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Objectives: Parks are more widely used by older adults in East Asia than in the United States. Parks are an important community asset for healthy aging; yet, little is known about park usage and features among older adults in China. Methods: The Community Park Audit Tool and the System for Observing Play and Recreation (SOPARC) were used to assess park features, PA levels and primary activities among 40,469 older adults in Nanchang, China. Results: None of the 8 parks observed had basketball courts or baseball fields and only one had a playground. Results indicated that about half of older adults were active in parks, with women, cooler temperatures, weekdays, and morning hours being related to higher levels of activity. Conclusions: Lessons from the construction of parks in China may be useful in increasing park use in older adults in western countries. Features such as exercise equipment, water features, and small exercise areas were common where western parks are often designed with features for teens and youth including basketball courts, baseball fields, and playgrounds.

Purpose of Review: Vitamin D deficiency may impact disease progression of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to review recent studies examining either vitamin D status or the effects of supplementation in patients with NAFLD, along with investigating the roles of genetic polymorphisms and the gut microbiome., Recent Findings: Six heterogeneous observational studies of vitamin D status, and four randomized controlled intervention trials of vitamin D supplementation in NAFLD were conflicting. All studies were hampered by the challenges of diagnosing NAFLD, were underpowered, and lacked data on clinically important outcomes. The results of three cross-sectional studies, including a Mendelian randomization study, provide limited evidence for a role for genetic modifiers of vitamin D status in NAFLD. Genetic and experimental evidence suggests that vitamin D and the vitamin D receptor (VDR) may influence the gut microbiome in health and disease., Summary: The evidence relating either lower vitamin D status to the prevalence and severity of NAFLD, or examining vitamin D supplementation in patients with NAFLD is inconclusive. Larger, higher quality trials with relevant endpoints are needed. Further mechanistic studies on the roles of vitamin D and VDR in influencing the gut-liver axis in NAFLD are warranted.

Background and Objectives: The Advanced Life Support in Obstetrics (ALSO) course is widely utilized in the United States as an evidence-based program that bridges knowledge gaps and improves skills via hands-on training, group learning, and memorization of standardized mnemonics in a team-based approach to patient care. This reduces communication barriers among maternity care providers, ultimately decreasing potential negative outcomes. A needs assessment identified that Serbian providers would benefit from structured learning and hands-on simulation approaches in obstetrics from a structured training like the ALSO course. The objective of this study was to explore the changes in clinicians' knowledge and preferred scenario responses in managing obstetrics cases before and after participation in the ALSO course., Methods: The ALSO training lasted 2 days and included lecture sessions, interactive workshops, a written knowledge test, and a simulated skills test. Participants completed an additional 20-item questionnaire assessing their knowledge and preferred scenario responses two weeks pre- and immediately post-ALSO training. Using a paired t test we assessed changes between pre- and posttest knowledge and preferred scenario response scores., Results: Twenty-seven participants provided complete data. For the entire sample, the pretest mean number of correct items on the knowledge and preferred scenario response assessment was 10.8 and the posttest mean number correct was 15.2, representing an increase of 4.4 correct answers (P<.001)., Conclusions: The current results suggest that the ALSO course can successfully increase knowledge and preferred scenario responses in Serbian providers and may be a viable approach to improving birth outcomes.

Citizen science is a growing method of scientific discovery and community engagement. To date, there is a paucity of data using citizen scientists to monitor community level physical activity, such as bicycling or walking; these data are critical to inform community level intervention. Volunteers were recruited from the local community to make observations at five local greenways. The volunteers picked their location, time to collect data and duration of data collection. Volunteer observations included recording estimated age, race or ethnicity and activity level of each individual they encountered walking, running or bicycling on the greenway. A total of 102 volunteers were recruited to participate in the study, of which 60% completed one or more observations. Average observational time lasted 81 minutes and resulted in recording the demographics and physical activity of a mean of 48 people per session. The majority of adult bicyclists observed were biking at a moderate pace (86%) and were white (72%) males (62%). Similar results were observed for those walking. We demonstrate the feasibility of using citizen scientists to address the current scarcity of data describing community-level physical activity behavior patterns. Future work should focus on refining the citizen science approach for the collection of physical activity data to inform community-specific interventions in order to increase greenway use.

While the fundamental mechanism by which cardiac cell therapy mitigates ventricular dysfunction in the post ischemic heart remains poorly defined, donor cell paracrine signaling is presumed to be a chief contributor to the afforded benefits. Of the many bioactive molecules secreted by transplanted cells, extracellular vesicles (EVs) and their proteinaceous, nucleic acid, and lipid rich contents, comprise a heterogeneous assortment of prospective cardiotrophic factors-whose involvement in the activation of endogenous cardiac repair mechanism(s), including reducing fibrosis and promoting angiogenesis, have yet to be fully explained. In the current study we aimed to interrogate potential mechanisms by which cardiac mesenchymal stromal cell (CMC)-derived EVs contribute to the CMC pro-angiogenic paracrine signaling capacity in vitro. Vesicular transmission and biological activity of human CMC-derived EVs was evaluated in in vitro assays for human umbilical vein endothelial cell (HUVEC) function, including EV uptake, cell survival, migration, tube formation, and intracellular pathway activation. HUVECs incubated with EVs exhibited augmented cell migration, tube formation, and survival under peroxide exposure; findings which paralleled enhanced activation of the archetypal pro-survival/pro-angiogenic pathways, STAT3 and PI3K-AKT. Cytokine array analyses revealed preferential enrichment of a subset of prototypical angiogenic factors, Ang-1 and Ang-2, in CMC EVs. Interestingly, pharmacologic inhibition of Tie2 in HUVECs, the cognate receptors of angiopoietins, efficiently attenuated CMC-EV-induced HUVEC migration. Further, in additional assays a Tie2 kinase inhibitor exhibited specificity to inhibit Ang-1-, but not Ang-2-, induced HUVEC migration. Overall, these findings suggest that the pro-angiogenic activities of CMC EVs are principally mediated by Ang-1-Tie2 signaling.

Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25-30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.

Background: Comprehensive School Physical Activity Programs (CSPAPs) are widely supported to increase physical activity (PA) in schools, but little has been reported to inform a comprehensive evaluation effort. The purpose of this report is to describe a comprehensive evaluation and monitoring strategy for CSPAP implementation., Methods: The System for Observing Staff Promotion of Activity and Nutrition (SOSPAN), System for Observing Student Movement in Academic Routines and Transitions (SOSMART), and System for Observing Play and Leisure Activity (SOPLAY) were employed to record student and staff behaviors (2642 total scans). To assess policies, practices, and environments, a CSPAP Policies and Practices questionnaire was used, which included components of the School Health Index, the School PA Policy Assessment, the School Environment and Policies Survey, and the School Health Policies and Practices Study. Youth PA (minutes/day) was assessed using accelerometers., Results: Working with school sites to ascertain the number of opportunities that are provided for PA and the amount of PA students engage in is challenging but feasible. The use of systematic observation, accelerometers, and questionnaires can provide a comprehensive representation of policies, practices, and behaviors to aid in establishing targeted PA action items., Conclusions: Developing an evaluation framework that was rigorous enough to assess the physical, social, and policy environment of a school in order to answer the overarching research questions of the study but flexible enough to be feasibly streamlined for utilization by a school implementation team proved to be challenging but possible., (Copyright © 2019. Published by Elsevier Ltd.)

The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework's major proposition is that it situates D&I sciences as targeted "sub-sciences" of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages., (© The Association for Clinical and Translational Science 2019.)

Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but enhance metastatic colonization, indicating tumour suppressing and promoting roles. Phytosterols and phytostanols in plants, like cholesterol in mammals, are essential components of the plasma membrane and biochemical precursors, and in human cells can alter LXR transcriptional activity. Here, a panel of breast cancer cell lines were treated with four dietary plant sterols and a stanol, alone or in combination with oxysterols. LXR activation and repression were measured by gene expression and LXR-luciferase reporter assays. Oxysterols activated LXR in all cell lines, but surprisingly phytosterols failed to modulate LXR activity. However, phytosterols significantly inhibited the ability of oxysterols to drive LXR transcription. These data support a role for phytosterols in modulating cancer cell behaviour via LXR, and therefore suggest merit in accurate dietary recordings of these molecules in cancer patients during treatment and perhaps supplementation to benefit recovery.

Background: The primary purpose of this study was to determine which physical activity (PA) opportunity elicits the most moderate to vigorous PA (MVPA) in after-school programs. This study used a 3-group cross-over design in which participants were exposed to 3 variations of activity structures: free play, organized, or a mixture., Methods: PA was measured using ActiGraph GT3X+ accelerometers. All data were transformed into percentage of time spent sedentary or in MVPA. Repeated-measures mixed-effects models were used to examine differences in MVPA and sedentary among the 3 activity sessions. Participants included 197 unique children, aged 5-12 years, and were 53% male and 55% white., Results: Statistically significant differences were observed in the percentage of time boys spent in MVPA during free play and mixed compared with organized only sessions (35.8% and 34.8% vs 29.4%). No significant difference was observed in the percentage of time girls spent in MVPA during free play compared with organized or mixed (27.2% and 26.1% vs 26.1%). Both boys and girls experienced ∼10% less time sedentary during free play compared with the others., Conclusion: Offering free play during PA opportunities can help children attain as much if not more MVPA compared with only offering organized, adult-led games.

Background: The connections between long sleep duration and obesity or weight gain warrant further examination. This meta-analysis aimed to evaluate whether long sleep duration was associated with the risk of obesity, weight gain, body mass index (BMI) change or weight change in adults., Methods: PubMed, Embase, Cochrane Library, Elsevier Science Direct, Science Online, MEDLINE and CINAHL were searched for English articles published before May 2017. A total of 16 cohort studies (n = 329 888 participants) from 8 countries were included in the analysis. Pooled relative risks (RR) or regression coefficients (β) with 95% confidence intervals (CI) were estimated. Heterogeneity and publication bias were tested, and sensitivity analysis was also performed., Results: We found that long sleep duration was associated with higher risk of obesity (RR [95% CI] = 1.04 [1.00-1.09], P = 0.037), but had no significant associations with weight gain, BMI change or weight change. Long sleep duration increased the risk of weight gain in three situations: among men, in studies with <5 years follow-up, and when sleep duration was 9 or more hours., Conclusions: Long sleep duration was associated with risk of obesity in adults. More cohort studies with objective measures are needed to confirm this relationship., (© The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Traditional and novel risk factors cannot sufficiently explain the differential susceptibility to cardiovascular disease (CVD). Epigenetics may serve to partially explain this residual disparity, with life course stressors shown to modify methylation of genes implicated in various diseases. Subclinical CVD is often comorbid with cognitive impairment (CI), which warrants research into the identification of common genes for both conditions., Methods: We conducted a systematic review of the existing literature to identify studies depicting the relationship between life course stressors, DNA methylation, subclinical CVD, and cognition., Results: A total of 16 articles (8 human and 8 animal) were identified, with the earliest published in 2008. Four genes (COMT, NOS3, Igfl1, and Sod2) were analyzed by more than one study, but not in association with both CVD and CI. One gene (NR3C1) was associated with both outcomes, albeit not within the same study. There was some consistency among studies with markers used for subclinical CVD and cognition, but considerable variability in stress exposure (especially in human studies), cell type/tissue of interest, method for detection of DNA methylation, and risk factors. Racial and ethnic differences were not considered, but analysis of sex in one human study found statistically significant differentially methylated X-linked loci associated with attention and intelligence., Conclusions: This review suggests the need for additional studies to implement more comprehensive and methodologically rigorous study designs that can better identify epigenetic biomarkers to differentiate individuals vulnerable to both subclinical CVD and associated CI.

Background: A recent meta-analysis reported that exercise interventions are effective for promoting weight loss in adolescents with overweight-obesity. However, the meta-analysis did not investigate whether there is an optimal exercise dose for promoting weight loss in overweight and obese adolescents. A common method of expressing exercise dose is the calculation of metabolic equivalents (METs), expressed as MET-h/week., Objectives: The objective of this study was to determine the association between exercise dose (MET-h/week) and weight loss [body weight, body mass index (BMI)] in adolescents with overweight-obesity., Data Sources: Trials included in the original meta-analysis were extracted, and a subsequent search to identify studies published between May 2015 and May 2018 was conducted. The search included electronic databases (PubMed, Web of Science SPORTDiscus, Google Scholar) and the reference lists of eligible articles and relevant reviews., Study Selection: The inclusion criteria were as follows: (i) randomized controlled trial; (ii) structured exercise intervention, alone or combined with other intervention components; (iii) control group received no structured exercise or behavioral modification designed to increase physical activity; (iv) participants overweight or obese (BMI ≥ 85th percentile); and (v) participants aged between 10 and 19 years., Appraisal and Synthesis Methods: Fifteen trials were extracted from the original meta-analysis. The current search identified an additional five trials (three articles). Data from 20 trials (16 articles) involving 1091 participants (54% female, 17% not reported) were included in the analysis. Effect sizes were reported as mean difference, and random effects meta-regression quantified the association between exercise dose and weight loss. Study quality was assessed using a modified Jadad's scale., Results: Total body weight change (decrease) ranged from - 2.7 to 19.3 (median 2.5) kg, and BMI change (decrease) ranged from - 1.6 to 6.3 (median 0.9) kg/m 2 . MET-h/week ranged from 5.4 to 36.0 (median 6.0). Each MET-h/week was associated with a 0.13 kg/m 2 (95% confidence interval [CI] 0.08-0.19) and 0.33 kg (95% CI 0.08-0.59) decrease in BMI and body weight, respectively., Limitations: The prescribed exercise dose for the majority of trials was low. As such, we were unable to discern whether there was an optimal exercise dose for weight loss (i.e., if the association between dose and weight loss was non-linear). Additionally, most trials had small sample sizes (median n = 34) and 17 trials had methodological limitations., Conclusions: Each MET-h/week was associated with a 0.13 kg/m 2 and 0.33 kg decrease in BMI and body weight, respectively. While this relationship appears to be linear, i.e., no optimal exercise dose, it should be emphasized that the exercise prescription dose for the majority of trials was low. Subsequent trials, with greater exercise dosage, are required to determine whether there is an 'optimal' dose for promoting weight loss in adolescents with overweight-obesity. However, the current findings lend support to the use of exercise prescription for promoting weight loss and improving health outcomes in this population.

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Preclinical investigations support the concept that donor cells more oriented towards a cardiovascular phenotype favor repair. In light of this philosophy, we previously identified HDAC1 as a mediator of cardiac mesenchymal cell (CMC) cardiomyogenic lineage commitment and paracrine signaling potency in vitro-suggesting HDAC1 as a potential therapeutically exploitable target to enhance CMC cardiac reparative capacity. In the current study, we examined the effects of pharmacologic HDAC1 inhibition, using the benzamide class 1 isoform-selective HDAC inhibitor entinostat (MS-275), on CMC cardiomyogenic lineage commitment and CMC-mediated myocardial repair in vivo. Human CMCs pre-treated with entinostat or DMSO diluent control were delivered intramyocardially in an athymic nude rat model of chronic ischemic cardiomyopathy 30 days after a reperfused myocardial infarction. Indices of cardiac function were assessed by echocardiography and left ventricular (LV) Millar conductance catheterization 35 days after treatment. Compared with naïve CMCs, entinostat-treated CMCs exhibited heightened capacity for myocyte-like differentiation in vitro and superior ability to attenuate LV remodeling and systolic dysfunction in vivo. The improvement in CMC therapeutic efficacy observed with entinostat pre-treatment was not associated with enhanced donor cell engraftment, cardiomyogenesis, or vasculogenesis, but instead with more efficient inhibition of myocardial fibrosis and greater increase in myocyte size. These results suggest that HDAC inhibition enhances the reparative capacity of CMCs, likely via a paracrine mechanism that improves ventricular compliance and contraction and augments myocyte growth and function.

The prevalence of overweight and obesity has been increasing globally. Recent studies suggest that eating frequency (EF) might be a factor influencing the development of overweight and obesity. This study aims to explore the association between eating frequency and obesity in Chinese adults. A cross-sectional study was conducted in Wuhan, China, from March to June 2016. A self-administered questionnaire and 24-h dietary recall were used to collect data on sociodemographic variables, lifestyle factors, nutrition knowledge, and eating frequency. Participants were divided into four groups according to eating frequency and meal timing: traditional time pattern (TTP), traditional time plus late snack pattern (TTLSP), irregular time pattern (ITP), and all-day pattern (ADP). We performed the chi-squared test and multiple logistic regression to assess associations among variables using JMP statistical software version 14.0.0 (SAS Institute Inc., Cary, NC, USA). Respondents were Chinese adults ( N = 2290; range 29⁻74 years; 1162 men). Lower education level, higher food budget, and lower nutrition knowledge were associated with higher likelihood of irregular EF patterns (TTLSP, ITP, or ADP). Men, non-smokers, and participants with less physical activity, lower education level, or lower nutrition knowledge were more likely to be obese. Body mass index (BMI) categorization was significantly different among EF pattern groups (χ² = 25.40, p = 0.003); however, this association was no longer significant in the regression model after adjustment for age, sex, education, smoking, food budget, nutrition knowledge, and physical activity. Thus, EF is not associated with obesity in Chinese adults.

Background: The objective of this paper is to derive a wrist-placed cut-point threshold for distinguishing sedentary behaviors from light-intensity walking using the ActiGraph GT3X+ in children., Methods: This study employed a cross-sectional study design, typically used in measurement-related studies. A sample of 167 children, ages 5⁻11 years (mean ± SD: 8.0 ± 1.8 years), performed up to eight seated sedentary activities while wearing accelerometers on both wrists. Activities included: reading books, sorting cards, cutting and pasting, playing board games, eating snacks, playing with tablets, watching TV, and writing. Direct observation verified sedentary behavior from light activity. Receiver operator characteristic (ROC) analyses were used to determine optimal cut-point thresholds. Quantile regression models estimated differences between dominant and non-dominant placement., Results: The optimal cut-point threshold for the non-dominant wrist was 203 counts/5 s with sensitivity, specificity, and area under the curve (AUC) of 71.56, 70.83, and 0.72, respectively. A 10-fold cross-validation revealed an average AUC of 0.70. Statistically significant ( p ≤ 0.05) differences in median counts ranging from 7 to 46 counts/5 s were found between dominant and non-dominant placement in five out of eight sedentary activities, with the dominant wrist eliciting higher counts/5 s., Conclusion: Results from this study support the recommendation to place accelerometers on the non-dominant wrist to minimize "noise" during seated sedentary behaviors.

Objectives: To comprehensively survey the sugar and nutrient contents of yogurt products available in UK supermarkets, in particular those marketed to children., Design: A cross-sectional survey of yogurt products available in the UK's supermarkets in November 2016., Methods: Data were collected from five major online UK supermarkets and a process flow strategy was used to place yogurts into eight categories: children's, dairy alternatives, dessert, drinks, fruit, flavoured, natural/Greek style and organic. A comprehensive database of product information for 921 unique products was created and analysed., Results: The total sugar, fat, protein, calcium and energy contents were highly variable across categories, and the ranges were extremely broad. Although lower than the dessert category, the medians (range) of the total sugar content of children's (10.8 g/100 g (4.8-14.5)), fruit (11.9 g/100 g (4.6-21.3)), flavoured (12.0 g/100 g (0.1-18.8)) and organic (13.1 g/100 g (3.8-16.9)) yogurt products were all well above 10 g/100 g, and represented >45% of total energy. Only two out of 101 children's yogurt and fromage frais products surveyed qualified as low sugar (≤5 g/100 g). Natural/Greek yogurts had dramatically lower sugar contents (5.0 g/100 g (1.6, 9.5), largely lactose) than all other categories. While low-fat (<3 g/100 g) products had less sugar and energy than higher fat yogurts, nonetheless 55% (285 of 518 low-fat yogurts) contained between 10 and 20 g sugar/100 g. Within the children's category, fromage frais had higher protein (5.3 g/100 g (3.3, 8.6) vs 3.2 (2.8, 7.1); p<0.0001) and calcium contents (150 mg/100 g (90, 240) vs 130.5 mg/100 g (114, 258); p=0.0015) than yogurts., Conclusions: While there is good evidence that yogurt can be beneficial to health, products on the market vary widely in total sugars. Fewer than 9%, and only 2% of the children's, products surveyed were low enough in sugar to earn 'green' in UK front of the pack labelling. Reformulation for the reduction of free sugars in yogurts is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue associated with high fat, high sugar diets. However, the molecular mechanisms mediating NAFLD pathogenesis are only partially understood. Here we adopt an iterative multi-scale, systems biology approach coupled to in vitro experimentation to investigate the roles of sugar and fat metabolism in NAFLD pathogenesis. The use of fructose as a sweetening agent is controversial; to explore this, we developed a predictive model of human monosaccharide transport, signalling and metabolism. The resulting quantitative model comprising a kinetic model describing monosaccharide transport and insulin signalling integrated with a hepatocyte-specific genome-scale metabolic network (GSMN). Differential kinetics for the utilisation of glucose and fructose were predicted, but the resultant triacylglycerol production was predicted to be similar for monosaccharides; these predictions were verified by in vitro data. The role of physiological adaptation to lipid overload was explored through the comprehensive reconstruction of the peroxisome proliferator activated receptor alpha (PPARα) regulome integrated with a hepatocyte-specific GSMN. The resulting qualitative model reproduced metabolic responses to increased fatty acid levels and mimicked lipid loading in vitro. The model predicted that activation of PPARα by lipids produces a biphasic response, which initially exacerbates steatosis. Our data support the evidence that it is the quantity of sugar rather than the type that is critical in driving the steatotic response. Furthermore, we predict PPARα-mediated adaptations to hepatic lipid overload, shedding light on potential challenges for the use of PPARα agonists to treat NAFLD., Competing Interests: The authors declare no competing interests.

Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments., Trial Registration Number: NCT02588664, recruiting. This article covers the development of consent process that is currentlty being employed in the study., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: In 2015, YMCA afterschool programs (ASPs) across South Carolina, USA pledged to achieve the YMCA physical activity standard calling for all children to accumulate 30 min of moderate-to-vigorous physical activity (MVPA) while attending their ASPs. This study presents the final two-year outcomes from the dissemination and implementation efforts associated with achieving this MVPA standard., Methods: Twenty ASPs were sampled from all South Carolina YMCA-operated ASPs (N = 97) and visited at baseline (2015) and first (2016) and second year (2017) follow-up. All ASPs were provided training to increase MVPA during the program by extending the scheduled time for activity opportunities and modifying commonly played games to increase MVPA. The RE-AIM framework was used to evaluate the statewide intervention. Accelerometer-derived MVPA was the primary outcome. Intent-to-treat (ITT) models were conducted summer 2017. Programs were also classified, based on changes in MVPA from 2015 to 2016 and 2016-2017, into one of three categories: gain, maintain, or lost. Implementation, within the three groups, was evaluated via direct observation and document review., Results: Adoption during the first year was 45% of staff attending training, with this increasing to 67% of staff during the second year. ITT models indicated no increase in the odds of accumulating 30 min of MVPA after the first year for either boys (odds ratio [OR] 1.06, 95CI 0.86-1.31) or girls (OR 1.14, 95CI 0.87-1.50), whereas an increase in the odds was observed during the second year for boys (OR 1.31, 95CI 1.04-1.64) and girls (OR 1.50 95CI 1.01-1.80). Programs that lost MVPA (avg. - 5 to - 7.5 min/d MVPA) elected to modify their program in a greater number of non-supportive ways (e.g., reduce time for activity opportunities, less time spent outdoors), whereas ASPs that gained MVPA (avg. + 5.5 to + 10.1 min MVPA) elected to modify their program in more supportive ways., Conclusions: The statewide study demonstrated minimal improvements in overall MVPA. However, child MVPA was dramatically influenced by ASPs who elected to modify their daily program in more supportive than non-supportive ways, with no one program modifying their program consistently across the multi-year initiative. These findings have important implications for organizations seeking to achieve the MVPA standard., Trial Registration: Clinical Trial Registration: NCT02394717 .

Background: Vitamin D deficiency has been associated with non-alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown., Objectives: The objectives of this study were to determine in UK children with biopsy-proven NAFLD (i) their vitamin D status throughout a 12-month period and (ii) interactions between key vitamin D-related genetic variants (nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7, vitamin D receptor, group-specific component, CYP2R1) and disease severity., Methods: In 103 paediatric patients with NAFLD, serum 25-hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy and examined in relation to NAFLD activity score and fibrosis stage., Results: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (<25 nmol·L -1 , 25.5%) or insufficient (<50 nmol·L -1 , 55.3%). Patients had significantly lower 25OHD levels in winter months (95% CI: 22.7-31.2 nmol·L -1 ) when compared with spring (30.5-42.1 nmol·L -1 ; P = 0.0089), summer (36.3-47.2 nmol·L -1 ; P < 0.0001) and autumn (34.2-47.5 nmol·L -1 ; P = 0.0003). Polymorphisms in the nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7 (rs3829251, rs12785878) and vitamin D receptor (rs2228570) genes were independently associated with increased steatosis; while a group-specific component variant (rs4588) was associated with increased inflammation in liver biopsies., Conclusions: Children with NAFLD in the UK have particularly low winter vitamin D status, with vitamin D insufficiency prevalent throughout the year. Polymorphisms in the vitamin D metabolic pathway are associated with histological severity of paediatric NAFLD., (© 2018 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

[This corrects the article DOI: 10.1186/s12953-018-0131-y.].

Rationale: Increasing evidence indicates the presence of lncRNAs in various cell types. Airn is an imprinting gene transcribed from the paternal chromosome. It is in antisense orientation to the imprinted, but maternally derived, Igf2r gene, on which Airn exerts its regulation in cis . Although Airn is highly expressed in the heart, functions aside from imprinting remain unknown., Objective: Here, we studied the functions of Airn in the heart, especially cardiomyocytes., Methods and Results: Silencing of Airn via siRNAs augmented cell death, vulnerability to cellular stress, and reduced cell migration. To find the cause of such phenotypes, the potential binding partners of Airn were identified via RNA pull-down followed by mass spectrometry, which indicated Igf2bp2 (insulin-like growth factor 2 mRNA-binding protein 2) and Rpa1 (replication protein A1) as potential binding partners. Further experiments showed that Airn binds to Igf2bp2 to control the translation of several genes. Moreover, silencing of Airn caused less binding of Igf2bp2 to other mRNAs and reduced translation of Igf2bp2 protein., Conclusions: Our study uncovers a new function of Airn and demonstrates that Airn is important for the physiology of cardiomyocytes., (© 2018 American Heart Association, Inc.)

This study aims to examine associations between body weight misperception and eating behaviors among Chinese adolescents. Students ( N = 2641) from a middle school and a high school in Wuhan, China participated in a cross-sectional study in May 2016. A questionnaire based on the World Health Organization&rsquo;s Global School-Based Student Health Survey was employed to assess responses. Self-reported data, including weight, height, body weight perception, and eating habits, were collected. Body Mass Index (BMI) for age z-score was calculated from self-reported height and weight using WHO AnthroPlus. We used descriptive, logistic regression analysis and a Kappa test to analyze the data using SPSS. Overall, 56.6% of participants did not correctly categorize their weight status; these were much more likely to be girls. Compared with the correctly-perceived group, those who underestimated their weight tended to report eating late at night, having dinners with family, and checking nutrition labels. In contrast, weight overestimating students were less likely to report eating late at night, having breakfasts with family, having dinners with family, and discussing nutrition topics over meals. Body weight misperception was associated with unhealthy eating behaviors among Chinese adolescents.

Afterschool youth physical activity (PA) programs provide opportunities for increasing children's time engaged in moderate-to-vigorous physical activity (MVPA). However, low program attendance reduces the benefits of participating in these programs. The purpose of this study was to determine if enjoyment, athletic competence and motivation for PA predict youth attendance at a free afterschool PA program from 3rd to 5th grade. Data were collected from a larger randomized community trial examining the effectiveness of an afterschool program for increasing opportunities to engage in MVPA. Data were collected twice annually (fall/spring) over 3 school years (3 rd - 5 th grade) in 9 schools. Analyses were stratified by grade and sex, and a series of multi-level linear regression models were utilized to determine if baseline levels of the psychosocial determinants predicted annual attendance as a percentage of afterschool sessions attended. Amotivation for PA was negatively associated with attendance in boys and non-self-determined extrinsic motivation was positively associated with attendance in girls in the 5 th grade. Age was associated with a 13.72% reduction in attendance in the 3rd grade, a 12.87% attendance reduction in the 4th grade, and a 7.93% attendance in reduction in the 5th grade. Race was also associated with attendance. Non-White youth attended the program 13.56% less in the 3rd grade, 17.35% less in the 4th grade, and 21.53% less in the 5th grade than White youth. The findings suggest that attendance to PA afterschool programming may be associated with children's motivational characteristics, but that other variables should be identified for further research.

Context: Because of persistent effects of early childhood caries and impacts of dental health professional shortages areas, the integration of oral health in primary care settings is a public health priority. In this study, we explored oral health interprofessional practice (OHIP) as an integrative pathway to reduce oral health disparities. OHIP can include performing oral health risk assessments, describing the importance of fluoride in the drinking water, implementing fluoride varnish application, and referring patients to a dental home., Objective: To conduct a formative evaluation of how 15 pediatric primary care practices implemented the adoption of OHIP in their clinical settings., Design: Using an ecological framework, we conducted a qualitative process evaluation to measure the factors that inhibited and facilitated OHIP adoption into pediatric settings. Document review analysis and qualitative interviews were conducted with pediatric practices to contextualize challenges and facilitators to OHIP adoption., Setting and Participants: A total of 15 Children's Health Insurance Program Reauthorization Act pediatric practices located in 13 South Carolina counties participated in this study., Main Outcome Measures: Outcomes of interest were the facilitators and challenges of OHIP adoption into pediatric primary care practices., Results: Thematic analysis revealed challenges for OHIP adoption including limited resources and capacity, role delineation for clinical and administrative staff, communication, and family receptiveness. OHIP training for clinical practitioners and staff and responsiveness from clinical staff and local dentists were facilitators of OHIP adoption. Twelve key recommendations emerged on the basis of participant experiences within OHIP, with developing an active dental referral network and encouraging buy-in from clinical staff for OHIP adoption as primary recommendations., Conclusion: We demonstrated the effectiveness of a learning collaborative meeting among pediatric primary care providers to adopt OHIPs. This work reveals an actionable pathway to support oral health equity advancement for children through an additional access point of preventive oral care, reinforcement of positive oral health behaviors, and interaction between parent and child for overall health and wellness of the family.

The gap between discovery of public health knowledge and application in practice settings and policy development is due in part to ineffective dissemination. This article describes (1) lessons related to dissemination from related disciplines (eg, communication, agriculture, social marketing, political science), (2) current practices among researchers, (3) key audience characteristics, (4) available tools for dissemination, and (5) measures of impact. Dissemination efforts need to take into account the message, source, audience, and channel. Practitioners and policy makers can be more effectively reached via news media, social media, issue or policy briefs, one-on-one meetings, and workshops and seminars. Numerous "upstream" and "midstream" indicators of impact include changes in public perception or awareness, greater use of evidence-based interventions, and changes in policy. By employing ideas outlined in this article, scientific discoveries are more likely to be applied in public health agencies and policy-making bodies.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients., Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE -/- ) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients., Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index ( r  = 0.520, p  < 0.0001)., Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted., Competing Interests: In accordance with Helsinki guidelines, informed written consent was obtained from adult patients and the caregivers of the children participating in this study. The study was approved by the Tayside Medical Ethics Committee and the King’s College Hospital NHS Foundation Trust LEC (REC number 09/H0808/15). All animal care and experimental procedures complied with the Animals (Scientific Procedures) Act 1986, and were approved by the University of Surrey Animal Ethics Committee. Animals received humane care and experiments were designed to minimise the number of animals used.Not applicable.The authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Targeting physical inactivity in children is pertinent to aiding in the decrease of childhood obesity rates. Only 33% of adolescents are obtaining the recommended goal of at least 60 min of physical activity per day. The objectives of this review are to summarize professional recommendations for physical activity and exercise in children and adolescents, and identify family-centred strategies that can be implemented by weight management clinicians. Clinically oriented recommendations and policy statements from professional organizations were identified through literature and internet searches, summarized using rubrics of aerobic, muscle strengthening and bone strengthening exercise, then examined for details on family-based focus, inclusion of child developmental stage and age, and application to the prevention and treatment of obesity. Current recommendations give guidelines for the amount of physical activity that children should acquire and how many days a week activities should occur. However, available guidelines need an improved approach to addressing the role of the parents and caregivers in targeting physical activity and weight management in youth. Efforts must be taken in order to make sure that the types of physical activity offered are both suitable and enjoyable. Sports, games, free play and other age appropriate activities are adequate ways to increase moderate to vigorous physical activity in children. Differentiating physical activities types in accordance with developmental stage, level of enjoyment, and family characteristics is needed to establish sustainable habits. One paediatric obesity program has developed approaches to teaching families fun and engaging ways to be active together., (© 2017 World Obesity Federation.)

Comprehensive school physical activity programs (CSPAPs) have been endorsed as a promising strategy to increase youth physical activity (PA) in school settings. A CSPAP is a five-component approach, which includes opportunities before, during, and after school for PA. Extensive resources are available to public health practitioners and school officials regarding what should be implemented, but little guidance and few resources are available regarding how to effectively implement a CSPAP. Implementation science provides a number of conceptual frameworks that can guide implementation of a CSPAP, but few published studies have employed an implementation science framework to a CSPAP. Therefore, we developed Be a Champion! (BAC), which represents a synthesis of implementation science strategies, modified for application to CSPAPs implementation in schools while allowing for local tailoring of the approach. This article describes BAC while providing examples from the implementation of a CSPAP in three rural elementary schools.

Limited information is available on the cost-effectiveness of interventions to achieve healthy eating and physical activity policies in afterschool programs (ASPs). The objective of this study is to present the costs associated with a comprehensive intervention in ASPs. Intervention delivery inputs (IDIs) associated with a group randomized delayed treatment controlled trial involving 20 ASPs serving >1700 children (5-12yrs) were catalogued prospectively across 2-years (2014-2015). IDIs, analyzed 2015, were expressed as increases in per-child per-week enrollment fees based on a 34-week school year in US$. Total IDIs for year-1 were $15,058 (+$0.58/child/week enrollment fee). In year-2, total costs were $13,828 (+$0.52/child/week) for the delayed group and $7916 (+$0.30/child/week) for the immediate group, respectively. Site leader and staff hourly wages represented 11-17% and 45-46% of initial training costs; travel and trainer wages represented 31-42% and 50-58% of booster costs. Overall, a 1% increase in boys and girls, separately, accumulating 30 mins/d of moderate-to-vigorous physical activity ranged from $0.05 to $0.26/child/week, while a one-day increase in serving a fruit/vegetable or water, or not serving sugar-added foods/beverages ranged from $0.16 to $0.87/child/week. Costs associated with implementing the intervention were minimal. Additional efforts to reduce costs and improve intervention effectiveness are necessary., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In 2015, YMCA-operated afterschool programs (ASPs) across South Carolina pledged to achieve the national standard that calls for every child to accumulate 30 min/day of moderate-to-vigorous physical activity (MVPA) during program time. This study shares the first-year findings related to the dissemination, implementation, and outcomes associated with the statewide intervention to achieve the MVPA Standard. Twenty ASPs were sampled from all YMCA-operated ASPs (N = 97) and visited at baseline (spring 2015) and first-year follow-up (spring 2016). Programs were provided standardized professional development training to increase the MVPA children accumulated while attending ASPs. The training focused on extending the scheduled time for activity opportunities and modifying commonly played games to increase MVPA. The RE-AIM framework was used to evaluate the statewide intervention. Accelerometer-derived MVPA was the primary outcome. Implementation was evaluated via direct observation. Intent-to-treat (ITT) and as-treated comparisons were conducted in summer 2016. Reach/adoption was variable, with attendance at trainings ranging from 0 to 100% across ASPs. Effectiveness of the intervention using ITT models indicated no changes from baseline in the percentage of programs meeting the MVPA standard for boys or girls. Implementation levels also varied and were related to increases in both boys' and girls' MVPA for moderate and high implementers. Findings indicate improvements in MVPA can be made from attending the trainings and implementing some or all of the training components. Additional work is necessary to identify ways to ensure staff attend trainings to implement strategies and to identify which specific factors contributed to increases in MVPA.

Physical inactivity is a growing issue in Chinese youth, but parks can facilitate traditional and non-traditional forms of physical activity for little to no cost. Despite this opportunity, very little is known regarding park use among Chinese youth. The purpose of this study was to conduct a cross-sectional observational study of park usage and physical activity of youth in municipal parks in Nanchang, China. Data were collected in June of 2014 in eight parks across Nanchang, Jiangxi a large city in southeast China. Physical activity was measured by a modified version of System for Observing Play and Recreation in Communities. Ordered hierarchic generalized linear models were estimated using a logit link function. The influence of the park was estimated using random effects, with fixed effects and park, environmental, and park user characteristics. Youth were most often seen active in the afternoon, on weekends, and during cooler times (≤ 29 °C). Paradoxically, more children were active when air quality was poorer. Older boys were more active than younger boys, but no differences were observed in girls. More children were seen active in unstructured play compared to structured activities. The results suggest parks are an important setting for physical activity among Chinese youth, and that unstructured activities can play an important role in promoting greater youth physical activity.

Platelet count has been shown to be lower and mean platelet volume (MPV) to be higher in acute myocardial infarction (MI). However, it is not known whether these changes persist post-MI or if these measures are able to distinguish between acute thrombotic and non-thrombotic MI. Platelet count and MPV were measured in 80 subjects with acute MI (thrombotic and non-thrombotic) and stable coronary artery disease (CAD) at cardiac catheterization (acute phase) and at >3-month follow-up (quiescent phase). Subjects were stratified using stringent clinical, biochemical, histological, and angiographic criteria. Outcome measures were compared between groups by analysis of variance. Forty-seven subjects met criteria for acute MI with clearly defined thrombotic (n = 22) and non-thrombotic (n = 12) subsets. Fourteen subjects met criteria for stable CAD. No significant difference was observed in platelet count between subjects with acute MI and stable CAD at the acute or quiescent phase. MPV was higher in acute MI (9.18 ± 1.21) compared to stable CAD (8.13 ± 0.66; P = 0.003) at the acute phase but not at the quiescent phase (8.48 ± 0.58 vs 8.94 ± 1.42; P = 0.19). No difference in platelet count or MPV was detected between thrombotic and non-thrombotic subsets at acute or quiescent phases. The power to detect differences in these measures between thrombotic and non-thrombotic subsets was 58%. Higher MPV at the time of acute MI is not observed by 3 months post-MI (quiescent phase). Platelet count and MPV do not differ in subjects with thrombotic versus non-thrombotic MI. Further investigation is warranted to evaluate the utility of these measures in the diagnosis of acute MI.

The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models., (© 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)