Development of a facial expression scale using footrot and mastitis as models of pain in sheep

Management of pain in sheep is limited by the challenges of recognising and accurately quantifying pain in this species. The use of facial expression scoring to assess pain is a well-utilised, practical tool in both humans and non-human animals. The objective of this study was to develop a standardised facial expression pain scale for adult sheep, that could be used reliably and accurately to detect pain associated with naturally occurring painful diseases, such as footrot and mastitis. We also investigated whether the scale could be reliably and accurately utilised by observers after training, enabling the development of an on-farm pain assessment tool. The Sheep Pain Facial Expression Scale (SPFES) was able to correctly identify sheep suffering from disease with a high degree of accuracy (AUC; Footrot: 0.81, Mastitis: 0.80). Diseased sheep scored higher on the scale than controls on the day of disease identification (P<0.05) and diseased sheep showed changes in their facial expression after treatment (P<0.001). The abnormal facial expressions of diseased sheep reduced over time, and at recovery were in line with control sheep. Control sheep did not change their facial expression over time. Five scorers who were trained to use the developed scale also assessed the facial expressions of sheep. The scorers were blind to treatment and session. Scorers reliably (ICC: 0.86) and accurately (α = 0.86) identified changes in the facial expression of sheep with footrot over time (P<0.05), and scored control sheep consistently low over time. The SPFES offers a reliable and effective method of assessing pain in sheep after minimal training.We would like to thank the EU VII Framework Program (FP7-KBBE-2010-4) for funding this study as part of the AWIN project. Boehringer Imgelheim Ltd are thanked for providing the meloxicam used in this study.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.applanim.2016.01.00

Pyothorax and pulmonary lymphomatoid granulomatosis in a cat

A 7-year-old female neutered British Short Hair cat was presented for further investigation and treatment of pleural effusion due to a possible pyothorax. Cytology and culture of the fluid identified pyothorax and a large mass/consolidated right caudal lung lobe was found on x-ray, ultrasound and CT scan. Lung lobectomy was performed and a diagnosis of pulmonary lymphomatoid granulomatosis (PLG) was confirmed by histopathology and immunohistochemistry. Despite medical treatment the patient was euthanized due to progression of the disease and deterioration of her clinical signs. This is the second case of PLG reported in a cat and the first case of PLG with concurrent pyothorax. PLG, despite being very rare, should be added to the list of differential diagnoses for pyothorax and solitary lung masses in cats.Non

Technical note: Validation of an automatic recording system to assess behavioural activity level in sheep (Ovis aries)

The welfare of an individual can be assessed by monitoring behavioural changes, such as inactivity, that may indicate injury or disease. In this study we validated the Actiwatch Mini® activity monitor (AM) for automatic recording of behavioural activity levels of nine Texel ewes. The AM devices were attached to collars placed around the necks of the ewes. AM recordings were taken at 25 second intervals for 21 consecutive days and in addition, direct behavioural observations made on days 9–13. AM recordings were compared with direct behavioural observations to investigate whether different levels of behaviour activity could be distinguished by the AM. Six different behaviours were matched to the activity scores recorded by the AM which were low activity (lying ruminating, lying), medium activity (standing, standing ruminating, and grazing) and high activity behaviours (walking). There were differences in the activity scores for all three scores. However, higher levels of accuracy in distinguishing between activity levels were achieved when combining high and medium activity level behaviours. This method of capturing data provides a practical tool in studies assessing the impact of disease or injury. For example, assessing the effects of lameness on the activity level of sheep at pasture, without the presence of an observer influencing behaviour.The authors thank the staff at the farm, at which data were collected, for supporting the study and for taking good care of the animals. This study was part of a project funded by the EU VII Framework programme Animal Welfare Indicators (Grant no. FP7-KBBE-2010-4) who had no involvement in the study design, data collection, data analysis or writing of the report. The Actiwatches’ were provided to AJM through funding from CHDI Foundation, Inc.This is the author accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0921448815001455

T Lymphocytes in Histiocytic Sarcomas of Flat-Coated Retriever Dogs.

Flat-Coated Retriever dogs are predisposed to the development of histiocytic sarcoma (HS), a poorly differentiated, highly malignant neoplasm. The authors have previously documented a significant lymphocytic infiltrate in such tumors. The objective of this study was to examine the presence and expression of regulatory T cells in HS tumor samples. Forty tumors were included in this study. All tumors were immunolabeled for CD3, CD79a, CD25, CD45RA, and FOXP3. The proportion of positive cells was compared between tumors presenting as a localized primary soft tissue mass (soft tissue origin HS) and disseminated HS affecting viscera, especially the spleen (splenic origin HS). By immunohistochemistry, 95% of infiltrating T cells were positive for Foxp3 in all sections, suggesting the presence of regulatory T cells. The proportion of cells positive for FOXP3 was higher in the tumors arising in soft tissues, whereas the proportion of CD45RA-positive cells was higher in the splenic origin HS. Canine HS has an aggressive clinical behavior and is uniformly fatal. The difference in the proportion of tumor-infiltrating lymphocytes positive for these 2 markers in the 2 locations may represent differences in tumor microenvironment between the 2 sites

Prevalence of pancreatic, hepatic and renal microscopic lesions in post-mortem samples from Cavalier King Charles spaniels.

OBJECTIVES: The objective of this study was to describe the prevalence of microscopic pancreatic, hepatic and renal lesions in post-mortem samples from Cavalier King Charles spaniels. METHODS: The prevalence of microscopic lesions was determined by routine histopathology and compared to ante-mortem clinical signs. RESULTS: There was evidence of chronic pancreatitis in 51·9% of the cases, and age correlated with severity. Renal lesions were diagnosed in 52·2% of cases, most of which were inflammatory. Ante-mortem diagnosis of pancreatic and renal disease was 25 and 16·7%, respectively. Primary hepatic lesions were diagnosed in 11·1% of cases; secondary hepatic lesions were diagnosed in 64·8%. CLINICAL SIGNIFICANCE: Pancreatic and renal lesions are common in Cavalier King Charles spaniels, but they have similar rates of hepatic disease as the general population. The increasing prevalence of pancreatic lesions with age suggests that it might be a progressive condition.A.C.C. Kent is very grateful to the Alice Noakes Trust for sponsorship of his Senior Clinical Training Scholarship.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley

Coagulation Tests and Selected Biochemical Analytes in Dairy Cows with Hepatic Lipidosis

The aim of this study was to determine the values and changes in conventional and optimised clotting tests, as well as in selected biochemical analytes during hepatic lipidosis in postpartum dairy cows. Ten healthy and ten Holstein cows with hepatic lipidosis were selected based upon clinical history, clinical examination, liver biopsy, flotation test and histological analysis of hepatic tissue. Prothrombin time (PT) and partial thromboplastin time (PTT) were determined in non-diluted and diluted blood plasma samples. Clotting times determined in diluted plasma samples were prolonged in cows with hepatic lipidosis and there was a difference in the PT value at both 50% and 25% plasma dilutions between both groups of animals (P = 0.004 and P = 0.001). Significant differences between healthy animals and cows with hepatic lipidosis were observed in blood serum values for free fatty acids (FFA), aspartate aminotransferase (AST) and triacyglycerols (P = 0.001, P = 0.007 and P = 0.044), respectively. FFA and liver biopsy are better diagnostic indicators for hepatic lipidosis than coagulation tests. The optimised PT is prolonged in cows with hepatic lipidosis and can detect this alteration that cannot be appreciated using conventional PT test

Breed, age and gender distribution of dogs with chronic hepatitis in the United Kingdom

AbstractStandardised histological criteria are now available for the diagnosis of canine chronic hepatitis (CH). CH is common in dogs, but no studies have reported breed, age and gender distributions in the United Kingdom (UK). The objective of this study was to determine which breeds had an increased risk for developing CH in the UK and to report the age and gender distribution for those breeds. The databases of six veterinary histopathology laboratories were searched for cases with a histological diagnosis of CH according to standardised criteria. The breed, age and gender of dogs was recorded and compared to a control population to calculate the odds ratio and 95% confidence intervals for developing CH.A total of 551 cases of CH were identified, consisting of 61 breeds. Nineteen breeds were represented by five or more cases. Breeds with an increased risk for developing CH included the American cocker spaniel, Cairn terrier, Dalmatian, Dobermann pinscher, English cocker spaniel, English springer spaniel, Great Dane, Labrador retriever and Samoyed. The median age at diagnosis for all breeds with CH was 8years (range 7months to 16years). Dalmatians, Dobermann pinschers and English springer spaniels with CH were significantly younger than Cairn terriers, English cocker spaniels and Labrador retrievers with CH. Females were over-represented when all cases were examined together. In conclusion, several breeds in the UK have an increased risk of CH, some of which have not been previously reported

Progressive Purkinje Cell Degeneration in tambaleante Mutant Mice Is a Consequence of a Missense Mutation in HERC1 E3 Ubiquitin Ligase

The HERC gene family encodes proteins with two characteristic domains: HECT and RCC1-like. Proteins with HECT domains have been described to function as ubiquitin ligases, and those that contain RCC1-like domains have been reported to function as GTPases regulators. These two activities are essential in a number of important cellular processes such as cell cycle, cell signaling, and membrane trafficking. Mutations affecting these domains have been found associated with retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six HERC genes have been reported which encode two subgroups of HERC proteins: large (HERC1-2) and small (HERC3-6). The giant HERC1 protein was the first to be identified. It has been involved in membrane trafficking and cell proliferation/growth through its interactions with clathrin, M2-pyruvate kinase, and TSC2 proteins. Mutations affecting other members of the HERC family have been found to be associated with sterility and growth retardation. Here, we report the characterization of a recessive mutation named tambaleante, which causes progressive Purkinje cell degeneration leading to severe ataxia with reduced growth and lifespan in homozygous mice aged over two months. We mapped this mutation in mouse chromosome 9 and then performed positional cloning. We found a G⇔A transition at position 1448, causing a Gly to Glu substitution (Gly483Glu) in the highly conserved N-terminal RCC1-like domain of the HERC1 protein. Successful transgenic rescue, with either a mouse BAC containing the normal copy of Herc1 or with the human HERC1 cDNA, validated our findings. Histological and biochemical studies revealed extensive autophagy associated with an increase of the mutant protein level and a decrease of mTOR activity. Our observations concerning this first mutation in the Herc1 gene contribute to the functional annotation of the encoded E3 ubiquitin ligase and underline the crucial and unexpected role of this protein in Purkinje cell physiology

A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention.

We show that BRAF(V600E) initiates an alternative pathway to colorectal cancer (CRC), which progresses through a hyperplasia/adenoma/carcinoma sequence. This pathway underlies significant subsets of CRCs with distinctive pathomorphologic/genetic/epidemiologic/clinical characteristics. Genetic and functional analyses in mice revealed a series of stage-specific molecular alterations driving different phases of tumor evolution and uncovered mechanisms underlying this stage specificity. We further demonstrate dose-dependent effects of oncogenic signaling, with physiologic Braf(V600E) expression being sufficient for hyperplasia induction, but later stage intensified Mapk-signaling driving both tumor progression and activation of intrinsic tumor suppression. Such phenomena explain, for example, the inability of p53 to restrain tumor initiation as well as its importance in invasiveness control, and the late stage specificity of its somatic mutation. Finally, systematic drug screening revealed sensitivity of this CRC subtype to targeted therapeutics, including Mek or combinatorial PI3K/Braf inhibition