Tenomodulin is Required for Tendon Endurance Running and Collagen I Fibril Adaptation to Mechanical Load

Tendons are dense connective tissues that attach muscles to bone with an indispensable role in locomotion because of their intrinsic properties of storing and releasing muscle-generated elastic energy. Tenomodulin (Tnmd) is a well-accepted gene marker for the mature tendon/ligament lineage and its loss-of -function in mice leads to a phenotype with distinct signs of premature aging on tissue and stem/progenitor cell levels. Based on these findings, we hypothesized that Tnmdmight be an important factor in the functional performance of tendons. Firstly, we revealed that Tnmd is amechanosensitive gene and that the C-terminus of the protein colocalizewith collagen I-type fibers in the extracellular matrix. Secondly, using an endurance training protocol, we compared Tnmd knockout mice with wild types and showed that Tnmd deficiency leads to significantly inferior running performance that further worsens with training. In these mice, endurance running was hindered due to abnormal response of collagen I cross-linking and proteoglycan genes leading to an inadequate collagen I fiber thickness and elasticity. In sum, our study demonstrates that Tnmd is required for proper tendon tissue adaptation to endurance running and aids in better understanding of the structural-functional relationships of tendon tissues. (C) 2017 The Authors. Published by Elsevier B.V

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.NIHR HT

The influence of social circumstances on ‘Risky’ patterns of alcohol consumption among mothers with pre-school aged children in England.

Background Social factors have been linked to patterns of alcohol use among women. However, conflicting evidence on the ways in which socio-economic circumstances are linked to women’s alcohol use impedes our understanding. Interest in women’s alcohol use has moved up the policy agenda. Nevertheless, existing research fails to attend to differences among groups of women according to their social circumstances, including whether or not they are mothers. Objectives This study aims to enhance our understanding of ‘risky’ patterns of alcohol use among mothers in the UK during very early motherhood. Methods Secondary analyses of 2000/1 data from the Millennium Cohort Study (MCS) was undertaken. Using a broad outcome measure of ‘risky’ alcohol use, patterns of consumption among a sub-set of mothers recruited in England (n = 7048) were explored according to a number of social and domestic variables. Using logistic regression, mutually adjusted analyses that included adjustment for age were undertaken. Odds ratios were calculated for the likelihood of ‘risky’ drinking according to mothers’ social circumstances and level of disadvantage. Results ‘Risky’ alcohol use was more likely with increased levels of disadvantage: disadvantaged childhood circumstances, lower levels of educational attainment, lower household income, younger age at first birth, lone parenthood. Conclusions Social gradients were evident for ‘risky’ alcohol use among mothers with 9 month old babies in England who took part in the MCS. These findings emphasise the importance of exploring patterns of alcohol use among sub-groups of the population that are currently under-represented in the research literature