Developing Communication Competency in the Veterinary Curriculum.

Veterinary graduates require effective clinical communication skills for a successful transition to practice. The ways of teaching and assessing veterinary communication skills have developed and are increasingly supported by research. However, some students have difficulty applying the skills learned in a simulated consultation to working with real clients, particularly in the second part of a standard consultation, where the student communicates the reasons for their clinical decision making and assists the client's treatment decisions. The authors explore three key developments in communication skills training in the Doctor of Veterinary Medicine program since 2015 at the University of Sydney: (1) Workshops were designed to include communication scenarios that were contextualised in ways that embraced a spectrum of care. These were facilitated within a clinical skills laboratory, and student surveys were used to evaluate this teaching and learning activity; (2) student and facilitator perceptions of the value of online communication skills training were evaluated using surveys; and (3) perceptions of the gap between pre-clinical training and the demonstration of communication competency in authentic clinical settings were evaluated using a survey. We conclude that the communications curriculum can be made more engaging and effective by student-centred design, which increases the realism and authenticity of the student's experience.

Genomic Analysis of Lymphoma Risk in Bullmastiff Dogs.

Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases. When fine-scale population structure was explored using NETVIEW, cases were distributed throughout an extended pedigree. When genotyped cases (n = 49) and dogs from the control group (n = 281) were compared in a genome-wide association analysis of lymphoma risk, the most prominent associated regions were detected on CFA13 and CFA33. The top SNPs in a 5.4 Mb region on CFA13 were significant at a chromosome-wide level, and the region was fine-mapped to ~1.2 Mb (CFA13: 25.2-26.4 Mb; CanFam3.1) with four potential functional candidates, including the MYC proto-oncogene bHLH transcription factor (MYC) and a region syntenic with the human and mouse lncRNA Pvt1 oncogene (PVT1). A 380 Kb associated region at CFA33: 7.7-8.1 Mb contained the coding sequence for SUMO specific peptidase7 (SENP7) and NFK inhibitor zeta (NFKBIZ) genes. These genes have annotations related to cancer, amongst others, and both have functional links to MYC regulation. Genomic signatures identified in lymphoma cases suggest that increased risk contributed by the regions identified by GWAS may complement a complex predisposing genetic background.

Review of Canine Lymphoma Treated with Chemotherapy-Outcomes and Prognostic Factors.

While canine lymphoma is a relatively common and important disease seen by veterinarians, there are limited comprehensive reviews of the literature regarding the remission and survival times following chemotherapy, and the associated prognostic factors. This comprehensive thematic review covers the available veterinary literature covering treatment outcomes and identified prognostic factors. A lack of standardised approaches to evaluate and report the outcomes was identified, including factors that would alter the duration of responses by weeks, or occasionally months. After publication of the suggested reporting criteria, this has improved but is still not uniformly applied. The prognostic factors included for evaluation varied from as few as three to seventeen, with over 50 studies using only univariate analysis. Individual papers reported much longer outcomes than others, but assessing the outcomes overall, there has been minimal change over the last 40 years. This supports the belief that novel approaches for lymphoma therapy will be required to substantively improve outcomes.

Cultural Competence Is Everyone's Business: Embedding Cultural Competence in Curriculum Frameworks to Advance Veterinary Education.

Cultural competence in professional and research practice is important to effectively deliver animal and One Health services and programs. Veterinarians work with culturally and linguistically diverse teams, clients, and communities. Cultural perspectives on the significance and perceptions of animals and differences in consultation and engagement protocols and strategies can influence client-practitioner and researcher-community relationships, impacting animal health, welfare, and/or research outcomes. Curricula have been proposed to build cultural capacity in graduates, but these have not been reported in veterinary programs, and early attempts to integrate cultural competency into the University of Sydney veterinary curriculum lacked a formal structure and were ad hoc with respect to implementation. To address this, the authors introduced a broad curriculum framework into the University of Sydney veterinary program, which defines cultural competence, perceptions of animals, effective communication, and community engagement in a range of contexts. Cultural competency learning outcomes were described for units of study. These were contextually relevant and aligned to course learning outcomes and University of Sydney graduate qualities. Constructive alignment was achieved by linking learning outcomes to teaching and learning activities and assessment. The continuum of cultural competency underpinned mapping of cultural competency across the curriculum with staged, vertical integration of key principles. Additionally, action to engage staff, students, and stakeholders in a cultural competence agenda assisted in sustaining curriculum change. The result was integration of cultural competency across the curriculum aligning with recommendations from accrediting bodies and with best practice models in medicine, nursing, and allied health programs.

Cerebellar Abiotrophy in Australian Working Kelpies Is Associated with Two Major Risk Loci.

An autosomal recessive form of inherited cerebellar abiotrophy (CA) that is characterized by a degeneration of Purkinje and granule cells in the cerebellar cortex occurs in the Australian working kelpie dog breed. The clinical signs of CA include ataxia, head tremor, motor in-coordination, wide-based stance, and high-stepping gait. Investigation of clinical and pathological features indicated two closely related diseases with differences in age of onset. A genome-wide association study on 45 CA affected and 290 normal healthy Kelpies identified two significantly associated loci, one on CFA9 and a second on CFA20. Dogs homozygous for the risk haplotype on CFA20 (23 dogs) show clinical signs before ten weeks of age. Missense variants in the sixth exon of disruptor of telomeric silencing 1-like (DOT1Lp.R200Q) and in the only exon of Leucine Rich Repeat And Ig Domain Containing 3 (LINGO3p.R359C), both on CFA20, segregate with the associated risk marker which has incomplete penetrance (42%). Affected dogs homozygous for the risk haplotype on CFA9 have later onset ataxia. A missense variant in exon 5 of Vacuole Membrane Protein 1 (VMP1 p.P160Q) on CFA9 segregates as a fully penetrant Mendelian recessive with later-onset CA. Across mammals, the variety of causative loci so far identified as influencing cerebellar disorders reinforces the complexity of the pathways that contribute to cerebellar development and function, and to the pathophysiological mechanisms that may lead to cerebellar ataxia.

Altered plasma cytokines in dogs with atopic dermatitis.

BACKGROUND: Canine (Canis lupus familiaris) atopic dermatitis (AD) shares similar clinical signs to human AD. The abnormal immune response of AD is orchestrated by T lymphocytes, and may include variable involvement of cytokines, regulatory T (Treg) cells, eosinophils, mast cells and other immune components. Helper T (Th)2 cytokines often predominate initially, followed by Th1 cytokines in more chronic phases. HYPOTHESIS/OBJECTIVES: Pro-inflammatory and Treg cytokines have been shown to play a role in human AD, yet their importance is not clear in canine AD. Hence, this study aimed to measure the concentrations of cytokines/chemokines not traditionally associated with Th1/Th2 response. ANIMALS: Canine AD patients (n = 27), compared to control dogs (n = 11). METHODS AND MATERIALS: A total of 19 plasma cytokines were assayed using canine specific multiplex immuno-assays. RESULTS: The plasma concentrations of CXC Motif Chemokine Ligand 8 (CXCL8), interleukin (IL)-7 and IL-15 cytokines were elevated in canine AD patients, compared to control dogs. In addition, stem-cell factor (SCF) concentrations were reduced in the plasma of canine AD patients compared to control dogs. Distinct cytokine profiles were found in dogs belonging to the Staffordshire breeds, a group with increased risk of AD. In particular, granulocyte-macrophage colony-stimulating factor (GM-CSF) had significantly elevated concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Some of the plasma cytokine alterations in canine AD described here, particularly of IL-7, have not been reported previously. Monitoring these distinctive cytokine alterations could be useful for diagnosis and monitoring of canine AD in dogs.

Demographic risk factors for lymphoma in Australian dogs: 6201 cases.

BACKGROUND: Lymphoma is common in the dog. Studies of population risk factors primarily have been derived from referral institution or insurance data. OBJECTIVE: To identify and quantify the host risk factors for lymphoma in a broad population of Australian dogs. ANIMALS: Data on 6201 client owned dogs were retrieved from a commercial veterinary laboratory, a general practice group and 2 referral hospitals. METHODS: Data collected included breed, sex, and neuter status. A reference population of 640 105 dogs was generated from the referral hospitals and from council registration data. The risk of lymphoma by sex and neuter status was calculated as odds ratios (OR). RESULTS: The study identified 30 breeds at increased risk of lymphoma, 15 that have not been reported previously, and 26 breeds at decreased risk, 18 that have not been reported previously. Males were over represented compared to females with an OR of 1.1 (95% CI, 1.1-1.2; P < .001). Neutered animals were at higher risk compared to intact animals with an OR of 3.2 (95% CI, 2.9-3.5) which was found in both males (OR, 2.8; 95% CI; 2.5-3.2) and females (OR, 4.4; 95% CI, 3.5-5.1). CONCLUSIONS AND CLINICAL IMPORTANCE: Breed, sex, and neuter status alter the risk of lymphoma in dogs. These 3 factors must be considered when evaluating lymphoma risk as potential markers of underlying differences in disease etiology. Comparison of breeds at increased and decreased risk could be advantageous when evaluating specific etiological factors.

Evaluating the Quality of Veterinary Students' Experiences of Learning in Clinics.

Educators seeking to evaluate the quality of students' experiences of clinic-based learning (CBL) face a challenging task. CBL programs provide multiple opportunities for learning and aim to develop a wide range of skills, knowledge, and capacities. While direct observation of learners provides important information about students' proficiency in performing various clinical tasks, more comprehensive measures are required to unpack and identify factors relating to practice readiness as a whole. This study identified variables that have a logical and statistically significant association with learning outcomes across the broad range of attributes expected of new graduate veterinarians. The research revealed that the extent of final-year veterinary students' practice readiness, as assessed by placement supervisors against criteria relevant to new graduate practice, is related to the quality of their conceptions of and approaches to CBL. Students' conceptions of and approaches to CBL were evaluated using quantitative survey instruments, with a 93% response rate (N=100) obtained for the two questionnaires. Descriptive and exploratory statistics were used to link qualitative differences in students' conceptions of and approaches to CBL with performance against criteria relevant to new graduate practice. Students who reported poorer-quality conceptions of and approaches to CBL (n=38) attained lower levels of achievement than students who reported better-quality conceptions of and approaches to CBL (n=55). Evaluation of students' conceptions of and approaches to CBL can be used by educators seeking to evaluate and improve the extent to which CBL programs are achieving their desired goals.

Therapy Development for the Lysosomal Storage Disease Fucosidosis using the Canine Animal Model.

Abstract Fucosidosis (OMIM 23000) is an inherited neurodegenerative lysosomal storage disease caused by a deficiency of the lysosomal hydrolase a-L-fucosidase due to mutations in the FUCA1 gene. Without enzyme-targeted therapy patients rarely survive beyond the first decade of life, and therapy options other than supportive care are limited. Hematopoietic transplants, first developed in the fucosidosis dog model, are the only treatment option available capable of delaying the disease course. However, due to the risks and exclusion criteria of this treatment additional therapies are required. The development of additional therapies including intravenous and intra-cerebrospinal fluid enzyme replacement therapy and gene therapy, which have been trialed in the canine model, will be discussed.

Canine atopic dermatitis: breed risk in Australia and evidence for a susceptible clade.

BACKGROUND: Genetic studies on canine atopic dermatitis (CAD) indicate that large populations from one geographical location are preferred for the identification of relevant susceptibility genes. Australian dogs are relatively isolated; studies on CAD in this population are limited. HYPOTHESIS/OBJECTIVES: To identify breeds at risk in the Australian dog population and to compare with worldwide breed predisposition. ANIMALS: Case records (n = 23,000) from University Veterinary Teaching Hospital (UVTH) dogs, including 722 with CAD. METHODS: The breed proportion of CAD and odds risk (OR) were calculated. A systematic review of 13 previous studies (1971-2010) was performed and compared to the study results by implementing an atopic dermatitis (AD)-to-reference population ratio (ADRPR). RESULTS: Eleven dog breeds with significant increased OR (≥1.0) were identified; all with breed CAD cases proportionally higher than their base hospital population. Gender risk in males from the pug dog breed (P = 0.007) was detected and the bichon frise breed had a similar trend (P = 0.05). Sixteen predisposed dog breeds were identified by systematic review. All breeds with significant increased OR in UVTH had ADRPR > 1.4; five (boxer, bulldog, Labrador retriever, pug, West Highland white terrier) were recognized as predisposed worldwide. One clade of breeds with common ancestry was highly represented in CAD cases worldwide and in Australia (81% of the significant OR cases). CONCLUSION AND CLINICAL IMPORTANCE: The use of a large population from one geographical location and ADRPR provided an objective comparison between worldwide AD studies; it identified one common clade of susceptible breeds. Breed genetics and related clinical presentation may help CAD diagnosis and treatment.

The effects of intracisternal enzyme replacement versus sham treatment on central neuropathology in preclinical canine fucosidosis.

BACKGROUND: Fucosidosis results from lack of α-L-fucosidase activity, with accumulation of fucose-linked substrates in the nervous system and viscera leading to progressive motor and mental deterioration, and death. The naturally occurring dog model of fucosidosis was used to evaluate the neuropathological responses to partial enzyme replacement, and substrate reduction in early disease following treatment with recombinant canine α-L-fucosidase delivered through cerebrospinal fluid. METHODS: Neuropathology in both treated (n = 3) and untreated fucosidosis-affected (n = 3) animals was evaluated with immunohistochemistry, image analysis, manual quantification and gene expression analysis and compared with unaffected age-matched controls (n = 3) in an extension of our previous biochemical report on the same cohort. Data were analyzed by ANOVA. RESULTS: Quantification demonstrated a consistent trend to reduction in vacuolation, pyramidal neuron loss, astrocytosis, microgliosis, perivascular storage, apoptosis, oligodendrocyte loss, and hypomyelination throughout the central nervous system of enzyme treated animals compared to placebo-treated, age-matched affected controls. Key lesions including lysosomal expansion in neurons of deep cortex, astrocytosis in cerebral cortex and medulla, and increased lysosomal membrane associated protein-1 (LAMP-1) gene expression were ameliorated in treated animals. There was no change in spheroid formation and loss of Purkinje cells, but Purkinje cell vulnerability to apoptosis was reduced with treatment. CONCLUSIONS: Despite reduced severity of fucosidosis neuropathology with partial enzyme replacement, more complete and sustained biochemical correction is required to halt neuropathological processes in this large animal model of lysosomal storage disease.

Mental time travel for self and other in three- and four-year-old children.

Humans possess the unique ability to mentally travel backward in time to re-experience past events (i.e., episodic memory) and forward in time to pre-experience future events (i.e., episodic foresight). Although originally viewed as different cognitive skills, they are now both viewed as components of the episodic memory system. Recently, it has been suggested that the episodic system may allow us to not only pre-experience and predict our own future but also that of another person. In the current study, we investigate this possibility by examining the ability of three- and four-year-old children to plan for their own future and for that of another person. We found that both three- and four-year-old children performed equally, when planning for their own future or when planning for the experimenter's future. These data are consistent with the finding that planning for someone else's future recruits the same neural structures that are used when planning for one's own future.

Cluster Analysis of Tumor Suppressor Genes in Canine Leukocytes Identifies Activation State.

Cells of the immune system undergo activation and subsequent proliferation in the normal course of an immune response. Infrequently, the molecular and cellular events that underlie the mechanisms of proliferation are dysregulated and may lead to oncogenesis, leading to tumor formation. The most common forms of immunological cancers are lymphomas, which in dogs account for 8%-20% of all cancers, affecting up to 1.2% of the dog population. Key genes involved in negatively regulating proliferation of lymphocytes include a group classified as tumor suppressor genes (TSGs). These genes are also known to be associated with progression of lymphoma in humans, mice, and dogs and are potential candidates for pathological grading and diagnosis. The aim of the present study was to analyze TSG profiles in stimulated leukocytes from dogs to identify genes that discriminate an activated phenotype. A total of 554 TSGs and three gene set collections were analyzed from microarray data. Cluster analysis of three subsets of genes discriminated between stimulated and unstimulated cells. These included 20 most upregulated and downregulated TSGs, TSG in hallmark gene sets significantly enriched in active cells, and a selection of candidate TSGs, p15 (CDKN2B), p18 (CDKN2C), p19 (CDKN1A), p21 (CDKN2A), p27 (CDKN1B), and p53 (TP53) in the third set. Analysis of two subsets suggested that these genes or a subset of these genes may be used as a specialized PCR set for additional analysis.

Oligodendrocyte loss during the disease course in a canine model of the lysosomal storage disease fucosidosis.

Hypomyelination is a poorly understood feature of many neurodegenerative lysosomal storage diseases, including fucosidosis in children and animals. To gain insight into hypomyelination in fucosidosis, we investigated lysosomal storage, oligodendrocyte death, and axonal and neuron loss in CNS tissues of fucosidosis-affected dogs aged 3 weeks to 42 months using immunohistochemistry, electron microscopy, and gene expression assays. Vacuole accumulation in fucosidosis oligodendrocytes commenced by 5 weeks of age; all oligodendrocytes were affected by 16 weeks. Despite progressive vacuolation, mature oligodendrocyte loss by apoptosis (caspase-6 positive) in the corpus callosum and cerebellar white matter stabilized by 16 weeks, with no further subsequent loss. Axonal neurofilament loss progressed only in late disease, suggesting that disturbed axon-oligodendrocyte interactions are unlikely to be the primary cause of hypomyelination. A 67% decline in the number of Purkinje cell layer oligodendrocytes coincided with a 67% increase in the number of caspase-6-positive Purkinje cells at 16 weeks, suggesting that early oligodendrocyte loss contributes to Purkinje cell apoptosis. Fucosidosis hypomyelination appeared to follow normal spatiotemporal patterns of myelination, with greater loss of oligodendrocytes and larger downregulation of CNP, MAL, and PLP1 genes at 16 weeks in the cerebellum versus the frontal cortex. These studies suggest that survival of oligodendrocytes in fucosidosis is limited during active myelination, although the mechanisms remain unknown.

An integrated genomics approach to identify genetic regions associated with neonatal growth trait in mice.

Neonatal growth during the early post-partum period is closely associated with lactation performance. Neonatal growth reflects milk output and is a complex variable trait among inbred mouse strains, but few studies have compared this trait systematically across more than a few strains. In the present study, 11 inbred strains of mice were measured for a neonatal growth phenotype during the first eight days of lactation. Significant differences in neonatal growth trait were observed with QSi5 (3.71±0.05 g) and DBA/1J (2.67±0.06 g) strains defining the two extremes of the phenotype. In silico association analysis was performed for trait variability using the high density SNP information on inbred strains of mice. We found strong evidence to refine a previously identified large neonatal growth QTL on mouse chromosome 9, Neogq1. When an integrated strategy that combined fine mapping and analysis of mammary transcriptome expression profiles of lactating mice with divergent phenotypes was applied, we identified neogenin (Neo1), a gene important for mammary gland morphogenesis, as a likely quantitative trait gene (QTG) underlying the Neogq1 QTL in mice.

Identification of gene sets and pathways associated with lactation performance in mice.

Mammary transcriptome analyses across the lactation cycle and transgenic animal studies have identified candidate genes for mammogenesis, lactogenesis and involution; however, there is a lack of information on pathways that contribute to lactation performance. Previously we have shown significant differences in lactation performance, mammary gland histology, and gene expression profiles during lactation [lactation day 9 (L9)] between CBA/CaH (CBA) and the superior performing QSi5 strains of mice. In the present study, we compared these strains at midpregnancy [pregnancy day 12 (P12)] and utilized these data along with data from a 14th generation of intercross (AIL) to develop an integrative analysis of lactation performance. Additional analysis by quantitative reverse transcription PCR examined the correlation between expression profiles of lactation candidate genes and lactation performance across six inbred strains of mice. The analysis demonstrated that the mammary epithelial content per unit area was similar between CBA and QSi5 mice at P12, while differential expression was detected in 354 mammary genes (false discovery rate < 0.1). Gene ontology and functional annotation analyses showed that functional annotation terms associated with cell division and proliferation were the most enriched in the differentially expressed genes between these two strains at P12. Further analysis revealed that genes associated with neuroactive ligand-receptor interaction and calcium signaling pathways were significantly upregulated and positively correlated with lactation performance, while genes associated with cell cycle and DNA replication pathways were downregulated and positively correlated with lactation performance. There was also a significant negative correlation between Grb10 expression and lactation performance. In summary, using an integrative genomic approach we have identified key genes and pathways associated with lactation performance.

Myelin genes are downregulated in canine fucosidosis.

The processes regulating the complex neurodegenerative cascade of vacuolation, neuroinflammation, neuronal loss and myelin deficits in fucosidosis, a neurological lysosomal storage disorder, remain unclear. To elucidate these processes the gene expression profile of the cerebral cortex from untreated and intrathecal enzyme replacement therapy treated fucosidosis pups and age-matched unaffected controls were examined. Neuroinflammation and cell death processes were identified to have a major role in fucosidosis pathophysiology with 37% of differentially expressed (DE) genes involved in these processes. Critical, specific, early decreases in expression levels of key genes in myelin assembly were identified by gene expression profiling, including myelin-associated glycoprotein (MAG), myelin and lymphocyte protein (MAL), and oligodendrocyte myelin paranodal and inner loop protein (OPALIN). These gene expression changes may be indicative of early neuronal loss causing reduced electrical impulses required for oligodendrocyte maturation.

Treatment of canine fucosidosis by intracisternal enzyme infusion.

The blood brain barrier is the major obstacle to treating lysosomal storage disorders of the central nervous system such as canine fucosidosis. This barrier was overcome by three, monthly injections of recombinant canine α-l-fucosidase enzyme were given intracisternally. In dogs treated from 8 weeks of age enzyme reached all areas of central nervous system as well as the cervical lymph node, bone marrow and liver. Brainstem and spinal cord samples from regions adjacent to the injection site had highest enzyme levels (39-73% of normal). Substantial enzyme activity (8.5-20% of normal controls) was found in the superficial brain compared to deeper regions (2.6-5.5% of normal). Treatment significantly reduced the fucosyl-linked oligosaccharide accumulation in most areas of CNS, liver and lymph node. In the surface and deep areas of lumbar spinal cord, oligosaccharide accumulation was corrected (79-80% reduction) to near normal levels (p<0.05). In the spinal meninges (thoracic and lumbar) enzyme activity (35-39% of normal control) and substrate reduction (58-63% affected vehicle treated samples) reached levels similar to those seen in phenotypically normal carriers (p<0.05).The procedure was safe and well-tolerated, treated (average 16%) dogs gained more weight (p<0.05) and there was no antibody formation or inflammatory reaction in plasma and CSF following treatments. The capacity of early ERT to modify progression of biochemical storage in fucosidosis is promising as this disease is currently only amenable to treatment by bone marrow transplantation which entails unacceptably high risks for many patients.

Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO).

The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) and IDO2, that it is highly regulated by type I (IFN-ß) and II interferons (IFN-γ), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.