A comparison between veterinary small animal general practitioners and emergency practitioners in Australia. Part 1: demographic and work-related factors.

Occupational stressors are commonly encountered in small animal veterinary practice and have been associated with burnout. The working context of veterinarians differs by specialty, and this can potentially lead to variable exposures to risk factors for burnout. The aim of this study was to explore differences in demographic and working conditions of veterinary general practitioners (GPs) and emergency practitioners (EPs) to compare exposure to different potential stressors. An anonymous, online survey was administered to veterinary GPs and EPs practicing in metropolitan regions of Australia. In total, 320 participant responses were analyzed (n = 237, 74.2% GPs and n = 83, 25.9% EPs). Significant differences (P < 0.05) in the demographics and work-related exposures were found between the two groups. GPs were found to be older than EPs with a greater number of years of experience in their field (P < 0.001). Most veterinary GPs worked only day shifts (207/236, 87.7%); where EPs worked a greater variety of shift patterns, with "only day shifts" being the least common shift pattern (P < 0.001). Most GPs worked a set and predictable roster pattern (195/236, 83.6%), while most EPs did not (51/83, 61.5%). EPs worked more weekends and public holidays (P < 0.001). The EP group performed more hours of work each week but worked less overtime. The main contributing factors for overtime were scheduling factors for GPs and staffing issues for EPs. EPs were commonly not able to take meal-breaks and GPs' meal-breaks were commonly interrupted by work. EPs were more frequently exposed to patient death, euthanasia (including for financial reasons), emotionally distressed clients and delivering negative news (P < 0.001). Both groups indicated that most work environments were collegiate and supportive, and a minority reported toxic colleagues (11.8%) or management teams (26.9%). Just under one-half of respondents reported having witnessed or experienced workplace bullying. Of our respondent group, 52.0% (166/319) were not satisfied with their remuneration. Desire to leave their principal area of practice was prevalent among this survey group (192/319, 60.2%) with approximately one-third considering leaving the veterinary profession. We discuss the implications of these workplace factors, including mitigation strategies.

A comparison between veterinary small animal general practitioners and emergency practitioners in Australia. Part 2: client-related, work-related, and personal burnout.

Burnout is reported to be common among veterinarians. However, there is limited research investigating the relationship between specific types of veterinary practice and burnout. A previous study found significant differences in work exposures between veterinary general practitioners (GPs) and emergency practitioners (EPs). The primary aim of this study was to investigate whether Australian veterinary EPs suffer from a higher level of burnout compared to veterinary GPs. The secondary aim of this study was to explore if the previously reported differences between GP and EP groups were positively associated with burnout. An anonymous, online survey incorporating the Copenhagen Burnout Inventory (CBI) was administered to veterinary GPs and EPs practicing in metropolitan regions of Australia. In total, 320 responses were analysed (n = 237, 74.2% GPs and n = 83, 25.9% EPs). Both groups suffered from moderate levels of burnout, but there were no significant differences in the severity of CBI burnout scores between the two groups. From the multivariable analysis four investigated factors were found to be significantly associated (p < 0.05) with the work-related CBI subscale: frequency of finishing work on time; adequate staffing; work satisfaction and seriously considering leaving their principal area of practice. Five factors were significantly associated (p < 0.05) with the client-related CBI subscale: position in practice; frequency of client adherence; work satisfaction; frequency of interacting with emotionally distressed clients and seriously considering leaving their principal area of practice. Four factors were significantly associated (p < 0.05) with the personal burnout CBI subscale: gender; seriously considering leaving their principal area of practice; frequency of interacting with emotionally distressed clients and the workplace environment. The total burnout score was also significantly associated (p < 0.05) with four factors: position in practice, workplace environment, appropriate staffing in the past week and client adherence. Future studies should focus on investigating effective strategies to mitigate these risk factors for both GPs and EPs, to reduce career attrition.

Histopathological Diagnosis of Nonalcoholic Steatohepatitis (NASH).

Fatty acid beta oxidation (FAO) is a predominant bioenergetic pathway in mammals. Substantial investigations have demonstrated that FAO activity is dysregulated in many pathophysiological conditions including nonalcoholic steatohepatitis (NASH). Convenient and quantitative assays of FAO activities are important for studies of cell metabolism and the biological relevance of FAO to health and diseases. However, most current FAO assays are based on non-physiological culture conditions, measure FAO activity indirectly or lack adequate quantification. We herein describe details of practical protocols for measurement of basal and genetically or pharmacologically regulated FAO activities in the mammalian system. We also discuss the advantages and disadvantages of these assays in the context of experimental purposes.

Effect of microaggregate filter passage on feline whole blood stored for 35 days.

OBJECTIVES: The aim of this study was to compare the characteristics of fresh and stored feline red blood cells (RBCs) after passage through an 18 µm microaggregate filter. METHODS: Nine cats were recruited for a single blood donation using an open collection system. A simulated transfusion using a syringe driver and microaggregate filter was performed over 2 h with half the blood on the day of donation and the other half after 35 days of storage. Differences in haematological parameters, haemolysis percentage and osmotic fragility (OF) were compared on the day of donation pre-filter passage (D0-) vs day of donation post-filter (D0+) or day 35 storage pre-filter (D35-) and post-filter (D35+). Blood was cultured at D0+ and D35+. RESULTS: There were no statistically significant differences in the D0- vs D0+ comparisons. There were statistically significant (P <0.05) increases in haemolysis percentage, red cell distribution width (RDW) percentage and mean OF, and decreases in packed cell volume (PCV), RBC count, haemoglobin and haematocrit for D0- vs D35-. The same was found for D0- vs D35+ with the addition of a significant increase in mean cell haemoglobin (MCH). For D35- vs D35+ only MCH significantly increased. At day 35, 6/9 units had haemolysis percentages that exceeded 1%. This increased to 8/9 of stored units post-filter passage. All blood units cultured negative. CONCLUSIONS AND RELEVANCE: Fresh RBCs exhibited no in vitro evidence of injury following passage through an 18 µm microaggregate filter. Increased MCH was observed in the stored blood and may represent haemolysis induced by the filter. All other changes can be explained by storage lesion rather than filter passage. The findings highlight the importance of blood banking quality controls and the need for further research to assess the effects of transfusion technique, specifically filter passage, on storage lesion-affected feline blood.

Quercetin Preserves Oral Cavity Health by Mitigating Inflammation and Microbial Dysbiosis.

Failure to attenuate inflammation coupled with consequent microbiota changes drives the development of bone-destructive periodontitis. Quercetin, a plant-derived polyphenolic flavonoid, has been linked with health benefits in both humans and animals. Using a systematic approach, we investigated the effect of orally delivered Quercetin on host inflammatory response, oral microbial composition and periodontal disease phenotype. In vivo, quercetin supplementation diminished gingival cytokine expression, inflammatory cell infiltrate and alveolar bone loss. Microbiome analyses revealed a healthier oral microbial composition in Quercetin-treated versus vehicle-treated group characterized by reduction in the number of pathogenic species including Enterococcus, Neisseria and Pseudomonas and increase in the number of non-pathogenic Streptococcus sp. and bacterial diversity. In vitro, Quercetin diminished inflammatory cytokine production through modulating NF-κB:A20 axis in human macrophages following challenge with oral bacteria and TLR agonists. Collectively, our findings reveal that Quercetin supplement instigates a balanced periodontal tissue homeostasis through limiting inflammation and fostering an oral cavity microenvironment conducive of symbiotic microbiota associated with health. This proof of concept study provides key evidence for translational studies to improve overall health.

Emphysematous Cystitis and Pneumoperitoneum in a Dog with Escherichia coli Urinary Tract Infection and Hyperadrenocorticism.

A 9 yr old male neutered Staffordshire bull terrier with a history of poorly controlled hyperadrenocorticism, urinary tract infections, and emphysematous cystitis (EC) was presented to a veterinary referral teaching hospital for vomiting. Abdominal radiographs revealed EC and a pneumoperitoneum. The urinary bladder was found to be intact based on ultrasound and a pre- and postiohexol contrast computed tomography study with retrograde contrast cystogram. Urine culture confirmed the presence of a recurrent Escherichia coli urinary tract infection. The patient was managed medically, primarily as an outpatient, and had complete resolution of all problems. This case represents an extremely rare form of EC with pneumoperitoneum, without evidence of concurrent urinary bladder rupture. Only six similar cases have been reported in humans, with no previous cases reported in veterinary medicine. This case demonstrated that surgery is not necessarily indicated in all cases of pneumoperitoneum. The patient remained alive at 2 mo follow-up, with no evidence of recurrence of EC.

A20 Restricts Inflammatory Response and Desensitizes Gingival Keratinocytes to Apoptosis.

The pathophysiology of periodontal disease involves a perturbed immune system to a dysbiotic microflora leading to unrestrained inflammation, collateral tissue damage, and various systemic complications. Gingival epithelial cells function as an important part of immunity to restrict microbial invasion and orchestrate the subsequent innate responses. A20 (TNFAIP3), an ubiquitin-editing enzyme, is one of the key regulators of inflammation and cell death in numerous tissues including gastrointestinal tract, skin, and lungs. Emerging evidence indicates A20 as an essential molecule in the oral mucosa as well. In this study, we characterized the role of A20 in human telomerase immortalized gingival keratinocytes (TIGKs) through loss and gain of function assays in preclinical models of periodontitis. Depletion of A20 through gene editing in TIGKs significantly increased IL-6 and IL-8 secretion in response to Porphyromonas gingivalis infection while A20 over-expression dampened the cytokine production compared to A20 competent cells through modulating NF-κB signaling pathway. In the subsequent experiments which assessed apoptosis, A20 depleted TIGKs displayed increased levels of cleaved caspase 3 and DNA fragmentation following P. gingivalis infection and TNF/CHX challenge compared to A20 competent cells. Consistently, there was reduced apoptosis in the cells overexpressing A20 compared to the control cells expressing GFP further substantiating the role of A20 in regulating gingival epithelial cell fate in response to exogenous insult. Collectively, our findings reveal first systematic evidence and demonstrate that A20 acts as a regulator of inflammatory response in gingival keratinocytes through its effect on NF-κB signaling and desensitizes cells to bacteria and cytokine induced apoptosis in the oral mucosa. As altered A20 levels can have profound effect on different cellular responses, future studies will determine whether A20-targeted therapies can be exploited to restrain periodontal inflammation and maintain oral mucosa tissue homeostasis.

A20 Orchestrates Inflammatory Response in the Oral Mucosa through Restraining NF-κB Activity.

Deregulated immune response to a dysbiotic resident microflora within the oral cavity leads to chronic periodontal disease, local tissue destruction, and various systemic complications. To preserve tissue homeostasis, inflammatory signaling pathways involved in the progression of periodontitis must be tightly regulated. A20 (TNFAIP3), a ubiquitin-editing enzyme, has emerged as one of the key regulators of inflammation. Yet, the function of A20 in the oral mucosa and the biological pathways in which A20 mitigates periodontal inflammation remain elusive. Using a combination of in vivo and ex vivo disease models, we report in this study that A20 regulates inflammatory responses to a keystone oral bacterium, Porphyromonas gingivalis, and restrains periodontal inflammation through its effect on NF-κB signaling and cytokine production. Depletion of A20 using gene editing in human macrophage-like cells (THP-1) significantly increased cytokine secretion, whereas A20 overexpression using lentivirus infection dampened the cytokine production following bacterial challenge through modulating NF-κB activity. Similar to human cells, bone marrow-derived macrophages from A20-deficient mice infected with P. gingivalis displayed increased NF-κB activity and cytokine production compared with the cells isolated from A20-competent mice. Subsequent experiments using a murine ligature-induced periodontitis model showed that even a partial loss of A20 promotes an increased inflammatory phenotype and more severe bone loss, further verifying the critical function of A20 in the oral mucosa. Collectively, to our knowledge, these findings reveal the first systematic evidence of a physiological role for A20 in the maintenance of oral tissue homeostasis as a negative regulator of inflammation.

Consequences and Management of Canine Brachycephaly in Veterinary Practice: Perspectives from Australian Veterinarians and Veterinary Specialists.

This article, written by veterinarians whose caseloads include brachycephalic dogs, argues that there is now widespread evidence documenting a link between extreme brachycephalic phenotypes and chronic disease, which compromises canine welfare. This paper is divided into nine sections exploring the breadth of the impact of brachycephaly on the incidence of disease, as indicated by pet insurance claims data from an Australian pet insurance provider, the stabilization of respiratory distress associated with brachycephalic obstructive airway syndrome (BOAS), challenges associated with sedation and the anaesthesia of patients with BOAS; effects of brachycephaly on the brain and associated neurological conditions, dermatological conditions associated with brachycephalic breeds, and other conditions, including ophthalmic and orthopedic conditions, and behavioural consequences of brachycephaly. In the light of this information, we discuss the ethical challenges that are associated with brachycephalic breeds, and the role of the veterinarian. In summary, dogs with BOAS do not enjoy freedom from discomfort, nor freedom from pain, injury, and disease, and they do not enjoy the freedom to express normal behaviour. According to both deontological and utilitarian ethical frameworks, the breeding of dogs with BOAS cannot be justified, and further, cannot be recommended, and indeed, should be discouraged by veterinarians.

Interplay of Toll-Like Receptor 9, Myeloid Cells, and Deubiquitinase A20 in Periodontal Inflammation.

Toll-like receptor 9 (TLR9)-deficient (TLR9-/-) mice are resistant to periodontitis, a disease characterized by a dysbiotic microbiota and deregulated immune response and resulting in tooth loss and various systemic conditions. However, the mechanisms and biological pathways by which TLR9 instigates periodontal inflammation are yet to be identified. In a ligature-induced model of periodontitis, we demonstrate that TLR9-/- mice exhibited significantly less alveolar bone loss than their wild-type (WT) counterparts. Consistent with the disease phenotype, gingival tissues showed significantly more inflammatory cell infiltration in the WT ligated but not in the TLR9-/- ligated mice compared to the unligated controls. The peritoneal infection model using Porphyromonas gingivalis, a keystone pathogen for periodontitis, revealed reduced neutrophils in TLR9-/- mice on day 1 postinfection compared to the levels in WT mice. Transcriptomics analyses showed increased expression of A20 (tumor necrosis factor alpha [TNF-α]-induced protein 3 [TNFAIP3]), an inhibitor of the NF-κB pathway and a negative regulator of TLR signaling, in ligated TLR9-/- mouse gingival tissues compared to its expression in the WT. Ex vivo, TLR9-/- bone marrow-derived macrophages produced more A20 than WT cells following P. gingivalis challenge. Clinically, A20 was modestly upregulated in human gingival tissue specimens from chronic periodontitis patients, further confirming the biological relevance of A20 in periodontal inflammation. We conclude that TLR9 modulates periodontal disease progression at both the cellular and molecular level and identify A20 as a novel downstream signaling molecule in the course of periodontal inflammation. Understanding the regulation of the TLR9 signaling pathway and the involvement of A20 as a limiting factor of inflammation will uncover alternative therapeutic targets to treat periodontitis and other chronic inflammatory diseases.

Hypoadrenocorticism in a kindred of Pomeranian dogs.

Three adult Pomeranian dogs, full siblings from 2 litters, were diagnosed with primary hypoadrenocorticism following onset of hypoadrenal crisis. Review of the family history revealed the dogs' maternal grandmother also had hypoadrenocorticism. All 4 dogs were pedigree-certified by the American Kennel Club. An inherited basis for hypoadrenocorticism is proposed in these Pomeranian dogs.

Hypoadrénocorticisme dans un parentage de chiens Poméraniens. Trois chiens Poméraniens adultes, tous issus de deux portées ayant les mêmes parents, ont été diagnostiqués d'hypoadrénocorticisme primaire après l'apparition d'une crise hypoadrénale. L'examen des antécédents familiaux a révélé que la grand-mère maternelle des chiens souffrait aussi d'hypoadrénocorticisme. Le pédigrée des 4 chiens a été certifié par l'American Kennel Club. Une hérédité d'hypoadrénocorticisme est proposée chez ces Poméraniens.(Traduit par Isabelle Vallières).

Plasma lactate concentration as a prognostic biomarker in dogs with gastric dilation and volvulus.

Initial and serial plasma lactate concentrations can be used to guide decision making in individual dogs with GDV but care is necessary in phrasing conversations with owners. Published data suggests that survival is more likely and the chance of complications less in dogs with an initial plasma lactate of <4 mmol/L. An initial lactate >6 mmol/L makes gastric necrosis and greater expense more likely. However, because of the overlap between groups and the good overall survival rates, exploratory laparotomy should always be recommended irrespective of the plasma lactate concentration. Falls in plasma lactate of greater than ~40% after fluid resuscitation are likely to indicate better survival. If the initial plasma lactate concentration is moderately to severely increased (5->10 mmol/L) and a sustained increase in plasma lactate occurs after fluid resuscitation, the cause should be aggressively pursued. Many dogs with persistent hyperlactatemia over 24-48 hours do not survive.

Spontaneous pneumothorax in 35 cats (2001-2010).

Thirty-five cases of spontaneous pneumothorax were reviewed. In contrast to dogs, cats with an established etiology all had spontaneous pneumothorax associated with lung disease. Underlying diseases identified in affected cats included inflammatory airway disease, neoplasia, heartworm infection, pulmonary abscess and lungworm infection. Many cats were managed successfully with observation alone or needle thoracocentesis and specific therapy for their primary lung disease. Cats who present with spontaneous pneumothorax may be treated successfully with non-surgical therapies and appear to have a better prognosis than previously extrapolated from canine studies.

Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division.

Polarized segregation of proteins in T cells is thought to play a role in diverse cellular functions including signal transduction, migration, and directed secretion of cytokines. Persistence of this polarization can result in asymmetric segregation of fate-determining proteins during cell division, which may enable a T cell to generate diverse progeny. Here, we provide evidence that a lineage-determining transcription factor, T-bet, underwent asymmetric organization in activated T cells preparing to divide and that it was unequally partitioned into the two daughter cells. This unequal acquisition of T-bet appeared to result from its asymmetric destruction during mitosis by virtue of concomitant asymmetric segregation of the proteasome. These results suggest a mechanism by which a cell may unequally localize cellular activities during division, thereby imparting disparity in the abundance of cell fate regulators in the daughter cells.

Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin.

A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8(+) T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8(+) T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS.

Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche.

CD8(+) T cells responding to intracellular infection give rise to cellular progeny that become terminally differentiated effector cells and self-renewing memory cells. T-bet and eomesodermin (Eomes) are key transcription factors of cytotoxic lymphocyte lineages. We show in this study that CD8(+) T cells lacking Eomes compete poorly in contributing to the pool of Ag-specific central memory cells. Eomes-deficient CD8(+) T cells undergo primary clonal expansion but are defective in long-term survival, populating the bone marrow niche and re-expanding postrechallenge. The phenotype of Eomes-deficient CD8(+) T cells supports the hypothesis that T-bet and Eomes can act redundantly to induce effector functions, but can also act to reciprocally promote terminal differentiation versus self-renewal of Ag-specific memory cells.

Factor analytic study of repetitive behaviours in young children with Pervasive Developmental Disorders.

The aim of the current study was to investigate the manifestation of repetitive behaviour profiles in young children with a Pervasive Developmental Disorder. The sample consisted of 137 developmentally delayed children with a DSM-IV-TR Pervasive Developmental Disorder (PDD) and 61 developmentally delayed children without a PDD. An exploratory factor analytic investigation using 12 ADI-R repetitive behaviour items from parent report of children with a PDD reported the emergence of two factors. The first factor consisted of higher-level, "insistence on sameness" behaviours, and the second of lower-level, repetitive "sensory-motor" behaviours. This factor structure was also applicable to a more general group of young children with developmental delay, regardless of their diagnosis. Correlational analyses highlighted contrasting relationships between developmental variables and the different repetitive behaviour factors. These relationships were different for children with a PDD and those without a PDD. The findings have potential implications for the early assessment and diagnosis of PDDs in young children.

Early features of autism: Repetitive behaviours in young children.

This study examined whether repetitive behaviours were a differentiating feature of autism in children aged less than 51 months. The study also examined the relationship between age (chronological and developmental) and repetitive behaviours in young children with autism. Standardised developmental and diagnostic assessments were conducted on 55 children aged between 22 and 51 months, consisting of 40 developmentally delayed children with DSM-IV-TR Autistic Disorder and 15 developmentally delayed children without Autistic Disorder. Results indicated that several measures of repetitive behaviour, particularly more complex high-level ones, were significantly positively associated with the probability of receiving a diagnosis of autism. No significant relationships were found between developmental age and the presence of repetitive behaviours in children with autism, but younger chronological age was associated more with simple or low-level repetitive behaviours.