1,590 research outputs found

    Incubation with sodium nitrite attenuates fatigue development in intact single mouse fibres at physiological PO2

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    This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordDietary nitrate (NO3−) supplementation, which increases plasma nitrite (NO2−) concentration, has been reported to attenuate skeletal muscle fatigue development. Sarcoplasmic reticulum (SR) calcium (Ca2+) release is enhanced in isolated single skeletal muscle fibres following NO3− supplementation or NO2− incubation at a supra‐physiological PO2 but it is unclear whether NO2− incubation can alter Ca2+ handling and fatigue development at a near‐physiological PO2. We hypothesised that NO2− treatment would improve Ca2+ handling and delay fatigue at a physiological PO2 in intact single mouse skeletal muscle fibres. Each muscle fibre was perfused with Tyrode's solution pre‐equilibrated with either 20% (PO2∼150 Torr) or 2% O2 (PO2 = 15.6 Torr) in the absence and presence of 100 µM NaNO2. At supra‐physiological PO2 (i.e. 20% O2), time to fatigue was lowered by 34% with NaNO2 (control: 257 ± 94 vs. NaNO2: 159 ± 46 s, d = 1.63, P0.05) but [Ca2+]c accumulation between contractions was lower, concomitant with a greater SR Ca2+ pumping rate (P<0.05) compared to the control condition. These results demonstrate that increased exposure to NO2− blunts fatigue development at near‐physiological, but not at supra‐physiological, PO2 through enhancing SR Ca2+ pumping rate in single skeletal muscle fibres. These findings extend our understanding of the mechanisms by which increased NO2− exposure can mitigate skeletal muscle fatigue development.Ministry of Science, Technology and InnovationConselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development)US Department of Health and Human Services (HHS)National Institutes of Health (NIH)National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS

    The African Women's Protocol: Bringing Attention to Reproductive Rights and the MDGs

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    Andrew Gibbs and colleagues discuss the African Women's Protocol, a framework for ensuring reproductive rights are supported throughout the continent and for supporting interventions to improve women's reproductive health, including the MDGs

    Weak-Field Gravity of Revolving Circular Cosmic Strings

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    A weak-field solution of Einstein's equations is constructed. It is generated by a circular cosmic string revolving in its plane about the centre of the circle. (The revolution is introduced to prevent the string from collapsing.) This solution exhibits a conical singularity, and the corresponding deficit angle is the same as for a straight string of the same linear energy density, irrespective of the angular velocity of the string.Comment: 13 pages, LaTe

    Can Reproductive Health Voucher Programs Improve Quality of Postnatal Care? A Quasi-Experimental Evaluation of Kenya’s Safe Motherhood Voucher Scheme

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    This study tests the group-level causal relationship between the expansion of Kenya’s Safe Motherhood voucher program and changes in quality of postnatal care (PNC) provided at voucher-contracted facilities. We compare facilities accredited since program inception in 2006 (phase I) and facilities accredited since 2010-2011 (phase II) relative to comparable non-voucher facilities. PNC quality is assessed using observed clinical content processes, as well as client-reported outcome measures. Two-tailed unpaired t-tests are used to identify differences in mean process quality scores and client-reported outcome measures, comparing changes between intervention and comparison groups at the 2010 and 2012 data collection periods. Difference-in-differences analysis is used to estimate the reproductive health (RH) voucher program’s causal effect on quality of care by exploiting group-level differences between voucher-accredited and non-accredited facilities in 2010 and 2012. Participation in the voucher scheme since 2006 significantly improves overall quality of postnatal care by 39% (p=0.02), where quality is defined as the observable processes or components of service provision that occur during a PNC consultation. Program participation since phase I is estimated to improve the quality of observed maternal postnatal care by 86% (p=0.02), with the largest quality improvements in counselling on family planning methods (IRR 5.0; p=0.01) and return to fertility (IRR 2.6; p=0.01). Despite improvements in maternal aspects of PNC, we find a high proportion of mothers who seek PNC are not being checked by any provider after delivery. Additional strategies will be necessary to standardize provision of packaged postnatal interventions to both mother and new-born. This study addresses an important gap in the existing RH literature by using a strong evaluation design to assess RH voucher program effectiveness on quality improvement

    Addressing Inequity to Achieve the Maternal and Child Health Millennium Development Goals: Looking Beyond Averages.

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    Inequity in access to and use of child and maternal health interventions is impeding progress towards the maternal and child health Millennium Development Goals. This study explores the potential health gains and equity impact if a set of priority interventions for mothers and under fives were scaled up to reach national universal coverage targets for MDGs in Tanzania. We used the Lives Saved Tool (LiST) to estimate potential reductions in maternal and child mortality and the number of lives saved across wealth quintiles and between rural and urban settings. High impact maternal and child health interventions were modelled for a five-year scale up, by linking intervention coverage, effectiveness and cause of mortality using data from Tanzania. Concentration curves were drawn and the concentration index estimated to measure the equity impact of the scale up. In the poorest population quintiles in Tanzania, the lives of more than twice as many mothers and under-fives were likely to be saved, compared to the richest quintile. Scaling up coverage to equal levels across quintiles would reduce inequality in maternal and child mortality from a pro rich concentration index of -0.11 (maternal) and -0.12 (children) to a more equitable concentration index of -0,03 and -0.03 respectively. In rural areas, there would likely be an eight times greater reduction in maternal deaths than in urban areas and a five times greater reduction in child deaths than in urban areas. Scaling up priority maternal and child health interventions to equal levels would potentially save far more lives in the poorest populations, and would accelerate equitable progress towards maternal and child health MDGs

    Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

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    Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions
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