Publications

Violent crime and outdoor physical activity among inner-city youth

Background. Previous studies have shown poor correlation between subjective assessments of neighborhood safety and physical activity. This study was performed to model relationships between adolescents' outdoor physical activity and objectively measured violent crime densities, along with other key environmental variables. Methods. Participants' physical activity was measured using a validated questionnaire. Multiple regression analysis was performed using outdoor physical activity away from school (OPA) as the dependent variable. Environmental factors included the density of violent crime within 1/2 mi of each participant's home, distance to nearest open play space, per capita income, and participants' subjective assessment of neighborhood safety. Results. Multiple regression analysis showed that distance to nearest open play space was inversely and significantly associated with boys' OPA, while density of violent crime within 1/2 mi of home was inversely and significantly associated with girls' OPA. Girls' perceptions that their neighborhood was safe for physical activity were also associated with higher levels of OPA, while boys' assessments of neighborhood safety were not significantly related to OPA. Conclusions. Neighborhood violent crime may be a significant environmental barrier to outdoor physical activity for urban dwelling Mexican-American adolescent girls. Future studies of physical activity and the environment should use objective measures of environmental factors.

Structured physical activity and psychosocial correlates in middle-school girls

Objective. Little is known about the types of physical activity (PA) in which adolescent girls participate. Understanding this, along with examining specific psychosocial correlates of PA, may help guide the development of effective interventions to prevent the decline in PA in female youth. Methods. 2791 sixth grade girls participating in the Trial of Activity for Adolescent Girls from six geographical locations completed surveys assessing participation in sports teams and activity classes/lessons in and out of school, self-efficacy for PA, PA enjoyment, physical education (PE) enjoyment, and perceived school climate for girls' PA (data collection: January–May 2003). Correlates of girls' participation in structured PA and sociodemographic differences were explored. Results. 89.5% of girls participated in structured PA: 39% at school and 86% outside of school. Across race/ethnicity, most reported activities were basketball (44%), cheerleading/dance (41%), and swimming (39%). Controlling for socioeconomic status, geographical location, and race/ethnicity, girls with a higher self-efficacy (OR=3.44, CI=1.72–6.92) and higher enjoyment of PE class (OR=1.97, CI=1.25–3.120) were more likely to participate in structured PA. PA enjoyment and perceived school climate for girls' PA were not associated with participation in structured PA. Conclusion. Interventions that increase self-efficacy and enjoyment of PE could result in greater participation in structured PA and higher overall PA levels among adolescent girls.

Two-Year Outcomes of a Primary Care–and Home-Based Intervention for Physical Activity, Sedentary Behavior, and Diet in Adolescents

Objective. Interventions to promote physical activity (PA) and healthy diet that are (a) conducted in a primary care setting, (b) based on theories of behavioral change, and (c) of long duration (>1 year) are recommended but few exist. We tested the effect, after 2 years of treatment, of a multicomponent intervention designed to promote PA and healthy diet among 819 adolescents between the ages of 11 and 15 years from San Diego. Methods. Treatment effects were assessed using sex-specific repeated-measures mixed model analyses. All behaviors measured were based on self-report. Results. After 2 years of treatment, boys in the intervention group maintained improved consumption of fruits and vegetables whereas the control group did not ( P = .006). Two-year treatment effects were also observed for sedentary behaviors in both boys ( P < .0001) and girls ( P = .012). Satisfaction with the program was high and of the intervention components, counselor calls were most liked, parental guidance was perceived as most valuable, and tip sheets were the most used. Conclusion: Two years of a primary care–based intervention that focus on behavioral change strategies, counselor calls, and parental guidance reduced sedentary behavior and increased boys’ fruit and vegetable consumption.

Angels in the details: Comment on “The relationship between destination proximity, destination mix and physical activity behaviors”

No abstract is provided for this article.

GHF-1, a Tissue-Specific Transcription Factor, is a Homeobox Protein

Micro-scale pedestrian streetscapes and physical activity in Hispanic/Latino adults: Results from HCHS/SOL

Density of Indoor Tanning Facilities in 116 Large U.S. Cities

Background U.S. adolescents and young adults are using indoor tanning at high rates, even though it has been linked to both melanoma and squamous cell cancer. Because the availability of commercial indoor tanning facilities may influence use, data are needed on the number and density of such facilities. Methods In March 2006, commercial indoor tanning facilities in 116 large U.S. cities were identified, and the number and density (per 100,000 population) were computed for each city. Bivariate and multivariate analyses conducted in 2008 tested the association between tanning-facility density and selected geographic, climatologic, demographic, and legislative variables. Results Mean facility number and density across cities were 41.8 (SD=30.8) and 11.8 (SD=6.0), respectively. In multivariate analysis, cities with higher percentages of whites and lower ultraviolet (UV)index scores had significantly higher facility densities than those with lower percentages of whites and higher UV index scores. Conclusions These data indicate that commercial indoor tanning is widely available in the urban U.S., and this availability may help explain the high usage of indoor tanning.

Transcriptional Control Mechanisms Which Regulate the Expression of Human Metallothionein Genes

The human genome contains at least 12 distinct metallothionein genes. The expression of these genes is regulated at the transcriptional levels by heavy metal ions, steroid hormones, interferon, interleukin 1 and phorbol esters. Comparisons of metallothionein gene sequences reveals a higher level of heterogeneity in the 5' flanking control regions than in the coding regions. This is due to the presence of distinct promoter elements on each of the genes. These elements are responsible for inducer and tissue specificity of metallothionein gene expression.

Quiescent Hepatic Stellate Cells Functionally Contribute to the Hepatic Innate Immune Response via TLR3

Toll-like Receptor 3 (TLR3) is a pathogen pattern recognition receptor that plays a key role in innate immunity. TLR3 signalling has numerous functions in liver, both in health and disease. Here we report that TLR3 is expressed by quiescent hepatic stellate cells (HSC) where it functions to induce transcription and secretion of functional interferons as well as a number of other cytokines and chemokines. Upon transdifferentiation into myofibroblasts, HSCs rapidly loose the ability to produce interferon gamma (IFNγ). Mechanistically, this gene silencing may be due to Polycomb complex mediated repression via methylation of histone H3 lysine 27. In contrast to wild type, quiescent HSC isolated from tlr3 knockout mice do not produce IFNγ in response to Poly(I∶C) treatment. Therefore, quiescent HSC may contribute to induction of the hepatic innate immune system in response to injury or infection.

Promoter Elements and Transcriptional Regulation of the Acetylcholinesterase Gene

The 5' region of the acetylcholinesterase gene from the electric ray Torpedo californica has been cloned and its cap site identified. The 5' untranslated region is divided into two exons where a small exon extending between bp -22 to -60 is alternatively spliced. Cap sites are defined at two positions, bp -138 and -143. Twenty-one base pairs 5' of the -143 cap site a repeating TATA sequence is found. Further upstream in the gene consensus sequences for Sp1, AP1, and AP2 factors are evident. The promoter region of the acetylcholinesterase gene enhances transcription of a luciferase reporter gene transfected into C2 myoblasts. However, increased transcription was not evident after C2 myoblasts were induced to form myotubes. Cotransfection of this construct with c-Jun (AP1) and AP2 expression vectors shows marked increases of transcription rates in HepG2 and C2 cells. Protein kinase A elicited regulation of expression is also evident in quail fibroblasts. In gel retardation experiments both recombinant c-Jun (AP1) and AP2 proteins bind to the appropriate Torpedo sequences. Cellular extracts from the Torpedo electric organ exhibit AP2 binding activity. Thus, although all facets of specific regulation expected upon differentiation of mammalian muscle cells were not evident, the 5'-flanking region from the Torpedo AChE gene contains consensus sequences and functional promoter elements typical of mammalian nerve and muscle systems.

Lactational delivery of Triclosan promotes non-alcoholic fatty liver disease in newborn mice

ABSTRACT Pediatric non-alcoholic fatty liver disease (NAFLD) is escalating in the United States, with a limited mechanistic understanding. Triclosan (TCS) is a high-volume antimicrobial additive that has been detected in human breastmilk and shown in adult mice to cause hepatosteatosis. To examine the effect of TCS presented to neonatal mice through lactation, we exposed pregnant females to TCS in their diet and evaluated its impact on nursing neonates. TCS is efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period. Lactational delivery stimulated hepatosteatosis, triglyceride accumulation, endoplasmic reticulum (ER) stress, inflammation, and liver fibrosis. These events were mirrored by inhibition of key metabolic regulators, FGF21 and AMPK. De novo lipogenesis (DNL) induced by lactational TCS exposure was blocked in mice deficient in hepatic ATF4 . In primary hepatocytes, siRNA specific inhibition of PERK, an ATF4 upstream activator and initiator of ER stress, blocked TCS induced DNL. Also, in the absence of PPARα, which targets regulation of ATF4, TCS induced triglyceride accumulation and the induction of DNL was blocked. The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. In summary, TCS exposure via lactation leads to early indicators of NAFLD development accompanied by hepatosteatosis that were mediated in a PERK-eIF2α-ATF4-PPARα cascade. These studies indicate that mother to child transmission of environmental toxicants such as TCS may underlie the recent increases in pediatric NAFLD.

The Active Living Research 2013 Conference: Achieving Change Across Sectors: Integrating Research, Policy, and Practice, Paradise Point Hotel, San Diego, California, USA, 26-28 February 2013.

No abstract is provided for this article.

Structure and tissue-specific expression of the human metallothionein IB gene.

The human metallothionein (MT) IB gene (hMT-IB) is located in a region of human DNA containing at least four tandemly arranged MT genes. As deduced from its sequence, hMT-IB is likely to encode a functional protein. However, the predicted amino acid sequence differed from the hMT-I amino acid sequence in four positions. Most remarkable was the presence of an additional cysteine. Like other MT genes, hMT-IB has at least two copies of the metal-responsive element upstream from the transcription initiation site. These elements probably are responsible for the metal responsiveness of the hMT-IB promoter, leading to inducible expression of fused heterologous genes. Unlike the hMT-IIA and hMT-IA genes described previously, which are expressed in many different cell types, a high level of expression of the endogenous hMT-IB gene could be detected only in human hepatoma and renal carcinoma cell lines. Therefore, this is the first MT gene described which exhibits tissue specificity of expression. This specificity is controlled by a cis-acting mechanism involving methylation, since incubation of nonexpressing cells with an inhibitor of DNA methylation led to activation of the hMT-IB gene. In support of this notion, we found that the 5' flanking region of the hMT-IB gene was highly methylated in HeLa cells, a nonexpressing cell type, but it was not methylated in a hepatoma (expressing) cell line.

Differences in Physical Activity Among Adults in Households With and Without Children

Background: The study aim was to assess the relation of parent status to physical activity (PA) and the impact of parental roles, age and number of children on PA. Methods: Data for 909 women and 965 men, aged 20–57, were analyzed. Mixed Models were used to assess differences in PA between parents and adults without children, with analyses stratified by sex. The primary outcome was accelerometer-measured total daily minutes of moderate-to-vigorous PA (MVPA). Results: Parenthood was not related to MVPA, but mothers reported more total PA than nonmothers. For mothers and fathers, self-reported household activity was higher and sitting time lower, compared with nonparents. Both men and women with children aged 0–5 reported the highest household activity and the lowest sitting time, with household PA higher and sitting time lower with more children. There was no evidence that leisure, transport, or occupational activity varied by parenthood. Conclusions: Considering the potential impact of child-rearing on parent time demands, there was little difference in parents’ objectively measured MVPA compared with nonparents. Educational interventions or extracurricular programs for students and parents could target families with school-aged children. Development of tools to obtain parent reports of child care-specific PA behaviors would be useful.

Soluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia

Parkinson's disease is characterized by accumulation of α-synuclein (αSyn). Release of oligomeric/fibrillar αSyn from damaged neurons may potentiate neuronal death in part via microglial activation. Heretofore, it remained unknown if oligomeric/fibrillar αSyn could activate the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome in human microglia and whether anti-αSyn antibodies could prevent this effect. Here, we show that αSyn activates the NLRP3 inflammasome in human induced pluripotent stem cell (hiPSC)-derived microglia (hiMG) via dual stimulation involving Toll-like receptor 2 (TLR2) engagement and mitochondrial damage. In vitro, hiMG can be activated by mutant (A53T) αSyn secreted from hiPSC-derived A9-dopaminergic neurons. Surprisingly, αSyn-antibody complexes enhanced rather than suppressed inflammasome-mediated interleukin-1β (IL-1β) secretion, indicating these complexes are neuroinflammatory in a human context. A further increase in inflammation was observed with addition of oligomerized amyloid-β peptide (Aβ) and its cognate antibody. In vivo, engraftment of hiMG with αSyn in humanized mouse brain resulted in caspase-1 activation and neurotoxicity, which was exacerbated by αSyn antibody. These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger inflammation in human microglia.

Policy-Relevant Spatial Indicators of Urban Liveability And Sustainability: Scaling From Local to Global

Urban liveability is a global priority for creating healthy, sustainable cities. Measurement of policy-relevant spatial indicators of the built and natural environment supports city planning at all levels of government. Analysis of their spatial distribution within cities, and impacts on individuals and communities, is crucial to ensure planning decisions are effective and equitable. This paper outlines challenges and lessons from a 5-year collaborative research program, scaling up a software workflow for calculating a composite indicator of urban liveability for residential address points across Melbourne, to Australia's 21 largest cities, and further extension to 25 global cities in diverse contexts.

Ethnic and Gender Trends for Cardiovascular Risk Behaviors in Anglo and Mexican American Children, Ages Four to Seven

Gender and ethnic trends were examined in 351 Mexican American and Anglo American children between the ages of four and seven. Four physiologic variables, seven observed and reported variables related to diet, and eight observed and reported variables related to physical activity were periodically assessed. Children were observed at home at meal times and at school (or a day care center) at lunch and recess. A linear regression model was used. Of the four physiologic variables, two variables (height and total skinfolds) showed significant ethnic differences, with Mexican American children showing greater skinfolds over time and the tendency to be shorter than Anglo American children. Of the variables related to diet, five of the seven variables showed gender or ethnic differences; percent of calories from fat and food preparation behaviors tended to place Mexican American children at greater risk. When examining physical activity, four of the eight variables showed gender and/or ethnic differences in trend. As children age, they get less active at home and more active at school. Anglo boys are the most active and are prompted more often to be active. They also participate in more organized physical activities as they get older.

The AP-1 complex and its role in transcriptional control by protein kinase C