A Trap

Just after I was discharged from the Army, my parents and other people often asked me what I disliked most about the Army. Was it the regimentation, the food, the officers, - what was my pet peeve? My reply has been very consistent: the pockets on Army fatigue pants

External mechanical perturbations challenge postural stability in dogs

This study aimed to explore the effect of external mechanical perturbations on postural stability (PS) in dogs using the body center of pressure (COP). Thirteen sound adult dogs were included in this study. PS was tested during quiet standing on a pressure measurement plate. The conditions included a standard standing measurement and external mechanical perturbations conducted using six settings on a motorized training platform with different intensities of speed and amplitude. Measurement conditions were compared using linear mixed-effects models, followed by multiple comparisons using Sidak’s alpha correction procedure. Compared with the standing measurement, external mechanical perturbations resulted in a significant increase in almost all COP parameters, indicating a challenge for the PS. Furthermore, an increase in amplitude had a greater effect than an increase in speed, whereas the combination of the highest intensities of amplitude and speed was not well tolerated by the dogs. The mediolateral COP displacement was significantly greater than the craniocaudal COP displacement during standing measurement and conditions with a small amplitude, whereas no significant difference was observed during settings with an increased amplitude. To the best of our knowledge, this is the first study to demonstrate the effects of a balance training device in dogs. Therefore, the intensity of the training programs on motorized platforms or similar devices can be controlled by the wobbling amplitude of the platform

Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care.

Osteoarthritis is the most common joint disease diagnosed in veterinary medicine and poses considerable challenges to canine welfare. This study aimed to investigate prevalence, duration and risk factors of appendicular osteoarthritis in dogs under primary veterinary care in the UK. The VetCompassTM programme collects clinical data on dogs attending UK primary-care veterinary practices. The study included all VetCompassTM dogs under veterinary care during 2013. Candidate osteoarthritis cases were identified using multiple search strategies. A random subset was manually evaluated against a case definition. Of 455,557 study dogs, 16,437 candidate osteoarthritis cases were identified; 6104 (37%) were manually checked and 4196 (69% of sample) were confirmed as cases. Additional data on demography, clinical signs, duration and management were extracted for confirmed cases. Estimated annual period prevalence (accounting for subsampling) of appendicular osteoarthritis was 2.5% (CI95: 2.4-2.5%) equating to around 200,000 UK affected dogs annually. Risk factors associated with osteoarthritis diagnosis included breed (e.g. Labrador, Golden Retriever), being insured, being neutered, of higher bodyweight and being older than eight years. Duration calculation trials suggest osteoarthritis affects 11.4% of affected individuals' lifespan, providing further evidence for substantial impact of osteoarthritis on canine welfare at the individual and population level

Heart-specific immune responses in an animal model of autoimmune-related myocarditis mitigated by an immunoproteasome inhibitor and genetic ablation

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy is often accompanied by immune-related pathology, with an increasing occurrence of high-risk ICI-related myocarditis. Understanding the mechanisms involved in this side effect could enable the development of management strategies. In mouse models, immune checkpoints, such as PD-1, control the threshold of self-antigen responses directed against cardiac troponin I (TnI). Here, we aimed at identifying how the immunoproteasome, the main proteolytic machinery in immune cells harboring three distinct protease activities in the LMP2, LMP7 and MECL1 subunit, affects TnI-directed autoimmune pathology of the heart. METHODS: TnI-directed autoimmune myocarditis (TnI-AM), a CD4(+) T cell-mediated disease, was induced in mice lacking all three immunoproteasome subunits, triple-ip(-/-), or lacking either the LMP2 or LMP7 gene, by immunization with a cardiac TnI peptide. Alternatively, prior to induction of TnI-AM or after establishment of AM, mice were treated with the immunoproteasome inhibitor ONX 0914. Immune parameters defining heart-specific autoimmunity were investigated in both experimental TnI-AM and in two cases of ICI-related myocarditis. RESULTS: All immunoproteasome-deficient strains showed mitigated autoimmune-related cardiac pathology with less inflammation, lower pro-inflammatory and chemotactic cytokines, less IL-17 production, and reduced fibrosis formation. Protection from TnI-directed autoimmune heart pathology with improved cardiac function in LMP7(-/-) mice involved a changed balance between effector and regulatory CD4(+) T cells in the spleen, with CD4(+) T cells from LMP7(-/-) mice showing a higher expression of inhibitory PD-1 molecules. Blocked immunoproteasome proteolysis, by treatment of TLR2 and TLR7/8-engaged CD14(+) monocytes with ONX 0914, diminished pro-inflammatory cytokine responses, thereby reducing the boost for the expansion of self-reactive CD4(+) T cells. Correspondingly, in mice, ONX 0914 treatment reversed cardiac autoimmune pathology, preventing both the induction and progression of TnI-AM, when self-reactive CD4+ T cells were primed. The autoimmune signature during experimental TnI-AM, with high immunoproteasome expression, immunoglobulinG deposition, IL-17 production in heart tissue and TnI-directed humoral autoimmune responses, was also present in two cases of ICI-related myocarditis, thus demonstrating the activation of heart-specific autoimmune reactions by ICI therapy. CONCLUSIONS: By reversing heart-specific autoimmune responses, immunoproteasome inhibitors applied to a mouse model demonstrate their potential to aid in the management of autoimmune myocarditis in humans, possibly including cases with ICI-related heart-specific autoimmunity