Examining the impact of a province-wide physical education policy on secondary students’ physical activity as a natural experiment

Abstract Background The purpose of this paper is to examine the impact of a province-wide physical education (PE) policy on secondary school students’ moderate to vigorous physical activity (MVPA). Methods Policy: In fall 2008, Manitoba expanded a policy requiring a PE credit for students in grades 11 and 12 for the first time in Canada. The PE curriculum requires grades 11 and 12 students to complete a minimum of 55 h (50% of course hours) of MVPA (e.g., ≥30 min/day of MVPA on ≥5 days a week) during a 5-month semester to achieve the course credit. Study Designs: A natural experimental study was designed using two sub-studies: 1) quasi-experimental controlled pre-post analysis of self-reported MVPA data obtained from census data in intervention and comparison [Prince Edward Island (PEI)] provinces in 2008 (n = 33,619 in Manitoba and n = 2258 in PEI) and 2012 (n = 41,169 in Manitoba and n = 4942 in PEI); and, 2) annual objectively measured MVPA in cohorts of secondary students in intervention (n = 447) and comparison (Alberta; n = 224) provinces over 4 years (2008 to 2012). Analysis: In Study 1, two logistic regressions were conducted to model the odds that students accumulated: i) ≥30 min/day of MVPA, and ii) met Canada's national recommendation of ≥60 min/day of MVPA, in Manitoba versus PEI after adjusting for grade, sex, and BMI. In Study 2, a mixed effects model was used to assess students’ minutes of MVPA per day per semester in Manitoba and Alberta, adjusting for age, sex, BMI, school location and school SES. Results In Study 1, no significant differences were observed in students achieving ≥30 (OR:1.13, 95% CI:0.92, 1.39) or ≥60 min/day of MVPA (OR:0.92, 95% CI: 0.78, 1.07) from baseline to follow-up between Manitoba and PEI. In Study 2, no significant policy effect on students’ MVPA trajectories from baseline to last follow-up were observed between Manitoba and Alberta overall (−1.52, 95% CI:-3.47, 0.42), or by covariates. Conclusions The Manitoba policy mandating PE in grades 11 and 12 had no effect on student MVPA overall or by key student or school characteristics. However, the effect of the PE policy may be underestimated due to the use of a nonrandomized research design and lack of data assessing the extent of policy implementation across schools. Nevertheless, findings can provide evidence about policy features that may improve the PE policy in Manitoba and inform future PE policies in other jurisdictions

Restoring ornithine transcarbamylase (OTC) activity in an OTC‐deficient mouse model using LUNAR‐OTC mRNA

Abstract Ornithine transcarbamylase (OTC) catalyses the reaction from ornithine to citrulline in the urea cycle. Ornithine transcarbamylase deficiency (OTCD) results in episodes of hyperammonemia. Arcturus Therapeutics developed a lipid nanoparticle (LNP)‐encapsulated OTC‐mRNA (LUNAR‐OTC) that results in a replacement enzyme and is currently undergoing clinical trials. In this study, the efficacy of LUNAR OTC‐mRNA drug in the spfash mouse model was examined by measuring the OTC enzyme activity and protein expression in the liver and plasma of OTC‐mRNA‐treated mice. Using purified citrulline‐D4 as the substrate improved the sensitivity of the OTC activity assay and allowed us to quantify the ornithine‐D4 product from the mouse plasma samples. OTC activity in the liver showed a clear dose response: The lowest dose, 0.3 mg/kg, resulted in higher activity than that of the untreated group, and the highest dose, 3 mg/kg, resulted in completely restored OTC activity in the liver. OTC activity in plasma was also dose‐dependent. A clear positive correlation between the OTC activity in the liver and that in the plasma suggests that the plasma OTC activity assay may serve as a surrogate for measuring OTC activity in liver biopsy samples. In addition, the OTC protein expression levels correlated well with the OTC activity in liver samples, but there was no quantifiable OTC protein in the plasma samples. This finding suggests that the sensitivity of the OTC activity assay is superior to that of the protein expression assay. Overall, the results of this study suggest that the OTC activity assay described here can be used as a clinical pharmacodynamic endpoint to measure the effectiveness of OTCD treatment