Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs.

BackgroundHistiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.ObjectiveTo characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.AnimalsOne hundred two dogs with HS, 62 dogs with meningioma.MethodsRetrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data.ResultsPredisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor.Conclusions and clinical importanceClinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities

Congenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation.

BackgroundCongenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog.Hypothesis/objectiveClinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies.AnimalsFour GR puppies from California were evaluated for generalized muscle weakness beginning at weaning. Biological specimens were collected from the affected puppies, and familial information was obtained. Blood or buccal swabs were obtained from 63 unaffected GRs.MethodsComplete physical, neurological, electrodiagnostic, and histological evaluations and biochemical quantification of muscle acetylcholine receptors were performed. Polymerase chain reaction was used to amplify the 17 exons of COLQ, and sequences were obtained by Sanger sequencing. Variant frequency was assessed in unrelated GRs and a public database.ResultsClinical, neurological, and electrodiagnostic evaluations confirmed a disorder of neuromuscular transmission in a GR family. Sequencing of all exons and splice sites of a primary candidate gene, COLQ, identified a point mutation that predicts an amino acid substitution (G294R). The primary COLQ transcript was absent from affected muscle samples. All affected puppies were homozygous for the mutation, which was not detected outside this GR family or in other breeds.Conclusions and clinical importanceWe confirmed the diagnosis of a CMS in GR puppies and identified a novel COLQ mutation. The COLQ gene encodes the collagenous tail of acetylcholinesterase, the enzyme responsible for termination of skeletal muscle contraction by clearing acetylcholine at the neuromuscular junction. Clinicians and breeders should be aware of this CMS in GR puppies with an early onset of weakness

Multicenter flow cytometry proficiency testing of canine blood and lymph node samples

Background: Flow cytometry (FC) is used increasingly in veterinary medicine for further characterization of hematolymphoid cells. Guidelines for optimizing assay performance and interpretation of results are limited, and concordance of results across laboratories is unknown. Objectives: This study aimed to determine inter-investigator agreement on the interpretation of FC results from split samples analyzed in different laboratories using various protocols, cytometers, and software; and on the interpretation of archived FC standard (FCS) data files contributed by the different investigators. Methods: This was a multicenter observational cross-sectional study. Anticoagulated blood or lymph node aspirate samples from nine client-owned dogs were aliquoted and shipped to participating laboratories. Samples were analyzed with individual laboratory-developed protocols. In addition, FCS files from a set of separate samples from 11 client-owned dogs were analyzed by participating investigators. A person not associated with the study tabulated the results and interpretations. Agreement of interpretations was assessed with Fleiss\u2019 kappa statistic. Results: Prolonged transit times affected sample quality for some laboratories. Overall agreement among investigators regarding the FC sample interpretation was strong (\u3ba = 0.86 \ub1 0.19, P <.001), and for specific categories, ranged from moderate to perfect. Agreement of the lymphoproliferation or other leukocyte sample category from the analysis of the FCS files was weak (\u3ba = 0.58 \ub1 0.05, P <.001). Conclusions: Lymphoproliferations were readily identified by FC, but identification of the categories of hematolymphoid neoplasia in fresh samples or archived files was variable. There is a need for a more standardized approach to maximize the enormous potential of FC in veterinary medicine

Genome-Wide Association Analysis Identifies a Mutation in the Thiamine Transporter 2 (SLC19A3) Gene Associated with Alaskan Husky Encephalopathy

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 – 43.36–43.38 Mb and SLC19A3.1 – 43.411–43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE.University of California, Davis. School of Veterinary Medicine. Center for Companion Animal Healt

Oral cytarabine ocfosfate pharmacokinetics and assessment of leukocyte biomarkers in normal dogs

BackgroundCytosine arabinoside (Ara-C) is a nucleoside analog prodrug utilized for immunomodulatory effects mediated by its active metabolite Ara-CTP. Optimal dosing protocols for immunomodulation in dogs have not been defined. Cytarabine ocfosfate (CO) is a lipophilic prodrug of Ara-C that can be administered PO and provides prolonged serum concentrations of Ara-C.ObjectivesProvide pharmacokinetic data for orally administered CO and determine accumulation and functional consequences of Ara-CTP within peripheral blood leukocytes.AnimalsThree healthy female hound dogs and 1 healthy male Beagle.MethodsProspective study. Dogs received 200 mg/m2 of CO PO q24h for 7 doses. Serum and cerebrospinal fluid (CSF) CO and Ara-C concentrations were measured by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Complete blood counts, flow cytometry, and leukocyte activation assays were done up to 21 days. Incorporation of Ara-CTP within leukocyte DNA was determined by LC-MS/MS.ResultsMaximum serum concentration (Cmax ) for Ara-C was 456.1-724.0 ng/mL (1.88-2.98 μM) and terminal half-life was 23.3 to 29.4 hours. Cerebrospinal fluid: serum Ara-C ratios ranged from 0.54 to 1.2. Peripheral blood lymphocyte concentrations remained within the reference range, but proliferation rates poststimulation were decreased at 6 days. Incorporation of Ara-CTP was not saturated and remained >25% of peak concentration at 13 days.Conclusions and clinical importanceOral CO may produce prolonged serum Ara-C half-lives at concentrations sufficient to induce functional changes in peripheral leukocytes and is associated with prolonged retention of DNA-incorporated Ara-CTP. Application of functional and active metabolite assessment is feasible and may provide more relevant data to determine optimal dosing regimens for Ara-C-based treatments

Diagnostic utility of aqueocentesis and aqueous humor analysis in dogs and cats with anterior uveitis.

ObjectiveTo evaluate diagnostic utility of aqueous humor analysis in animals with anterior uveitis.AnimalsClient-owned dogs (n = 12) and cats (n = 10).ProceduresExamination findings and diagnostic test results including aqueous humor cytology were compared.ResultsDisease duration prior to aqueocentesis was not significantly different between dogs with idiopathic anterior uveitis and those with an etiologic diagnosis, but was shorter in cats with feline infectious peritonitis (FIP) than those with idiopathic uveitis. Microbial nucleic acids, antigens, or antibodies against them were seldom found in blood/serum; however, serum feline coronavirus titers ≥1:6400 were detected only in cats with FIP. Aqueous humor cytology was diagnostic in no cats and two dogs, both with neoplasia. Although aqueous humor contained predominantly neutrophils in cats with FIP and large reactive lymphocytes and plasma cells appeared more frequent in cats with idiopathic uveitis, neither clinical nor cytologic assessment of anterior chamber contents differed significantly between cats with idiopathic or FIP-associated uveitis. Cytologically assessed plasma cell number was correlated with keratic precipitates and disease duration. Clinically detectable hyphema and cytologic erythrocyte number were correlated. However, cytologic cell grades and clinical grade of flare or cell numbers within the anterior chamber were not correlated.ConclusionsAqueous humor cytology permitted diagnosis of neoplasia in dogs with anterior uveitis but was generally not helpful in cats. Poor correlation between clinical and cytologic assessment of cell numbers and type within the anterior chamber dictates that clinical grading should not be the sole criterion for electing to perform aqueocentesis

Treatment of feline intermediate- to high-grade lymphoma with a modified university of Wisconsin-Madison protocol: 119 cases (2004-2012).

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison (UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval (PFI) and survival time (MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longer PFI and MST than those with partial or no response (PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001)

The use of gamification in workplace learning to encourage employee motivation and engagement

When we think about playing a game, be it a card game, board game, sport, or video game, we generally associate the act of playing with a positive experience like having fun, enjoying the interaction with others, or feeling a greater motivation to reach a certain goal. By contrast, workplace learning is often perceived as being dull. Employees are likely at some point in their career to find themselves stuck in a rigidly defined seminar for a long period of time or in front of their computer navigating through a mandatory e-learning course on a dry topic such as standards of business conduct of safety policies. In recent years, organizations have tried to leverage the motivating quality of games for more serious learning contexts. Gamification entails transferring those elements and principles from games to nongaming context that improve user experience and engagement. In this chapter, we will specifically focus on the context of workplace learning