545 research outputs found

    Running impact forces: from half a leg to holistic understanding – comment on Nigg et al.

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    Running impact forces have immediate relevance for the muscle tuning paradigm proposed here and broader relevance for overuse injuries, shoe design and running performance. Here, we consider their mechanical basis. Several studies demonstrate that the vertical ground reaction force-time (vGRFT) impulse, from touchdown to toe-off, corresponds to the instantaneous accelerations of the body’s entire mass (Mb) divided into two or more portions. The simplest, a two-mass partitioning of the body (lower-limb, M1=0.08•Mb; remaining mass, M2=0.92•Mb) can account for the full vGRFT waveform under virtually all constant-speed, level-running conditions. Model validation data indicate that: 1) the non-contacting mass, M2, often accounts for one-third or more of the early “impact” portion of the vGRFT, and 2) extracting a valid impact impulse from measured force waveforms requires only lower-limb motion data and the fixed body mass fraction of 0.08 for M1

    An Investigation into the Measurement and Prediction of Mechanical Stiffness of Lower-limb Prostheses used for Running

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    Two energy return prosthesis are subjected to three different statically applied loading methods. This initial study proposes that statically applied loading to a sport prosthesis using several controlled methods were statistically robust enough to derive a mechanical stiffness value. However, any predicted stiffness is drawn into question when allowing any movement of the distal end. This uncertainty will make any evaluation or prescription of lower-limb prosthesis technology based upon their stiffness incorrect. In addition, the peak calculated stiffness at the expected bodyweight induced ground impact load of a runner is judged the most representative assessment method. This study attempts to build on previous research advocating the need to monitor the performance of prosthesis lower-limb technology in disability sport. Practitioner Summary: This paper extends previous research regarding the fairness of prosthetics technology used in running with a lower-limb amputation. It pilots a quantitative assessment of high activity prosthetics technology and ultimately demonstrates how incorrect assessment can lead to incorrect specification of running prosthesis for elite level spor

    Sprinting with an amputation: Some race-based lower-limb step observations.

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    BACKGROUND: T44 sprinting with an amputation is still in a state of relative infancy. Future scope for athletic training and prosthetic limb development may be assisted with a better understanding of information derived from T44 athletes when under race-based conditions. OBJECTIVES: To investigate the behaviour of step count and step frequency when under competitive conditions. STUDY DESIGN: The study comprises two elements: (1) a video-based analysis of race-based limb-to-limb symmetry and (2) a video-based analysis of race-based step count. METHODS: Video analysis of several major events from 1996-2012 are assessed for step count and step limb-to-limb symmetry characteristics. RESULTS: The video analysis highlights limb-to-limb imbalances greater than those indicated in the previous literature. A low step count is determined to be desirable for success in the 100-m event. CONCLUSION: Future analysis of athletes with a lower-limb amputation would be worthwhile when placed under race-based conditions as the limb-to-limb behaviour is more exaggerated than those seen in typical studies held within a laboratory setting. The within-event behaviour of step counts requires further investigation to establish where these take place or whether it is a cumulative step length issue. CLINICAL RELEVANCE: This article increases the understanding of the race-based behaviour of amputee athletes and provides more information to contribute to any discussions on the performance of lower-limb prostheses

    Lower limb stiffness and maximal sprint speed in 11-16-year-old boys

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    The purpose of the study was to examine the relationship between vertical stiffness, leg stiffness and maximal sprint speed in a large cohort of 11-16-year-old boys. Three-hundred and thirty-six boys undertook a 30 m sprint test using a floor-level optical measurement system, positioned in the final 15 m section. Measures of speed, step length, step frequency, contact time and flight time were directly measured whilst force, displacement, vertical stiffness and leg stiffness, were modeled from contact and flight times, from the two fastest consecutive steps for each participant over two trials. All force, displacement and stiffness variables were significantly correlated with maximal sprint speed (p 0.7) relationship with sprint speed, while vertical center of mass displacement, absolute vertical stiffness, relative peak force, and maximal leg spring displacement had large (r > 0.5) relationships. Relative vertical stiffness and relative peak force did not significantly change with advancing age (p > 0.05), but together with maximal leg spring displacement accounted for 96% of the variance in maximal speed. It appears that relative vertical stiffness and relative peak force are important determinants of sprint speed in boys aged 11-16 years, but are qualities that may need to be trained due to no apparent increases from natural development. Practitioners may wish to utilize training modalities such as plyometrics and resistance training to enable adaptation to these qualities due to their importance as predictors of speed in youth

    The Dynamic Processing of CD46 Intracellular Domains Provides a Molecular Rheostat for T Cell Activation

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    Adequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated.Here, we first report the novel role of CD46 in terminating T cell activation. Second, we demonstrate that its functions as an activator and inhibitor of T cell responses are mediated through the temporal processing of its cytoplasmic tails. Cyt1 processing is required to turn T cell activation on, while processing of Cyt2 switches T cell activation off, as demonstrated by proliferation, CD25 expression and cytokine secretion. Both tails require processing by Presenilin/γSecretase (P/γS) to exert these functions. This was confirmed by expressing wild-type Cyt1 and Cyt2 tails and uncleavable mutant tails in primary T cells. The role of CD46 tails was also demonstrated with T cells expressing CD19 ectodomain-CD46 C-Terminal Fragment (CTF) fusions, which allowed specific triggering of each tail individually.We conclude that CD46 acts as a molecular rheostat to control human T cell activation through the regulation of processing of its cytoplasmic tails

    The correct prednisone starting dose in polymyalgia rheumatica is related to body weight but not to disease severity

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    <p>Abstract</p> <p>Background</p> <p>the mainstay of treatment of polymyalgia rheumatica (PMR) is oral glucocorticoids, but randomized controlled trials of treatment are lacking. As a result, there is no evidence from controlled studies on the efficacy of different initial doses or glucocorticoid tapering. The aim of this study is to test if 12.5 mg prednisone/day is an adequate starting dose in PMR and to evaluate clinical predictors of drug response.</p> <p>Methods</p> <p>60 consecutive PMR patients were treated with a starting dose of 12,5 mg/day prednisone. Clinical, laboratory, and, in a subset of 25 patients, ultrasonographic features were recorded as possible predictors of response to prednisone. Remission was defined as disappearance of at least 75% of the signs and symptoms of PMR and normalization of ESR and CRP within the first month, a scenario allowing steroid tapering.</p> <p>Results</p> <p>47/60 (78.3%) patients responded to 12.5 mg of prednisone after a mean interval of 6.6 ± 5.2 days. In univariate analysis, body weight and gender discriminated the two groups. In multivariate analysis, the only factor predicting a good response was low weight (p = 0.004); the higher response rate observed in women was explained by their lower weight. The mean prednisone dose per kg in the responders was 0.19 ± 0.03 mg in comparison with 0.16 ± 0.03 mg for non responders (p = 0.007).</p> <p>Conclusions</p> <p>12.5 mg prednisone is a sufficient starting dose in ¾ of PMR patients. The main factor driving response to prednisone in PMR was weight, a finding that could help in the clinical care of PMR patients and in designing prospective studies of treatment.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01169597">NCT01169597</a></p

    Immunopathogenesis of rheumatoid arthritis

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    Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. The majority of evidence, derived from genetics, tissue analyses, models, and clinical studies, points to an immune-mediated etiology associated with stromal tissue dysregulation that together propogate chronic inflammation and articular destruction. A pre-RA phase lasting months to years may be characterized by the presence of circulating autoantibodies, increasing concentration and range of inflammatory cytokines and chemokines, and altered metabolism. Clinical disease onset comprises synovitis and systemic comorbidities affecting the vasculature, metabolism, and bone. Targeted immune therapeutics and aggressive treatment strategies have substantially improved clinical outcomes and informed pathogenetic understanding, but no cure as yet exists. Herein we review recent data that support intriguing models of disease pathogenesis. They allude to the possibility of restoration of immunologic homeostasis and thus a state of tolerance associated with drug-free remission. This target represents a bold vision for the future of RA therapeutics

    Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

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    Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA
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