Perceived Urban Environment Attributes and Device-Measured Physical Activity in Latin America: An 8-Nation Study.

INTRODUCTION: Attributes of the neighborhood-built environment are associated with self-reported physical activity, but only a few studies have concentrated on device-measured physical activity in Latin America. This study examines the associations of perceived neighborhood-built environment attributes, device-measured sedentary time, and light-intensity and moderate-to-vigorous physical activity in adults from 8 Latin American countries. METHODS: Data from Estudio Latinoamericano de Nutrición y Salud adult study, an observational multicountry study (N=2,478), were analyzed in 2020. Data were collected between 2014 and 2015. Perceived neighborhood-built environment attributes were measured using the Neighbourhood Environment Walkability Survey. Sedentary time, light-intensity physical activity, and moderate-to-vigorous physical activity data were collected using accelerometers. RESULTS: No associations between perceived neighborhood-built environment attributes and sedentary time were found. Positive perceptions of walking/cycling facilities (ß=6.50, 95% CI=2.12, 10.39) were associated with more light-intensity physical activity. Perceptions of better aesthetics (Argentina) and better walking/cycling facilities (Brazil and Ecuador) were positively associated with light-intensity physical activity. Land use mix-diversity (ß=0.14, 95% CI=0.03, 0.25), walking/cycling facilities (ß=0.16, 95% CI=0.05, 0.27), aesthetics (ß=0.16, 95% CI=0.02, 0.30), and safety from traffic (ß=0.18, 95% CI=0.05, 0.24) were positively associated with moderate-to-vigorous physical activity. Land use mix-diversity, street connectivity, and safety from traffic were positively associated with moderate-to-vigorous physical activity in Venezuela. CONCLUSIONS: These findings have implications for policy recommendations, which can guide policies to promote physical activity in the region. Land use mix-diversity, walking/cycling facilities, aesthetics, and safety from traffic can maintain or increase the levels of light-intensity and moderate-to-vigorous physical activity among Latin American adults.

Capacidad de investigación en obesidad infantil en Latinoamérica y en las poblaciones latinas de Estados Unidos: estado de la investigación, problemas, oportunidades y líneas de trabajo para el futuro.

La obesidad infantil es un problema grave en Latinoamérica y entre la población latina de EE. UU. Para ser eficaces, las políticas de salud pública tienen que estar guiadas por evidencias contextuales pertinentes, lo cual exige una capacidad de investigación sostenida a través del tiempo. Los objetivos de este estudio son determinar la productividad de la investigación enfocada en las poblaciones latinas en Latinoamérica y Estados Unidos, y examinar los dominios de la capacidad de investigación (infraestructuras, programas de formación, mentoría, financiamiento y redes de contactos). Realizamos una revisión exploratoria de artículos indexados relacionados con la obesidad infantil publicados entre junio de 2015 y diciembre de 2019. Recabamos información sobre las percepciones de los investigadores latinoamericanos respecto a la capacidad de investigación en obesidad infantil a través de una encuesta en línea. Identificamos 612 artículos relacionados con la obesidad infantil (505 de Latinoamérica, 124 de EE. UU. y 17 de colaboraciones entre EE. UU. y Latinoamérica). Brasil, México, Chile, Colombia y Estados Unidos son los países con más publicaciones. Encontramos aproximadamente el mismo número de artículos sobre obesidad, nutrición y actividad física; sin embargo, observamos que la capacidad de investigación sobre actividad física está rezagada en otros dominios (formación en investigación, financiamiento y oportunidades para establecer contactos). Otras áreas de investigación complementarias, como el comportamiento sedentario, la ciencia de sistemas y los estudios de políticas, son poco frecuentes en Latinoamérica, pero más habituales en Estados Unidos, mientras que la investigación sobre el sueño es incipiente en ambas regiones. Para cumplir la promesa de crear un programa eficaz de colaboración transfronteriza para la prevención de la obesidad infantil será necesario invertir en todos los dominios de la capacidad de investigación y en todos los temas pertinentes.

Perceived Health Risks Among Firefighters; The New Jersey Firefighter Health Survey.

OBJECTIVE: There is a growing literature on the risk of chronic disease among firefighters, including cardiovascular disease (CVD) and cancer. However there is little information on firefighter's perception thereof. METHODS: Firefighters attending a union convention in New Jersey completed a survey with four domains: firefighting experience; perceived additional risk for chronic diseases (six-point Likert scale); cancer screening history; demographics, and risk behaviors. RESULTS: Among 167 enrolled firefighters, all were men and 86.6% active career. Median perceived risk ranged from high risk (colon, hematologic, breast, prostate, and testicular cancers) to very high risk (CVD, pulmonary diseases, all cancers, lung and oral cancer). CONCLUSIONS: NJ Firefighters attributed considerable additional risk to acquiring chronic disease as a result of their firefighting activities. Understanding firefighter perceptions of their own morbidity and mortality will help develop future firefighter preparatory programs.

Global, regional, and national trends and patterns in physical activity research since 1950: a systematic review.

BACKGROUND: National, regional and global scientific production and research capacity for physical activity - PA may contribute to improving public health PA policies and programs. There is an uneven distribution of research productivity by region and country income group, where countries with the highest burden of non-communicable diseases attributable to physical inactivity having low research productivity. A first step towards improving global research capacity is to objectively quantify patterns, trends, and gaps in PA research. This study describes national, regional and global trends and patterns of PA research from 1950 to 2019. METHODS: A systematic review using searches in PubMed, SCOPUS and ISI Web of Knowledge databases was conducted in August 2017 and updated between January and May 2020. The review was registered at the PROSPERO database number CRD42017070153. PA publications per 100,000 inhabitants per country was the main variable of interest. Descriptive and time-trend analyses were conducted in STATA version 16.0. RESULTS: The search retrieved 555,468 articles of which 75,756 were duplicates, leaving 479,712 eligible articles. After reviewing inclusion and exclusion criteria, 23,860 were eligible for data extraction. Eighty-one percent of countries (n = 176) had at least one PA publication. The overall worldwide publication rate in the PA field was 0.46 articles per 100,000 inhabitants. Europe had the highest rate (1.44 articles per 100,000 inhabitants) and South East Asia had the lowest (0.04 articles per 100,000 inhabitants). A more than a 50-fold difference in publications per 100,000 inhabitants was identified between high and low-income countries. The least productive and poorest regions have rates resembling previous decades of the most productive and the richest. CONCLUSION: This study showed an increasing number of publications over the last 60 years with a growing number of disciplines and research methods over time. However, striking inequities were revealed and the knowledge gap across geographic regions and by country income groups was substantial over time. The need for regular global surveillance of PA research, particularly in countries with the largest data gaps is clear. A focus on the public health impact and global equity of research will be an important contribution to making the world more active.

Is the perceived neighborhood built environment associated with domain-specific physical activity in Latin American adults? An eight-country observational study.

BACKGROUND: Characteristics of the neighborhood built environment are associated with physical activity (PA). However, few studies with representative samples have examined environmental correlates of domain-specific PA in Latin America. We examined the associations of the perceived neighborhood built environment with domain-specific PA in a large sample of adults from eight Latin American countries. METHODS: This study examined data from 8185 adults (aged 18-65 years) from eight Latin American countries. The Neighbourhood Environment Walkability Survey - Abbreviated (NEWS-A) scale was used to assess perceptions of land use mix-diversity, land use mix-access, street connectivity, walking/cycling facilities, aesthetics, safety from traffic, and safety from crime. Perceived proximity from home to public open spaces (metropolitan parks, playgrounds, public squares) and to shopping centers was also measured. Transport-related and leisure-time PA were assessed using the long form of the International Physical Activity Questionnaire. Both logistic and linear regression models were estimated on pooled data. RESULTS: Perceptions of higher land use mix-access (OR: 1.40; 95% CI: 1.22,1.61), the existence of many alternative routes in the neighbourhood (1.12; 1.04,1.20), slow speed of traffic (1.19; 1.03,1.35) and few drivers exceeding the speed limits (1.09; 1.03,1.15) were associated with greater odds of reporting at least 10 min/week of transport-related PA. Perceptions of higher levels of land use mix-diversity, better aesthetics and greater safety from crime, the presence of crosswalks and pedestrian signals, and greater proximity of shopping centers were associated with more min/week of transport-related PA. Perceptions of higher land use mix-diversity (1.12; 1.05,1.20), higher land use mix-access (1.27; 1.13,1.43), more walking/cycling facilities (1.18; 1.09,1.28), and better aesthetics (1.10; 1.02,1.18) were associated with greater odds of engaging in at least 10 min/week of leisure-time PA versus none. Perceptions of higher land use mix-diversity were associated with more min/week of leisure PA. CONCLUSIONS: Different perceived neighborhood built environment characteristics were associated with domain-specific PA among adults from Latin America countries. Interventions designed to modify perceptions of the neighbourhood built environment might influence initiation or maintenance of domain-specific PA. TRIAL REGISTRATION: ClinicalTrials. Gov NCT02226627 . Retrospectively registered on August 27, 2014.

National physical activity and sedentary behaviour policies in 76 countries: availability, comprehensiveness, implementation, and effectiveness.

BACKGROUND: Evidence on current, national physical activity (PA) and sedentary behaviour (SB) policies is limited. We, therefore, analysed availability, comprehensiveness, implementation, and effectiveness of PA and SB policies internationally. METHODS: In this cross-sectional study, Global Observatory for Physical Activity (GoPA!) Country Contacts from 173 countries were asked to provide data on their national PA and SB policies by completing GoPA! Policy Inventory. Data were collected for 76 countries (response rate = 44%). RESULTS: Formal written policies for PA and SB were found in 92% (95% confidence interval [CI]: 86, 98) and 62% (95% CI: 50, 75) of countries, respectively. Sixty-two percent (95% CI: 51, 73) of countries have national PA guidelines, while 40% (95% CI: 29, 52) have SB guidelines. Fifty-two (95% CI: 40, 64) and 11% (95% CI: 3, 19) of countries have quantifiable national targets for PA and SB, respectively. The most represented ministries/departments involved in the promotion of more PA and/or less SB were in the sport (reported by 99% countries; 95% CI: 96, 100), health (97%; 95% CI: 94, 100), education (94%; 95% CI: 88, 100), and recreation and leisure (85%; 95% CI: 71, 99) sectors. The median score (0-10) for the comprehensiveness of PA and SB policies was 4 (95% CI: 4, 5) and 2 (95% CI: 2, 3), respectively. For PA and SB policy implementation it was 6 (95% CI: 5, 6). For the effectiveness of PA and SB policies it was 4 (95% CI: 3, 5) and 3 (95% CI: 2, 4), respectively. PA and SB policies were generally best developed in high-income countries and countries of European and Western-Pacific regions. CONCLUSIONS: Most of the included countries have PA policies, but their comprehensiveness, implementation, and effectiveness are generally low-to-moderate. SB policies are less available, comprehensive, implemented, and effective than PA policies. PA and SB policies are better developed in high-income countries, compared with low- and lower-middle-income countries, and in countries of European and Western-Pacific regions, compared with other world regions. More investment is needed in development and implementation of comprehensive and effective PA and SB policies, particularly in low- and lower-middle-income countries.

Comparison of self-report versus accelerometer - measured physical activity and sedentary behaviors and their association with body composition in Latin American countries.

BACKGROUND: Most population-based studies from Latin America have used questionnaires to measure physical activity (PA) and sedentary behaviors (SB). Low reliability and validity of the questionnaires has limited the capacity to examine associations between PA and health. The purpose of this study was to compare self-reported and accelerometer-measured PA and SB and their associations with body composition in Latin American countries. METHODS: Data were obtained from the Latin American Study of Nutrition and Health (aged 15-65 years), collected from September 2014 to February 2015. PA and SB were assessed using the International Physical Activity Questionnaire (long version) and the Actigraph GT3X+ accelerometer. Outcomes of interest included: body mass index (BMI), waist (WC) and neck circumference (NC). We used the Pearson and intraclass correlation coefficient, Bland-Altman plots, and multilevel linear regression models. RESULTS: Mean moderate-to-vigorous physical activity (MVPA) by accelerometer and IPAQ were 34.4 min/day (95% CI: 33.4 to 35.4) and 45.6 min/day (95% CI: 43.2 to 48.1), respectively. For SB (accelerometer and IPAQ) the means were 573.1 (95% CI: 568.2 to 577.9) and 231.9 min/day (95% CI: 225.5 to 238.3). MVPA, measured by the accelerometer was negatively associated with BMI (ß = -1.95; 95% CI: -2.83 to -1.08), WC (ß = -5.04; 95% CI: -7.18 to -2.89) and NC (ß = -1.21; 95% CI: -1.79 to -0.63). The MVPA estimated through IPAQ was not significantly associated with any of the three outcome variables. SB, measured by the accelerometer, was positively associated with BMI (ß = 0.26; 95% CI: 0.08 to 0.44) and WC (ß = 0.48; 95% CI: 0.13 to 0.91). SB estimated through IPAQ was positively associated with NC only. CONCLUSIONS: Low correlation coefficients were observed for accelerometer-derived and IPAQ-reported estimates of PA and SB. Caution is advised when making comparisons between accelerometer-measured and self-reported PA and SB. Further, studies examining associations between movement and health should discuss the impact of PA and SB measurement methodology on the results obtained.

Methodological design for the assessment of physical activity and sedentary time in eight Latin American countries - The ELANS study.

Worldwide studies of physical activity and sedentary time have historically under-represented low- and middle-income countries due to the lack of surveillance data. The purpose of this paper is to describe the methods and procedures used for the assessment of physical activity and sedentary time in the Latin American Study of Nutrition and Health (Estudio Latinoamericano de Nutrición y Salud; ELANS). ELANS is a multicentre, cross-sectional and surveillance study of a nationally representative sample from eight Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela. Two instruments were used to evaluate different domains and intensities of physical activity and sedentary time: self-reported data and a triaxial accelerometer (model GT3X+). ELANS will generate important self-reported and objective information for the Latin American populations, namely:•evidence on the distribution of physical activity and sedentary time across population subgroups (e.g. sex, age, socioeconomic- and educational level). These sets of information will increase the evidence base and can help to inform future intervention strategies in Latin America;•self-reported and objective information on physical activity and sedentary time.

Anthropometry, dietary intake, physical activity and sitting time patterns in adolescents aged 15-17 years: an international comparison in eight Latin American countries.

BACKGROUND: Although there is high prevalence of obesity and other cardiovascular risk factors among Latin American adolescents, there is limited evidence on dietary intake and physical activity (PA) patterns in this population. Therefore, we characterized anthropometry, dietary intake, PA and sitting time (ST) in adolescents aged 15-17 years from eight Latin American countries. METHODS: Six hundred seventy-one adolescents (41.4% girls) from the Latin American Study of Nutrition and Health (ELANS) were included. Nutritional status was classified by four BMI (kg/m2) categories. Waist circumference (WC) was categorized as above or below thresholds. Dietary intake was assessed through two non-consecutive 24-h dietary recalls. PA and ST were measured using the International Physical Activity Questionnaire (IPAQ). We calculated overall and country-specific estimates by sex and tested for differences between boys and girls. RESULTS: Differences in the prevalence of overweightness (15.1 and 21.6%) and obesity (8.5 and 6.5%) between boys and girls, respectively, were statistically insignificant (p = 0.059). Average energy intake was 2289.7 kcal/day (95% CI: 2231-2350) for boys and 1904.2 kcal/day (95% CI: 1840-1963) for girls (p < 0.001). In relation to macronutrient intake for boys and girls, respectively, the average intake (expressed as percentage of total energy) was 15.0 and 14.9% for protein; 55.4 and 54.9% for carbohydrates; 14.1 and 14.5% for added sugar; 29.5 and 30.1% for total fat; and 9.6 and 9.9% for saturated fat (p > 0.05 for all outcomes). There was no statistically significant difference in the prevalence of total energy (TE) saturated fat and added sugar (>10% of TE) between girls and boys (49.6% versus 44.8 and 81.7% versus 76.1%, respectively). Prevalence of physical inactivity was 19% in boys and 43.7% in girls (p < 0.001). Median levels of vigorous-intensity PA and total PA were significantly higher for boys than for girls (p < 0.05 for both outcomes); whereas levels of ST were similar (273.7 versus 220.0 min/day for boys and girls, respectively; p > 0.05). CONCLUSIONS: These findings highlight the high prevalence of poor dietary intake and physical inactivity in adolescents from Latin American countries. Therefore, effective and sustainable strategies and programmes are needed that promote healthier diets, regular PA and reduce ST among Latin American adolescents. TRIAL REGISTRATION: Clinical Trials NCT02226627. Retrospectively registered on August 27, 2014.

Socio-demographic patterning of objectively measured physical activity and sedentary behaviours in eight Latin American countries: Findings from the ELANS study.

Physical activity (PA) and sedentary behaviours (SB) are two independent risk factors for non-communicable diseases. However, there is a lack of objectively measured information on PA and SB in low- and middle-income countries. The aim of this study was to use objective data to characterise socio-demographic patterns of PA and SB in eight Latin American countries. 2732 participants (aged 15-65 years) from the Latin American Study of Nutrition and Health (ELANS) were included. PA and SB data were collected using accelerometers. Overall and country-specific average levels of time spent in PA and SB were compared by sex, age, socioeconomic and education level. Overall, the mean time spent in SB was 571.6 min/day, ranging from 553.8 min/day in Chile to 596.7 min/day in Peru. Average levels of light, moderate-to-vigorous physical activity (MVPA) and total PA were 311.1 min/day (95% CI: 307.7; 314.5), 34.9 min/day (95% CI: 34.0; 35.9) and 7531.2 MET-min/week (95% CI: 7450.4; 7611.9), respectively. MVPA and total PA were higher in men than women. The prevalence of physical inactivity was 40.6%, ranging from 26.9% (Chile) to 47% (Costa Rica and Venezuela). Women were more physically inactive than men (47.7% versus 33.0%). SB levels were highest among those with higher education; PA graded positively with socioeconomic level. Our findings can inform the planning of health policies and programmes designed to reduce levels of physical inactivity, as well as inform the local and cultural adaptation of these policies and programmes for implementation in Latin America. Highlights Worldwide studies of physical activity (PA) and sedentary behaviours (SB) have historically under-represented Latin American countries due to the lack of surveillance data. Across eight Latin American countries, the ELANS study collected data on PA and SB using an objective method (accelerometers) which we have analysed to quantify and characterise socio-demographic patterns. Over four-in-ten participants were physically inactive (40.6%); with a gender gap (47.7% women; 33.0% men); and striking differences between countries (47% Costa Rica and Venezuela; 26.9% Chile). In all countries, levels of moderate-to-vigorous physical activity (MVPA) were lowest, and levels of SB were highest, among participants in the higher education groups. Our findings on the unequal distribution of PA and SB increases the evidence base and can help to inform future intervention strategies in Latin America.

Original research Socio-demographic patterning of self-reported physical activity and sitting time in Latin American countries: findings from ELANS.

BACKGROUND: Low levels of physical activity (PA) and prolonged sitting time (ST) increase the risk of non-communicable diseases and mortality, and can be influenced by socio-demographic characteristics. The aim of this study was to use self-report data to characterise socio-demographic patterns of PA and ST in eight Latin American countries. METHODS: Data were obtained from the Latin American Study of Nutrition and Health (ELANS), a household population-based, multi-national, cross-sectional survey (n = 9218, aged 15-65 years), collected from September 2014 to February 2015. Transport and leisure PA and ST were assessed using the International Physical Activity Questionnaire-long version. Overall and country-specific mean and median levels of time spent in transport and leisure PA and ST were compared by sex, age, socioeconomic and education level. RESULTS: Mean levels of transport and leisure PA were 220.3 min/week (ranging from 177.6 min/week in Venezuela to 275.3 min/week in Costa Rica) and 316.4 min/week (ranging from 272.1 min/week in Peru to 401.4 min/week in Ecuador). Transport and leisure PA were higher (p < 0.005) in men than women with mean differences of 58.0 and 34.0 min/week. The mean and median for transport PA were similar across age groups (15-29 years: mean 215.5 and median 120 min/week; 30-59 years: mean 225.0 and median 120 min/week; ≥60 years: mean 212.0 and median 120 min/week). The median time spent in transport and leisure PA between three strata of socioeconomic and education levels were similar. The prevalence of not meeting PA recommendations were 69.9% (95% CI: 68.9-70.8) for transport and 72.8% (95% CI: 72.0-73.7) for leisure. Men, younger people (15-29 years), individuals with higher socioeconomic and education levels spent significantly (p < 0.001) more time sitting than women, older people (30-59 years and ≥ 60 years) and those in the middle and low socioeconomic and education groups, respectively. CONCLUSIONS: Transport and leisure PA and ST range widely by country, sex, and age group in Latin America. Programs for promoting leisure and transport PA and reducing ST in Latin America should consider these differences by age and gender and between countries. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02226627. Retrospectively registered on August 27, 2014.

The development of the Comprehensive Analysis of Policy on Physical Activity (CAPPA) framework.

BACKGROUND: Policy analysis is considered essential for achieving successful reforms in health promotion and public health. The only framework for physical activity (PA) policy analysis was developed at a time when the field of PA policy research was in its early stages. PA policy research has since grown, and our understanding of what elements need to be included in a comprehensive analysis of PA policy is now more refined. This study developed a new conceptual framework for PA policy analysis - the Comprehensive Analysis of Policy on Physical Activity (CAPPA) framework. METHODS: The development of the CAPPA framework was based on: (i) an extensive review of literature; (ii) an open discussion between the authors; (iii) three rounds of a Delphi process; and (iv) two-rounds of consultations with PA policy stakeholders. RESULTS: The CAPPA framework specifies 38 elements of a comprehensive analysis of PA policies in the following six categories, which comprise the building blocks of the framework: (i) purpose of analysis (including auditing and assessment of policies); (ii) policy level (including: international; national; subnational; local; and institutional policies); (iii) policy sector (including: health; sport; recreation and leisure; education; transport; environment; urban/rural planning and design; tourism; work and employment; public finance; and research sectors); (iv) type of policy (including: formal written policies; unwritten formal statements; written standards and guidelines; formal procedures; and informal policies); (v) stage of policy cycle (including: agenda setting; formulation; endorsement/legitimisation; implementation; evaluation; maintenance; termination; and succession); and (vi) scope of analysis (including availability; context; processes; actors; political will; content; and effects). Based on the CAPPA framework, we also proposed broad and inclusive definitions of PA policy and PA policy analysis. CONCLUSION: The CAPPA framework may be used to guide future studies related to PA policy and to provide a context for the analysis of its specific components. The framework could be used in the same way for sedentary behaviour policy research. Future research should examine the extent to which PA policy analysis has covered each of the elements specified in the CAPPA framework and analyse the elements for which evidence is lacking. Future studies should also determine whether the existing tools allow for auditing and assessment of all the CAPPA elements and develop new tools if needed to allow for a more comprehensive PA policy analysis.

Association of moderate-to-vigorous physical activity with neck circumference in eight Latin American countries.

BACKGROUND: Physical activity is a cornerstone in the prevention and treatment of obesity. There are relatively few studies that explore the effect of accelerometer-determined moderate-to-vigorous physical activity (MVPA) on neck circumference (NC), most of them confined to single high-income countries. The present study investigated the association of accelerometer-determined MVPA with NC in adolescents and adults from eight Latin American countries, which are mostly upper-middle income countries. METHODS: The sample consisted of 2370 participants (47.8% male) from the Latin American Study of Nutrition and Health, a multicenter cross-sectional nutrition and health surveillance study of a nationally representative sample from eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru, and Venezuela). Times (min/day) in MVPA (defined as time accumulated at ≥1952 activity counts/min) was assessed by ActiGraph GT3X+ accelerometer over 7 days. NC for adolescent was categorized as abnormal if circumference was > 34.5 cm for boys and > 31.25 for girls, whereas for adults the cut-off points for abnormal were > 39 cm for men and > 35 cm women. Multilevel logistic models, including country and region as random effects and adjusted for sex, age, socioeconomic level, and educational level, were used to study the association between MVPA and NC. RESULTS: The average time of MVPA was 34.88 min/day, ranging from 31.16 in Venezuela to 40.27 in Chile. Concerning NC, 37.0% of the sample was classified as having elevated NC. Chile was the country with the highest percentage of people with elevated NC (56.9%), and Colombia had the lowest percentage (24.8%). Overall, the MVPA (min/day) was associated with elevated NC (OR = 0.994, CI95% = 0.990-0.998). In Costa Rica and Peru, there were significant associations between MVPA and NC when analyzed by country. CONCLUSIONS: The present study provided evidence of significant associations between MVPA and NC in adolescents and adults from Latin America, independent of sex, age, socioeconomic level, and educational level. This analysis of accelerometry data and NC represents the first examination of these associations in eight Latin America countries. Further research is required to understand the differences between countries in the observed associations. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02226627 . Retrospectively registered on August 27, 2014.

Combining Hyperpolarized Real-Time Metabolic Imaging and NMR Spectroscopy To Identify Metabolic Biomarkers in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that progresses without any symptom, and oftentimes, it is detected at an advanced stage. The lack of prior symptoms and effective treatments have created a knowledge gap in the management of this lethal disease. This issue can be addressed by developing novel noninvasive imaging-based biomarkers in PDAC. We explored in vivo hyperpolarized (HP) 13C MRS of pyruvate to lactate conversion and ex vivo 1H NMR spectroscopy in a panel of well-annotated patient-derived PDAC xenograft (PDXs) model and investigated the correlation between aberrant glycolytic metabolism and aggressiveness of the tumor. Real-time metabolic imaging data demonstrate the immediate intracellular conversion of HP 13C pyruvate to lactate after intravenous injection interrogating upregulated lactate dehydrogenase (LDH) activity in aggressive PDXs. Total ex vivo lactate measurement by 1H NMR spectroscopy showed a direct correlation with in vivo dynamic pyruvate-to-lactate conversion and demonstrated the potential of dynamic metabolic flux as a biomarker of total lactate concentration and aggressiveness of the tumor. Furthermore, the metabolite concentrations were very distinct among all four tumor types analyzed in this study. Overexpression of LDH-A and hypoxia-inducible factor (HIF-1α) plays a significant role in the conversion kinetics of HP pyruvate-to-lactate in tumors. Collectively, these data identified aberrant metabolic characteristics of pancreatic cancer PDXs and could potentially delineate metabolic targets for therapeutic intervention. Metabolic imaging with HP pyruvate and NMR metabolomics may enable identification and classification of aggressive subtypes of patient-derived xenografts. Translation of this real-time metabolic technique to the clinic may have the potential to improve the management of patients at high risk of developing pancreatic diseases.

Hypoxia-induced autophagy of stellate cells inhibits expression and secretion of lumican into microenvironment of pancreatic ductal adenocarcinoma.

Lumican is secreted by pancreatic stellate cells and inhibits cancer progression. Extracellular lumican inhibits cancer cell replication and restrains growth of early-stage pancreatic adenocarcinoma (PDAC) such that patients with tumors containing stromal lumican experience a three-fold longer survival after treatment. In the present study, patient tumor tissues, ex-vivo cultures of patient-derived xenografts (PDX), PDAC stellate and tumor cells were used to investigate whether hypoxia (1% O2) within the tumor microenvironment influences stromal lumican expression and secretion. We observed that hypoxia significantly reduced lumican expression and secretion from pancreatic stellate cells, but not cancer cells. Although hypoxia enhanced lactate dehydrogenase A (LDHA) expression and lactate secretion from all cells, neither hypoxia-induced nor exogenous lactate influenced lumican expression. Autophagy was induced by hypoxia in ex vivo cultures of PDX and pancreatic stellate cells, but not cancer cells cultured in 2D. Autophagic flux inhibitors, bafilomycin A1, chloroquine diphosphate salt, and ammonium chloride prevented hypoxia-mediated reduction in lumican expression in stellate cells. Furthermore, inhibition of AMP-regulated protein kinase (AMPK) phosphorylation or hypoxia-inducible factor (HIF)-1α expression within hypoxic stellate cells restored lumican expression levels. Hypoxia did not affect lumican mRNA expression, indicating that hypoxia-induced reduction of lumican occurs post-transcriptionally; in addition, AMPK inhibition prevented hypoxia-reduced phosphorylation of the mTOR/p70S6K/4EBP signaling pathway, a key contributor to protein synthesis. Taken together, these findings demonstrate that hypoxia reduces stromal lumican in PDAC through autophagy-mediated degradation and reduction in protein synthesis within pancreatic cancer stellate cells.

Antineoplastic effects of auranofin in human pancreatic adenocarcinoma preclinical models.

BACKGROUND: Auranofin, a Food and Drug Administration-approved anti-rheumatic agent with anticancer properties for lung and ovarian cancer, has never been studied for pancreatic cancer. We hypothesize that auranofin may prevent pancreatic ductal adenocarcinoma progression by inhibition of Txnrd1 and HIF-1α. METHODS: In vitro sensitivity of human pancreatic ductal adenocarcinoma cell lines was determined based on IC50. Western blot assays were used to interrogate mechanisms of apoptosis and resistance. Ex vivo live tissue slice assays of xenografts allowed for testing of a larger number of PDX samples with high efficiency. In vivo pancreatic ductal adenocarcinoma orthotopic mouse models using MiaPaCa-2 Luc + cells were designed to determine optimal dose and antitumor effect. RESULTS: We found that 10 of 15 tested pancreatic ductal adenocarcinoma cell lines were sensitive to auranofin based on IC50s below 5 µmol/L. Ex vivo tissue growth inhibition greater than 44% was observed for 13 PDX tissue cases treated with 10 µmol/L auranofin. High Txnrd1 expression was observed for resistant cell lines. In vivo studies showed 15 mg/kg IP as the optimal dose with absence of gross solid organ metastasis up to 13 weeks post-treatment (median survival 8 and 12 weeks, respectively; P = .0953). CONCLUSIONS: We have demonstrated that auranofin prevents pancreatic ductal adenocarcinoma progression using multiple models. Our study suggests inhibition of Txnrd1 and HIF-1α as possible mechanisms of action, and Txnrd1 as a biomarker of resistance. Based on these data, an off-label Phase 0 clinical trial with this FDA-approved drug should be considered for patients with pancreatic cancer.