929 research outputs found

    Strategies Used by Healthy Kids, Healthy Communities Partnerships to Prevent Childhood Obesity

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    IntroductionHealthy Kids, Healthy Communities (HKHC) is an initiative of the Robert Wood Johnson Foundation to prevent obesity among high-risk children by changing local policies, systems, and environments. In 2009, 105 community partnerships applied for funding from HKHC. Later that year, the Centers for Disease Control and Prevention (CDC) released recommended community strategies to prevent obesity by changing environments and policies. The objective of this analysis was to describe the strategies proposed by the 41 HKHC partnerships that received funding and compare them to the CDC recommendations.MethodsWe analyzed the funded proposals to assess the types and prevalence of the strategies proposed and mapped them onto the CDC recommendations.ResultsThe most prevalent strategies proposed by HKHC-funded partnerships were providing incentives to retailers to locate and serve healthier foods in underserved areas, improving mechanisms for purchasing food from farms, enhancing infrastructure that supports walking and cycling, and improving access to outdoor recreational facilities.ConclusionThe strategies proposed by HKHC partnerships were well aligned with the CDC recommendations. The popular strategies proposed by HKHC partnerships were those for which there were existing examples of successful implementation. Our analysis provides an example of how information from communities, obtained through grant-writing efforts, can be used to assess the status of the field, guide future research, and provide direction for future investments

    The extracellular calcium-sensing receptor, CaSR, in fetal development

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    In fetal mammals, serum levels of both total and ionized calcium significantly exceed those in the adult. This relative fetal hypercalcemia is crucial for skeletal development and is maintained irrespectively of maternal serum calcium levels. Elegant studies by Kovacs and Kronenberg have previously addressed the role of the CaSR in creating and maintaining this relative fetal hypercalcemia, through the regulation of parathyroid hormone-related peptide secretion. More recently we have shown that the CaSR is widely distributed throughout the developing fetus, where the receptor plays major, unexpected roles in ensuring growth and maturation of several organs. In this article, we present evidence for a role of the CaSR in the control of skeletal development, and how fetal hypercalcemia, acting through the CaSR, regulates lung development

    Emerging roles of the extracellular calcium-sensing receptor in nutrient sensing: control of taste modulation and intestinal hormone secretion

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    The extracellular Ca-sensing receptor (CaSR) is a sensor for a number of key nutrients within the body, including Ca ions (Ca2+) and l-amino acids. The CaSR is expressed in a number of specialised cells within the gastrointestinal (GI) tract, and much work has been done to examine CaSR's role as a nutrient sensor in this system. This review article examines two emerging roles for the CaSR within the GI tract – as a mediator of kokumi taste modulation in taste cells and as a regulator of dietary hormone release in response to l-amino acids in the intestine

    The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR

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    Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory disease

    A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes

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    Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK. Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups. Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008). Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors

    Treatment of autosomal dominant hypocalcemia Type 1 with the calcilytic NPSP795 (SHP635)

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    Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain‐of‐function mutations of the calcium‐sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to 4 distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration‐dependent manner up to 129% above baseline (p=0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol and little calcium supplementation. NPSP795 was generally safe and well‐tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half‐maximally activated (EC50) at lower concentrations of extracellular calcium (Ca2+o) compared to wild type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose‐dependent manner, and thus, serves as proof‐of‐concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype, or the response to calcilytics, suggesting that other parameters impact the response to the drug

    Centrifuge modelling of screw piles for offshore wind energy foundations

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    Screw piles (helical piles) can provide a viable, cost-effective and low-noise installation alternative to increasing the size of existing foundation solutions (e.g. monopiles) to meet the demand for the advancement of offshore wind energy into deeper water. Significant upscaling of widely used onshore screw pile geometries will be required to meet the loading conditions of a jacket supported offshore wind turbine. This increase in size will lead to greater installation force and torque. This paper presents preliminary results from centrifuge tests investigating the requirements to install screw piles designed for an offshore wind energy application using specially developed equipment. Results indicate that the equipment is suitable to investigate these screw pile requirements and that significant force is required for such upscaled screw piles, with 19 MN vertical force and 7 MNm torque for the standard design. Optimisation of the screw pile geometry, reduced these forces by 29 and 11% for the vertical and rotational forces respectively
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