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Objectives To describe the association and its magnitude between body mass index category, sex, and cardiovascular disease risk parameters in school aged children in highly developed countries. Design Systematic review and meta-analysis. Quality of included studies assessed by an adapted version of the Cochrane Collaboration’s risk of bias assessment tool. Results of included studies in meta-analysis were pooled and analysed by Review Manager version 5.1. Data sources Embase, PubMed, EBSCOHost’s cumulative index to nursing and allied health literature, and the Web of Science databases for papers published between January 2000 and December 2011. Review methods Healthy children aged 5 to 15 in highly developed countries enrolled in studies done after 1990 and using prospective or retrospective cohort, cross sectional, case-control, or randomised clinical trial designs in school, outpatient, or community settings. Included studies had to report an objective measure of weight and at least one prespecified risk parameter for cardiovascular disease.Results We included 63 studies of 49 220 children. Studies reported a worsening of risk parameters for cardiovascular disease in overweight and obese participants. Compared with normal weight children, systolic blood pressure was higher by 4.54 mm Hg (99% confidence interval 2.44 to 6.64; n=12 169, eight studies) in overweight children, and by 7.49 mm Hg (3.36 to 11.62; n=8074, 15 studies) in obese children. We found similar associations between groups in diastolic and 24 h ambulatory systolic blood pressure. Obesity adversely affected concentrations of all blood lipids; total cholesterol and triglycerides were 0.15 mmol/L (0.04 to 0.25, n=5072) and 0.26 mmol/L (0.13 to 0.39, n=5138) higher in obese children, respectively. Fasting insulin and insulin resistance were significantly higher in obese participants but not in overweight participants. Obese children had a significant increase in left ventricular mass of 19.12 g (12.66 to 25.59, n=223), compared with normal weight children. Conclusion Having a body mass index outside the normal range significantly worsens risk parameters for cardiovascular disease in school aged children. This effect, already substantial in overweight children, increases in obesity and could be larger than previously thought. There is a need to establish whether acceptable parameter cut-off levels not considering weight are a valid measure of risk in modern children and whether methods used in their study and reporting should be standardised.

A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable ␤-globin mRNA was rendered unstable by insertion of the 2,500-nucleotide Cox-2 3 untranslated region (3 UTR). The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. Constitutively active MAPKAPK-2 was also able to stabilize chimeric ␤-globin-Cox-2 transcripts. The MAPKAPK-2 substrate hsp27 may be involved in stabilization, as ␤-globin-Cox-2 transcripts were partially stabilized by phosphomimetic mutant forms of hsp27. A short (123-nucleotide) fragment of the Cox-2 3 UTR was necessary and sufficient for the regulation of mRNA stability by the p38 cascade and interacted with a HeLa protein immunologically related to AU-rich element/poly(U) binding factor 1.

Analysis 2.12. Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 12 Serious adverse events in adult prophylaxis (on-treatment

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