Publications

The John Muir Trail (JMT) in the Sierra Nevada Mountains of California is one of the most popular alpine wilderness trails in the United States, where backpackers depend on trailside water sources for more than 335 km (208 miles). This study addressed the risk of acquiring waterborne disease by analyzing prevalence and changes in coliform bacteria and Escherichia coli (E. coli) in lakes and streams adjacent to the central JMT. Chlorophyll-a levels were also measured as an indicator of high elevation eutrophication. Categories of environmental land use which might affect water quality were defined as: Pristine areas rarely traversed by humans; Backpack off-trail areas not traversed by pack or stock animals; and Multiuse areas with backpacker and animal use. We analyzed surface water at 36 different sites three separate times over an eight week period in the summer of 2008. Chlorophyll-a concentration increased significantly in Backpack and Multiuse sites over the summer months, but not in Pristine sites. Similar results were obtained for coliforms, with prevalence also increasing significantly over the summer months in Backpack and Multiuse sites. There was a much higher prevalence of E. coli in Multiuse sites compared to Pristine and Backpack sites. Our study provides evidence pack and stock animals serve as a source of microbial contamination of water along this section of trail.

Abstract T cell activation is an important mechanism in HIV-associated immune depletion. We have previously demonstrated an association between the hyperactivation of CD4(+) and CD8(+) T cells and low CD4 status in HIV-infected Ugandan children. In this study, we explore differences in activation between naive and memory T cells in HIV-infected Ugandan children. A significant correlation between CD4- and CD8-mediated immune activation and CD4 status was observed only in the memory T cells. Antiretroviral (ART) untreated and treated HIV-positive and HIV-negative children displayed similar profiles of activation and distribution within the CD4(+) naive T cells. In contrast, significantly higher immune activation of the memory CD4(+) T cell subset was seen in ART-untreated children when compared to ART-treated or HIV-negative children. ART-mediated viral suppression led to the correction of CD4(+) immune activation to levels seen in uninfected children but did not increase the size of the memory CD4(+) T cell population. High levels of CD8(+) immune activation were also found in both naive and memory cell subsets. Antiretroviral treatment led to the normalization of CD8(+) T cell activation but did not correct the distribution of naive CD8(+) T cells. We also assessed PD-1 expression on CD8(+) T cells as a measure of immune dysfunction. Upregulation of PD-1 was highest in untreated children but persisted in ART-treated children compared to uninfected children. The mechanisms of immunopathogenesis in pediatric HIV infection likely involve distinct contributions from individual naive and memory T cells subsets.

OBJECTIVE

To assess by race/ethnicity long-term changes in metabolic parameters and body composition among treatment-naive persons initiating antiretroviral therapy (ART).

METHODS

We compared changes in 398 participants (African American n = 243, Latino n = 43, white n = 112) initiating ART. At baseline, 1-month (metabolic parameters only) and 4-month follow-up intervals (anthropometric measurements) were performed and fasting metabolic parameters measured. Rates of change over time and overall mean changes from baseline were compared.

RESULTS

Latinos had the greatest increase in glucose and insulin resistance and greatest loss of mid-arm and mid-thigh subcutaneous tissue areas. On average, mid-arm and mid-thigh nonsubcutaneous tissue areas increased in all races. Waist subcutaneous tissue area decreased only for Latinos. Visceral tissue area increased the most for Latinos and whites. For all groups, the initial increase in high-density lipoprotein cholesterol was sustained. The initial increase in low-density lipoprotein cholesterol was followed by a gradual decline in all groups. Triglycerides increased for all groups; the increase being the least for African Americans.

CONCLUSIONS

In this prospective long-term evaluation, changes in metabolic parameters and body composition varied across race groups. Latinos experienced the most unfavorable changes. Such changes should be monitored over time as the identified differences may impact ART selection.

Reports of pain and physical exam findings for musculoskeletal disorders (MSDs) are two common outcome measures independently used to assess work-related MSDs in the scientific literature. How these measures correlate with each other, however, is largely unknown. We recruited 520 sewing machine operators to describe the correlation between subjective self-reported pain and physical findings of MSDs in three upper body regions including the neck/shoulder, elbow/forearm, and hand/wrist. Self-reports of pain and physical findings resulted in different and partly non-overlapping classifications of subjects as MSD cases in our study. Both outcome measures were found to be consistently associated with 'having a medical history of MSDs', 'perceived physical exertion', 'perceived job insecurity' (neck/shoulder), being of older age (arm/forearm), and female gender (arm/forearm and hand/wrist); however, we observed inconsistency for the measures for a number of other job related factors such as 'operating a single machine' and 'number of work hours per week'. Because to date no agreed upon "gold standard" for diagnosing MSDs exists, our findings suggest that research results can be very different when using self-reported measures versus physical exam findings. Also, in order to evaluate the success of an intervention, screening, or surveillance program for work related MSDs, it is important to define clearly which outcome measure best to employ.

Epithelial-mesenchymal interactions are essential for tissue patterning during organogenesis. Distal lung epithelium and its adjacent mesenchyme comprise the epithelial-mesenchymal signaling unit that regulates lung branching morphogenesis. Tissue recombination experiments have demonstrated the importance of mesenchymal signals in inducing lung epithelial differentiation and branching, but the role of the epithelium in regulating mesenchymal signals has not been well characterized. Using transgenic mice, we ablated distal lung epithelial cells during lung development by inducing the expression of a constitutively active proapoptotic Bax protein under the surfactant protein C (SP-C) promoter. We found that epithelial cell ablation results in impaired lung branching morphogenesis, which progresses to emphysematous airspaces in the adults. Mesenchymal expression of fibroblast growth factor 10 (Fgf-10), whose strict spatial and temporal expression is critical for proper lung branching morphogenesis, is disrupted and loses its localized pattern. Interestingly, the expression of sonic hedgehog (Shh), an epithelial gene known to modulate Fgf-10 expression, is unchanged, indicating the existence of other distal epithelial signals that regulate mesenchymal Fgf-10expression. We propose that distal SP-C expressing lung epithelial cells provide essential signals for the downregulation of Fgf-10 expression in the distal mesenchyme during lung development. 292:123-130, 2009. (c) 2008 Wiley-Liss, Inc.

STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte and eosinophil homing into the airways in allergic pulmonary inflammation, and thus is a potential therapeutic target in asthma. However, the critical cellular source of STAT6-mediated chemokine production has not been defined. In this study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2 lymphocyte and eosinophil recruitment into the allergic airway. In contrast, STAT6 in airway-lining cells did not mediate chemokine production or support cellular recruitment. Selective depletion of CD11b(+) myeloid cells in the lung identified these cells as the critical cellular source for the chemokines CCL17 and CCL22. These data reveal that CD11b(+) myeloid cells in the lung help orchestrate the adaptive immune response in asthma, in part, through the production of STAT6-inducible chemokines and the recruitment of Th2 lymphocytes into the airway.

BACKGROUND

Area-level socioeconomic status (SES) may play an important role in drug abuse patterns, including related health outcomes. This may be particularly relevant for gamma-hydroxybutyrate (GHB), which is prototypical of "party" drug abuse.

METHODS

We retrospectively reviewed GHB-related cases reported to the California Poison Control System (CPCS; January 1, 1999 through June 30, 2007). We limited analysis to CPCS calls containing a residential zip code (ZC). The CPCS data were extracted for key case characteristics, including the residential ZC. We linked cases to corresponding 2000 U.S. Census data for area-level measures of SES and demographics. We used multiple logistic regression analysis to test the associations between area-level SES and GHB case severity, taking into account area-level demographics and individual-level GHB high-risk behaviors.

RESULTS

We analyzed 210 cases. Taking into account area-level demographics (age and racial mix; urbanicity) and GHB-related high-risk behaviors (use of GHB congeners; GHB-dependence; co-ingestion of other agents), we associated higher area-level SES with greater GHB case severity. There was 40% increased likelihood of major GHB adverse health outcomes for every $100,000 incremental increase in median home values (OR 1.41; 95% CI 1.1-1.8). For median annual household income (per $10,000), the association was similar (OR 1.39; 95% CI 1.0-1.9).

CONCLUSION

Higher area-level SES is associated with greater GHB-related case severity. This study may serve as a model using a geographic information system (GIS) approach to study the population-based correlates of drugs of abuse reported through poison control surveillance.

OBJECTIVES

We investigated the Latino paradox in a managed care setting and examined the role of birthplace.

METHODS

We evaluated 133,155 non-Latino Whites and 5,237 Latinos (36% born in the United States, 34% in Central and South America, 21% in Mexico, and 8% in the Caribbean Islands) who were enrolled in an integrated healthcare delivery system in northern California. Baseline data were from 1964-1973, and the median followup was 34 years. Main outcome measures were cause-specific and all-cause mortality.

RESULTS

In fully-adjusted analyses, and compared with non-Latino Whites, the risk of death from circulatory causes was significantly lower among US-born Latinos (hazard ratio [HR] .79, 95% confidence interval [CI] .66-.93), among Central and South America-born Latinos (HR .76, 95% CI .63-.91), and Caribbean-born Latinos (HR .66, 95% CI .47-0.93). Risk of death by malignant neoplasms was significantly lower among US-born Latinos (HR .68, 95% CI .56-.83). Risk of respiratory death was significantly lower among Central and South America-born Latinos (HR .50, 95% CI .32-.80). All-cause mortality risk was significantly decreased in US-born Latinos (HR .79, 95% CI .71-.87), Central and South America-born Latinos (HR .81, 95% CI .73-.90), and Caribbean-born Latinos (HR .76, 95% CI .63-.93) but not in Mexico-born Latinos.

CONCLUSIONS

In our managed care setting, the Latino paradox phenomenon varied by birthplace; it was more evident among US-born Latinos. This subgroup experienced lower circulatory, cancer, and all-cause mortality than did non-Latino Whites, despite higher prevalences of current smoking, obesity, and asymptomatic hyperglycemia.