Functional assay for assessment of agonistic or antagonistic activity of angiotensin AT2 receptor ligands reveals that EMA401 and PD123319 have agonistic properties.

With the discovery of the protective arm of the renin-angiotensin system (RAS), interest has grown in protective RAS-related receptors such as the angiotensin AT2-receptor [AT2R] as potential new drug targets. While it is known that AT2R couple to Gi, it is also apparent that they do not signal via inhibition of adenylyl cyclase/decrease in cAMP, as do many Gi-coupled receptors. Thus, standard commercially-available assays cannot be applied to test for agonistic or antagonistic properties of AT2R ligands. This lack of standard assays has hampered the development of new drugs targeting the AT2R. Therefore, we aimed at developing a reliable, technically easy assay for the determination of intrinsic activity of AT2R ligands, primarily for distinguishing between AT2R agonists and antagonists. We found that measurement of NO release by DAF-FM fluorescence in primary human aortic endothelial cells (HAEC) or in AT2R-transfected CHO cells is a reliable assay for the characterization of AT2R ligands. While testing the assay, we made several novel findings, including: a) C21 is a full agonist at the AT2R (with the same efficacy as angiotensin II); b) C21 has no intrinsic activity at the receptor Mas; c) AT2R-transfected HEK-293 cells are unresponsive to AT2R stimulation; d) EMA401 and PD123319, which are commonly regarded as AT2R antagonists, are partial agonists at the AT2R. Collectively, we have developed and tested an assay based on the measurement and quantification of NO release in HAEC or in AT2R-CHO cells that is suitable for the characterisation of novel and established AT2R ligands.

A Driver in Health Outcomes: Developing Discrete Categories of Transportation Insecurity.

Research suggests that transportation is an important social determinant of health, because the ability to get around is consequential for accessing health care and nutritious food and for making social connections. We used an inductive mixed-methods approach and a quantitative k-means clustering approach to identify 5 categories of transportation insecurity using the validated 16-item Transportation Security Index. The resulting 5-category measure distinguished among respondents with qualitatively different experiences of transportation insecurity. Analyzing data from 2018 that were representative of the US adult population aged 25 years or older, we demonstrated a nonparametric association between transportation insecurity and 2 different health measures (self-rated health and depressive symptoms). There was a threshold relationship between self-rated health and any level of transportation insecurity. High transportation insecurity had a very strong relationship with depressive symptoms. The categorical Transportation Security Index will be useful for clinicians who wish to screen for transportation-related barriers to health care. It will also facilitate research investigating the influence of transportation insecurity on health outcomes and provide the basis for interventions designed to address health disparities.

Constitutive depletion of brain serotonin differentially affects rats' social and cognitive abilities.

Central serotonin appears a promising transdiagnostic marker of psychiatric disorders and a modulator of some of their key behavioral symptoms. In adult male Tph2 -/- rats, constitutively lacking central serotonin, we tested individual's cognitive, social and non-social abilities and characterized group's social organization under classical and ethological testing conditions. Using unsupervised machine learning, we identified the functions most dependent on serotonin. Although serotonin depletion did not affect cognitive performances in classical testing, in the home-cage it induced compulsive aggression and sexual behavior, hyperactive and hypervigilant stereotyped behavior, reduced self-care and exacerbated corticosterone levels. This profile recalled symptoms of impulse control and anxiety disorders. Serotonin appeared essential for behavioral adaptation to dynamic social environments. Our animal model challenges the essential role of serotonin in decision-making, flexibility, impulsivity, and risk-taking. These findings highlight the importance of studying everyday life functions within the dynamic social living environment to model complexity in animal models.

Disparities in trajectories of changes in the unhealthy food environment in New York City: A latent class growth analysis, 1990-2010.

Disparities in availability of food retailers in the residential environment may help explain racial/ethnic and socio-economic differences in obesity risk. Research is needed that describes whether food environment dynamics may contribute to equalizing conditions across neighborhoods or to amplifying existing inequalities over time. This study improves the understanding of how the BMI-unhealthy food environment has evolved over time in New York City. We use longitudinal census tract-level data from the National Establishment Time-Series (NETS) for New York City in the period 1990-2010 and implement latent class growth analysis (LCGA) to (1) examine trajectories of change in the number of unhealthy food outlets (characterized as selling calorie-dense foods such as pizza and pastries) at the census tract-level, and (2) examine how trajectories are related to socio-demographic characteristics of the census tract. Overall, the number of BMI-unhealthy food outlets increased between 1990 and 2010. We summarized trajectories of evolutions with a 5-class model that indicates a pattern of fanning out, such that census tracts with a higher initial number of BMI-unhealthy food outlets in 1990 experienced a more rapid increase over time. Finally, fully adjusted logistic regression models reveal a greater increase in BMI-unhealthy food outlets in census tracts with: higher baseline population size, lower baseline income, and lower proportion of Black residents. Greater BMI-unhealthy food outlet increases were also noted in the context of census tracts change suggestive of urbanization (increasing population density) or increasing purchasing power (increasing income).

Street Audits to Measure Neighborhood Disorder: Virtual or In-Person?

Neighborhood conditions may influence a broad range of health indicators, including obesity, injury, and psychopathology. In particular, neighborhood physical disorder-a measure of urban deterioration-is thought to encourage crime and high-risk behaviors, leading to poor mental and physical health. In studies to assess neighborhood physical disorder, investigators typically rely on time-consuming and expensive in-person systematic neighborhood audits. We compared 2 audit-based measures of neighborhood physical disorder in the city of Detroit, Michigan: One used Google Street View imagery from 2009 and the other used an in-person survey conducted in 2008. Each measure used spatial interpolation to estimate disorder at unobserved locations. In total, the virtual audit required approximately 3% of the time required by the in-person audit. However, the final physical disorder measures were significantly positively correlated at census block centroids (r = 0.52), identified the same regions as highly disordered, and displayed comparable leave-one-out cross-validation accuracy. The measures resulted in very similar convergent validity characteristics (correlation coefficients within 0.03 of each other). The virtual audit-based physical disorder measure could substitute for the in-person one with little to no loss of precision. Virtual audits appear to be a viable and much less expensive alternative to in-person audits for assessing neighborhood conditions.

Using GPS Data to Study Neighborhood Walkability and Physical Activity.

INTRODUCTION: Urban form characteristics intended to support pedestrian activity, collectively referred to as neighborhood walkability, are thought to increase total physical activity. However, little is known about how neighborhood walkability influences utilization of neighborhood space by residents and their overall physical activity. METHODS: Sociodemographic information and data on mobility and physical activity over 1-week periods measured by GPS loggers and accelerometers were collected from 803 residents of New York City between November 2010 and November 2011. Potentially accessible neighborhood areas were defined as land area within a 1-kilometer distance of the subject's home (radial buffer) and within a 1-kilometer journey on the street network from the home (network buffer). To define actual areas utilized by subjects, a minimum convex polygon was plotted around GPS waypoints falling within 1 kilometer of the home. A neighborhood walkability scale was calculated for each neighborhood area. Data were analyzed in 2014. RESULTS: Total residential neighborhood space utilized by subjects was significantly associated with street intersection density and was significantly negatively associated with residential density and subway stop density within 1 kilometer of the home. Walkability scale scores were significantly higher within utilized as compared with non-utilized neighborhood areas. Neighborhood walkability in the utilized neighborhood area was positively associated with total weekly physical activity (32% [95% CI=17%, 49%] more minutes of moderate-equivalent physical activity across the interquartile range of walkability). CONCLUSION: Neighborhood walkability is associated with neighborhood spaces utilized by residents and total weekly physical activity.

Development and deployment of the Computer Assisted Neighborhood Visual Assessment System (CANVAS) to measure health-related neighborhood conditions.

Public health research has shown that neighborhood conditions are associated with health behaviors and outcomes. Systematic neighborhood audits have helped researchers measure neighborhood conditions that they deem theoretically relevant but not available in existing administrative data. Systematic audits, however, are expensive to conduct and rarely comparable across geographic regions. We describe the development of an online application, the Computer Assisted Neighborhood Visual Assessment System (CANVAS), that uses Google Street View to conduct virtual audits of neighborhood environments. We use this system to assess the inter-rater reliability of 187 items related to walkability and physical disorder on a national sample of 150 street segments in the United States. We find that many items are reliably measured across auditors using CANVAS and that agreement between auditors appears to be uncorrelated with neighborhood demographic characteristics. Based on our results we conclude that Google Street View and CANVAS offer opportunities to develop greater comparability across neighborhood audit studies.

Assessment of long-term health risks after accidental exposure using haemoglobin adducts of epichlorohydrin.

On September 9th, 2002, two goods trains collided in Bad Münder, Lower Saxony, causing the release of more than 40 metric tonnes of epichlorohydrin (1-chloro-2,3-epoxypropane) into the environment. A human biomonitoring study was performed to evaluate the accidental exposure to epichlorohydrin and to assess the possible long-term, i.e. carcinogenic health effects. This was done on the basis of a biochemical effect monitoring using the N-(3-chloro-2-hydroxypropyl)valine and the N-(2,3-dihydroxypropyl)valine haemoglobin adducts of epichlorohydrin in blood to respond to missing ambient monitoring immediately after the crash. N-(3-chloro-2-hydroxypropyl)valine adduct levels above the LOQ (25 pmol/g globin) ranged from 32.0 to 116.4 pmol/g globin in 6 out of 628 samples. The N-(2,3-dihydroxypropyl)valine adduct was not detected above the LOD (10 pmol/g globin) in any of the blood samples. Based on the quantified N-(3-chloro-2-hydroxypropyl)valine adduct values, the body doses after two days of exposure were estimated to be in the range of 1.7-6.2 nmol/kg body weight. The reverse estimation of the external exposure leads to cumulative additional lifetime cancer risks ranging from 2.61×10(-8) to 9.48×10(-8). The estimated excess lifetime cancer risks have to be assessed as extremely low. Our biomonitoring study facilitated the dialogue between individuals and groups concerned and authorities, because suspected or occurred exposures and risks to human health could be quantified and interpreted in a sound manner.

Comparing nutrition environments in bodegas and fast-food restaurants.

Many small grocery stores or "bodegas" sell prepared or ready-to-eat items, filling a niche in the food environment similar to fast-food restaurants. However, little comparative information is available about the nutrition environments of bodegas and fast-food outlets. This study compared the nutrition environments of bodegas and national chain fast-food restaurants using a common audit instrument, the Nutrition Environment Measures Study in Restaurants (NEMS-R) protocol. The analytic sample included 109 bodegas and 107 fast-food restaurants located in New York City neighborhoods in the upper third and lower third of the census tract poverty rate distribution. Inter-rater reliability was evaluated in 102 food outlets, including 31 from the analytic sample and 71 from a supplementary convenience sample. The analysis compared scores on individual NEMS-R items, a total summary score, and subscores indicating healthy food availability, nutrition information, promotions of healthy or unhealthy eating, and price incentives for healthy eating, using t tests and χ(2) statistics to evaluate differences by outlet type and neighborhood poverty. Fast-food restaurants were more likely to provide nutrition information, and bodegas scored higher on healthy food availability, promotions, and pricing. Bodegas and fast-food restaurants had similar NEMS-R total scores (bodegas 13.09, fast food 14.31; P=0.22). NEMS-R total scores were higher (indicating healthier environments) in low- than high-poverty neighborhoods among both bodegas (14.79 vs 11.54; P=0.01) and fast-food restaurants (16.27 vs 11.60; P<0.01). Results imply different policy measures to improve nutrition environments in the two types of food outlets.

Neighbourhood food environments and body mass index among New York City adults.

BACKGROUND: Studies evaluating the impact of the neighbourhood food environment on obesity have summarised the density or proximity of individual food outlets. Though informative, there is a need to consider the role of the entire food environment; however, few measures of whole system attributes have been developed. New variables measuring the food environment were derived and used to study the association with body mass index (BMI). METHODS: Individual data on BMI and sociodemographic characteristics were collected from 48 482 respondents of the 2002-2006 community health survey in New York City and linked to residential zip code-level characteristics. The food environment of each zip code was described in terms of the diversity of outlets (number of types of outlets present in a zip code), the density of outlets (outlets/km(2)) and the proportion of outlets classified as BMI-unhealthy (eg, fast food, bodegas). RESULTS: Results of the cross-sectional, multilevel analyses revealed an inverse association between BMI and food outlet density (-0.32 BMI units across the IQR, 95% CI -0.45 to -0.20), a positive association between BMI and the proportion of BMI-unhealthy food outlets (0.26 BMI units per IQR, 95% CI 0.09 to 0.43) and no association with outlet diversity. The association between BMI and the proportion of BMI-unhealthy food outlets was stronger in lower (

Length of residence and social integration: the contingent effects of neighborhood poverty.

Given the well-established benefits of social integration for physical and mental health, studies have begun to explore how access to social ties and social support may be shaped by the residential context in which people live. As a critical health exposure, social integration may be one important mechanism by which places affect health. This paper brings together research on two previously studied contextual determinants of social integration. Specifically, we use multi-level data from the Chicago Community Adult Health Survey to investigate the relationships between an individual's length of residence and measures of social integration. We then investigate the extent to which these relationships are moderated by neighborhood poverty. We find that the relationship between length of residence and some measures of social integration are stronger in poor neighborhoods than in more affluent ones.

Socio-economic status, neighbourhood food environments and consumption of fruits and vegetables in New York City.

OBJECTIVE: Recommendations for fruit and vegetable consumption are largely unmet. Lower socio-economic status (SES), neighbourhood poverty and poor access to retail outlets selling healthy foods are thought to predict lower consumption. The objective of the present study was to assess the interrelationships between these risk factors as predictors of fruit and vegetable consumption. DESIGN: Cross-sectional multilevel analyses of data on fruit and vegetable consumption, socio-demographic characteristics, neighbourhood poverty and access to healthy retail food outlets. SETTING: Survey data from the 2002 and 2004 New York City Community Health Survey, linked by residential zip code to neighbourhood data. SUBJECTS: Adult survey respondents (n 15 634). RESULTS: Overall 9?9% of respondents reported eating $5 servings of fruits or vegetables in the day prior to the survey. The odds of eating $5 servings increased with higher income among women and with higher educational attainment among men and women. Compared with women having less than a high-school education, the OR was 1?12 (95% CI 0?82, 1?55) for high-school graduates, 1?95 (95% CI 1?43, 2?66) for those with some college education and 2?13 (95% CI 1?56, 2?91) for college graduates. The association between education and fruit and vegetable consumption was significantly stronger for women living in lower- v. higher-poverty zip codes (P for interaction,0?05). The density of healthy food outlets did not predict consumption of fruits or vegetables. CONCLUSIONS: Higher SES is associated with higher consumption of produce, an association that, in women, is stronger for those residing in lower-poverty neighbourhoods.

Neighborhood walkability and active travel (walking and cycling) in New York City.

Urban planners have suggested that built environment characteristics can support active travel (walking and cycling) and reduce sedentary behavior. This study assessed whether engagement in active travel is associated with neighborhood walkability measured for zip codes in New York City. Data were analyzed on engagement in active travel and the frequency of walking or biking ten blocks or more in the past month, from 8,064 respondents to the New York City 2003 Community Health Survey (CHS). A neighborhood walkability scale that measures: residential, intersection, and subway stop density; land use mix; and the ratio of retail building floor area to retail land area was calculated for each zip code. Data were analyzed using zero-inflated negative binomial regression incorporating survey sample weights and adjusting for respondents' sociodemographic characteristics. Overall, 44 % of respondents reported no episodes of active travel and among those who reported any episode, the mean number was 43.2 episodes per month. Comparing the 75th to the 25th percentile of zip code walkability, the odds ratio for reporting zero episodes of active travel was 0.71 (95 % CI 0.61, 0.83) and the exponentiated beta coefficient for the count of episodes of active travel was 1.13 (95 % CI 1.06, 1.21). Associations between lower walkability and reporting zero episodes of active travel were significantly stronger for non-Hispanic Whites as compared to non-Hispanic Blacks and to Hispanics and for those living in higher income zip codes. The results suggest that neighborhood walkability is associated with higher engagement in active travel.

Using Google Street View to audit neighborhood environments.

BACKGROUND: Research indicates that neighborhood environment characteristics such as physical disorder influence health and health behavior. In-person audit of neighborhood environments is costly and time-consuming. Google Street View may allow auditing of neighborhood environments more easily and at lower cost, but little is known about the feasibility of such data collection. PURPOSE: To assess the feasibility of using Google Street View to audit neighborhood environments. METHODS: This study compared neighborhood measurements coded in 2008 using Street View with neighborhood audit data collected in 2007. The sample included 37 block faces in high-walkability neighborhoods in New York City. Field audit and Street View data were collected for 143 items associated with seven neighborhood environment constructions: aesthetics, physical disorder, pedestrian safety, motorized traffic and parking, infrastructure for active travel, sidewalk amenities, and social and commercial activity. To measure concordance between field audit and Street View data, percentage agreement was used for categoric measures and Spearman rank-order correlations were used for continuous measures. RESULTS: The analyses, conducted in 2009, found high levels of concordance (≥80% agreement or ≥0.60 Spearman rank-order correlation) for 54.3% of the items. Measures of pedestrian safety, motorized traffic and parking, and infrastructure for active travel had relatively high levels of concordance, whereas measures of physical disorder had low levels. Features that are small or that typically exhibit temporal variability had lower levels of concordance. CONCLUSIONS: This exploratory study indicates that Google Street View can be used to audit neighborhood environments.

Disparities in neighborhood food environments: implications of measurement strategies.

Public health researchers have begun to map the neighborhood "food environment" and examine its association with the risk of overweight and obesity. Some argue that "food deserts"­areas with little or no provision of fresh produce and other healthy food­may contribute to disparities in obesity, diabetes, and related health problems. While research on neighborhood food environments has taken advantage of more technically sophisticated ways to assess distance and density, in general, it has not considered how individual or neighborhood conditions might modify physical distance and thereby affect patterns of spatial accessibility. This study carried out a series of sensitivity analyses to illustrate the effects on the measurement of disparities in food environments of adjusting for cross-neighborhood variation in vehicle ownership rates, public transit access, and impediments to pedestrian travel, such as crime and poor traffic safety. The analysis used geographic information systems data for New York City supermarkets, fruit and vegetable markets, and farmers' markets and employed both kernel density and distance measures. We found that adjusting for vehicle ownership and crime tended to increase measured disparities in access to supermarkets by neighborhood race/ethnicity and income, while adjusting for public transit and traffic safety tended to narrow these disparities. Further, considering fruit and vegetable markets and farmers' markets, as well as supermarkets, increased the density of healthy food outlets, especially in neighborhoods with high concentrations of Hispanics, Asians, and foreign-born residents and in high-poverty neighborhoods.

Disparities in the food environments of New York City public schools.

BACKGROUND: Studies of the food environment near schools have focused on fast food. Research is needed that describes patterns of exposure to a broader range of food outlet types and that examines the influence of neighborhood built environments. PURPOSE: Using data for New York City, this paper describes the prevalence of five different food outlet types near schools, examines disparities by economic status and race/ethnicity in access to these food outlets, and evaluates the extent to which these disparities are explained by the built environment surrounding the school. METHODS: National chain and local fast-food restaurants, pizzerias, small grocery stores ("bodegas"), and convenience stores within 400 m of public schools in New York City were identified by matching 2005 Dun & Bradstreet data to 2006-2007 school locations. Associations of student poverty and race/ethnicity with food outlet density, adjusted for school level, population density, commercial zoning, and public transit access, were evaluated in 2009 using negative binomial regression. RESULTS: New York City's public school students have high levels of access to unhealthy food near their schools: 92.9% of students had a bodega within 400 m, and pizzerias (70.6%); convenience stores (48.9%); national chain restaurants (43.2%); and local fast-food restaurants (33.9%) were also prevalent within 400 m. Racial/ethnic minority and low-income students were more likely to attend schools with unhealthy food outlets nearby. Bodegas were the most common source of unhealthy food, with an average of nearly ten bodegas within 400 m, and were more prevalent near schools attended by low-income and racial/ethnic minority students; this was the only association that remained significant after adjustment for school and built-environment characteristics. CONCLUSIONS: Nearly all New York City public school students have access to inexpensive, energy-dense foods within a 5-minute walk of school. Low-income and Hispanic students had the highest level of exposure to the food outlets studied here.

Using Google Earth to conduct a neighborhood audit: reliability of a virtual audit instrument.

Over the last two decades, the impact of community characteristics on the physical and mental health of residents has emerged as an important frontier of research in population health and health disparities. However, the development and evaluation of measures to capture community characteristics is still at a relatively early stage. The purpose of this work was to assess the reliability of a neighborhood audit instrument administered in the city of Chicago using Google Street View by comparing these "virtual" data to those obtained from an identical instrument administered "in-person". We find that a virtual audit instrument can provide reliable indicators of recreational facilities, the local food environment, and general land use. However, caution should be exercised when trying to gather more finely detailed observations. Using the internet to conduct a neighborhood audit has the potential to significantly reduce the costs of collecting data objectively and unobtrusively.

Measurement of the local food environment: a comparison of existing data sources.

Studying the relation between the residential environment and health requires valid, reliable, and cost-effective methods to collect data on residential environments. This 2002 study compared the level of agreement between measures of the presence of neighborhood businesses drawn from 2 common sources of data used for research on the built environment and health: listings of businesses from commercial databases and direct observations of city blocks by raters. Kappa statistics were calculated for 6 types of businesses-drugstores, liquor stores, bars, convenience stores, restaurants, and grocers-located on 1,663 city blocks in Chicago, Illinois. Logistic regressions estimated whether disagreement between measurement methods was systematically correlated with the socioeconomic and demographic characteristics of neighborhoods. Levels of agreement between the 2 sources were relatively high, with significant (P < 0.001) kappa statistics for each business type ranging from 0.32 to 0.70. Most business types were more likely to be reported by direct observations than in the commercial database listings. Disagreement between the 2 sources was not significantly correlated with the socioeconomic and demographic characteristics of neighborhoods. Results suggest that researchers should have reasonable confidence using whichever method (or combination of methods) is most cost-effective and theoretically appropriate for their research design.

Mobility disability and the urban built environment.

Research on the effects of the built environment in the pathway from impairment to disability has been largely absent. Using data from the Chicago Community Adult Health Study (2001-2003), the authors examined the effect of built environment characteristics on mobility disability among adults aged 45 or more years (n = 1,195) according to their level of lower extremity physical impairment. Built environment characteristics were assessed by using systematic social observation to independently rate street and sidewalk quality in the block surrounding each respondent's residence in the city of Chicago (Illinois). Using multinomial logistic regression, the authors found that street conditions had no effect on outdoor mobility among adults with only mild or no physical impairment. However, among adults with more severe impairment in neuromuscular and movement-related functions, the difference in the odd ratios for reporting severe mobility disability was over four times greater when at least one street was in fair or poor condition (characterized by cracks, potholes, or broken curbs). When all streets were in good condition, the odds of reporting mobility disability were attenuated in those with lower extremity impairment. If street quality could be improved, even somewhat, for those adults at greatest risk for disability in outdoor mobility, the disablement process could be slowed or even reversed.