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Serum and liver samples from 35, 2-year-old dairy heifers that had fractured one or both humeri post-calving between July and December 2019 were submitted to a diagnostic laboratory for analysis. Serum samples were analysed for albumin, β-hydroxybutyrate (BHB), creatinine, Ca, Mg, phosphate, non-esterified fatty acids (NEFA), and serum Cu concentration. Liver samples were analysed for liver Cu concentration. Data were compared to published reference intervals. Data values for heifers that prior to fracture had grazed fodder beet were also compared to values for those that had grazed pasture.Sixty-nine percent of heifers with humeral fracture had serum creatinine concentrations below the lower value of the reference range (55-130 µmol/L). In 3/32 (9%) heifers, serum NEFA concentrations were increased above the reference value indicating body fat mobilisation (≥1.2 mmol/L for peri-partum cows) and in 20/35 (57%) heifers BHB serum concentrations were above the reference value indicating subclinical ketosis (≥1.1 mmol/L for peri-partum cows). In 24/35 (69%) heifers, liver Cu concentration was low (≤ 44 µmol/kg) or marginal (45-94 µmol/kg). The concentration of Cu in serum was low (≤ 4.5 µmol/L) in 2/33 (6%) heifers and marginal (4.6-7.9 µmol/L) in 5/33 (15%) heifers. There was moderate positive correlation between the logged concentrations of Cu in paired liver and serum samples,In some of these heifers with humeral fractures, there was evidence for protein and/or energy malnutrition in the form of elevated NEFA and BHB concentrations and low creatinine concentrations in serum. Liver Cu concentrations were also reduced in most affected heifers. However, the absence of a control group means it is not possible to determine if these are risk factors for fracture or features common to all periparturient heifers. Clinical trials and molecular studies are needed to determine the true contribution of Cu and protein-energy metabolism to the pathogenesis of spontaneous humeral fractures in dairy heifers.BHB: ß-hydroxybutyrate; NEFA: Non-esterified fatty acids.

Outbreaks of humeral fractures in dairy cows have been reported in New Zealand for several years. Gross, histologic, and histomorphometric findings in the humerus from primiparous cows with spontaneous humeral fracture were compared to age-matched control cows. Affected cows had a complete nonarticular spiral fracture of the humerus. Histologically affected humeri had a thicker growth plate with abnormal architecture, thinner cortex with increased abnormal resorption, increased resorption in the distal humerus, decreased trabecular density, abnormal trabecular architecture, presence of growth arrest lines and woven bone formation. Histomorphometry showed reduction in bone volume, trabecular perimeter, and trabecular width. Cows grazed on fodder beet had thicker growth plates with an abnormal appearance compared with cows grazed on pasture, and cows with low/marginal liver copper concentration had more resorption cavities in the distal humerus and thinner cortical bone compared with cows with adequate liver copper concentration. Decreased trabecular density (OR = 249.5), abnormal cortical resorption (OR = 54.2), presence of woven bone formation in the proximal metaphysis (OR = 37.2), and the number of resorption cavities in the distal humerus were significantly associated with a high probability of fracture. Ribs had enlargement of the costochondral junction with fractures in different stages of healing. Histology of the ribs revealed abnormal growth plate appearance, presence of fracture lines, callus tissue, fibrosis, and microfractures. Cows with humeral fracture have osteoporosis due to decreased bone formation and increased bone resorption, likely associated with inadequate feed quality and perhaps copper deficiency leading to a reduction in bone strength and fracture.

The incidence of spontaneous humeral fractures in first-lactation dairy heifers in New Zealand has emphasised the need to understand the thoracic limb bone growth of dairy heifers. Previous research has indicated that a predisposing factor to spontaneous humeral fracture is nutrition. In addition, it has been hypothesised that liver copper concentration affects bone strength and may be a potential factor associated with humeral fracture risk. The aim of this study was to compare bone morphology in the mid-diaphysis of the metacarpus and humerus of heifers affected and unaffected by spontaneous humeral fractures, and determine the effect of copper status at death on bone morphology. The metacarpus and humerus were collected from heifers affected and unaffected by humeral fractures, and scanned using peripheral quantitative computed tomography (pQCT). The mid-diaphysis of the humerus of the affected group had reduced cortical bone mineral density and a trend for reduced cortical content and total bone content, which contributed to a reduced stress–strain index. The trend for reduced bone length in affected humeri provides additional support for the hypothesis of inhibited humeral growth. Heifers with low copper liver concentrations had reduced humerus lengths and reduced cortical bone mineral densities. These data support the hypothesis that the developmental window for humeral fracture is recent, and possibly associated with periods of inadequate nutrition.

Serum and liver samples from 35, 2-year-old dairy heifers that had fractured one or both humeri post-calving between July and December 2019 were submitted to a diagnostic laboratory for analysis. Serum samples were analysed for albumin, β-hydroxybutyrate (BHB), creatinine, Ca, Mg, phosphate, non-esterified fatty acids (NEFA), and serum Cu concentration. Liver samples were analysed for liver Cu concentration. Data were compared to published reference intervals. Data values for heifers that prior to fracture had grazed fodder beet were also compared to values for those that had grazed pasture. Sixty-nine percent of heifers with humeral fracture had serum creatinine concentrations below the lower value of the reference range (55–130 µmol/L). In 3/32 (9%) heifers, serum NEFA concentrations were increased above the reference value indicating body fat mobilisation (≥1.2 mmol/L for peri-partum cows) and in 20/35 (57%) heifers BHB serum concentrations were above the reference value indicating subclinical ketosis (≥1.1 mmol/L for peri-partum cows). In 24/35 (69%) heifers, liver Cu concentration was low (≤ 44 µmol/kg) or marginal (45–94 µmol/kg). The concentration of Cu in serum was low (≤ 4.5 µmol/L) in 2/33 (6%) heifers and marginal (4.6–7.9 µmol/L) in 5/33 (15%) heifers. There was moderate positive correlation between the logged concentrations of Cu in paired liver and serum samples, r(31) = 0.43; (95% CI = 0.1–0.79; p = 0.014). One heifer had a serum phosphate concentration below the lower limit of the reference range (< 1.10 mmol/L). For all heifers, the concentrations of albumin, Ca, and Mg in serum were within the reference intervals (23–38 g/L, 2.00–2.60 mmol/L, and 0.49–1.15 mmol/L respectively). Over winter, 15/35 (43%) heifers grazed predominantly pasture, 14/35 (40%) grazed fodder beet and 6/35 (17%) had a mixed diet. In some of these heifers with humeral fractures, there was evidence for protein and/or energy malnutrition in the form of elevated NEFA and BHB concentrations and low creatinine concentrations in serum. Liver Cu concentrations were also reduced in most affected heifers. However, the absence of a control group means it is not possible to determine if these are risk factors for fracture or features common to all periparturient heifers. Clinical trials and molecular studies are needed to determine the true contribution of Cu and protein-energy metabolism to the pathogenesis of spontaneous humeral fractures in dairy heifers. BHB: ß-hydroxybutyrate; NEFA: Non-esterified fatty acids

Supplemental material, sj-pdf-1-vet-10.1177_03009858221122500 for Osteoporosis is the cause of spontaneous humeral fracture in dairy cows from New Zealand by Alvaro Wehrle-Martinez, Kevin Lawrence, Penny J. Back, Chris W. Rogers, Michaela Gibson and Keren E. Dittmer in Veterinary Pathology

Made available in DSpace on 2019-10-06T15:53:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-02 GPD Charitable Trust Leverhulme Trust The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution. Transmissible Cancer Group Department of Veterinary Medicine University of Cambridge Animal Management in Rural and Remote Indigenous Communities (AMRRIC) World Vets Animal Shelter Stichting Dierenbescherming Suriname Sikkim Anti-Rabies and Animal Health Programme Department of Animal Husbandry Livestock Fisheries and Veterinary Services Government of Sikkim Royal (Dick) School of Veterinary Studies Roslin Institute University of Edinburgh Easter Bush Campus ConserLab Animal Preventive Medicine Department Faculty of Animal and Veterinary Sciences University of Chile Corozal Veterinary Hospital University of Panamá St. George's University Nakuru District Veterinary Scheme Ltd Animal Medical Centre International Animal Welfare Training Institute UC Davis School of Veterinary Medicine Centro Universitário de Rio Preto (UNIRP) Department of Clinical and Veterinary Surgery São Paulo State University (UNESP) Ladybrand Animal Clinic Veterinary Clinic Sr. Dog's World Vets Latin America Veterinary Training Center National Veterinary Research Institute Animal Clinic Intermunicipal Stray Animals Care Centre (DIKEPAZ) Animal Protection Society of Samoa Faculty of Veterinary Science University of Zulia Veterinary Clinic BIOCONTROL Faculty of Veterinary Medicine School of Health Sciences University of Thessaly Veterinary Clinic El Roble Animal Healthcare Network Faculty of Animal and Veterinary Sciences University of Chile OnevetGroup Hospital Veterinário Berna Universidade Vila Velha Veterinary Clinic Zoovetservis École Inter-états des Sciences et Médecine Vétérinaires de Dakar Department of Small Animal Medicine Faculty of Veterinary Medicine Utrecht University Vetexpert Veterinary Group Veterinary Clinic Lopez Quintana Clinique Veterinaire de Grand Fond Saint Gilles les Bains Department of Veterinary Sciences University of Messina Facultad de Medicina Veterinaria y Zootecnia Universidad Autónoma del Estado de México School of Veterinary Medicine Universidad de las Américas Cancer Development and Innate Immune Evasion Lab Champalimaud Center for the Unknown Touray and Meyer Vet Clinic Hillside Animal Hospital Kampala Veterinary Surgery Asavet Veterinary Charities Vets Beyond Borders Faculty of Veterinary Medicine Autonomous University of Yucatan Laboratorio de Patología Veterinaria Universidad de Caldas Interdisciplinary Centre of Research in Animal Health (CIISA) Faculty of Veterinary Medicine University of Lisbon Four Paws International Help in Suffering Veterinary Clinic Dr José Rojas Department of Biotechnology Balochistan University of Information Technology Engineering and Management Sciences Corozal Veterinary Clinic Veterinary Clinic Vetmaster State Hospital of Veterinary Medicine Jomo Kenyatta University of Agriculture and Technology Laboratory of Biomedicine and Regenerative Medicine Department of Clinical Sciences Faculty of Animal and Veterinary Sciences University of Chile Faculty of Veterinary and Agricultural Sciences University of Melbourne Animal Anti Cruelty League Clinical Sciences Department Faculty of Veterinary Medicine Bucharest Department of Pathology Faculty of Veterinary Medicine Ankara University Faculty of Veterinary Sciences National University of Asuncion Lilongwe Society for Protection and Care of Animals (LSPCA) Wellcome Sanger Institute Department of Cellular and Molecular Medicine University of California San Diego Department of Clinical and Veterinary Surgery São Paulo State University (UNESP) Leverhulme Trust: 102942/Z/13/A

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution. DOI: http://dx.doi.org/10.7554/eLife.14552.001, eLife digest A unique cancer called canine transmissible venereal tumour (CTVT) causes ugly tumours to form on the genitals of dogs. Unlike most other cancers, CTVT is contagious: the cancer cells can be directly transferred from one dog to another when they mate. The disease originated from the cancer cells of one individual dog that lived approximately 11,000 years ago. CTVT now affects dogs all over the world, which makes it the oldest and most widespread cancer known in nature. Like healthy cells, cancer cells contain compartments known as mitochondria that produce the chemical energy needed to power vital processes. Inside the mitochondria, there is some DNA that encodes the proteins that mitochondria need to perform this role. Changes (or mutations) to this mitochondrial DNA (mtDNA) may stop the mitochondria from working properly. CTVT cells have previously been found to occasionally capture mtDNA from normal dog cells, which suggests that replenishing their mtDNA may help promote CTVT cell growth. Furthermore, these captured mtDNAs act as genetic "flags" that can help trace the spread of the disease. Here, Strakova, Ní Leathlobhair et al. analysed the mtDNA in CTVT tumours collected from over 400 dogs in 39 countries. The analysis shows that CTVT cells have captured mtDNA from normal dog cells on at least five occasions. Over the last 2,000 years, the disease appears to have spread rapidly around the world, perhaps transported by dogs travelling on ships along historic trade routes. CTVT may have only reached the Americas within the last 500 years, possibly carried there by dogs brought by Europeans. Likewise, CTVT probably only came to Australia after European contact. The experiments also revealed that the most damaging types of mutations were absent from the mtDNA of CTVT, which suggests that fully functioning mitochondria play an important role in CTVT. Unexpectedly, Strakova, Ní Leathlobhair et al. found evidence that certain sections of mtDNA in some CTVT cells have been exchanged, or shuffled, with the mtDNA captured from normal dog cells. This type of “recombination” is not usually thought to occur in mtDNA, and has not previously been detected in cancer. Future studies will determine if this process is widespread in other types of cancer, including in humans. DOI: http://dx.doi.org/10.7554/eLife.14552.002

Sporidesmin toxicosis, or facial eczema, is a hepatogenous (secondary) photosensitisation of ruminants that is of economic importance in New Zealand. The disease has been described in an alpaca (Vi...

Osteosarcoma (OSA) is a malignant heterogeneous primary bone tumor responsible for up to 90% of all primary bone tumors in dogs. In this study, osteocalcin (OC) and osteonectin (ON) immunoreactivity was evaluated in 23 canine OSAs, 4 chondrosarcomas, 4 fibrosarcomas, 2 hemangiosarcomas, and 4 histiocytic sarcomas. The effects of three different decalcification agents (ethylenediaminetetraetic acid [EDTA], formic acid and hydrochloric acid [HCl]) on the immunoreactivity for OC and ON was also assessed. Immunoreactivity to OC was present in 19/23 (83%) cases of OSA and all cases of chondrosarcoma. In three OSAs the extracellular matrix showed immunoreactivity to OC. None of the fibrosarcomas, histiocytic sarcomas or hemangiosarcomas showed immunoreactivity to OC. The sensitivity and specificity for OC in canine OSA in this study was 83% and 71% respectively. For ON, 100% of both OSAs (23/23) and non-OSAs (14/14) showed cytoplasmic immunoreactivity to this antibody, giving a sensitivity of 100% but a complete lack of specificity. There were no significant differences in immunoreactivity for OC and ON between the different decalcification agents used. In conclusion, OC showed high sensitivity for identifying OSA but it failed to distinguish between OSA and chondrosarcoma, and the osteoid produced by neoplastic cells in most cases did not show immunoreactivity to OC. These factors may limit the practical utility of OC in the diagnosis of OSA in dogs when chondrosarcoma is a differential diagnosis. ON showed no specificity in detecting OSA and has little practical application for the diagnosis of OSA in dogs.