Novel MRI and histopathological findings in a young Bullmastiff cross dog with mitochondrial fission encephalopathy.

A 9-month-old male Bullmastiff cross dog was presented with a history of progressive proprioceptive ataxia and behavior changes. Neuroanatomical localization was multifocal with forebrain and vestibulo-cerebellum involvement. MRI identified moderate diffuse cerebral sulci widening, dilation of the ventricular system, and rounded, well-defined, bilaterally symmetrical T2W, FLAIR, and T2* hyperintense intra-axial lesions affecting the olivary nuclei. Histopathological examination was indicative of a primary mitochondrial disorder. This was confirmed following genetic analysis which identified mitochondrial fission encephalopathy with a homozygous frameshift variant in the MFF gene. This case report documents diagnostic imaging and histopathological findings not previously reported in dogs affected with mitochondrial fission encephalopathy, suggesting a different selective regional vulnerability of the neurons.

Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria.

Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

Babesia gibsoni Infection in a Cat with Immune-Mediated Haemolytic Anaemia and Thrombocytopenia.

Tick-borne haemoparasite Babesia gibsoni has been detected rarely in cats, in surveys of apparently healthy animals. In stored blood from a 6-year-old male-neutered domestic shorthair cat in Hong Kong, B. gibsoni DNA was detected retrospectively using PCR for Babesia spp. 18S rRNA and mitochondrial cytochrome B genes, followed by sequencing and basic local alignment search tool (BLAST) analysis. The cat presented with severe haemolytic anaemia and thrombocytopenia. The cat responded to supportive care and glucocorticoids and was clinically normal despite persistent subclinical thrombocytopenia until six months after presentation, when it succumbed to a fatal haemorrhagic episode. Necropsy revealed severe intestinal and pulmonary haemorrhage and hypocellular bone marrow with megakaryocytosis but no other causes of immune-mediated thrombocytopenia (IMTP) or immune-mediated haemolytic anaemia (IMHA). Blood stored on days 158 and 180 tested PCR negative for Babesia spp. This report demonstrates that geographic range of B. gibsoni detection in cats includes Hong Kong. The exclusion of other causes suggests that B. gibsoni might have potentially played a role in triggering immune-mediated disease in this case.

Diagnostic features of type II fibrinoid leukodystrophy (Alexander disease) in a juvenile Beagle dog.

A 3-month-old female entire Beagle presented with a progressive history of caudotentorial encephalopathy. Reactive encephalopathies were ruled out and tests for the most common infectious diseases agents were negative. Magnetic resonance imaging of the brain using a 1.5 Tesla scanner showed diffuse, bilateral, T2-weighted and T2-weighted-FLAIR hyperintense, T1-weighted hypointense, noncontrast-enhancing lesions involving the white matter of the cerebellum, brainstem, spinal cord, and forebrain to a lesser extent. There was cerebellar enlargement. Abnormalities were not detected on cerebrospinal fluid examination. Given the progressive nature of the disease and suspected poor prognosis the dog was euthanized. Histopathological analysis of the brain was consistent with fibrinoid leukodystrophy, also known as Alexander disease. Based on the classification used in humans, this is a description of MRI of a case of type II Alexander disease in veterinary medicine, with characteristics different to other described leukoencephalopathies in dogs.

Vitamin D status in chimpanzees in human care: a Europe wide study.

While vitamin D deficiency is a public health concern in humans, comparatively little is known about vitamin D levels in non-human primates. Vitamin D plays a crucial role in overall health and its deficiency is associated with a range of disorders, including cardiovascular disease, which is a leading cause of death in great apes. Serum samples (n = 245) from chimpanzees (Pan troglodytes) housed at 32 European zoos were measured for 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and total 25-hydroxyvitamin D (25-OHD) using liquid chromatography and tandem mass spectrometry. Of these samples, 33.1% indicated inadequate vitamin D status, using the human reference interval (25-OHD < 50 nmol/L). The season of the year, health status of the animal, and the provision of daily outdoor access had a significant effect on vitamin D status. This is the first large-scale study on vitamin D status of non-human great apes in human care. Inadequate 25-OHD serum concentrations are widespread in the chimpanzee population in Europe and could be a risk factor for the development of idiopathic myocardial fibrosis, a major cause of mortality in this species, as well as other diseases. A review of husbandry and nutrition practices is recommended to ensure optimal vitamin D supply for these endangered animals.

Anatomy, histology, development and functions of Ossa cordis: A review.

This systematic review highlights the similarities and variations in Ossa cordis prevalence, histology and anatomical location between differing veterinary species and in humans. In addition, it also identifies associated factors such as aging and cardiovascular disease for each species in relation to functional roles and developmental mechanisms that these bone structures may play. The potential functions of Ossa cordis are presented, ranging from aiding cardiac contraction and conduction, providing cardiac structure, and protecting components of the heart, through to counteracting high mechanical stress. Furthermore, this review discusses the evidence and rationale behind the theories regarding the formation and development of Ossa cordis in different veterinary species and in people.

Human health implications from consuming eggs produced near a derelict metalliferous mine: a case study.

Lead pollution from metalliferous mines can have major environmental and health effects long after the mines have closed. Animals living near derelict mine sites can inadvertently ingest lead-contaminated soils, causing them to accumulate lead and potentially experience significant adverse health effects. Human food products, such as eggs, produced near metalliferous mines may also be contaminated with lead. The focus of this case study was to determine whether free-range chickens living near a derelict lead mine had high lead body burdens, whether they were producing eggs with elevated lead concentrations, and whether these eggs could be hazardous to human health. Soil samples and chicken egg, feather, blood, and bone samples were collected from a small farm near an abandoned metalliferous mine. The soil in and around the chicken pens contained lead concentrations that were elevated above established soil lead baseline concentrations. The lead concentrations in the chicken feather, blood, and bone samples were consistent with lead toxicity and indicated long-term, continuous exposure. Finally, the lead concentrations in the eggs were significantly greater than those found in commercial eggs. Based on previously established lead benchmark dose levels, humans, and in particular, children, could experience adverse health impacts if they routinely consumed these eggs. Environmental lead contamination continues to pose a major health risk for humans, and further research, understanding, and awareness are required to safeguard the public from the risks of consuming food produced near derelict mines.

Standardisation of canine meningioma grading: Inter-observer agreement and recommendations for reproducible histopathologic criteria.

The human grading system is currently applied to canine meningioma, although it has not been validated in dogs. The present study focused on standardising the human grading system applied to canine meningioma. Four veterinary neuropathologists graded 186 canine meningiomas as follows: Grade I tumour, with <4 mitoses/2.37 mm2 ; Grade II tumour, with ≥4 mitoses/2.37 mm2 , brain invasion or at least three of the following criteria: sheeting architecture, hypercellularity, small cells, macronucleoli, necrosis; Grade III tumour, with ≥20 mitoses/2.37 mm2 or anaplasia. Slides with grading disagreement were reviewed to define a consensus diagnosis and to assess reproducible criteria. Concordance between histologic grade and the consensus diagnosis, as well as intra- and inter-observer agreements for each criterion, were statistically analysed. Concordance between histologic grade and consensus diagnosis ranged from 59% to 100%, with lower concordance for Grade I and II tumours. The lowest inter-observer agreement was recorded for macronucleoli, small cells, hypercellularity and sheeting architecture. Tumour invasion and necrosis displayed fair agreement, while moderate agreement was reached for mitotic grade and anaplasia. The following recommendations were issued to improve the reproducibility of canine meningioma grading: (1) Assess mitotic grade in consecutive HPFs within the most mitotically active area; (2) Define invasion as neoplastic protrusions within central nervous tissue without pial lining; (3) Report spontaneous necrosis; (4) Report prominent nucleoli when visible at ×100; (5) Report pattern loss when visible at ×100 in >50% of the tumour; (6) Report necrosis, small cells, hypercellularity and macronucleoli, even when focal; (7) Report anaplasia if multifocal.

Periodontal health, neutrophil activity and cardiovascular health in captive chimpanzees.

OBJECTIVE: To investigate the association of dental and cardiac disease in a cohort of captive chimpanzees DESIGN: 12 captive chimpanzees underwent periodontal and cardiac examinations under anaesthesia during a relocation to a new enclosure. Blood samples were taken for analysis of circulating markers of cardiac health, nutritional status and isolation of neutrophils for functional assays. They were then observed for three years for signs of heart disease. RESULTS: Although the chimpanzees displayed large quantities of supragingival plaque, they had low bleeding scores. Peripheral blood neutrophils responded to innate and adaptive immune stimuli. In the follow up period two animals died and post mortem confirmed heart disease. Levels of NT-proBNP were found to be high in chimpanzees that died from heart disease. CONCLUSIONS: Whilst there appeared to be a correlation between probing depth and age, there appeared to be no correlation between dental data and heart data in this cohort.

Histopathological Characterization of Colitis in Captive Western Lowland Gorillas (Gorilla gorilla ssp gorilla).

In captive gorillas, ulcerative colitis is an important cause of morbidity and mortality with no established definitive aetiopathogenesis. The aim of the study was to characterize histopathologically colonic lesions in captive western lowland gorillas (Gorilla gorilla ssp gorilla) and to apply the Nancy index, a disease activity scoring system for ulcerative colitis in humans. Colon samples from 21 animals were evaluated on the basis of histopathological characteristics for the diagnosis of inflammatory bowel disease in humans and divided into acute or chronic changes. The most common acute changes included the presence of neutrophils in the lamina propria (17/18; 94%), mucosal and submucosal oedema (12/18; 67%) and crypt abscesses (8/18; 44%). The most common chronic changes were lamina proprial lymphoplasmacytic infiltrates (17/18; 94%) and crypt dilation or distortion (6/18; 33%). Based on the Nancy index, 4/21 (19%) cases were grade 4 (the highest grade), 2/21 (10%) were grade 3, 11/21 (52%) were grade 2 and 4/21 (19%) cases were grade 0. The colonic changes were comparable to the acute phase of ulcerative colitis in humans. No unifying aetiopathogenesis could be identified. The Nancy index proved to be a valuable tool for the standardization of disease grading and established a basis for future studies of gorilla colitis.

Myelopathy secondary to an intramedullary arteriovenous malformation in a mature dog.

A 2-year-old crossbreed dog was presented for evaluation of a 6-week history of progressive paraparesis. Magnetic resonance imaging and computed tomography angiography of the thoracic and lumbar spinal cord disclosed multifocal, anomalous, small, vascular structures, distributed throughout the subarachnoid space of the included section of the spinal cord. An additional focal intramedullary lesion was identified extending from T9 to T10 to T12. Histopathological examination confirmed the presence of an intramedullary arteriovenous malformation affecting the thoracic spinal cord and leading to diffuse congestion and focal hemorrhages into the affected spinal cord.

Non-Infectious, Necrotizing and Granulomatous Aortitis in a Female Gorilla.

A 41-year-old female captive gorilla with progressive weight loss and hydrothorax of unknown origin was euthanized and submitted for necropsy. The ascending aorta showed intimal aortic thickenings, consistent with so called 'tree bark' changes. Microscopic examination revealed a non-infectious, necrotizing and granulomatous aortitis with no evidence of systemic vasculitis or infectious disease elsewhere in the body. While rare, large vessel vasculitides should be considered as a differential diagnosis in gorillas presenting with progressive non-specific signs and vascular intimal changes.

Discovery of os cordis in the cardiac skeleton of chimpanzees (Pan troglodytes).

Cardiovascular diseases, especially idiopathic myocardial fibrosis, is one of the most significant causes of morbidity and mortality in captive great apes. This study compared the structure and morphology of 16 hearts from chimpanzees (Pan troglodytes) which were either healthy or affected by myocardial fibrosis using X-ray microtomography. In four hearts, a single, hyperdense structure was detected within the right fibrous trigone of the cardiac skeleton. High resolution scans and histopathology revealed trabecular bones in two cases, hyaline cartilage in another case and a focus of mineralised fibro-cartilaginous metaplasia with endochondral ossification in the last case. Four other animals presented with multiple foci of ectopic calcification within the walls of the great vessels. All hearts affected by marked myocardial fibrosis presented with bone or cartilage formation, and increased collagen levels in tissues adjacent to the bone/cartilage, while unaffected hearts did not present with os cordis or cartilago cordis. The presence of an os cordis has been described in some ruminants, camelids, and otters, but never in great apes. This novel research indicates that an os cordis and cartilago cordis is present in some chimpanzees, particularly those affected by myocardial fibrosis, and could influence the risk of cardiac arrhythmias and sudden death.

Idiopathic Myocardial Fibrosis in Captive Chimpanzees (Pan troglodytes).

Cardiovascular disorders and predominantly idiopathic myocardial fibrosis are frequently associated with mortality among zoo-housed chimpanzees (Pan troglodytes). Formalin-fixed whole hearts of deceased chimpanzees housed in zoos (n = 33) and an African sanctuary (n = 2) underwent detailed macroscopic and histopathologic examination using a standardized protocol. Archived histological slides from the hearts of 23 additional African sanctuary-housed chimpanzees were also examined. Myocardial fibrosis (MF) was identified in 30 of 33 (91%) of the zoo-housed chimpanzees but none of the 25 sanctuary-housed chimpanzees. MF was shown to be characterized by both interstitial and replacement fibrosis. Immunophenotyping demonstrated that the fibrotic lesions were accompanied by the increased presence of macrophages, alpha smooth muscle actin-positive myofibroblasts, and a minimal to mild T-cell-dominant leukocyte infiltration. There was no convincing evidence of cardiotropic viral infection or suggestion that diabetes mellitus or vitamin E or selenium deficiency were associated with the presence of the lesion. However, serum vitamin D concentrations among zoo-housed chimpanzees were found to be lower in seasons of low ultraviolet light levels.

Anatomy and Pathology of the Texel Sheep Larynx.

Laryngeal chondritis, or "Texel throat", is a disease affecting the upper respiratory tract of sheep with breeds like the Texel appearing to be predisposed. Previous work suggests the conformation of these breeds of sheep may be predisposing these animals to laryngeal disease. This study evaluated the anatomy of the Texel sheep larynx and describes incidental pathology. Forty-three larynges from rams of the Texel and Bluefaced Leicester breeds of sheep were measured and photographed. A larynx from each breed was submitted for computed tomography (CT) and magnetic resonance imaging (MRI). Measurements, photography, CT, and MRI demonstrated a difference in the anatomy of the larynx between breeds and a higher proportion of Texel sheep had laryngeal lesions. This study supports the hypothesis that the anatomy of the Texel sheep could be pre-disposing the breed to laryngeal chondritis.

Myoinositol CEST signal in animals with increased Iba-1 levels in response to an inflammatory challenge-Preliminary findings.

Neuroinflammation plays an important role in the pathogenesis of a range of brain disorders. Non-invasive imaging of neuroinflammation is critical to help improve our understanding of the underlying disease mechanisms, monitor therapies and guide drug development. Generally, MRI lacks specificity to molecular imaging biomarkers, but molecular MR imaging based on chemical exchange saturation transfer (CEST) can potentially detect changes of myoinositol, a putative glial marker that may index neuroinflammation. In this pilot study we aimed to investigate, through validation with immunohistochemistry and in vivo magnetic resonance spectroscopy (MRS), whether CEST imaging can reflect the microglial response to a mild inflammatory challenge with lipopolysaccharide (LPS), in the APPSwe/ PS1 mouse model of Alzheimer's disease and wild type controls. The response to the immune challenge was variable and did not align with genotype. Animals with a strong response to LPS (Iba1+, n = 6) showed an increase in CEST contrast compared with those who did not (Iba1-, n = 6). Changes of myoinositol levels after LPS were not significant. We discuss the difficulties of this mild inflammatory model, the role of myoinositol as a glial biomarker, and the technical challenges of CEST imaging at 0.6ppm.

Pathological Findings in the Pituitary Glands of Dogs and Cats.

With the exception of classic functional adenomas in dogs and horses, pituitary lesions are infrequently described in the veterinary literature. Approximately 10% of pituitary glands from asymptomatic humans contain abnormalities, but the equivalent proportion in small animals is unknown. Pituitary glands from 136 dogs and 65 cats collected during routine necropsies were examined to determine the prevalence of pituitary lesions and their histopathological diagnosis. Lesions were characterized in sections stained with hematoxylin and eosin, periodic acid-Schiff (PAS), Gordon and Sweet's and reticulin stains, and immunohistochemistry for adrenocorticotropic hormone (ACTH), growth hormone, melanocyte stimulating hormone-α, and prolactin. Pituitary abnormalities were identified in 36 of 136 (26.4%) dogs and 10 of 65 (15.3%) cats. Cystic changes were the most common lesion, occurring in 18 (13.2%) dogs and 8 (12.3%) cats. Pituitary neoplasia was detected in 14.1% (12/85) of middle-aged and old dogs; 1 (1.5%) cat had pituitary nodular hyperplasia. PAS and reticulin stains helped differentiate ACTH-immunoreactive adenomas from hyperplastic nodules: adenomas contained PAS-positive intracytoplasmic granules and loss of the normal reticulin network. One dog had a pituitary carcinoma with infiltration into the thalamus. Other pituitary abnormalities included secondary metastases (2 dogs) and hypophysitis (4 dogs, 1 cat). In most cases, the lesion appeared to be subclinical and could be considered incidental, whereas clinical manifestations were apparent in only 4 dogs (2.9%) and none of the cats with pituitary lesions. Pituitary abnormalities are common in dogs and cats, and their clinical relevance requires further investigation.

A Novel 3D Skin Explant Model to Study Anaerobic Bacterial Infection.

Skin infection studies are often limited by financial and ethical constraints, and alternatives, such as monolayer cell culture, do not reflect many cellular processes limiting their application. For a more functional replacement, 3D skin culture models offer many advantages such as the maintenance of the tissue structure and the cell types present in the host environment. A 3D skin culture model can be set up using tissues acquired from surgical procedures or post slaughter, making it a cost effective and attractive alternative to animal experimentation. The majority of 3D culture models have been established for aerobic pathogens, but currently there are no models for anaerobic skin infections. Footrot is an anaerobic bacterial infection which affects the ovine interdigital skin causing a substantial animal welfare and financial impact worldwide. Dichelobacter nodosus is a Gram-negative anaerobic bacterium and the causative agent of footrot. The mechanism of infection and host immune response to D. nodosus is poorly understood. Here we present a novel 3D skin ex vivo model to study anaerobic bacterial infections using ovine skin explants infected with D. nodosus. Our results demonstrate that D. nodosus can invade the skin explant, and that altered expression of key inflammatory markers could be quantified in the culture media. The viability of explants was assessed by tissue integrity (histopathological features) and cell death (DNA fragmentation) over 76 h showing the model was stable for 28 h. D. nodosus was quantified in all infected skin explants by qPCR and the bacterium was visualized invading the epidermis by Fluorescent in situ Hybridization. Measurement of pro-inflammatory cytokines/chemokines in the culture media revealed that the explants released IL1ß in response to bacteria. In contrast, levels of CXCL8 production were no different to mock-infected explants. The 3D skin model realistically simulates the interdigital skin and has demonstrated that D. nodosus invades the skin and triggered an early cellular inflammatory response to this bacterium. This novel model is the first of its kind for investigating an anaerobic bacterial infection.

A RETROSPECTIVE REVIEW OF WESTERN LOWLAND GORILLA (GORILLA GORILLA GORILLA) MORTALITY IN EUROPEAN ZOOLOGIC COLLECTIONS BETWEEN 2004 AND 2014.

An understanding of the main causes of mortality among captive gorillas is imperative to promoting their optimal care, health, and welfare. A retrospective observational review of mortality among the European zoo-housed western lowland gorilla ( Gorilla gorilla gorilla) population from 2004 to 2014 was carried out. This is the first published study of mortality in this population. Relevant postmortem data were requested from each collection reporting a death during the study period. Age at death enabled grouping into discrete age categories. Deaths were classified according to cause. The main causes of death overall and for each age category and sex were identified. In total, 151 gorillas from 50 European collections died during the study period. Postmortem data were available for 119 (79%) of the deaths, of which 102 (86%) were classified by cause. Diseases of the digestive system were responsible for most (23%) deaths overall. Also of significance (each accounting for 15% overall mortality) were deaths due to external causes (especially trauma) among young gorillas and cardiovascular disease among adult and aged animals. Being a male gorilla was associated with an 8.77- and 5.40-fold increase in risk of death due to cardiovascular and respiratory disease, respectively. Death due to external causes was 4.45 times more likely among females than males. There was no statistically significant difference in life expectancy between male and female gorillas. The authors conclude that further work is needed to understand risk factors involved in the main causes of death and suggest a need for standardization with regard the approach to postmortem examination and data collection, sample collection, and storage across European zoos.