Browsing by Author "Scott, W. Michael"

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    Influence of Microarchitecture on the Mechanical Fatigue Behaviour of Equine Subchondral Bone
    (2023-09-12) Koshyk, Andrew; Edwards, William Brent; Manske, Sarah Lynn; Scott, W. Michael; Sparks, Holly Danielle; Lievers, William Brent
    Fractures of the equine metacarpophalangeal (MCP) joint are among the most common and fatal injuries experienced by racehorses. These bone injuries are a direct result of repetitive, high intensity loading of the skeleton during racing and training and there is consensus that they represent a mechanical fatigue phenomenon. Existing work has found the fatigue life of bone to be strongly determined by bone microarchitecture and the resulting stressed volume (i.e., the volume of bone stressed above yield). The purpose of this study was to quantify the influence of bone microarchitecture on the mechanical fatigue behaviour of equine subchondral bone from the MCP joint. Forty-eight subchondral bone samples were prepared from the third metacarpal (MC3) and proximal phalanx (P1) and subsequently imaged using high resolution micro-computed tomography (μCT) to quantify microarchitectural features of interest, including bone volume fraction, tissue mineral density, pore size, pore spacing, and pore number. Samples were cyclically loaded in compression to a stress of 70 MPa, and fatigue life was defined as the number of cycles until failure. Finite element models were created from the μCT images and used to quantify the stressed volume. Based on the expected log point-wise predictive density (ELPD), stressed volume was a strong predictor of fatigue life in both the MC3 and P1. Normalized stress (i.e., initial nominal strain) was also a strong predictor of fatigue life in samples from the MC3, but not for samples from the P1. This disparity can be attributed to differences in microstructure homogeneity. A regional analysis indicated fatigue life was more strongly associated with bone volume fraction in the superficial (r2 = 0.32, p < 0.001) and middle (r2 = 0.70, p < 0.001) regions of the subchondral bone, indicating that the cortical plate plays a more prominent role in the fatigue resistance of subchondral bone. By improving our understanding of the variance in fatigue life measurements, this research helps begin to clarify the underlying mechanisms of the mechanical fatigue process and provide a basic understanding of subchondral bone injuries in the equine fetlock joint.
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    Mild Equine Asthma: Effects of Commonly Used Treatments on the Respiratory Microbiota, Inflammatory Gene Expression, and Aerobic Performance during High-Intensity Exercise
    (2019-04-29) Bond, Stephanie Laura; Léguillette, Renaud; Scott, W. Michael; Bayly, Warwick M.; Easton, Paul A.
    Mild equine asthma (MEA) is an inflammatory airway disease of the horse which affects a large proportion of the equine population. The pathogenesis of MEA is not fully elucidated, however, it is widely assumed to be a multifactorial disease, with expression of clinical signs largely influenced by environment. There is very little information available on the effects of treatment, which is typically focused on reducing airway inflammation through corticosteroid administration. Investigations into the equine respiratory environment in states of health and MEA were performed using: i) High-throughput sequencing techniques (16S and ITS2) to report the respiratory microbiota and mycobiota respectively, and ii) changes in relative inflammatory mRNA cytokine expression in bronchoalveolar lavage fluid (BALF). Changes in expression of inflammatory cytokine mRNA, equine herpesvirus (EHV)-1,2,4,5 glycoprotein B gene expression and changes in respiratory bacterial and fungal communities following dexamethasone treatment of healthy horses and those with MEA are explored. A portable equine ergospirometry system was used to determine the efficacy of treatment designed to reduce lung inflammation on aerobic (V̇O2peak) and anaerobic performance in horses with MEA. There were clear differences between the lower respiratory tract environment in healthy horses versus MEA. There was a clear separation in both the microbiota - Streptococcus was increased in horses with MEA – and relative inflammatory cytokine expression. Horses with MEA had a lower concentration of IL-10 in BALF than healthy controls, consistent with human asthmatics. There was significant up-regulation of IL-17 in horses with MEA, suggesting these horses exhibit “allergic” airway inflammation in response to environmental antigens. The single most important factor in the prevention and treatment of MEA appears to be environmental improvement, manifest by reduced inhaled particulate matter. Treatment with injected dexamethasone in horses with MEA was associated with down-regulation of IL-5, indicating a shift away from a dysregulated Th-2 response. Treatment with dexamethasone significantly affected the microbiota diversity, but not the mycobiota, which was overwhelmed by the effect of a sustained dusty environment. There is strong evidence that without environmental modifications, corticosteroid therapy alone fails to normalize airway neutrophilia. Treatment significantly increased V̇O2peak by an average 11.7% (saline) to 14.6% (dexamethasone).
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    Proteoglycan-4 in Equine Joint Disease, Exercise, and in vitro Cartilage Repair
    (2020-05-25) Matheson, Austyn Reid; Schmidt, Tannin A.; Scott, W. Michael; Herzog, Walter; Matyas, John Robert
    Proteoglycan-4 (PRG4) and hyaluronan (HA) are biological macromolecules with varied and diverse functions distributed throughout the body. In synovial fluid (SF), PRG4 and HA provide independent and synergistic contributions to tissue health and cartilage boundary lubrication. The biological consequences of joint injury or disease such as osteoarthritis (OA) may include altered concentration, structure, and function of PRG4 and HA, leading to degraded SF quality and function, changes which are not fully understood. Furthermore, the effects of joint disease on circulating (serum) PRG4 and HA, both of unknown origin and function in blood, requires clarification. Monitoring changes to PRG4 and HA to elucidate the effects on SF and serum may facilitate the development of therapeutics, biomarkers, or novel biomaterials to restore joint health and function. The objectives of this thesis were to 1) investigate clinically relevant changes to PRG4 and HA composition in SF and serum, and SF biomechanical function from equine cases of joint disease and injury, 2) to investigate the effect of exercise on equine serum PRG4, and 3) to characterize the effect of recombinant human PRG4 (rhPRG4) integration on the biomechanical, architectural, and biological aspects of a collagen-based scaffold for cartilage repair. A combination of novel and previously characterized biochemical and biomechanical techniques were used to evaluate SF and serum composition, the lubricating ability of SF and tissue-engineered collagen-scaffolds, and the in vitro bioactivity of rhPRG4-integrated collagen-scaffolds. The composition of equine SF changed in acute joint injury compared to SF from normal horses. Both PRG4 concentration and HA molecular weight were altered, with decreased SF viscosity, yet no associated detectable effects on serum PRG4. The concentration of serum PRG4 in a group of racehorses decreased significantly five minutes post-exercise, perhaps clearing from the circulation. Hence, serum PRG4 and HA concentrations alone may not be useful biomarkers for equine joint disease. rhPRG4-integrated scaffolds had enhanced lubricating properties, a highly porous architecture, and supported cell infiltration and growth across most concentrations tested. Collectively these results indicate that PRG4 is an essential lubricant, an indicator for injury, and a promising therapeutic for integration within cartilage repair biomaterials.
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    Scoping Review of kinetic based methods for objective gait analysis in horses
    (2022-07-29) Devolin, Alanna; Murari, Kartikeya; Ganshorn, Heather; Scott, W. Michael
    Background: Gait analysis for horses can be performed either subjectively or objectively. The subjective method observes horses in motion. Whereas for an objective analysis, data on specific gait parameters are collected and reviewed. Objective gait analysis can be broken down into two disciplines: kinetic and kinematic based. Kinetic methods rely on applied force(s) data and kinematic methods analyze temporal and spatial parameters of gait. Objective: To complete a scoping review of kinetic based methods used for objective gait analysis Eligibility Criteria: Any articles (peer reviewed) and conference papers (peer reviewed and published) will be included in this study. Articles must include a kinetic based means of gait analysis that has been applied to horses. Kinematic based methods of analysis and any articles with humans or other animals will be excluded. Sources of evidence: Searches will be conducted in MEDLINE, CAB Abstracts, SportDiscus, Compendex, and IEEE Xplore.