Point-of-care motion capture and biomechanical assessment improve clinical utility of dynamic balance testing for lower extremity osteoarthritis.

Musculoskeletal conditions impede patient biomechanical function. However, clinicians rely on subjective functional assessments with poor test characteristics for biomechanical outcomes because more advanced assessments are impractical in the ambulatory care setting. Using markerless motion capture (MMC) in clinic to record time-series joint position data, we implemented a spatiotemporal assessment of patient kinematics during lower extremity functional testing to evaluate whether kinematic models could identify disease states beyond conventional clinical scoring. 213 trials of the star excursion balance test (SEBT) were recorded by 36 subjects during routine ambulatory clinic visits using both MMC technology and conventional clinician scoring. Conventional clinical scoring failed to distinguish patients with symptomatic lower extremity osteoarthritis (OA) from healthy controls in each component of the assessment. However, principal component analysis of shape models generated from MMC recordings revealed significant differences in subject posture between the OA and control cohorts for six of the eight components. Additionally, time-series models of subject posture change over time revealed distinct movement patterns and reduced overall postural change in the OA cohort compared to the controls. Finally, a novel metric quantifying postural control was derived from subject specific kinematic models and was shown to distinguish OA (1.69), asymptomatic postoperative (1.27), and control (1.23) cohorts (p = 0.0025) and to correlate with patient-reported OA symptom severity (R = -0.72, p = 0.018). Time series motion data have superior discriminative validity and clinical utility than conventional functional assessments in the case of the SEBT. Novel spatiotemporal assessment approaches can enable routine in-clinic collection of objective patient-specific biomechanical data for clinical decision-making and monitoring recovery.

Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II intervenes into the unprecedented S-oxygenation of homocysteine to engender the corresponding sulfenic acid species that further participates into the prosthetic heme modification through the formation of an unusual Fe(II) sulfonium. In addition, our ex cellulo studies performed on cancer cells, models of neurodegenerative diseases and ulcerative colitis suggest the likelihood of this scenario in a subset of cancer cells, as well as in a cellular model of Parkinson's disease. Our findings expand the repertoire of heme modifications promoted by biological compounds and point out another deleterious trait of disturbed homocysteine levels that could participate in the aetiology of these diseases.