51 research outputs found

    Social support for youth physical activity: Importance of siblings, parents, friends and school support across a segmented school day

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    <p>Abstract</p> <p>Background</p> <p>Whilst evidence exists for the influence of encouragement on physical activity participation, the diversity of support sources and the type of physical activity examined previously is limited. This study examined the importance of perceived encouragement from parents, siblings/cousins, friends, and schools on participation levels across three time-specific activity opportunities that are available during a school day (after-school physical activities, lunchtime activity, and active transportation to and from school).</p> <p>Methods</p> <p>A cross-sectional sample of 12–18 year old high school students (n = 3,471) were recruited from low SES schools within South Auckland, New Zealand and categorised as either Junior (Years 9–11) or Senior (Years 12 & 13) students. Participants reported their physical activity levels and quantity of encouragement received from their parent(s), friend(s), sibling(s)/cousin(s), and school to be active. For each physical activity variable participants were dichotomized as being either "active" or "less active". For each social support source, participants were grouped into either receiving "high" or "low" levels of support. Binary logistic regression analyzes were conducted to calculate odd ratios and 95% confidence intervals.</p> <p>Results</p> <p>Low parental support (Juniors, OR: 0.47, 95% CI: 0.38–0.58; Seniors, OR: 0.41, 95% CI: 0.29–0.60) and low peer support (Juniors, OR: 0.61, 95% CI: 0.51–0.74; Seniors, OR: 0.49, 95% CI: 0.35–0.69) were associated with reduced odds of being regularly active after school. For lunchtime activity, low peer support (Juniors, OR: 0.39, 95% CI: 0.32–0.48; Seniors, OR: 0.41, 95% CI: 0.29–0.57) was associated with reduced odds of being categorized as active. While no variables were significantly related to active transportation among senior students, low peer support was associated with reduced odds of actively commuting for Junior students (OR: 0.78, 95% CI: 0.66–0.92). Irrespective of the activity examined, no significant difference was noted for students receiving high support from two parents than students reporting high support from their sole parent in a single parent family.</p> <p>Conclusion</p> <p>The importance of encouragement from parents, siblings, friends, and schools on physical activity is dependant on the time-specific activity examined. It is clear that proximal social networks need to be considered during the development of physical activity promotion strategies.</p

    Total Synthesis of Irciniastatin A (Psymberin)

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    The total synthesis of (+)-iriciniastatin A (psymberin) is reported in 19 steps and 6% overall yield. Key reactions include a highly convergent enolsilane-oxocarbenium ion union to generate the C8-C25 fragment and a late-stage coupling of a hemiaminal and acid chloride to complete the synthesis

    Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis

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    <p>Abstract</p> <p>Background</p> <p>Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected.</p> <p>Methods</p> <p>Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (<it>P </it>= 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression.</p> <p>Results</p> <p>The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 μg/hour/ml (<it>P </it>= 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 μg/hour/ml (<it>P </it>= 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 μg/ml (<it>P </it>= 0.20) at 1 month after the start of treatment and 4.0 and 4.6 μg/ml (<it>P </it>= 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 μg/ml and even 4 μg/ml</p> <p>Conclusion</p> <p>Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.</p

    Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

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    International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

    Comparison of methods for estimation of absolute vegetation and soil fractional cover using MODIS normalized BRDF-adjusted reflectance data

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    Green vegetation (GV), nonphotosynthetic vegetation (NPV), and soil are important ground cover components in terrestrial ecosystems worldwide. There are many good methods for observing the dynamics of GV with optical remote sensing, but there are fewer good methods for observing the dynamics of NPV and soil. Given the difficulty of remotely deriving information on NPV and soil, the purpose of this study is to evaluate several methods for the retrieval of information on fractional cover of GV, NPV, and soil using 500-m MODIS nadir BRDF-adjusted reflectance (NBAR) data. In particular, three spectral mixture analysis (SMA) techniques are evaluated: simple SMA, multiple-endmember SMA (MESMA), and relative SMA (RSMA). In situ cover data from agricultural fields in Southern Australia are used as the basis for comparison. RSMA provides an index of fractional cover of GV, NPV, and soil, so a method for converting these to absolute fractional cover estimates is also described and evaluated. All methods displayed statistically significant correlations with in situ data. All methods proved equally capable at predicting the dynamics of GV. MESMA predicted NPV dynamics best. RSMA predicted dynamics of soil best. The method for converting RSMA indices to fractional cover estimates provided estimates that were comparable to those provided by SMA and MESMA. Although it does not always provide the best estimates of ground component dynamics, this study shows that RSMA indices are useful indicators of GV, NPV, and soil cover. However, our results indicate that the choice of unmixing technique and its implementation ought to be application-specific, with particular emphasis on which ground cover retrieval requires the greatest accuracy and how much ancillary data is available to support the analysis.Gregory S. Okin, Kenneth D. Clarke, Megan M. Lewi

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Total Synthesis and Structure Confirmation of Leptofuranin D

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