3,090 research outputs found

    Flavanol-Rich Cacao Mucilage Juice Enhances Recovery of Power but Not Strength from Intensive Exercise in Healthy, Young Men

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    This is the final version. Available from MDPI via the DOI in this record(1) Background: Mucilage within cacao pods contains high levels of polyphenols. We investigated whether consumption of cacao juice enhances the recovery of muscle function following intensive knee extension exercise. (2) Methods: Ten recreationally active males completed two trials of 10 sets of 10 single leg knee extensions at ~80% one repetition maximum. Participants consumed each supplement (ZumoCacao® juice, CJ or a dextrose drink, PL) for 7 days prior to and 48 h post exercise. Knee extension maximum voluntary contraction (MVC) and a counter movement jump (CMJ) were performed at baseline, immediately, 24 h, and 48 h post-exercise. Venous blood samples were collected at each time point and analyzed for indices of inflammation, oxidative damage, and muscle damage. (3) Results: CMJ height recovered faster with CJ at 24 h and 48 h post-exercise (p 0.05). There was also no effect of the trial on any blood markers (all p > 0.05). (4) Conclusions: Supplementation with CJ for 7 days prior to and 2 days after intensive knee extensor exercise improved functional recovery as shown by an improved recovery of CMJ up to 48 h post-exercise. However, the precise mechanism of action is unclear and requires further investigation.Industria Agricola ZumoCaca

    Adenosine metabolic signature in circulating CD4+ T cells predicts remission in rheumatoid arthritis

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    \ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Objectives Long-term outcomes in rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate (MTX) remains the first-line disease modifying therapy, however there are no biomarkers with which to identify those most likely to achieve remission. To address this unmet need we explored metabolic pathways involved in MTX mechanism of action within circulating CD4+T cells in a cohort of treatment naive patients with early RA. Methods Purified CD4+T cells were isolated from peripheral blood of 68 patients with early RA commencing MTX. The expression of a range of putative MTX metabolism and mechanism of action targets were explored by flow-cytometry and transcriptional analysis. From these data significant predictors of Disease Activity Score 28-C reactive protein (DAS28-CRP) remission (<2.4 at 6 months) were determined by logistic regression (clinical; flow-cytometry data) and linear modelling (gene expression data). Results Low baseline DAS28-CRP was associated with remission at 6 months (p=0.02). Expression of the ectonucleotidase CD39, involved in ATP-ADP conversion during adenosine synthesis, was higher on CD4+CD25 High regulatory T cells at baseline in those achieving remission (molecules of equivalent fluorescence 1264 vs 847; p=0.007). Expression of other adenosine signalling elements in CD4+T cells were also upregulated at baseline in patients achieving remission: AMPD1 (p<0.001), ADORA2b (p=0.039) and ADORA3 (p=0.047). When combined into a single predictive metric, a combination of these variables outperformed baseline DAS28-CRP in prediction of early remission (area under the curve 0.92 vs 0.67, p=0.001) Conclusions Adenosine signalling is important in the achievement of early remission with MTX in RA and biomarkers of adenosine activity may hold utility for the stratification of therapy in early disease

    Point-of-care testing and treatment of sexually transmitted and genital infections during pregnancy in Papua New Guinea (WANTAIM trial): protocol for an economic evaluation alongside a cluster-randomised trial

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    Introduction: Left untreated, sexually transmitted and genital infections (henceforth STIs) in pregnancy can lead to serious adverse outcomes for mother and child. Papua New Guinea (PNG) has among the highest prevalence of curable STIs including syphilis, chlamydia, gonorrhoea, trichomoniasis and bacterial vaginosis, and high neonatal mortality rates. Diagnosis and treatment of these STIs in PNG rely on syndromic management. Advances in STI diagnostics through point-of-care (PoC) testing using GeneXpert technology hold promise for resource-constrained countries such as PNG. This paper describes the planned economic evaluation of a cluster-randomised cross-over trial comparing antenatal PoC testing and immediate treatment of curable STIs with standard antenatal care in two provinces in PNG. Methods and analysis: Cost-effectiveness of the PoC intervention compared with standard antenatal care will be assessed prospectively over the trial period (2017–2021) from societal and provider perspectives. Incremental cost-effectiveness ratios will be calculated for the primary health outcome, a composite measure of the proportion of either preterm birth and/or low birth weight; for life years saved; for disability-adjusted life years averted; and for non-health benefits (financial risk protection and improved health equity). Scenario analyses will be conducted to identify scale-up options, and budget impact analysis will be undertaken to understand short-term financial impacts of intervention adoption on the national budget. Deterministic and probabilistic sensitivity analysis will be conducted to account for uncertainty in key model inputs. Ethics and dissemination: This study has ethical approval from the Institutional Review Board of the PNG Institute of Medical Research; the Medical Research Advisory Committee of the PNG National Department of Health; the Human Research Ethics Committee of the University of New South Wales; and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings will be disseminated through national stakeholder meetings, conferences, peer-reviewed publications and policy briefs

    Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

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    Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

    11β-HSD1 contributes to age-related metabolic decline in male mice

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    The aged phenotype shares several metabolic similarities with that of circulatory glucocorticoid excess (Cushing’s syndrome), including type 2 diabetes, obesity, hypertension, and myopathy. We hypothesise that local tissue generation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts 11-dehydrocorticosterone to active corticosterone in rodents (corticosterone to cortisol in man), plays a role in driving age-related chronic disease. In this study, we have examined the impact of ageing on glucocorticoid metabolism, insulin tolerance, adiposity, muscle strength, and blood pressure in both wildtype (WT) and transgenic male mice with a global deletion of 11β-HSD1 (11β-HSD1−/−) following 4 months high-fat feeding. We found that high fat-fed 11β-HSD1−/− mice were protected from age-related glucose intolerance and hyperinsulinemia when compared to age/diet-matched WTs. By contrast, aged 11β-HSD1−/− mice were not protected from the onset of sarcopenia observed in the aged WTs. Young 11β-HSD1−/− mice were partially protected from diet-induced obesity; however, this partial protection was lost with age. Despite greater overall obesity, the aged 11β-HSD1−/− animals stored fat in more metabolically safer adipose depots as compared to the aged WTs. Serum analysis revealed both WT and 11β-HSD1−/− mice had an age-related increase in morning corticosterone. Surprisingly, 11β-HSD1 oxo-reductase activity in the liver and skeletal muscle was unchanged with age in WT mice and decreased in gonadal adipose tissue. These data suggest that deletion of 11β-HSD1 in high fat-fed, but not chow-fed, male mice protects from age-related insulin resistance and supports a metabolically favourable fat distribution

    Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England

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    Context: Adrenal insufficiency and Cushing’s syndrome are known adverse events of glucocorticoids. However, no population estimates of dose-related risks are available. Objective: To investigate dose-related risks of adrenal dysfunction and death in adults with six chronic inflammatory diseases treated with oral glucocorticoids. Design and setting: Retrospective record-linkage open-cohort study spanning primary and hospital care in England. Patients: 70,638 people oral glucocorticoid-users and 41,166 non-users aged ≥18 years registered in 389 practices in 1998-2017. Main outcome measures: Incidence rates and hazard ratios (HRs) of diagnosed adrenal dysfunction and death. Results: During a median follow-up of 5.5 years, 183 patients had glucocorticoid-induced adrenal insufficiency and 248 glucocorticoid-induced Cushing’s syndrome. A total of 22,317 (31.6%) and 7,544 (18.3%) deaths occurred amongst glucocorticoid users and non-users, respectively. Incidence of all outcomes increased with higher current daily and cumulative doses. For adrenal insufficiency, the increases in HRs were of 1.07 (95% CI 1.04-1.09) for every increase of 5mg per day and of 2.25 (95% CI 2.15-2.35) per 1000mg of cumulative prednisolone-equivalent dose over the past year. The respective increases in HRs for Cushing’s syndrome were of 1.09 (95% CI 1.08-1.11) and 2.31 (95% CI 2.23-2.40) and for mortality of 1.26 (95% CI 2.24-1.28) and 2.05 (95% CI 2.04-2.06). Conclusion: We report a high glucocorticoid dose-dependent increased risk of adrenal adverse events and death. The low observed absolute risk of adrenal insufficiency highlights a potential lack of awareness, and a need for increased physician and patient education about the risks of adrenal dysfunction induced by glucocorticoids

    Muscle fiber conduction velocity is more affected after eccentric than concentric exercise

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    It has been shown that mean muscle fiber conduction velocity (CV) can be acutely impaired after eccentric exercise. However, it is not known whether this applies to other exercise modes. Therefore, the purpose of this experiment was to compare the effects of eccentric and concentric exercises on CV, and amplitude and frequency content of surface electromyography (sEMG) signals up to 24 h post-exercise. Multichannel sEMG signals were recorded from biceps brachii muscle of the exercised arm during isometric maximal voluntary contraction (MVC) and electrically evoked contractions induced by motor-point stimulation before, immediately after and 2 h after maximal eccentric (ECC group, N = 12) and concentric (CON group, N = 12) elbow flexor exercises. Isometric MVC decreased in CON by 21.7 ± 12.0% (± SD, p < 0.01) and by 30.0 ± 17.7% (p < 0.001) in ECC immediately post-exercise when compared to baseline. At 2 h post-exercise, ECC showed a reduction in isometric MVC by 24.7 ± 13.7% (p < 0.01) when compared to baseline, while no significant reduction (by 8.0 ± 17.0%, ns) was observed in CON. Similarly, reduction in CV was observed only in ECC both during the isometric MVC (from baseline of 4.16 ± 0.3 to 3.43 ± 0.4 m/s, p < 0.001) and the electrically evoked contractions (from baseline of 4.33 ± 0.4 to 3.82 ± 0.3 m/s, p < 0.001). In conclusion, eccentric exercise can induce a greater and more prolonged reduction in muscle force production capability and CV than concentric exercis

    Targeting deforestation rates in climate change policy: a "Preservation Pathway" approach

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    We present a new methodological approach to incorporating deforestation within the international climate change negotiating regime. The approach, called "Preservation Pathway" combines the desire for forest preservation with the need to reduce emissions associated with forest loss by focusing on the relative rate of change of forest cover as the criteria by which countries gain access to trading preserved forest carbon stocks. This approach avoids the technically challenging task of quantifying historical or future deforestation emission baselines. Rather, it places emphasis on improving quantification of contemporary stocks and the relative decline in deforestation rates necessary to preserve those stocks. This approach places emphasis on the complete emissions trajectory necessary to attain an agreed-upon preserved forest and as such, meets both forest conservation and climate goals simultaneously
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