Publications

(1) Background: Findings from observational studies of relations between neighborhood environments and health outcomes underscore the importance of both objective and perceived experiences of those environments. A clearer understanding of the factors associated with discrepancies between these two assessment approaches is needed to tailor public health interventions to specific populations. This study examined how individual and neighborhood characteristics affect perceptions of supermarket distance, particularly when perceptions do not match objective measures. (2) Methods: Participants were older adults (n = 880) participating in the Senior Neighborhood Quality of Life Study in the Seattle/King County, WA or Baltimore/Washington, DC regions. Two main analyses were conducted. The primary outcome for Analysis I was participants' geographic information systems (GIS)-based objective network distance to the closest supermarket. Generalized linear mixed models with block group-level random effects were used to assess associations between objective supermarket distance and individual/neighborhood characteristics. The primary outcome for Analysis II was a categorical "accuracy" variable, based on participants' perceived distance to the nearest supermarket/grocery store relative to the objective distance, assuming a walking speed of 1.0 m/s. Multivariate log-linear models fit neural networks were used to assess influential covariates. (3) Results: Several significant associations with objective distance to the nearest supermarket were observed, including a negative relationship with body mass index (BMI) (95% CI = -45.56, -0.23), having walked to the supermarket in the last 30 days (-174.86, -59.42), living in a high-walkability neighborhood, and residing in Seattle/King County (-707.69, -353.22). In terms of participants' distance accuracy, 29% were classified as accurate, 33.9% were "Underestimators", 24.0% "Overestimators", and 13.2% responded "Don't Know". Compared to Accurate participants, Overestimators were significantly less likely to have walked to the supermarket in the last 30 days, and lived objectively closer to a supermarket; Underestimators perceived significantly higher pedestrian safety and lived objectively further from a supermarket; and Don't Know were more likely to be women, older, not living independently, and not having recently walked to the supermarket. (4) Conclusions: Both modifiable and nonmodifiable factors influence the accuracy of older adults' perceptions of their proximity to the nearest supermarket. Recent experience in walking to the closest supermarket, along with personal safety, represent potentially modifiable perceived environmental factors that were related to older adults' accuracy of perceptions of their neighborhood food environment.

ATF is a cellular transcription factor involved in the regulation of multiple adenovirus E1A- and cellular cAMP-inducible promoters. Using DNA affinity chromatography, we have purified ATF and found that a series of polypeptides copurify in a sequence-specific manner. We demonstrate that these polypeptides represent a family of proteins that are related by DNA-binding specificity and by immunological cross-reactivity. This family includes the transcription factor AP-1, whose recognition sequence, GTGAGTCAA, differs from the ATF consensus, GTGACGTCAA, by the absence of a cytosine residue. Our results further indicate that there are multiple forms of both ATF and AP-1. The immunological cross-reactivity and related DNA-binding specificities suggest that ATF and AP-1 contain similar amino acid sequences and may have originated from a common gene.

Youth advocacy for obesity prevention is a promising but under-evaluated intervention.The aims of this study are to evaluate a youth advocacy program's outcomes related to youth perceptions and behaviors, develop an index of youth advocacy readiness, and assess potential predictors of advocacy readiness.Youth ages 9-22 in an advocacy training program (n = 92 matched pairs) completed surveys before and after training.Youth outcomes and potential predictors of advocacy readiness were assessed with evaluated scales.All 20 groups who completed the evaluation study presented their advocacy projects to a decision maker.Two of six perception subscales increased following participation in the advocacy program: self-efficacy for advocacy behaviors (p < .001)and participation in advocacy (p < .01).Four of five knowledge and skills subscales increased: assertiveness (p < .01),health advocacy history (p < .001),knowledge of resources (p < .01),and social support for health behaviors (p < .001).Youth increased days of meeting physical activity recommendations (p < .05).In a mixed regression model, four subscales were associated with the advocacy readiness index: optimism for change (B = 1.46, 95 % CI = .49-2.44), sports and physical activity enjoyment (B = .55,95 % CI = .05-1.05), roles and participation (B = 1.81, 95 % CI = .60-3.02), and advocacy activities (B = 1.49, 95 % CI = .64-2.32).The youth advocacy readiness index is a novel way to determine the effects of multiple correlates of advocacy readiness.Childhood obesity-related advocacy training appeared to improve youths' readiness for advocacy and physical activity.

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg-Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.

Study objectives To describe the prevalence of parental prompting to smoke (eg, parent requests that their child light the parent's cigarette in his/her own mouth) in a sample of families, and to assess the agreement between child and parent reports of the prompting behaviors. Design, setting, and participants A total of 3,624 adolescents from 10 middle/junior high schools completed baseline surveys. Parents identified as smokers in these surveys were contacted to complete a telephone survey. These analyses included 270 parent/child pairs. Fifty-one percent of parents were Latino American, 51% had the equivalent of a high-school diploma, 83% were employed when surveyed, and the median household monthly income was between $2,200 and $2,599. Measurements and results Students completed a paper-and-pencil survey assessing demographic characteristics, seven parental prompts to smoke, past month smoking, parental smoking, acculturation, and familism. A similar questionnaire was developed to collect information by telephone from smoking parents. Concordance between child- and parent-reported prompting was > 85% for five of seven prompts. However, the reported prevalence of six of the seven prompts was lower among parents than children. Thirty-two percent of mothers and 17% of fathers reported prompting their children to bring cigarettes to parents (the most common prompt). Students reported that 62% of their mothers and 54% of their fathers prompted them to bring their cigarettes, a substantial discrepancy in both cases. Conclusions Child-reported prompting prevalence was consistently higher than parents' reports, with the biggest discrepancies between requests to clean ashtrays and bring cigarettes, the two most common prompts. In subsequent studies of parental prompting, it is advisable to collect data from both children and parents and to validate the accuracy of the sources.

Background: Physical activity (PA) declines as children and adolescents age. The purpose of this study was to examine how specific school factors relate to youth PA, TV viewing, and body mass index (BMI). Methods: A sample of 12‐ to 18‐year‐old adolescents in 3 cities (N = 165, 53% females, mean age 14.6 ± 1.7 years, 44% nonwhite) completed surveys assessing days of physical education (PE) class per week, school equipment accessibility, after‐school supervised PA, and after‐school field access. Regression analyses were conducted to examine relationships between these school factors and PA at school facilities open to the public (never active vs active), overall PA level (days per week physically active for 60 minutes), BMI z score, and TV watching (hours per week). Results: Adjusting for demographics, days of PE per week and access to school fields after school were correlated with overall PA (β= 0.286, p = .002, semipartial correlation .236 and β= 0.801, p = .016, semipartial correlation .186, respectively). The association between after‐school field access and overall PA was mediated by use of publicly accessible school facilities for PA. After‐school supervised PA and school PA equipment were not associated with overall PA. In adjusted regression analyses including all school factors, days of PE remained correlated to overall PA independent of other school factors (β= 0.264, p = .007, semipartial correlation = .136). There were no associations between school factors and BMI or TV watching. Conclusions: Based on these study findings, PE is a promising intervention to address improving overall adolescent PA within the school setting.

Abstract The nature of immune cells recruited at the sites of antigen exposure and the cytokine microenvironment play a key role at shaping immune responses. Using a model sublingual vaccine with Bacillus anthracis edema toxin as an adjuvant, we show that alteration of IKKβ signaling in myeloid cells (IKKβΔMye) enhanced the magnitude of Ab and T cell responses, compared to control mice. While this model vaccine failed to induce S-IgA Abs in control mice, significant S-IgA Ab responses were induced in mucosal secretions of IKKβΔMye mice. We also established that the sublingual vaccine recruited lower numbers of CD11b+F4/80+Gr1high and CD11b+F4/80-Gr1high, but higher number of CD11b+F4/80+Gr1- cells in the sublingual tissues of IKKβΔMye mice. In contrast, higher numbers of CD11b+F4/80+Gr1high and CD11b+F4/80-Gr1high, but lower number of CD11b+F4/80+Gr1- cells were recruited in the sublingual tissues of control and IL-17A KO mice. Lack of IL-17A signaling did not affect the magnitude of Ab responses to the sublingual vaccine. However, the profile of B cell epitope responses was affected in IL-17A KO mice. Furthermore, CD11b+ cells isolated from IKKβΔMye mice assisted B cell-differentiation and induced production of IgA Abs by IL-17Rhigh B lymphocytes in vitro. Our results support the existence of an IKKβ-IL-17 axis for regulation of mucosal immunity and identify IKKβ signaling as a potential target for improving induction of mucosal immunity by sublingual vaccines.

Summary Whereas treatments that reactivate exhausted T cells are available, strategies to rejuvenate terminally differentiated senescent lymphocytes are yet to be developed. Senescent T cells, with short telomeres and inactive telomerase, are different from exhausted cells, and may form due to defective telomere transfer reactions upon contact with antigen presenting cells (APCs). Senescent T cells are characterized by presence of sestrin-MAPK kinase activation complexes (sMACs), large immune-inhibitory protein assemblies of sestrins bound to a stress/energy sensing kinase (AMPK) and three functional effector kinases (ERK, JNK and p38 MAPKs). Here we described first in class Disruptors of the Sestrin-MAPK immune-inhibitory Complex (DOS), which target sMAC to ubiquitin-dependent proteasomal degradation, resulting in long-term sestrin transcriptional inhibition, increased T cell fitness, and generation of long-lived stem like memory features. Strikingly, the DOS generated stem T cells present de novo antigen-specific T-cell receptor DNA rearrangements that precede their future expansion. Although largely senescent at the point of treatment, the DOS regenerated T cells, with stem features and new TCRs, initiated immune-protective rejuvenation-dependent responses to new challenges, with or without vaccination. Therefore, it is possible to generate new T cell clones from formerly senescent cells and expand immune specificity. Highlights DOS are the first sestrin-MAPK binding disruptors DOS rejuvenate T cells (DOS-juvenation) DOS-juvenated T cells protect old mice from lethal infections, with or without vaccination DOS-juvenated T cells exist as stem-like cells that undergo antigen-specific TCR revisions