An antisense noncoding RNA enhances translation via localized structural rearrangements of its cognate mRNA.

A large portion of eukaryotic genes are associated with noncoding, natural antisense transcripts (NATs). Despite sharing extensive sequence complementarity with their sense mRNAs, mRNA-NAT pairs elusively often evade dsRNA-cleavage and siRNA-triggered silencing. More surprisingly, some NATs enhance translation of their sense mRNAs by yet unknown mechanism(s). Here, we show that translation enhancement of the rice (Oryza sativa) PHOSPHATE1.2 (PHO1.2) mRNA is enabled by specific structural rearrangements guided by its noncoding antisense RNA (cis-NATpho1.2). Their interaction in vitro revealed no evidence of widespread intermolecular dsRNA formation, but rather specific local changes in nucleotide base pairing, leading to higher flexibility of PHO1.2 mRNA at a key high guanine-cytosine�(GC) regulatory region inhibiting translation, ∼350-nt downstream of the start codon. Sense-antisense RNA interaction increased formation of the 80S complex in PHO1.2, possibly by inducing structural rearrangement within this inhibitory region, thus making this mRNA more accessible to 60S. This work presents a framework for nucleotide resolution studies of functional mRNA-antisense pairs.

The hospital Israelita Albert Einstein standards for constitutional sequence variants classification: version 2023.

BACKGROUND: Next-generation sequencing has had a significant impact on genetic disease diagnosis, but the interpretation of the vast amount of genomic data it generates can be challenging. To address this, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology have established guidelines for standardized variant interpretation. In this manuscript, we present the updated Hospital Israelita Albert Einstein Standards for Constitutional Sequence Variants Classification, incorporating modifications from leading genetics societies and the ClinGen initiative. RESULTS: First, we standardized the scientific publications, documents, and other reliable sources for this document to ensure an evidence-based approach. Next, we defined the databases that would provide variant information for the classification process, established the terminology for molecular findings, set standards for disease-gene associations, and determined the nomenclature for classification criteria. Subsequently, we defined the general rules for variant classification and the Bayesian statistical reasoning principles to enhance this process. We also defined bioinformatics standards for automated classification. Our workgroup adhered to gene-specific rules and workflows curated by the ClinGen Variant Curation Expert Panels whenever available. Additionally, a distinct set of specifications for criteria modulation was created for cancer genes, recognizing their unique characteristics. CONCLUSIONS: The development of an internal consensus and standards for constitutional sequence variant classification, specifically adapted to the Brazilian population, further contributes to the continuous refinement of variant classification practices. The aim of these efforts from the workgroup is to enhance the reliability and uniformity of variant classification.

Who Benefits? A Mixed Methods Study Assessing Community Use of a Major Metropolitan Park During the COVID-19 Pandemic.

By providing spaces for recreation, physical activity, social gatherings, and time in nature, urban parks offer physical, mental, and social benefits to users. However, many urban residents face barriers to park use. The COVID-19 pandemic introduced new potential barriers to urban park access and use, including changes to daily life and employment, closure of park amenities and restrictions to public movement, and risk from the coronavirus itself. The mixed-methods PARCS study measured use and perceptions of a large urban park in St. Louis, Missouri before, during, and after local COVID-19 contingency measures and restrictions. We examine data from 1,157 direct observation assessments of park usership, an online survey of park users (n=561), interviews with key stakeholders (n=27), four focus groups (n=30), and a community-based participatory research sub-study (n=66) to comprehensively characterize the effects of the COVID-19 pandemic on park use. Park users who felt unsafe from the coronavirus experienced 2.65 higher odds of reducing park use. However, estimated park visits during COVID-19 contingency measures (n=5,023,759) were twice as high as post-contingency (n=2,277,496). Participants reported using the park for physical activity, recreation, time in nature, and socializing during the contingency period. Black, Hispanic/Latino, and young people were less likely to visit the park than others, suggesting an additional, disproportionate impact of the pandemic on minoritized and socioeconomically disadvantaged communities. This study highlights the role of public spaces like parks as resources for health and sites where urban health inequities can be alleviated in times of public crisis.

When Moving Is the Only Option: The Role of Necessity Versus Choice for Understanding and Promoting Physical Activity in Low- and Middle-Income Countries.

Given its origins in high-income countries, the field of physical activity and public health research and promotion has broadly followed a choice-based model. However, a substantial amount of the physical activity occurring routinely in many settings, particularly in low- and middle-income countries (LMICs), is the result of economic necessity and is not due to true, free choices. We propose the "necessity- versus choice-based physical activity models" framework as a conceptual tool to ground physical activity and public health research and promotion efforts in LMICs, helping ensurethat these efforts are relevant, ethical, responsive, and respectful to local contexts. Identifying ways to ensure that LMIC populations can maintain high levels of active transport while increasing opportunities for active leisure must be prioritized. To promote equity, physical activity research, programs, and policies in LMICs must focus on improving the conditions under which necessity-driven physical activity occurs for a vast majority of the population.

Thermomorphogenesis: opportunities and challenges in post-transcriptional regulation.

Plants exposed to mildly elevated temperatures display morphological and developmental changes collectively termed thermomorphogenesis. This adaptative process has several undesirable consequences for food production, including yield reduction and increased vulnerability to pathogens. Understanding thermomorphogenesis is, thus, critical for understanding how plants will respond to conditions of increasingly warmer temperature, such as those caused by climate change. Recently, major advances in that direction have been made, and it has become apparent that plants resort to a broad range of molecules and molecular mechanisms to perceive and respond to increases in environmental temperature. However, most effort has been focused on regulation of transcription and protein abundance and activity, with an important gap encompassing nearly all processes involving RNA (i.e. post-transcriptional regulation). Here, current knowledge of thermomorphogenesis involving transcriptional, post-transcriptional, and post-translational regulation is summarized, focusing on opportunities and challenges in understanding post-transcriptional regulation-a fertile field for exciting new discoveries.

Clayton copula for survival data with dependent censoring: An application to a tuberculosis treatment adherence data.

Ignoring the presence of dependent censoring in data analysis can lead to biased estimates, for example, not considering the effect of abandonment of the tuberculosis treatment may influence inferences about the cure probability. In order to assess the relationship between cure and abandonment outcomes, we propose a copula Bayesian approach. Therefore, the main objective of this work is to introduce a Bayesian survival regression model, capable of taking into account the dependent censoring in the adjustment. So, this proposed approach is based on Clayton's copula, to provide the relation between survival and dependent censoring times. In addition, the Weibull and the piecewise exponential marginal distributions are considered in order to fit the times. A simulation study is carried out to perform comparisons between different scenarios of dependence, different specifications of prior distributions, and comparisons with the maximum likelihood inference. Finally, we apply the proposed approach to a tuberculosis treatment adherence dataset of an HIV cohort from Alvorada-RS, Brazil. Results show that cure and abandonment outcomes are negatively correlated, that is, as long as the chance of abandoning the treatment increases, the chance of tuberculosis cure decreases.

The transcription and export complex THO/TREX contributes to transcription termination in plants.

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.

An evidence-based assessment of the impact of the Olympic Games on population levels of physical activity.

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.

Associations of accelerometer measured school- and non-school based physical activity and sedentary time with body mass index: IPEN Adolescent study.

BACKGROUND: This study examined the strength, shape and direction of associations of accelerometer-assessed overall, school- and non-school-based moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) with BMI among adolescents across the world. Second, we examined whether these associations differed by study site and sex. METHODS: Cross-sectional data from the IPEN Adolescent study, an observational multi-country study, were used. Participants wore an accelerometer for seven days, reported height and weight, and completed a socio-demographic survey. In total, 4852 adolescents (46.6% boys), aged 11-19 years (mean age = 14.6, SD = 1.7 years) were included in the analyses, using generalized additive mixed models. RESULTS: Adolescents accumulated on average 41.3 (SD = 22.6) min/day of MVPA and 531.8 (SD = 81.1) min/day of ST, and the prevalence of overweight and obesity was 17.2% (IOTF), but these mean values differed by country. Linear negative associations of accelerometer-based MVPA and ST with standardized BMI scores and the likelihood of being overweight/obese were found. School-based ST and non-school-based MVPA were more strongly negatively associated to the outcomes than non-school based ST and school-based MVPA. Study site moderated the associations; adolescent sex did not. No curvilinear associations were found. CONCLUSIONS: This multi-country study confirmed the importance of MVPA as a potential protective factor against overweight/obesity in adolescents. Non-school-based MVPA seemed to be the main driver of these associations. Unexpected results were found for ST, calling for further examination in methodologically sound international studies but using inclinometers or pressure sensors to provide more precise ST measures.

Social Distancing, Mask Use, and Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Brazil, April-June 2020.

We assessed the associations of social distancing and mask use with symptomatic, laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in Porto Alegre, Brazil. We conducted a population-based case-control study during April-June 2020. Municipal authorities furnished case-patients, and controls were taken from representative household surveys. In adjusted logistic regression analyses of 271 case-patients and 1,396 controls, those reporting moderate to greatest adherence to social distancing had 59% (odds ratio [OR] 0.41, 95% CI 0.24-0.70) to 75% (OR 0.25, 95% CI 0.15-0.42) lower odds of infection. Lesser out-of-household exposure (vs. going out every day all day) reduced odds from 52% (OR 0.48, 95% CI 0.29-0.77) to 75% (OR 0.25, 95% CI 0.18-0.36). Mask use reduced odds of infection by 87% (OR 0.13, 95% CI 0.04-0.36). In conclusion, social distancing and mask use while outside the house provided major protection against symptomatic infection.

Modulation of Shoot Phosphate Level and Growth by PHOSPHATE1 Upstream Open Reading Frame.

Inorganic orthophosphate (Pi) is an essential nutrient for plant growth, and its availability strongly impacts crop yield. PHOSPHATE1 (PHO1) transfers Pi from root to shoot via Pi export into root xylem vessels. In this work, we demonstrate that an upstream open reading frame (uORF) present in the 5' untranslated region of the Arabidopsis (Arabidopsis thaliana) PHO1 inhibits its translation and influences Pi homeostasis. The presence of the uORF strongly inhibited the translation of a PHO1 5'UTR-luciferase construct in protoplasts. A point mutation removing the PHO1 uORF (ΔuORF) in transgenic Arabidopsis resulted in increased association of its mRNA with polysomes and led to higher PHO1 protein levels, independent of Pi availability. Interestingly, deletion of the uORF led to higher shoot Pi content and was associated with improved shoot growth under low external Pi supply and no deleterious effects under Pi-sufficient conditions. We further show that natural accessions lacking the PHO1 uORF exhibit higher PHO1 protein levels and shoot Pi content. Increased shoot Pi content was linked to the absence of the PHO1 uORF in a population of F2 segregants. We identified the PHO1 uORF in genomes of crops such as rice (Oryza sativa), maize (Zea mays), barley (Hordeum vulgare), and wheat (Triticum aesativum), and we verified the inhibitory effect of the rice PHO1 uORF on translation in protoplasts. Our work suggests that regulation of PHO1 expression via its uORF might be a genetic resource useful-both in natural populations and in the context of genome editing-toward improving plant growth under Pi-deficient conditions.

Ultra-fast, high throughput and inexpensive detection of SARS-CoV-2 seroconversion using Ni2+ magnetic beads.

To monitor the levels of protecting antibodies raised in the population in response to infection and/or to immunization with SARS-CoV-2, we need a technique that allows high throughput and low-cost quantitative analysis of human IgG antibodies reactive against viral antigens. Here we describe an ultra-fast, high throughput and inexpensive assay to detect SARS-CoV-2 seroconversion in humans. The assay is based on Ni2+ magnetic particles coated with His tagged SARS-CoV-2 antigens. A simple and inexpensive 96 well plate magnetic extraction/homogenization process is described which allows the simultaneous analysis of 96 samples and delivers results in 7 min with high accuracy.

The structure of CO2 and CH4 at the interface of a poly(urethane urea) oligomer model from the microscopic point of view.

The world desperately needs new technologies and solutions for gas capture and separation. To make this possible, molecular modeling is applied here to investigate the structural, thermodynamic, and dynamical properties of a model for the poly(urethane urea) (PUU) oligomer model to selectively capture CO2 in the presence of CH4. In this work, we applied a well-known approach to derive atomic partial charges for atoms in a polymer chain based on self-consistent sampling using quantum chemistry and stochastic dynamics. The interactions of the gases with the PUU model were studied in a pure gas based system as well as in a gas mixture. A detailed structure characterization revealed high interaction of CO2 molecules with the hard segments of the PUU. Therefore, the structural and energy properties explain the reasons for the greater CO2 sorption than CH4. We find that the CO2 sorption is higher than the CH4 with a selectivity of 7.5 at 298 K for the gas mixture. We characterized the Gibbs dividing surface for each system, and the CO2 is confined for a long time at the gas-oligomer model interface. The simulated oligomer model showed performance above the 2008 Robeson's upper bound and may be a potential material for CO2/CH4 separation. Further computational and experimental studies are needed to evaluate the material.

Reliability of streetscape audits comparing on-street and online observations: MAPS-Global in 5 countries.

BACKGROUND: Microscale environmental features are usually evaluated using direct on-street observations. This study assessed inter-rater reliability of the Microscale Audit of Pedestrian Streetscapes, Global version (MAPS-Global), in an international context, comparing on-street with more efficient online observation methods in five countries with varying levels of walkability. METHODS: Data were collected along likely walking routes of study participants, from residential starting points toward commercial clusters in Melbourne (Australia), Ghent (Belgium), Curitiba (Brazil), Hong Kong (China), and Valencia (Spain). In-person on the street and online using Google Street View audits were carried out by two independent trained raters in each city. The final sample included 349 routes, 1228 street segments, 799 crossings, and 16 cul-de-sacs. Inter-rater reliability analyses were performed using Kappa statistics or Intraclass Correlation Coefficients (ICC). RESULTS: Overall mean assessment times were the same for on-street and online evaluations (22 ± 12 min). Only a few subscales had Kappa or ICC values < 0.70, with aesthetic and social environment variables having the lowest overall reliability values, though still in the "good to excellent" category. Overall scores for each section (route, segment, crossing) showed good to excellent reliability (ICCs: 0.813, 0.929 and 0.885, respectively), and the MAPS-Global grand score had excellent reliability (ICC: 0.861) between the two methods. CONCLUSIONS: MAPS-Global is a feasible and reliable instrument that can be used both on-street and online to analyze microscale environmental characteristics in diverse international urban settings.

The microbiome of a shell mound: ancient anthropogenic waste as a source of Streptomyces degrading recalcitrant polysaccharides.

Metagenome amplicon DNA sequencing and traditional cell culture techniques are helping to uncover the diversity and the biotechnological potential of prokaryotes in different habitats around the world. It has also had a profound impact on microbial taxonomy in the last decades. Here we used metagenome 16S rDNA amplicon sequencing to reveal the microbiome composition of different layers of an anthropogenic soil collected at a shell mound Sambaqui archeological site. The Samabaqui soil microbiome is mainly composed by phyla Acidobacteria, Rokubacteria, Proteobacteria and Thaumarchaeota. Using culture-dependent analysis we obtained few Streptomyces isolates from the Sambaqui soil. One of the isolates, named Streptomyces sp. S3, was able to grow in minimal medium containing recalcitrant polysaccharides including chitin, xylan, carboxymethylcellulose or microcrystalline cellulose as sole carbon sources. The activities of enzymes degrading these compounds were confirmed in cell free supernatants. The genome sequence revealed not only an arsenal of genes related to polysaccharides degradation but also biosynthetic gene clusters which may be involved in the production of biotechnologically interesting secondary metabolites.

Control of Cognate Sense mRNA Translation by cis-Natural Antisense RNAs.

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.

Towards better evidence-informed global action: lessons learnt from the Lancet series and recent developments in physical activity and public health.

In the past few decades, the field of physical activity has grown and evolved in scope, depth, visibility and impact around the world. Global progress has been observed in research and practice in physical activity regarding surveillance, health outcomes, correlates/determinants, interventions, translation and policy. The 2012 and 2016 Lancet series on physical activity provide some of the most comprehensive global analysis on various topics within physical activity. Based on the Lancet series and other key developments in the field, literature searches, and expert group meetings and consultation, we provide a global summary on the progress of, gaps in and future directions for physical activity research in the following areas: (1) surveillance and trends, (2) correlates and determinants, (3) health outcomes and (4) interventions, programmes and policies. Besides lessons learnt within each specific area, several recommendations are shared across areas of research, including improvement in measurement, applying a global perspective with a growing emphasis on low-income and middle-income countries, improving inclusiveness and equity in research, making translation an integral part of research for real-world impact, taking an 'upstream' public health approach, and working across disciplines and sectors to co-design research and co-create solutions. We have summarised lessons learnt and recommendations for future research as 'roadmaps' in progress to encourage moving the field of physical activity towards achieving population-level impact globally.

Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions.

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.

Do associations of sex, age and education with transport and leisure-time physical activity differ across 17 cities in 12 countries?

BACKGROUND: Leisure-time and transport activity domains are studied most often because they are considered more amenable to intervention, but to date evidence on these domains is limited. The aim of the present study was to examine patterns of socio-demographic correlates of adults' leisure-time and transport physical activity and how these associations varied across 17 cities in 12 countries. METHODS: Participants (N = 13,745) aged 18-66 years in the IPEN Adult study and with complete data on socio-demographic and self-reported physical activity characteristics were included. Participants reported frequency and duration of leisure-time and transport activities in the last 7 days using the self-administered International Physical Activity Questionnaire-Long Form. Six physical activity outcomes were examined in relation with age, education, and sex, and analyses explored variations by city and curvilinear associations. RESULTS: Sex had the most consistent results, with five of six physical activity outcomes showing females were less active than males. Age had the most complex associations with self-report transport and leisure-time physical activity. Compared to older people, younger adults were less likely to engage in transport physical activity, but among those who did, younger people were likely to engage in more active minutes. Curvilinear associations were found between age and all three leisure-time physical activity outcomes, with the youngest and the oldest being more active. Positive associations with education were found for leisure-time physical activity only. There were significant interactions of city with sex and education for multiple physical activity outcomes. CONCLUSIONS: Although socio-demographic correlates of physical activity are widely studied, the present results provide new information. City-specific findings suggest there will be value in conducting more detailed case studies. The curvilinear associations of age with leisure-time physical activity as well as significant interactions of leisure-time activity with sex and education should be further investigated. The findings of lower leisure-time physical activity among females as well as people with low education suggest that greater and continued efforts in physical activity policies and programs tailored to these high-risk groups are needed internationally.

Development and validation of the neighborhood environment walkability scale for youth across six continents.

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.