442 research outputs found

    Predictors of time to return to play and reinjury following hamstring strain injuries with and without tendon involvement in professional football

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    Background: Hamstring strain injury (HSI) is the single most commonly (~12%) sustained injury in professional football. It is suggested HSIs extending into the intramuscular tendon are more prone to reinjury, resulting in greater time-loss and delayed time to return to play (TtRtP). Currently, there is a lack of evidence regarding the effects of HSI with and without intramuscular involvement as well as the impact of factors such as removal of a player and grade. Objectives: 1) Describe the number of HSIs using the British Athletics Muscle Injury Classification (BAMIC); 2) Determine if intramuscular tendon HSI results in extended TtRtP and higher reinjury risk; 3) Determine the predictors of TtRtP and reinjury. Methods: A retrospective study in one English Premier League football club over four seasons. Players included underwent an MRI within 7 days of injury and were graded by a Radiologist using the BAMIC (0a-4). TtRtP and injury recurrence rates were recorded along with information on whether the players were removed from play. Data were analysed using a Kruskal-Wallis test and linear regression. Results: Twenty-nine HSI across 24 players (age = 26.1 ± 3.8 years) were recorded over 4 seasons. There was a significant difference in TtRtP between grades 1a and 2c (P = 0.027). No significant difference was observed in TtRtP between 2b and 2c and no greater risk of reinjury. Grade of HSI (P = < 0.000) and removal of the player (P = 0.001) were significant predictors of TtRtP. An increase in grade of HSI resulted in an additional 4 days TtRtP and removal from the field of play (P = 0.001) resulted in an additional 10 days. Conclusion: HSIs extending into the intramuscular tendon (2b cf. 2c) do not influence TtRtP or reinjury, however TtRtP is affected by the removal of a player and overall grade

    Easy to Swallow “Instant” Jelly Formulations for Sustained Release Gliclazide Delivery

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    © 2020 The Authors. Published by Elsevier Inc. on behalf of the American Pharmacists Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).It is a challenge to safely administer sustained release medicines to patients with dysphagia. Sustained release tablets must not be crushed and multiparticulates with large particle sizes cause gritiness reducing patient acceptability. The aim of this study was to develop “instant” jellies as delivery vehicles incorporating sustained release microparticles for patients with dysphagia. Dry powder mixtures containing gelling agents such as sodium alginate and calcium ions were hydrated in 20 mL of water and formed a jelly texture within 10 min. The “instant” jellies demonstrated comparable properites to commercial “read-to-eat” jellies in appearance, rheological/textural properties and in vitro swallowing performance in an artificial throat model. Gliclazide sustained release microparticles were produced by fluidized bed coating using Eudragit® NM 30 D and achieved 99% production yield and final coated particle size (D50) of 198 4.3 µm. Sustained gliclazide release was achieved over 15 h and the incorporation of the particles into the jellies significantly decreased the drug release rate. This novel drug delivery system offers a patient-centric solution to the long-standing challenge of administering sustained release medicines to patients with dysphagia and can potentially be used for paediatric patients.Peer reviewe

    Streptomyces: A Screening Tool for Bacterial Cell Division Inhibitors

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    Cell division is essential for spore formation but not for viability in the filamentous streptomycetes bacteria. Failure to complete cell division instead blocks spore formation, a phenotype that can be visualized by the absence of gray (in Streptomyces coelicolor) and green (in Streptomyces venezuelae) spore-associated pigmentation. Despite the lack of essentiality, the streptomycetes divisome is similar to that of other prokaryotes. Therefore, the chemical inhibitors of sporulation in model streptomycetes may interfere with the cell division in rod-shaped bacteria as well. To test this, we investigated 196 compounds that inhibit sporulation in S. coelicolor. We show that 19 of these compounds cause filamentous growth in Bacillus subtilis, consistent with impaired cell division. One of the compounds is a DNA-damaging agent and inhibits cell division by activating the SOS response. The remaining 18 act independently of known stress responses and may therefore act on the divisome or on divisome positioning and stability. Three of the compounds (Fil-1, Fil-2, and Fil-3) confer distinct cell division defects on B. subtilis. They also block B. subtilis sporulation, which is mechanistically unrelated to the sporulation pathway of streptomycetes but is also dependent on the divisome. We discuss ways in which these differing phenotypes can be used in screens for cell division inhibitors

    Testing a model of antecedents and consequences of defensive pessimism and self-handicapping in school physical education

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    There has been very limited research on the use of self-worth protection strategies in the achievement context of school physical education (PE). Thus, this study aimed to examine some antecedents and consequences of defensive pessimism and self-handicapping. The sample comprised 534 (females n = 275; males n = 259) British pupils recruited from two schools who responded to established questionnaires. Results of structural equation modelling analysis indicated that self-handicapping and defensive pessimism were positively predicted by fear of failure and negatively predicted by competence valuation. In addition, defensive pessimism was negatively predicted by physical self-concept. In turn, defensive pessimism negatively predicted enjoyment in PE and intentions to participate in future optional PE programs. Self-handicapping did not predict enjoyment or intentions. Results from multi-sample structural equation modelling showed the specified model to be largely invariant across males and females. The findings indicate that although both strategies aim to protect one’s self-worth, some of their antecedents and consequences in PE may differ

    A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: self-controlled case-series analysis of national data

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    Background and Aims: Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs.Design: This was a self-controlled case-series study.Setting: Scotland, 1 January 2015-30 November 2020.Participants: The study population of non-cirrhotic, DAA-treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day-case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non-viral injecting related admission and drug-related mortality) were defined using ICD codes.Measurements: Self-controlled case-series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90-day exposure risk periods thereafter.Findings: A total of 6050 PWID were treated with DAAs in the sampling time-frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80-0.99; 0.89, 95% CI = 0.80-0.99; 0.86, 95% CI = 0.77-0.96; 0.88, 95% CI = 0.78-0.99, respectively]. For non-viral injecting-related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64-0.90; 0.75, 95% CI = 0.62-0.90; 0.79, 95% CI = 0.66-0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end.Conclusions: Among people who inject drugs in Scotland, direct-acting antiviral treatment appears to be associated with a small, non-durable reduction in the risk of drug-related hospital admission, but not drug-related mortality. Direct-acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug-related health harms.</p

    Evaluation of the Ability of LL-37 to Neutralise LPS In Vitro and Ex Vivo

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    BACKGROUND: Human cathelicidin LL-37 is a cationic antimicrobial peptide (AMP) which possesses a variety of activities including the ability to neutralise endotoxin. In this study, we investigated the role of LPS neutralisation in mediating LL-37's ability to inhibit Pseudomonas aeruginosa LPS signalling in human monocytic cells. METHODOLOGY/PRINCIPAL FINDINGS: Pre-treatment of monocytes with LL-37 significantly inhibited LPS-induced IL-8 production and the signalling pathway of associated transcription factors such as NF-ÎşB. However, upon removal of LL-37 from the media prior to LPS stimulation, these inhibitory effects were abolished. These findings suggest that the ability of LL-37 to inhibit LPS signalling is largely dependent on extracellular LPS neutralisation. In addition, LL-37 potently inhibited cytokine production induced by LPS extracted from P. aeruginosa isolated from the lungs of cystic fibrosis (CF) patients. In the CF lung, polyanionic molecules such as glycosaminoglycans (GAGs) and DNA bind LL-37 and impact negatively on its antibacterial activity. In order to determine whether such interactions interfere with the LPS neutralising ability of LL-37, the status of LL-37 and its ability to bind LPS in CF sputum were investigated. Overall our findings suggest that in the CF lung, the ability of LL-37 to bind LPS and inhibit LPS-induced IL-8 production is attenuated as a result of binding to DNA and GAGs. However, LL-37 levels and its concomitant LPS-binding activity can be increased with a combination of DNase and GAG lyase (heparinase II) treatment. CONCLUSIONS/SIGNIFICANCE: Overall, these findings suggest that a deficiency in available LL-37 in the CF lung may contribute to greater LPS-induced inflammation during CF lung disease

    Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services:REAL WORLD DATA

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    BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population
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