Sex-specific adipose tissue imprinting of regulatory T cells.

Adipose tissue is an energy store and a dynamic endocrine organ1,2. In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism3,4. Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes5,6. Regulatory T (Treg) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT7-9. Here we uncover pronounced sexual dimorphism in Treg cells in the VAT. Male VAT was enriched for Treg cells compared with female VAT, and Treg cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. Heightened inflammation in the male VAT facilitated the recruitment of Treg cells via the CCL2-CCR2 axis. Androgen regulated the differentiation of a unique IL-33-producing stromal cell population specific to the male VAT, which paralleled the local expansion of Treg cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident Treg cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in Treg cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.

Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia.

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans1. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies2. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism3, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.

A20 controls RANK-dependent osteoclast formation and bone physiology.

The anti-inflammatory protein A20 serves as a critical brake on NF-κB signaling and NF-κB-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been associated with several inflammatory disorders, including rheumatoid arthritis (RA), and experimental studies in mice have demonstrated that myeloid-specific A20 deficiency causes the development of a severe polyarthritis resembling human RA. Myeloid A20 deficiency also promotes osteoclastogenesis in mice, suggesting a role for A20 in the regulation of osteoclast differentiation and bone formation. We show here that osteoclast-specific A20 knockout mice develop severe osteoporosis, but not inflammatory arthritis. In vitro, osteoclast precursor cells from A20 deficient mice are hyper-responsive to RANKL-induced osteoclastogenesis. Mechanistically, we show that A20 is recruited to the RANK receptor complex within minutes of ligand binding, where it restrains NF-κB activation independently of its deubiquitinating activity but through its zinc finger (ZnF) 4 and 7 ubiquitin-binding functions. Together, these data demonstrate that A20 acts as a regulator of RANK-induced NF-κB signaling to control osteoclast differentiation, assuring proper bone development and turnover.

The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.

PURPOSE OF REVIEW: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models. RECENT FINDINGS: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Engaging participants with research findings: A rights-informed approach.

BACKGROUND: Sharing research findings with participants is recognized as an ethical imperative for the research community. However, most discourse on this topic in mainstream public health takes a paternalistic approach, with researchers retaining the power to choose if, when, and how research findings are shared. METHODS: Fieldwork took place from August 2018 to January 2019 and again from August 2019 to December 2019 among two communities in the south Indian state of Kerala. We integrated participant engagement with study findings into the research protocol, using various collaborative strategies identified during the design stage, forming partnerships with participants and determining appropriate forms of dissemination for different participant groups during fieldwork. RESULTS: Findings from previous research projects undertaken with these communities by other researchers had not been shared with them. This was interpreted by the communities as researchers not being interested in making a difference to their situation. In the current study, building reciprocal relationships that minimized power disparities, and providing outputs in tailored formats that promoted active engagement were key factors that enabled participants to engage with results. This engagement added value by enabling us to co-develop study recommendations. This process also enabled the community to have ownership of the results and use them to advocate for health system change to improve access to health care. CONCLUSION: Research should be transformative for participating communities. Participants have a right to know the results of the research they participate in since their knowledge provides the research data which can in turn promote community change. Operationalising this requires researchers to build partnerships with participants and their communities from the outset. The role of participants must be reimagined, and adequate resources should be built into the research process. This is both socially responsible and ethical, but also improves the impact and legitimacy of research for the participants and the communities that they represent. PATIENT OR PUBLIC CONTRIBUTION: Participants of our research contributed to the design of various aspects of the engagement processes including the venue, the formats used for engagement, interpretation of the findings and recommendations from our research.

Behaviour change techniques in cardiovascular disease smartphone apps to improve physical activity and sedentary behaviour: Systematic review and meta-regression.

BACKGROUND: Smartphone apps are increasingly used to deliver physical activity and sedentary behaviour interventions for people with cardiovascular disease. However, the active components of these interventions which aim to change behaviours are unclear. AIMS: To identify behaviour change techniques used in smartphone app interventions for improving physical activity and sedentary behaviour in people with cardiovascular disease. Secondly, to investigate the association of the identified techniques on improving these behaviours. METHODS: Six databases (Medline, CINAHL Plus, Cochrane Library, SCOPUS, Sports Discus, EMBASE) were searched from 2007 to October 2020. Eligible studies used a smartphone app intervention for people with cardiovascular disease and reported a physical activity and/or sedentary behaviour outcome. The behaviour change techniques used within the apps for physical activity and/or sedentary behaviour were coded using the Behaviour Change Technique Taxonomy (v1). The association of behaviour change techniques on physical activity outcomes were explored through meta-regression. RESULTS: Forty behaviour change techniques were identified across the 19 included app-based interventions. Only two studies reported the behaviour change techniques used to target sedentary behaviour change. The most frequently used techniques for sedentary behaviour and physical activity were habit reversal and self-monitoring of behaviour respectively. In univariable analyses, action planning (ß =0.42, 90%CrI 0.07-0.78) and graded tasks (ß =0.33, 90%CrI -0.04-0.67) each had medium positive associations with increasing physical activity. Participants in interventions that used either self-monitoring outcome(s) of behaviour (i.e. outcomes other than physical activity) (ß = - 0.47, 90%CrI -0.79--0.16), biofeedback (ß = - 0.47, 90%CrI -0.81--0.15) and information about health consequences (ß = - 0.42, 90%CrI -0.74--0.07) as behaviour change techniques, appeared to do less physical activity. In the multivariable model, these predictors were not clearly removed from zero. CONCLUSION: The behaviour change techniques action planning and graded tasks are good candidates for causal testing in future experimental smartphone app designs.

Heterogeneous nitration reaction of BSA protein with urban air: improvements in experimental methodology.

Gas-phase ozone (O3) and nitrogen dioxide (NO2) can react with environmentally exposed proteins to induce chemical modifications such as the formation of nitrotyrosine (NTyr). Certain proteins with these modifications have also been shown to promote adverse health effects and can trigger an immune response. It is hypothesized that proteinaceous material suspended in the atmosphere as particulate matter, e.g., embedded in pollen, can undergo heterogenous reactions to produce chemically modified proteins that impact human health, especially in urban areas. To investigate the protein modification process under ambient outdoor reaction conditions, bovine serum albumin (BSA) protein samples were loaded onto filters and exposed to urban air in Denver, Colorado (USA). Losses and measurement artifacts were measured independently to calculate nitration effects on the protein via high-performance liquid chromatography and to support the experimental methodology. O3 loss from inlet lines using three commonly used particulate filters was quantified, showing a range of ambient O3 concentration losses from 3.2% for Kynar® (polyvinylidene fluoride) filters to > 60% for commonly used HEPA filters. Protein mass extraction efficiency was calculated as a function of filter material and protein mass using both native and nitrated BSA. Finally, we show examples of BSA samples nitrated by exposure to urban air as a proof-of-concept for future studies, highlighting the potential for atmospherically relevant NTyr formation. The methodology vetted here provides support for a wide variety of experimental efforts related to exposure of analytes to O3 and more broadly to an expanding field of protein modification in ambient air.

Cardiovascular Rehabilitation for transient ischaemic Attack and Mild Stroke: the CRAMS effectiveness-implementation hybrid study protocol.

BACKGROUND: Internationally, stroke and cardiac rehabilitation clinicians agree that current cardiac rehabilitation models are a suitable secondary prevention program for people following a transient ischaemic attack (TIA) or mild stroke. There is strong evidence for exercise-based cardiac rehabilitation in people with heart disease, however, the evidence for cardiac rehabilitation post-TIA or stroke is limited. Here we will explore the effectiveness and implementation of an integrated (TIA, mild stroke, heart disease) traditional exercise-based cardiovascular rehabilitation (CVR) program for people with TIA or mild stroke over 6-months. METHODS: This type 1 effectiveness-implementation hybrid study will use a 2-arm single-centre assessor-blind randomised controlled trial design, recruiting 140 participants. Adults who have had a TIA or mild stroke in the last 12-months will be recruited by health professionals from hospital and primary healthcare services. Participants will be assessed and randomly allocated (1:1) to the 6-week CVR program or the usual care 6-month wait-list control group. Distance completed in the 6-min walk test will be the primary effectiveness outcome, with outcomes collected at baseline, 6-weeks (complete CVR) and 6-months in both groups. Other effectiveness outcome measures include unplanned cardiovascular disease-related emergency department and hospital admissions, daily minutes of accelerometer moderate-to-vigorous physical activity, body mass index, waist circumference, blood pressure, quality of life, anxiety and depression. Implementation outcomes will be assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, including a cost-effectiveness analysis. Semi-structured interviews will be conducted with participants and CVR program health professionals, investigating the acceptability, value, and impact of the CVR program. Qualitative analyses will be guided by the Consolidated Framework for Implementation Research. DISCUSSION: Few studies have assessed the effectiveness of cardiac rehabilitation for people with TIA and mild stroke, and no studies appear to have investigated the cost-effectiveness or implementation determinants of such programs. If successful, the CVR program will improve health outcomes and quality of life of people who have had a TIA or mild stroke, guiding future research, policy, and clinical practice, reducing the risk of repeat heart attacks and strokes for this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621001586808 , Registered 19 November 2021.

Children's moderate-to-vigorous physical activity on weekdays versus weekend days: a multi-country analysis.

PURPOSE: The Structured Days Hypothesis (SDH) posits that children's behaviors associated with obesity - such as physical activity - are more favorable on days that contain more 'structure' (i.e., a pre-planned, segmented, and adult-supervised environment) such as school weekdays, compared to days with less structure, such as weekend days. The purpose of this study was to compare children's moderate-to-vigorous physical activity (MVPA) levels on weekdays versus weekend days using a large, multi-country, accelerometer-measured physical activity dataset. METHODS: Data were received from the International Children's Accelerometer Database (ICAD) July 2019. The ICAD inclusion criteria for a valid day of wear, only non-intervention data (e.g., baseline intervention data), children with at least 1 weekday and 1 weekend day, and ICAD studies with data collected exclusively during school months, were included for analyses. Mixed effects models accounting for the nested nature of the data (i.e., days within children) assessed MVPA minutes per day (min/day MVPA) differences between weekdays and weekend days by region/country, adjusted for age, sex, and total wear time. Separate meta-analytical models explored differences by age and country/region for sex and child weight-status. RESULTS/FINDINGS: Valid data from 15 studies representing 5794 children (61% female, 10.7 ± 2.1 yrs., 24% with overweight/obesity) and 35,263 days of valid accelerometer data from 5 distinct countries/regions were used. Boys and girls accumulated 12.6 min/day (95% CI: 9.0, 16.2) and 9.4 min/day (95% CI: 7.2, 11.6) more MVPA on weekdays versus weekend days, respectively. Children from mainland Europe had the largest differences (17.1 min/day more MVPA on weekdays versus weekend days, 95% CI: 15.3, 19.0) compared to the other countries/regions. Children who were classified as overweight/obese or normal weight/underweight accumulated 9.5 min/day (95% CI: 6.9, 12.2) and 10.9 min/day (95% CI: 8.3, 13.5) of additional MVPA on weekdays versus weekend days, respectively. CONCLUSIONS: Children from multiple countries/regions accumulated significantly more MVPA on weekdays versus weekend days during school months. This finding aligns with the SDH and warrants future intervention studies to prioritize less-structured days, such as weekend days, and to consider providing opportunities for all children to access additional opportunities to be active.

An Aboriginal and Torres Strait Islander Cardiac Rehabilitation program delivered in a non-Indigenous health service (Yeddung Gauar): a mixed methods feasibility study.

BACKGROUND: There is limited evidence of Aboriginal and Torres Strait Islander people attending cardiac rehabilitation (CR) programs despite high levels of heart disease. One key enabler for CR attendance is a culturally safe program. This study evaluates improving access for Aboriginal and Torres Strait Islander women to attend a CR program in a non-Indigenous health service, alongside improving health workforce cultural safety. METHODS: An 18-week mixed-methods feasibility study was conducted, with weekly flexible CR sessions delivered by a multidisciplinary team and an Aboriginal and/or Torres Strait Islander Health Worker (AHW) at a university health centre. Aboriginal and Torres Strait Islander women who were at risk of, or had experienced, a cardiac event were recruited. Data was collected from participants at baseline, and at every sixth-session attended, including measures of disease risk, quality-of-life, exercise capacity and anxiety and depression. Cultural awareness training was provided for health professionals before the program commenced. Assessment of health professionals' cultural awareness pre- and post-program was evaluated using a questionnaire (n = 18). Qualitative data from participants (n = 3), the AHW, health professionals (n = 4) and referrers (n = 4) was collected at the end of the program using yarning methodology and analysed thematically using Charmaz's constant comparative approach. RESULTS: Eight referrals were received for the CR program and four Aboriginal women attended the program, aged from 24 to 68 years. Adherence to the weekly sessions ranged from 65 to 100%. At the program's conclusion, there was a significant change in health professionals' perception of social policies implemented to 'improve' Aboriginal people, and self-reported changes in health professionals' behaviours and skills. Themes were identified for recruitment, participants, health professionals and program delivery, with cultural safety enveloping all areas. Trust was a major theme for recruitment and adherence of participants. The AHW was a key enabler of cultural authenticity, and the flexibility of the program contributed greatly to participant perceptions of cultural safety. Barriers for attendance were not unique to this population. CONCLUSION: The flexible CR program in a non-Indigenous service provided a culturally safe environment for Aboriginal women but referrals were low. Importantly, the combination of cultural awareness training and participation in the program delivery improved health professionals' confidence in working with Aboriginal people. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) 12618000581268, http://www.ANZCTR.org.au/ACTRN12618000581268.aspx , registered 16 April 2018.

Modification of lactoferrin by peroxynitrite reduces its antibacterial activity and changes protein structure.

Lactoferrin (LF) is a multifunctional protein that plays important physiological roles as one of the most concentrated proteins in many human and other mammalian fluids and tissues. In particular, LF provides antibacterial properties to human milk, saliva, and tear fluid. LF also protects against stress-induced lipid peroxidation at inflammation sites through its iron-binding ability. Previous studies have shown that LF can be efficiently nitrated via biologically relevant mediators such as peroxynitrite (ONOO- ), which are also present at high intracellular concentrations during inflammation and nitrosative stress. Here, we examine changes in antibacterial properties and structure of LF following ONOO- treatment. The reaction induces nitration of tyrosine and tryptophan residues, which are commonly used as biomarker molecules for several diseases. Treatment with ONOO- at a 10/1 M ratio of ONOO- to tyrosine inhibited all antibacterial activity exhibited by native LF. Secondary structural changes in LF were assessed using circular dichroism spectroscopy. Nitration products with and without the addition of Fe3+ show significant reduction in alpha-helical properties, suggesting partial protein unfolding. Iron-binding capacity of LF was also reduced after treatment with ONOO- , suggesting a decreased ability of LF to protect against cellular damage. LC-MS/MS spectrometry was used to identify LF peptide fragments nitrated by ONOO- , including tyrosine residue Y92 located in the iron-binding region. These results suggest that posttranslational modification of LF by ONOO- could be an important pathway to exacerbate infection, for example, in inflamed tissues and to reduce the ability of LF to act as an immune responder and decrease oxidative damage.

Built Environment, Physical Activity, and Obesity: Findings from the International Physical Activity and Environment Network (IPEN) Adult Study.

Creating more physical activity-supportive built environments is recommended by the World Health Organization for controlling noncommunicable diseases. The IPEN (International Physical Activity and Environment Network) Adult Study was undertaken to provide international evidence on associations of built environments with physical activity and weight status in 12 countries on 5 continents (n > 14,000). This article presents reanalyzed data from eight primary papers to identify patterns of findings across studies. Neighborhood environment attributes, whether measured objectively or by self-report, were strongly related to all physical activity outcomes (accelerometer-assessed total physical activity, reported walking for transport and leisure) and meaningfully related to overweight/obesity. Multivariable indexes of built environment variables were more strongly related to most outcomes than were single-environment variables. Designing activity-supportive built environments should be a higher international health priority. Results provide evidence in support of global initiatives to increase physical activity and control noncommunicable diseases while achieving sustainable development goals.

Androgens stimulate erythropoiesis through the DNA-binding activity of the androgen receptor in non-hematopoietic cells.

BACKGROUND: Androgens function through DNA and non-DNA binding-dependent signalling of the androgen receptor (AR). How androgens promote erythropoiesis is not fully understood. DESIGN AND METHODS: To identify the androgen signalling pathway, we treated male mice lacking the second zinc finger of the DNA-binding domain of the AR (ARΔZF2 ) with non-aromatizable 5α-dihydrotestosterone (5α-DHT) or aromatizable testosterone. To distinguish direct hematopoietic and non-hematopoietic mechanisms, we performed bone marrow reconstitution experiments. RESULTS: In wild-type mice, 5α-DHT had greater erythroid activity than testosterone, which can be aromatized to estradiol. The erythroid response in wild-type mice following 5α-DHT treatment was associated with increased serum erythropoietin (EPO) and its downstream target erythroferrone, and hepcidin suppression. 5α-DHT had no erythroid activity in ARΔZF2 mice, proving the importance of DNA binding by the AR. Paradoxically, testosterone, but not 5α-DHT, suppressed EPO levels in ARΔZF2 mice, suggesting testosterone following aromatization may oppose the erythroid-stimulating effects of androgens. Female wild-type mice reconstituted with ARΔZF2 bone marrow cells remained responsive to 5α-DHT. In contrast, ARΔZF2 mice reconstituted with female wild-type bone marrow cells showed no response to 5α-DHT. CONCLUSION: Erythroid promoting effects of androgens are mediated through DNA binding-dependent actions of the AR in non-hematopoietic cells, including stimulating EPO expression.

"Everything is provided free, but they are still hesitant to access healthcare services": why does the indigenous community in Attapadi, Kerala continue to experience poor access to healthcare?

BACKGROUND: Inequity in access to healthcare services is a constant concern. While advances in healthcare have progressed in the last several decades, thereby significantly improving the prevention and treatment of disease, these benefits have not been shared equally. Excluded communities such as Indigenous communities typically face a lack of access to healthcare services that others do not. This study seeks to understand why the indigenous communities in Attapadi continue to experience poor access to healthcare in spite of both financial protection and adequate coverage of health services. METHODS: Ethnographic fieldwork was carried out among the various stakeholders living in Attapadi. A total of 47 in-depth interviews and 6 focus group discussions were conducted amongst the indigenous community, the healthcare providers and key informants. The data was coded utilising a reflexive and inductive approach leading to the development of the key categories and themes. RESULTS: The health system provided a comprehensive financial protection package in addition to a host of healthcare facilities for the indigenous communities to avail services. In spite of this, they resisted attempts by the health system to improve their access. The failure to provide culturally respectful care, the discrimination of the community at healthcare facilities, the centralisation of the delivery of services as well as the lack of power on the part of the indigenous community to negotiate with the health system for services that were less disruptive for their lives were identified as the barriers to improving healthcare access. The existing power differentials between the community and the health system stakeholders also ensured that meaningful involvement of the community in the local health system did not occur. CONCLUSION: Improving access to health care for indigenous communities would require UHC interventions to be culturally safe, locally relevant and promote active involvement of the community at all stages of the intervention. Continuing structural power imbalances that affect access to resources and prevent meaningful involvement of indigenous communities also need to be addressed.

Correction to: Physical activity intensity, bout-duration, and cardiometabolic risk markers in children and adolescents.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction to: A closer look at the relationship among accelerometer-based physical activity metrics: ICAD pooled data.

Following publication of the original article [1], the author reported that the name of the collaborator group was missing from the author group.

A closer look at the relationship among accelerometer-based physical activity metrics: ICAD pooled data.

BACKGROUND: Accelerometers are widely used to assess child physical activity (PA) levels. Using the accelerometer data, several PA metrics can be estimated. Knowledge about the relationships between these different metrics can improve our understanding of children's PA behavioral patterns. It also has significant implications for comparing PA metrics across studies and fitting a statistical model to examine their health effects. The aim of this study was to examine the relationships among the metrics derived from accelerometers in children. METHODS: Accelerometer data from 24,316 children aged 5 to 18 years were extracted from the International Children's Accelerometer Database (ICAD) 2.0. Correlation coefficients between wear time, sedentary behavior (SB), light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA), moderate- and vigorous-intensity PA (MVPA), and total activity counts (TAC) were calculated. RESULTS: TAC was approximately 22X103 counts higher (p < 0.01) with longer wear time (13 to 18 h/day) as compared to shorter wear time (8 to < 13 h/day), while MVPA was similar across the wear time categories. MVPA was very highly correlated with TAC (r = .91; 99% CI = .91 to .91). Wear time-adjusted correlation between SB and LPA was also very high (r = -.96; 99% CI = -.96, - 95). VPA was moderately correlated with MPA (r = .58; 99% CI = .57, .59). CONCLUSIONS: TAC is mostly explained by MVPA, while it could be more dependent on wear time, compared to MVPA. MVPA appears to be comparable across different wear durations and studies when wear time is ≥8 h/day. Due to the moderate to high correlation between some PA metrics, potential collinearity should be addressed when including multiple PA metrics together in statistical modeling.

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.

Associations of built environment and proximity of food outlets with weight status: Analysis from 14 cities in 10 countries.

The study aimed to examine associations of neighborhood built environments and proximity of food outlets (BE measures) with body weight status using pooled data from an international study (IPEN Adult). Objective BE measures were calculated using geographic information systems for 10,008 participants (4463 male, 45%) aged 16-66 years in 14 cities. Participants self-reported proximity to three types of food outlets. Outcomes were body mass index (BMI) and overweight/obesity status. Male and female weight status associations with BE measures were estimated by generalized additive mixed models. Proportion (95% CI) of overweight (BMI 25 to <30) ranged from 16.6% (13.1, 19.8) to 41.1% (37.3, 44.7), and obesity (BMI ≥ 30) from 2.9% (1.3, 4.4) to 31.3% (27.7, 34.7), with Hong Kong being the lowest and Cuernavaca, Mexico highest for both proportions. Results differed by sex. Greater street intersection density, public transport density and perceived proximity to restaurants (males) were associated with lower odds of overweight/obesity (BMI ≥ 25). Proximity to public transport stops (females) was associated with higher odds of overweight/obesity. Composite BE measures were more strongly related to BMI and overweight/obesity status than single variables among men but not women. One standard deviation improvement in the composite measures of BE was associated with small reductions of 0.1-0.5% in BMI but meaningful reductions of 2.5-5.3% in the odds of overweight/obesity. Effects were linear and generalizable across cities. Neighborhoods designed to support public transport, with food outlets within walking distance, may contribute to global obesity control.