelvic limb ataxia. The underlying cause in this case remains unknown but calcinosis circumscripta should be included in the differential diagnosis of cervical myelopathy in rabbits. [Extracted from the article]

Polyglucosan bodies are accumulations of insoluble glucose polymers and proteins that form intracytoplasmic inclusions in the brain, large numbers of which can be indicative of neurodegenerative diseases such as Lafora disease. Montserrat orioles ( Icterus oberi ) are an icterid passerine endemic to Montserrat with conservation populations maintained in captivity abroad. We demonstrate that polyglucosan bodies are unusually abundant in the cerebellar molecular and Purkinje cell layers and cerebellar peduncles of captive-bred and wild-caught Montserrat orioles. The bodies are periodic acid-Schiff positive and diastase resistant and label with concanavalin A and for ubiquitin, consistent with those seen in humans. We found no association of the polyglucosan bodies with concurrent neurological lesions or clinical signs, nor with EPM2 A and EPM2B gene mutations associated with Lafora disease. We conclude that an abundance of cerebellar polyglucosan bodies may be a normal finding in aged Montserrat orioles and not a threat to the captive breeding population., 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.

Background: The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport., Methods: To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer., Findings: Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer., Interpretation: We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer., Funding: Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute., Competing Interests: Declaration of interests OW: Personal fees from Amgen, Bayer, BMS, Celgene, Daiicgi Sankyo, Eisai, Incyte, Ipsen, Merck, MSD, Novartis, Pierre Fabre, Roche, Servier; honoraria for lectures and/or presentations from Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, MSD, Novartis, Roche, Zentiva; support for attending meetings and/or travel: Abbvie, AstraZeneca, Bayer, BMS, Gilead, Ipsen, Medac, Merck, Pierre Fabre, Roche. SZ: Consultancy and/or speaker’s bureau: Abbvie, BioMarin, Boehringer Ingelheim, Gilead, GSK, Ipsen, Madrigal, Merck/MSD, NovoNordisk, SoBi. JUM: Grants or contracts from any entity, AstraZeneca, consulting fees: AstraZeneca, Roche, Ipsen, Eisai; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Roche, Ipsen, Eisai. The other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non-human primate species but are poorly documented in Goeldi's monkeys., Methods: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan-herpesvirus PCR analysis., Results: All animals were euthanised and exhibited poor-to-emaciated body condition. Three OCSCCs arose from the maxillary oral mucosa and a single OCSCC was primarily mandibular, with bone invasion evident in three cases. Histologically, one OCSCC in situ was diagnosed, whilst the rest were typically invasive OCSCCs. Neoplastic cells were immunopositive for pancytokeratin and E-cadherin. All examined cases were negative for regional lymph node (RLN) and/or distant metastases, cyclooxygenase-2 (COX-2) immunoexpression, and panherpesvirus PCR expression., Conclusions: OCSCCs in Goeldi's monkeys may be deeply invasive, but not readily metastatic. No herpesvirus-association or COX-2 expression was evident; the latter suggesting that NSAIDs are unlikely to be a viable chemotherapeutic treatment., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This retrospective study documents the occurrence of single and multiple cutaneous apocrine gland tumours (CATs) on the dorsal midline of 16 captive African wild dogs (AWDs, Lycaon pictus) derived from 161 submissions to diagnostic laboratories in South Africa, France and Germany between 1997 and 2022. Animals included in the study came from zoological institutions in South Africa (n = 2), France (n = 5) and Germany (n = 1) and ranged from 5 to 14 years of age. Fifteen affected animals were female (94%) and one was male. CATs presented as raised, hairless, multilobular, grey firm masses, consistently located along the dorsal midline. Apart from a single cutaneous apocrine adenoma and a cystadenoma occurring concurrently with two non-cystic adenocarcinomas, neoplasms were consistent with malignant cutaneous apocrine adenocarcinomas with lymphatic spread and visceral metastases. Advanced age and female sex were identified as risk factors. A genetic component or association with the increasing use of GnRH agonist contraceptives was suspected but could not be established. This study highlights the need for close clinical monitoring of AWDs over the age of 5 years for the development of CATs along the dorsal midline and supports early surgical intervention. More research is needed to determine the role of inbreeding, endocrine changes and husbandry factors that may play a role in the development of CATs on the dorsal midline of AWDs., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Full medical histories from captive Alaotran gentle lemurs or Bandro ( Hapalemur alaotrensis ) > 1 yr old that died between 1990 and 2016 were requested from holding institutions. Eighty-six individuals died during the period analyzed. Full postmortem reports were received from 40 (46.5%) animals from 16 different institutions across Europe (15) and North America (1). Eighteen animals (45%) showed azotemia within three months of death, with accompanying histological renal lesions. Another 17 (42.5%) showed histological renal lesions, but no renal function assessment was carried out antemortem, or results were within normal limits. Only five animals (12.5%) showed no renal lesions. Of the 35 (87.5%) animals with histological renal lesions, 18 were females, and 17 were males, 11 were wild caught, and 24 were captive born. Twenty-seven animals were euthanized, seven were found dead, and in one case, no details were provided. Sixty-four blood samples from 22 animals were available. Azotemia was observed on average 407 d antemortem, with a case observed as early as 2,318 d antemortem. Twenty-nine urinalyses from 12 animals were carried out antemortem. All animals showed hematuria or proteinuria in at least one antemortem sample. A pH decrease from 8.5 to 5.0 was observed in two animals antemortem. Gross renal lesions most frequently reported were irregular surface ( n = 14), abnormal shape ( n = 12), and/or presence of cysts ( n = 9). The most common histological lesions were interstitial nephritis ( n = 25), interstitial fibrosis ( n = 26), tubule dilation ( n = 16), and glomerulosclerosis ( n = 12). Development of additional diagnostic tools, standardization of ante- and postmortem diagnostic protocols, and further investigation into potential etiologies, such as diets offered in captivity and genetic factors, should be considered as the next steps for the veterinary management of this species in captivity.

The African wild dog ( Lycaon pictus ) is listed as Endangered by the International Union for Conservation of Nature and is part of captive breeding programs designed to support free-living populations and genetic diversity. This study's aim was to identify common causes of morbidity and mortality objectively in United Kingdom captive African wild dogs to inform management recommendations that will improve health and welfare and reduce disease prevalence. Data were gathered from 140 individual dogs housed in 10 institutions, with morbidity records for 122 individuals and 70 postmortem reports. Descriptive statistics including the Mann-Whitney U test and odds ratios were used to analyze morbidity and mortality across age and sex. The most common cause of death for African wild dogs, excluding those,< 7 d old, was trauma (23%), followed by geriatric (18%), degenerative (15%), and neoplastic (14%) conditions. The most common morbidity was also trauma (62%), of which 76% was caused by intraspecific aggression. Integumentary disease secondary to trauma was the most common morbidity by body system. Eight independent incidents of barbiturate toxicosis from consumption of contaminated carcasses, affecting 18 animals, were identified. Records for neonatal deaths were incomplete and conclusions limited; neonatal loss was estimated at 20.5%. Recommendations include research into factors affecting intraspecific aggression in captivity, operant conditioning for hand injection, provision of dietary carcasses from reputable sources, and improved record-keeping.

Objective: Investigating the effect of ferroptosis in the tumour microenvironment to identify combinatory therapy for liver cancer treatment., Design: Glutathione peroxidase 4 (GPx4), which is considered the master regulator of ferroptosis, was genetically altered in murine models for hepatocellular carcinoma (HCC) and colorectal cancer (CRC) to analyse the effect of ferroptosis on tumour cells and the immune tumour microenvironment. The findings served as foundation for the identification of additional targets for combine therapy with ferroptotic inducer in the treatment of HCC and liver metastasis., Results: Surprisingly, hepatocyte-restricted GPx4 loss does not suppress hepatocellular tumourigenesis. Instead, GPx4-associated ferroptotic hepatocyte death causes a tumour suppressive immune response characterised by a CXCL10-dependent infiltration of cytotoxic CD8 + T cells that is counterbalanced by PD-L1 upregulation on tumour cells as well as by a marked HMGB1-mediated myeloid derived suppressor cell (MDSC) infiltration. Blocking PD-1 or HMGB1 unleashes T cell activation and prolongs survival of mice with Gpx4 -deficient liver tumours. A triple combination of the ferroptosis inducing natural compound withaferin A, the CXCR2 inhibitor SB225002 and α-PD-1 greatly improves survival of wild-type mice with liver tumours. In contrast, the same combination does not affect tumour growth of subcutaneously grown CRC organoids, while it decreases their metastatic growth in liver., Conclusion: Our data highlight a context-specific ferroptosis-induced immune response that could be therapeutically exploited for the treatment of primary liver tumours and liver metastases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This retrospective study examines pathologic findings in 593 captive cephalopods (340 octopuses, 130 cuttlefish, 33 squid, and 90 nautiluses; 22 species in total) submitted to International Zoo Veterinary Group Pathology between May 2003 and August 2022. Common octopus, European common cuttlefish, hummingbird bobtail squid, and chambered nautilus were the most numerous species from the included orders of Octopoda, Sepiida, Sepiolida, and Nautilida, respectively. Commonly identified conditions included coccidiosis and renal dicyemid mesozoan infection in octopuses, amebiasis in squid, bacterial infections in cuttlefish, and idiopathic multisystemic inflammatory disease in nautiluses. Coccidiosis was most frequent in common octopuses, giant Pacific octopuses, and California 2-spot octopuses (present in 68.4%, 46.3%, and 23.8% of these species, respectively) and was the attributed cause of death in 32.3%, 36.0%, and 60.0% of such cases, respectively. Ulcerative dermatitis (UD) was common, affecting squid, cuttlefish, and octopuses, while many nautiluses exhibited black shell disease and/or UD. Notable differences in the prevalence of UD were detected between laboratory and aquaria-housed decapodiforms; 52.2% for laboratory squid versus 20.0% in aquaria; 51.3% in laboratory cuttlefish versus 11.0% in aquaria. All octopuses and nautiluses in the study were derived from aquaria. Semelparity-associated death in Coleoidea species was identified in 22.4% of octopuses, 11.5% of cuttlefish, and 6.1% of squid. This report aims to provide an overview and reassessment of species-specific disease patterns under aquarium and laboratory management as a starting point for future developments in husbandry and disease investigation.

Cowpox virus is considered to be a re-emerging zoonotic pathogen and a public health threat due to increasing numbers of cases in humans and animals in Europe over the past decade, including within the United Kingdom (UK). We present epidemiological data and diagnostic features of 27 recent, naturally occurring cowpox cases in zoo and wild animals across the UK, including the first reports of cowpox in two snow leopards (Panthera uncia), a Bengal tiger (Panthera tigris tigris), three Chilean pudus (Pudu puda), a Malayan tapir (Tapirus indicus) and a Eurasian otter (Lutra lutra), and the first reports of Orthopoxvirus infection in a lar gibbon (Hylobates lar), a Southern tamandua (Tamandua tetradactyla) and an aardvark (Orycteropus afer). This study provides a detailed overview of cowpox infections in a wide range of non-domestic animal species, presents a range of methods for diagnosis and demonstrates the value of retrospective analysis of pathology surveillance in revealing epidemiological links., (Copyright © 2023 University of Liverpool, UK. Published by Elsevier Ltd.. All rights reserved.)

Seba's short-tailed bats (Carollia perspicillata) are a frugivorous species native to Central and South America. Despite their importance as a reservoir for zoonotic pathogens and their popularity in zoological collection and as research models, there are relatively few reports on non-zoonotic diseases of bats. Mites of the genus Demodex are obligate commensals of the skin of a range of mammals, are highly host-specific and are not associated with clinical disease when present in low numbers. However, infestation with high numbers can result in severe or even fatal disease and substantially affect the well-being of the animals. The clinical, pathological and parasitological findings in 12 Seba's short-tailed bats with demodicosis from a colony kept at Munich Zoo Hellabrunn between 1992 and 2021 are described in this report. From 2002, skin lesions became apparent on the head, especially the periocular region, nose and ears, as well as the genital area of some animals. In advanced cases, skin changes were also present on the abdomen, back and extremities. Gross findings typically included alopecia and thickening of the skin, with the formation of papules, reflecting cystically dilated hair follicles containing myriads of demodecid mites. Histologically, lesions were characterized by a paucicellular lymphocytic dermatitis and folliculitis with perifollicular fibrosis, epidermal hyperplasia, orthokeratotic hyperkeratosis and disproportionately high numbers of intrafollicular arthropods. Demodex carolliae was identified morphologically by light, phase-contrast and electron microscopy. Further characterization was achieved by extraction of parasitic DNA and partial gene sequencing of two mitochondrial genes, 16S rDNA and cox1. This is the first clinicopathological description of generalized demodicosis in Seba's short-tailed bats and includes the first molecular characterization of D. carolliae with provision of a GenBank entry., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Elasmobranchs (sharks and rays) are charismatic cartilaginous fish, popular in public aquaria. Almost 200 shark and ray species are listed as threatened by the International Union for Conservation of Nature (IUCN), demonstrating the importance of captive breeding and research programmes. Limited studies investigate diseases of elasmobranchs in captive and free-living environments, and among available literature neoplasia is rarely reported, with even fewer cases of lymphoid neoplasia documented. This article outlines the first reports of lymphoid neoplasia in three elasmobranch species in which haematopoietic neoplasms have not been reported to date. It summarizes signalment, history and histopathologic findings in an undulate ray, Raja undulata (Lacepede), a common smooth-hound, Mustelus mustelus (Linnaeus) and a bat ray, Myliobatis californica (Gill). Lesions were confirmed in a wide range of tissues and evidence of lymphoid leukaemia was seen in two cases. This small-scale review demonstrates that lymphoid neoplasia should be considered as a differential diagnosis in elasmobranchs presenting with lethargy and anorexia and highlights the challenges of immunohistochemical work up., (© 2022 John Wiley & Sons Ltd.)

Objective: Freezing of gait (FOG) is an episodic, debilitating phenomenon that is common among people with Parkinson disease. Multiple approaches have been used to quantify FOG, but the relationships among them have not been well studied. In this cross-sectional study, we evaluated the associations among FOG measured during unsupervised daily-living monitoring, structured in-home FOG-provoking tests, and self-report., Methods: Twenty-eight people with Parkinson disease and FOG were assessed using self-report questionnaires, percentage of time spent frozen (%TF) during supervised FOG-provoking tasks in the home while off and on dopaminergic medication, and %TF evaluated using wearable sensors during 1 week of unsupervised daily-living monitoring. Correlations between those 3 assessment approaches were analyzed to quantify associations. Further, based on the %TF difference between in-home off-medication testing and in-home on-medication testing, the participants were divided into those responding to Parkinson disease medication (responders) and those not responding to Parkinson disease medication (nonresponders) in order to evaluate the differences in the other FOG measures., Results: The %TF during unsupervised daily living was mild to moderately correlated with the %TF during a subset of the tasks of the in-home off-medication testing but not the on-medication testing or self-report. Responders and nonresponders differed in the %TF during the personal "hot spot" task of the provoking protocol while off medication (but not while on medication) but not in the total scores of the self-report questionnaires or the measures of FOG evaluated during unsupervised daily living., Conclusion: The %TF during daily living was moderately related to FOG during certain in-home FOG-provoking tests in the off-medication state. However, this measure of FOG was not associated with self-report or FOG provoked in the on-medication state. These findings suggest that to fully capture FOG severity, it is best to assess FOG using a combination of all 3 approaches., Impact: These findings suggest that several complementary approaches are needed to provide a complete assessment of FOG severity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

T memory stem cells (T SCM ) display increased self-renewal and prolonged survival capabilities, thus preventing T cell exhaustion and promoting effective anti-tumor T cell responses. T SCM cells can be expanded by Urolithin A (UA), which is produced by the commensal gut microbiome from foods rich in ellagitannins and is known to improve mitochondrial health. Oral UA administration to tumor-bearing mice conferred strong anti-tumor CD8 + T cell immunity, whereas ex vivo UA pre-treated T cells displayed improved anti-tumor function upon adoptive cell transfer. UA-induced T SCM formation depended on Pink1-mediated mitophagy triggering cytosolic release of the mitochondrial phosphatase Pgam5. Cytosolic Pgam5 dephosphorylated β-catenin, which drove Wnt signaling and compensatory mitochondrial biogenesis. Collectively, we unravel a critical signaling pathway linking mitophagy to T SCM formation and suggest that the well-tolerated metabolic compound UA represents an attractive option to improve immune therapy., Competing Interests: Declaration of interests The authors have filed patents regarding the use of Urolithin in tumor therapy and CAR T cell generation. M.D. is an employee of AstraZeneca, UK. C.R. is CEO and a board member of Amazentis SA; P.A.A. is an employee of Vandria SA. F.R.G. has received consulting fees from Amazentis., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

An inflammatory microenvironment, either conferred by an underlying chronic overt or smoldering inflammatory condition constitutes a prerequisite and fuel to essentially all cancers. The complex reciprocal interplay of different cell types in the tumor microenvironment (TME) determines patient outcome. Apart from the actual tumor cells, local and recruited nonmalignant cells as well as the intestinal microbiome actively shape polarization and plasticity of cells in the TME, thereby augmenting protumorigenic and prometastatic inflammatory processes. Here, we address the universality of inflammation in carcinogenesis, review distinct forms of tumor related inflammation and highlight critical processes in the TME actively sustaining a nurturing incubator for cancer progression and therapy resistance., Competing Interests: Declaration of interests F.R.G. has received consulting fees from Amazentis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mast cells (MCs) are crucial players in the relationship between the tumor microenvironment (TME) and cancer cells and have been shown to influence angiogenesis and progression of human colorectal cancer (CRC). However, the role of MCs in the TME is controversially discussed as either pro- or anti-tumorigenic. Genetically engineered mouse models (GEMMs) are the most frequently used in vivo models for human CRC research. In the murine intestine there are at least three different MC subtypes: interepithelial mucosal mast cells (ieMMCs), lamina proprial mucosal mast cells (lpMMCs) and connective tissue mast cells (CTMCs). Interepithelial mucosal mast cells (ieMMCs) in (pre-)neoplastic intestinal formalin-fixed paraffin-embedded (FFPE) specimens of mouse models (total lesions n = 274) and human patients (n = 104) were immunohistochemically identified and semiquantitatively scored. Scores were analyzed along the adenoma-carcinoma sequence in humans and 12 GEMMs of small and large intestinal cancer. The presence of ieMMCs was a common finding in intestinal adenomas and carcinomas in mice and humans. The number of ieMMCs decreased in the course of colonic adenoma-carcinoma sequence in both species (p < 0.001). However, this dynamic cellular state was not observed for small intestinal murine tumors. Furthermore, ieMMC scores were higher in GEMMs with altered Wnt signaling (active β-catenin) than in GEMMs with altered MAPK signaling and wildtypes (WT). In conclusion, we hypothesize that, besides stromal MCs (lpMMCs/CTMCs), particularly the ieMMC subset is important for onset and progression of intestinal neoplasia and may interact with the adjacent neoplastic epithelial cells in dependence on the molecular environment. Moreover, our study indicates the need for adequate GEMMs for the investigation of the intestinal immunologic TME.

The mountain chicken frog ( Leptodactylus fallax ) is a critically endangered species highly reliant on ex situ conservation programs. In captivity, cholelithiasis has been reported during clinical examinations using diagnostic imaging and observed during postmortem examinations. Some individuals have presented with nonspecific clinical signs potentially associated with this condition, but little is known about its clinical relevance. A retrospective evaluation of ultrasonographic ( n = 139) and radiographic ( n = 156) images and histopathology samples ( n = 32) obtained between 2014 and 2020 from 133 individuals was performed. An ultrasound scoring system was developed to evaluate changes in the gallbladder, with 38% (53/139) of the images showing abnormal contents. Gallbladder distension appeared associated with these findings (generalized estimating equation model, P < 0.001). In contrast, radiography proved to have low overall sensitivity (48%) when compared to ultrasonography for identifying abnormal gallbladder contents. A weak level of agreement (Cohen's kappa = 0.535) was observed between the imaging modalities. Histologically, cholecystitis was present in 86% (12/14) of the individuals, thickening of the gallbladder wall in 71% (10/14), and intrahepatic cholangitis in 90% (18/20). There was no evidence of cholestasis in any of the affected individuals. A significant difference was observed in the hepatic melanomacrophage density between animals with and without cholelithiasis (Welch two-sample t test, P < 0.001). This study provides an overview on the use of diagnostic imaging modalities to evaluate cholelithiasis and proposes a convenient ultrasound score to standardize monitoring of the condition in L. fallax . It is also the first systematic review of histopathological changes associated with cholelithiasis in this species.

Toxoplasma gondii is an extremely successful zoonotic protozoan parasite that has been demonstrated in a wide range of endo- and poikilothermic species. Although infection is widespread amongst domestic animals, overt disease other than abortion in small ruminants is sporadic. This survey evaluates toxoplasmosis in zoo animals based on a systematic review of pathology archive material ( n = 33,506 submissions) over a 16-year study period. A total of 126 submissions, deriving from 32 zoos, two educational facilities and two private owners, were included in the study, based on gross lesions, cytological, histological and immunohistological diagnosis of toxoplasmosis. Clinical history, signalment, annual distribution and post-mortem findings were evaluated. A total of 31 species (mammalian 97%/avian 3%) were represented in the study material. Ring-tailed lemurs, slender tailed meerkats, Pallas' cats, and squirrel monkeys were most affected. An unusual outbreak occurred in Asian small-clawed otters, in which toxoplasmosis has not been reported to date. Clinically, animals over 12 months of age presented with non-specific symptoms (anorexia, weight loss, lethargy, debilitation), neurological, gastrointestinal or respiratory signs and sudden death. Systemic disease predominated, with a propensity for encephalitis in meerkats and Pallas' cats and systemic disease involving lymphoid tissues in ring-tailed lemurs. Cases in the UK occurred year-round, with species-specific peaks and increases between August and November. This study reinforces the importance of toxoplasmosis as a significant cause of sporadic and epizootic mortalities in a wide range of zoo animals. Feral cat control is crucial to reduce infection pressure.

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs.

Avian malaria is caused by infection with haemoprotozoa of the genus Plasmodium . Infection is endemic in large parts of the world and is typically subclinical in birds that are native to these regions. Several penguin species have evolved in non-endemic regions without the selective pressure that these parasites exert and are highly susceptible to infection when transplanted to endemic regions, for example, in the context of zoological collections or rehabilitation centers. Avian malaria in penguins typically causes acute mortality without premonitory signs, or less commonly, nonspecific signs of morbidity, followed by mortality. Additionally, infection is reported in wild penguins, though the significance of these infections remains equivocal. As global temperatures continue to increase, avian malaria is likely to pose a continued and further threat to conservation efforts in captive environments. Intra vitam diagnosis currently relies on the evaluation of blood smears and molecular methods. The former is unreliable in penguins, as the acute clinical course typically does not allow the development of parasitemia. This absence of parasitemia also makes speciation challenging. Current molecular methods typically target the Cytochrome B or 18s subunit and have proven variably sensitive and specific. Reliable intra vitam diagnosis of avian malaria and further information about the causative agents at a species level would be very valuable in understanding the epidemiology and likely future course of avian malaria infection in penguins, and in particular, the implications avian malaria may have for conservation efforts. This paper provides an overview of malaria in penguins, discusses its changing impact on management and conservation, offers a summary of current diagnostics, and suggests future direction for the development of diagnostic tests. The latter will be key in understanding and managing this disease.

Purpose: Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland's Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE., Methods: We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC)., Results: Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE., Conclusion: While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE., Competing Interests: The authors have declared that no competing interests exist.

Langurs are Asian primates belonging to the Colobinae subfamily. Langur populations are declining, with most species categorized as threatened by the International Union for Conservation of Nature. Investigation into the threats to population viability and sustainability would be beneficial but there is limited literature available on common diseases or causes of death in these species, either in captive or free-ranging settings. This study aimed to evaluate the most common causes of morbidity and mortality in Trachypithecus species submitted for postmortem examination by six United Kingdom zoological institutions between 2001 and 2020, to inform best practice husbandry guidelines. Necropsy and histopathology reports from 88 individuals of Trachypithecus species from six zoological organizations in the United Kingdom were analyzed. Species included Javan langurs ( Trachypithecus auratus ; n = 35), dusky langurs ( Trachypithecus obscurus ; n = 28), François' langurs ( Trachypithecus francoisi ; n = 16), purple-faced langurs ( Trachypithecus vetulus ; n = 4), silvered langurs ( Trachypithecus cristatus ; n = 4), and Phayre's langur ( Trachypithecus phayrei ; n = 1). Morbidities and causes of death were recorded. Gastrointestinal diseases and systemic infections were the leading causes of death (27.4% and 21.0% of cases where cause of death was known, respectively); linear foreign bodies were the most common cause of death. Interstitial pneumonia was frequently observed secondary to systemic infection. Heart abnormalities, anthracosis, and hemosiderosis were common but not directly associated with mortality. Further investigation is necessary to assess the importance of these conditions and whether they predispose to other diseases. This study provides a baseline for future research evaluating captive and free-ranging langur health and highlights husbandry practices that may decrease morbidity in these species.

Limited availability of in vivo experimental models for invasive colorectal cancer (CRC) including metastasis and high tumor budding activity is a major problem in colorectal cancer research. In order to compare feline and human intestinal carcinomas, tumors of 49 cats were histologically subtyped, graded and further characterized according to the human WHO classification. Subsequently, feline tumors were compared to a cohort of 1004 human CRC cases. Feline intestinal tumors closely resembled the human phenotype on a histomorphological level. In both species, adenocarcinoma not otherwise specified (ANOS) was the most common WHO subtype. In cats, the second most common subtype of the colon (36.4%), serrated adenocarcinoma (SAC), was overrepresented compared to human CRC (8.7%). Mucinous adenocarcinoma (MAC) was the second most common subtype of the small intestine (12.5%). Intriguingly, feline carcinomas, particularly small intestinal, were generally of high tumor budding (Bd) status (Bd3), which is designated an independent prognostic key factor in human CRC. We also investigated the relevance of feline CTNNB1 exon 2 alterations by Sanger sequencing. In four cases of feline colonic malignancies (3 ANOS, 1 SAC), somatic missense mutations of feline CTNNB1 (p.D32G, p.D32N, p.G34R, and p.S37F) were detected, indicating that mutational alterations of the WNT/β-catenin signaling pathway potentially play an essential role in feline intestinal tumorigenesis comparable to humans and dogs. These results indicate that spontaneous intestinal tumors of cats constitute a useful but so far underutilized model for human CRC. Our study provides a solid foundation for advanced comparative oncology studies and emphasizes the need for further (molecular) characterization of feline intestinal carcinomas.