OBJECTIVE To describe clinical findings and diagnostic test results and identify potential prognostic indicators for calves with septic arthritis. DESIGN Retrospective case series. ANIMALS 64 calves with septic arthritis. PROCEDURES The medical record database for a veterinary teaching hospital was searched to identify calves ≤ 6 months old that were treated for septic arthritis between 2009 and 2014. Data evaluated included signalment, history, physical examination and diagnostic test results, treatment, and outcome. Descriptive data were generated, and calves were assigned to 2 groups (neonatal [≤ 28 days old] or postneonatal [29 to 180 days old]) on the basis of age at hospital admission for comparison purposes. RESULTS 64 calves had 92 infected joints; 17 calves had polyarthritis. Carpal joints were most frequently affected followed by the stifle and tarsal joints. Forty-nine bacterial isolates were identified from synovial specimens for 38 calves, and the most commonly identified isolates were catalase-negative Streptococcus spp (n = 14) and Mycoplasma bovis (9). Calves in the neonatal group had a shorter interval between onset of clinical signs and hospitalization and were more likely to have an infected carpal joint than calves in the postneonatal group. Outcome was positive for 35 calves. Synovial fluid total nucleated cell count was positively associated with a positive outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that empirical antimicrobial treatment for calves with septic arthritis should target gram-positive catalase-negative cocci and M bovis and that synovial fluid total nucleated cell count might be a useful prognostic indicator.

Displaying a strong antiproliferative activity on a wide variety of cancer cells, EAPB0203 and EAPB0503 belong to the imidazo[1,2-a]quinoxalines family of imiquimod structural analogues. EAPB0503 has been shown to inhibit tubulin polymerization. The aim of the present study is to characterize the interaction of EAPB0203 and EAPB0503 with tubulin. We combine experimental approaches at the cellular and the molecular level both in vitro and in silico in order to evaluate the interaction of EAPB0203 and EAPB0503 with tubulin. We examine the influence of EAPB0203 and EAPB0503 on the cell cycle and fate, explore the binding interaction with purified tubulin, and use a computational molecular docking model to determine the binding modes to the microtubule. We then use a drug combination study with other anti-microtubule agents to compare the binding site of EAPB0203 and EAPB0503 to known potent tubulin inhibitors. We demonstrate that EAPB0203 and EAPB0503 are capable of blocking human melanoma cells in G2 and M phases and inducing cell death and apoptosis. Second, we show that EAPB0203 and EAPB0503, but also unexpectedly imiquimod, bind directly to purified tubulin and inhibit tubulin polymerization. As suggested by molecular docking and binding competition studies, we identify the colchicine binding site on β-tubulin as the interaction pocket. Furthermore, we find that EAPB0203, EAPB0503 and imiquimod display antagonistic cytotoxic effect when combined with colchicine, and disrupt tubulin network in human melanoma cells. We conclude that EAPB0203, EAPB0503, as well as imiquimod, interact with tubulin through the colchicine binding site, and that the cytotoxic activity of EAPB0203, EAPB0503 and imiquimod is correlated to their tubulin inhibiting effect. These compounds appear as interesting anticancer drug candidates as suggested by their activity and mechanism of action, and deserve further investigation for their use in the clinic.

Objective To determine the influence of screw head diameter on equine condylar fracture fixation with 5.5 mm cortical screws. Study design Ex vivo, biomechanical study, blinded, matched‐pair design. Sample population Fifteen pairs of equine third metacarpal (MC3) bones. Methods Lateral condylar fractures were simulated by parasagittal osteotomies and repaired pairwise by 2 × 5.5 mm cortical screws of 8 mm (standard) or 10 mm (modified) head diameter. Interfragmentary compression at maximum screw insertion torque was measured. The instrumented specimens were pairwise stratified for biomechanical testing under the following modalities (n = 5): (1) screw insertion torque to failure, (2) quasi‐static axial load to failure, and (3) cyclic axial load to 2 mm displacement followed by failure. Tests (1) and (2) were analyzed for yield, maximum, and failure torque/angle and load/displacement, respectively. Number of cycles to 2 mm displacement and failure was assessed from test (3). Results Maximum insertion torque was greater, and failure angle smaller, when constructs repaired with modified screws were tested (8.1 ± 0.5 vs. 7.4 ± 0.5 Nm; P = .0047 and 550 ± 104 vs. 1130 ± 230; P = .008). Axial yield (7118 ± 707 vs. 5740 ± 2267 N; P = .043) and failure load (12 347 ± 3359 vs. 8695 ± 2277 N; P = .043) were greater for specimens repaired with modified screws. No difference was detected between constructs in the number of cycles to 2 mm displacement. Conclusion Condylar MC3 osteotomies repaired with modified 5.5 mm cortical screws sustained greater maximal hand torque insertion, smaller insertion failure angle and 1.4 fold greater quasi‐static failure forces than constructs repaired with standard 5.5 mm screws. Clinical significance Use of modified screws with larger heads may improve the fixation of condylar fractures in horses. These results provide evidence to justify clinical evaluation in horses undergoing fracture repair.

A fracture-related infection (FRI) is a serious complication that can occur after surgical fixation of bone fractures. Affected patients may encounter delayed healing and functional limitations. Although it is well established that Staphylococcus aureus (S. aureus) is the main causative pathogen of an FRI, the pathophysiology of an S. aureus-induced FRI is not well characterised over time. Therefore, an experimental study in mice comparing S. aureus-inoculated and non-inoculated groups was performed that particularly focused on staphylococcal abscess communities (SACs) and host cellular response. C57Bl/6N female mice received a double osteotomy of the femur, which was stabilised using a titanium 6-hole MouseFix locking plate and four screws. Animals were either S. aureus-inoculated or non-inoculated and euthanised between 1 and 28 d post-surgery. Histopathological evaluation showed normal bone healing for non-inoculated mice, whereas inoculated mice had no fracture consolidation and severe osteolysis. Within the bone marrow of inoculated mice, SACs were observed from 7 d, which increased in size and number over time. A fibrin pseudocapsule enclosed the SACs, which were surrounded by many Ly6G+ neutrophils with some Ly6C+ monocytes and F4/80+ macrophages, the majority of which were viable. The abscesses were encapsulated by fibrin(ogen), collagen and myofibroblasts, with regulatory T cells and M2 macrophages at the periphery. Only bone marrow monocytes and neutrophils of inoculated mice displayed functional suppression of T cells, indicative of myeloid-derived suppressor cells. The present study revealed that an FRI in mice is persistent over time and associated with osteolysis, SAC formation and an immunosuppressive environment.