329 research outputs found

    From Construction Workers to Architects: Developing Scientific Research Capacity in Low-Income Countries

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    Solving global health challenges in a sustainable manner depends on explicitly addressing scientific capacity-building needs, as well as establishing long-term, meaningful partnerships with colleagues in the developing world

    Renin inhibition by substituted piperidines: A novel paradigm for the inhibition of monomeric aspartic proteinases?

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    BackgroundThe aspartic proteinase renin catalyses the first and rate-limiting step in the conversion of angiotensinogen to the hormone angiotensin II, and therefore plays an important physiological role in the regulation of blood pressure. Numerous potent peptidomimetic inhibitors of this important drug target have been developed, but none of these compounds have progressed past clinical phase II trials. Limited oral bioavailability or excessive production costs have prevented these inhibitors from becoming new antihypertensive drugs. We were interested in developing new nonpeptidomimetic renin inhibitors.ResultsHigh-throughput screening of the Roche compound library identified a simple 3,4-disubstituted piperidine lead compound. We determined the crystal structures of recombinant human renin complexed with two representatives of this new class. Binding of these substituted piperidine derivatives is accompanied by major induced-fit adaptations around the enzyme's active site.ConclusionsThe efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases

    Reliability of the modified child and adolescent physical activity and nutrition survey, physical activity (CAPANS-PA) questionnaire among chinese-australian youth

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    Background : Evidence suggests that differences exist in physical activity (PA) participation among Culturally and Linguistically Diverse (CALD) children and adolescents. It is possible that these differences could be influenced by variations in measurement technique and instrument reliability. However, culturally sensitive instruments for examining PA behaviour among CALD populations are lacking. This study tested the reliability of the Child and Adolescent Physical Activity and Nutrition Survey (CAPANS-PA) recall questionnaire among a sample of Chinese-Australian youth.Methods : The psychometric property of the CAPANS-PA questionnaire was examined among a sample of 77 Chinese-Australian youth (aged 11 - 14 y) who completed the questionnaire twice within 7 days. Test-retest reliability of individual items and scales within the CAPANS-PA questionnaire was determined using Kappa statistics for categorical variables and intraclass correlation coefficients (ICC) for continuous variables.Results : The CAPANS-PA questionnaire demonstrated acceptable test-retest reliability for frequency and duration of time spent in weekly Moderate to Vigorous Physical Activity (MVPA) (ICC &ge; 0.70) for all participants. Test-retest reliability for time spent in weekly sedentary activities was acceptable for females (ICC = 0.82) and males (ICC = 0.72).Conclusions : The results suggest the CAPANS-PA questionnaire provides reliable estimates for type, frequency and duration of MVPA participation among Chinese-Australian youth. Further investigation into the reliability of the sedentary items within the CAPANS-PA is required before these items can be used with confidence. This study is novel in that the reliability of instruments among CALD groups nationally and internationally remains sparse and this study contributes to the wider body of available psychometrically tested instruments. In addition, this study is the first to our knowledge to successfully engage and investigate the basic health enhancing behaviours of Chinese-Australian adolescents.<br /

    Effectiveness of YouRAction, an Intervention to Promote Adolescent Physical Activity Using Personal and Environmental Feedback: A Cluster RCT

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    Background: In this study the one and six months effects of the computer-tailored YouRAction (targeting individual level determinants) and YouRAction+e (targeting in addition perceived environmental determinants) on compliance with the moderate-to-vigorous physical activity (MVPA) guideline and weight status are examined. In addition the use and appreciation of both interventions are studied. Methods: A three-armed cluster randomized trial was conducted in 2009-2010 with measurements at baseline, one and six months post intervention. School classes were assigned to one of the study arms (YouRaction, YouRAction+e and Generic Information (GI) control group). MVPA was derived from self-reports at baseline, one and six months post intervention. Body Mass Index and waist circumference were measured at baseline and six months post intervention in a random sub-sample of the population. Use of the interventions was measured by webserver logs and appreciation by self-reports. Multilevel regression analyses were conducted to study the effects of the intervention against the GI control group. ANOVA's and chi-square tests were used to describe differences in use and appreciation between study arms. Results: There were no statistically significant intervention effects on compliance with the MVPA guideline, overweight or WC. Access to the full intervention was significantly lower for YouRAction (24.0%) and YouRAction+e (21.7%) compared to the GI (54.4%). Conclusion: This study could not demonstrate that the YouRAction and YouRAction+e interventions were effective in promoting MVPA or improve anthropometric outcomes among adolescents, compared to generic information. Insufficient use and exposure to the intervention content may be an explanation for the lack of effects
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