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The global pandemic of physical inactivity requires a multisectoral, multidisciplinary public-health response. Scaling up interventions that are capable of increasing levels of physical activity in populations across the varying cultural, geographic, social, and economic contexts worldwide is challenging, but feasible. In this paper, we review the factors that could help to achieve this. We use a mixed-methods approach to comprehensively examine these factors, drawing on the best available evidence from both evidence-to-practice and practice-to-evidence methods. Policies to support active living across society are needed, particularly outside the health-care sector, as demonstrated by some of the successful examples of scale up identified in this paper. Researchers, research funders, and practitioners and policymakers in culture, education, health, leisure, planning, and transport, and civil society as a whole, all have a role. We should embrace the challenge of taking action to a higher level, aligning physical activity and health objectives with broader social, environmental, and sustainable development goals.

Pre-Olympic Games predictions commonly include an increase in population-based physical activity in the host city, as often stated in the bid, but the post-Olympic Games effects on physical activity have not been summarised. In this Series paper, we aim to do the following: examine mentions of a physical activity legacy in pre-Olympic bid documentation; analyse existing physical activity surveillance data collected before, during, and after the Olympic Games in hosting areas around the world; and evaluate Google Trends data surrounding the London 2012 Olympic Games as a case study of community interest in the topic of exercise during the time of the Olympic Games. Before 2007, little mention of physical activity was made in pre-Olympic Games documentation, but, after that, most documents had targets for population physical activity or sports participation. The synthesis of available surveillance data indicates that there was no change in the prevalence of physical activity or sports participation, except for the 2008 Summer Olympics in Beijing and the 1998 Winter Olympics in Nagano; although, the increase in participation in Nagano might not be attributable to the Olympic Games since there was no change in participation in winter sports. The Google Trends data showed an acute spike in searches with the term “Olympic” immediately associated with the London Olympic Games period and showed a sustained peri-Olympic increase in searches with the term “exercise”. By themselves, the Olympic Games have not improved population-wide physical activity but might be an important missed public health opportunity. Such a legacy will require strategic planning and partnerships across the International Olympic Committee and the Olympic, sport, and public health agencies and a thorough evaluation framework implemented throughout the pre-Olympic Games and post-Olympic Games period in the host country.

Physical inactivity is an important contributor to non-communicable diseases in countries of high income, and increasingly so in those of low and middle income. Understanding why people are physically active or inactive contributes to evidence-based planning of public health interventions, because effective programmes will target factors known to cause inactivity. Research into correlates (factors associated with activity) or determinants (those with a causal relationship) has burgeoned in the past two decades, but has mostly focused on individual-level factors in high-income countries. It has shown that age, sex, health status, self-efficacy, and motivation are associated with physical activity. Ecological models take a broad view of health behaviour causation, with the social and physical environment included as contributors to physical inactivity, particularly those outside the health sector, such as urban planning, transportation systems, and parks and trails. New areas of determinants research have identified genetic factors contributing to the propensity to be physically active, and evolutionary factors and obesity that might predispose to inactivity, and have explored the longitudinal tracking of physical activity throughout life. An understanding of correlates and determinants, especially in countries of low and middle income, could reduce the effect of future epidemics of inactivity and contribute to effective global prevention of non-communicable diseases.

BACKGROUND: Parks are valuable resources for physical activity (PA) given their widespread availability and low cost to maintain and use. Both proximity to parks and the availability of particular features are important correlates of PA. However, few studies have explored multiple measures of proximity simultaneously or the specific facilities associated with park use and park-based PA among adults, let alone differences across socio-demographic characteristics. The purpose of this study was to examine associations between park proximity and park facilities and adults’ park use and park-based PA, while also exploring differences by gender, age, race, and income. METHODS: Data on monthly park use and weekly amount of PA undertaken in parks were collected via a mail survey of adults from randomly-selected households (n = 893) in Kansas City, Missouri (KCMO) in 2010–2011. Three measures of park proximity were calculated within 1 mile of participating households: distance to the closest park, number of parks, and total park area. All parks in KCMO were audited using the Community Park Audit Tool to determine the availability of 14 park facilities within 1 mile of each participant (e.g., trail, playground, tennis court). Multilevel logistic regression was used to examine the relationship between each of park use and park-based PA and 1) three measures of park proximity, and 2) the availability of 14 park facilities within 1 mile of participants. Separate analyses were conducted by gender, age, race, and income, while controlling for all socio-demographic characteristics and BMI. RESULTS: Across all sub-samples, distance to the closest park was not significantly related to either park use or park-based PA. However, numerous significant associations were found for the relationship of number of parks and amount of park space within 1 mile with both outcomes. As well, diverse facilities were associated with park use and park-based PA. For both park proximity and facilities, the significant relationships varied widely across gender, age, race, and income groups. CONCLUSIONS: Both park proximity and park facilities are related to park use and park-based PA. Understanding how such associations vary across demographic groups is important in planning for activity-friendly parks that are responsive to the needs of neighborhood residents.

Background Long intergenic non-coding RNAs (lincRNAs) can act as regulators of expression of protein-coding genes. Trans -natural antisense transcripts ( trans -NATs) are a type of lincRNAs that contain sequence complementary to mRNA from other loci. The regulatory potential of trans -NATs has been poorly studied in eukaryotes and no example of trans -NATs regulating gene expression in plants are reported. The goal of this study was to identify lincRNAs, and particularly trans -NATs, in Arabidopsis thaliana that have a potential to regulate expression of target genes in trans at the transcriptional or translational level. Results We identified 1001 lincRNAs using an RNAseq dataset from total polyA + and polysome-associated RNA of seedlings grown under high and low phosphate, or shoots and roots treated with different phytohormones, of which 550 were differentially regulated. Approximately 30% of lincRNAs showed conservation amongst Brassicaceae and 25% harbored transposon element (TE) sequences. Gene co-expression network analysis highlighted a group of lincRNAs associated with the response of roots to low phosphate. A total of 129 trans -NATs were predicted , of which 88 were significantly differentially expressed under at least one pairwise comparison. Five trans -NATs showed a positive correlation between their expression and target mRNA steady-state levels, and three showed a negative correlation. Expression of four trans -NATs positively correlated with a change in target mRNA polysome association. The regulatory potential of these trans -NATs did not implicate miRNA mimics nor siRNAs. We also looked for lincRNAs that could regulate gene expression in trans by Watson-Crick DNA:RNA base pairing with target protein-encoding loci. We identified 100 and 81 with a positive or negative correlation, respectively, with steady-state level of their predicted target. The regulatory potential of one such candidate lincRNA harboring a SINE TE sequence was validated in a protoplast assay on three distinct genes containing homologous TE sequence in their promoters. Construction of networks highlighted other putative lincRNAs with multiple predicted target loci for which expression was positively correlated with target gene expression. Conclusions This study identified lincRNAs in Arabidopsis with potential in regulating target gene expression in trans by both RNA:RNA and RNA:DNA base pairing and highlights lincRNAs harboring TE sequences in such activity.

Cis-Natural Antisense Transcripts (cis-NATs), which overlap protein coding genes and are transcribed from the opposite DNA strand, constitute an important group of noncoding RNAs. Whereas several examples of cis-NATs regulating the expression of their cognate sense gene are known, most cis-NATs function by altering the steady-state level or structure of mRNA via changes in transcription, mRNA stability, or splicing, and very few cases involve the regulation of sense mRNA translation. This study was designed to systematically search for cis-NATs influencing cognate sense mRNA translation in Arabidopsis (Arabidopsis thaliana). Establishment of a pipeline relying on sequencing of total polyA⁺ and polysomal RNA from Arabidopsis grown under various conditions (i.e. nutrient deprivation and phytohormone treatments) allowed the identification of 14 cis-NATs whose expression correlated either positively or negatively with cognate sense mRNA translation. With use of a combination of cis-NAT stable over-expression in transgenic plants and transient expression in protoplasts, the impact of cis-NAT expression on mRNA translation was confirmed for 4 out of 5 tested cis-NAT:sense mRNA pairs. These results expand the number of cis-NATs known to regulate cognate sense mRNA translation and provide a foundation for future studies of their mode of action. Moreover, this study highlights the role of this class of noncoding RNAs in translation regulation.

Clonal hematopoiesis (CH) is characterized by the expansion of hematopoietic stem cell clones carrying somatic mutations that confer a proliferative advantage, encompassing conditions such as Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Clonal Cytopenia of Undetermined Significance (CCUS), each with varying clinical implications. This prospective 8-year cohort study of 173 patients investigated the prevalence, clinical outcomes, and genetic evolution of CHIP and CCUS in individuals over 75 years of age without prior hematologic disease, analyzing mortality rates, changes in allelic frequency over time, clinical characteristics, and associations with comorbidities such as osteoporosis, cardiovascular disease, and cancer. Through next-generation sequencing of 173 patients, we identified a 30.6% prevalence of CH, with DNMT3A , TET2 , and ASXL1 as the most frequently mutated genes. While no significant associations were found between CH and cardiovascular disease or overall cytopenias, CH was correlated with a higher prevalence of osteoporosis, and high-risk CH was associated with cytopenias. Although not statistically significant ( p  = 0.09), survival curves suggested a potential trend toward higher mortality among patients with clonal hematopoiesis, supporting the need for further investigation in larger cohorts.

Transcription termination has important regulatory functions, impacting mRNA stability, localization and translation potential. Failure to appropriately terminate transcription can also lead to read-through transcription and the synthesis of antisense RNAs which can have profound impact on gene expression. The Transcription-Export (THO/TREX) protein complex plays an important role in coupling transcription with splicing and export of mRNA. However, little is known about the role of the THO/TREX complex in the control of transcription termination. In this work, we show that two proteins of the THO/TREX complex, namely TREX COMPONENT 1 (TEX1 or THO3) and HYPER RECOMBINATION1 (HPR1 or THO1) contribute to the correct transcription termination at several loci in Arabidopsis thaliana. We first demonstrate this by showing defective termination in tex1 and hpr1 mutants at the nopaline synthase (NOS) terminator present in a T-DNA inserted between exon 1 and 3 of the PHO1 locus in the pho1-7 mutant. Read-through transcription beyond the NOS terminator and splicing-out of the T-DNA resulted in the generation of a near full-length PHO1 mRNA (minus exon 2) in the tex1 pho1-7 and hpr1 pho1-7 double mutants, with enhanced production of a truncated PHO1 protein that retained phosphate export activity. Consequently, the strong reduction of shoot growth associated with the severe phosphate deficiency of the pho1-7 mutant was alleviated in the tex1 pho1-7 and hpr1 pho1-7 double mutants. Additionally, we show that RNA termination defects in tex1 and hpr1 mutants leads to 3'UTR extensions in several endogenous genes. These results demonstrate that THO/TREX complex contributes to the regulation of transcription termination.

Background The IPEN International Physical Activity and Environment Network Adolescent project was conducted using common study protocols to document the strength, shape, and generalizability of associations of perceived neighborhood environment attributes with adolescents’ physical activity and overweight/obesity using data from 15 countries. Countries did not use identical versions of the Neighborhood Environment Walkability Scale for Youth (NEWS-Y) to measure perceived neighborhood environment attributes. Therefore, this study derived a measurement model for NEWS-Y items common to all IPEN Adolescent countries and developed a scoring protocol for the IPEN Adolescent version of the NEWS-Y (NEWS-Y-IPEN) that maximizes between-country comparability of responses. Additionally, this study examined between- and within-country variability, and construct validity of the NEWS-Y-IPEN subscales in relation to neighborhood-level socio-economic status and walkability. Methods Adolescents and one of their parents ( N  = 5714 dyads) were recruited from neighborhoods varying in walkability and socio-economic status. To measure perceived neighborhood environment, 14 countries administered the NEWS-Y to parents and one country to adolescents. Confirmatory factor analysis was used to derive comparable country-specific measurement models of the NEWS-Y-IPEN. Country-specific standard deviations quantified within-country variability in the NEWS-Y-IPEN subscales, while linear mixed models determined the percentage of subscale variance due to between-country differences. To examine the construct validity of NEWS-Y-IPEN subscales, we estimated their associations with the categorical measures of area-level walkability and socio-economic status. Results Final country-specific measurement models of the factor-analyzable NEWS-Y-IPEN items provided acceptable levels of fit to the data and shared the same factorial structure with five latent factors (Accessibility and walking facilities; Traffic safety; Pedestrian infrastructure and safety; Safety from crime; and Aesthetics). All subscales showed sufficient levels of within-country variability. Residential density had the highest level of between-country variability. Associations between NEWS-Y-IPEN subscales and area-level walkability and socio-economic status provided strong evidence of construct validity. Conclusions A robust measurement model and common scoring protocol of NEWS-Y for the IPEN Adolescent project (NEWS-Y-IPEN) were derived. The NEWS-Y-IPEN possesses good factorial and construct validity, and is able to capture between-country variability in perceived neighborhood environments. Future studies employing NEWS-Y-IPEN should use the proposed scoring protocol to facilitate cross-study comparisons and interpretation of findings.

Background Studies of correlates of active transport to and from school (ATS) focus mainly on children, have a limited conceptualisation of ATS trips, lack heterogeneity in built environments, and rarely consider effect modifiers. This study aimed to estimate associations of parent-perceived neighbourhood environment characteristics with self-reported ATS among adolescents from 14 countries, and whether associations differ by sex, city/region, and distance to school. Methods Observational cross-sectional design. Data were from the International Physical activity and Environment Network (IPEN) Adolescent study and included 6302 adolescents (mean age 14.5 ± 1.7 years, 54% girls) and a caretaker from 16 diverse sites. Adolescents self-reported usual travel to and from school by walking and bicycling (days/week) and time it would take to walk. Parents completed the Neighbourhood Environment Walkability Scale for Youth (13 scores computed). Generalised additive mixed models estimated associations of parent neighbourhood perceptions with 1) any active transport to/from school, 2) regular walking (5–10 times/week), 3) regular cycling to/from school, and 4) profiles of ATS generated using latent profile analyses. Interactions were also explored. Results Overall, 58.7% reported any ATS, 39.9% regularly walked, 7.7% regularly cycled, and four profiles of ATS were identified: walk to and from school; walk from school; cycle to and from school; no ATS. Distance to school was negatively associated with all outcomes, though evidence was weak for regular cycling to/from school. Land use mix – diversity was positively related to all ATS outcomes except those related to cycling. Accessibility and walking facilities were associated with higher odds of any ATS, regular walking to/from school, and the profile walking to and from school. Residential density was negatively related to regular cycling to/from school. Positive associations were observed between traffic safety and any ATS, and between safety from crime, aesthetics, and odds of regular cycling to/from school. Distance to school, adolescent sex, and city moderated several associations. Conclusions Parent perceptions of compact, mixed-use development, walking facilities, and both traffic and crime-related safety were important supportive correlates of a range of ATS outcomes among adolescents in high- and low-middle-income countries. Policies that achieve these attributes should be prioritised to support more widespread ATS.