Publications

OBJECTIVE

The study goals were (1) to assess the feasibility of using an existing telephone health information and referral service for low-income, ethnically diverse women to recruit women for research participation; (2) to assess the feasibility of recruiting low-income, African American and Latino men into health research through the women callers to the telephone service; and (3) to describe the challenges women face and the strategies they use when talking to men about the men's health and research participation.

DESIGN

We recruited women for individual semi-structured qualitative interviews via the Every Woman Counts (EWC) telephone information and referral service, a California Department of Health Services Cancer Detection Program. This paper describes our eligibility and recruitment assessment, and our qualitative data from 23 interviews with low-income African American and Latino women who called EWC.

RESULTS

We found that it was feasible to recruit women, but not to recruit men through women who call this telephone service. Almost 50% (113) of women demographically eligible for recruitment, completed our screening questionnaire, despite calling EWC for a different purpose. Some 48% (54) of those women were eligible for an interview. Of interview-eligible women, 58% (10) of African Americans and 35% (13) of Latinos completed an interview. Only 17% (4) of women referred a man for participation in an interview for our study. Several themes emerged from our analysis of interview data: (1) women's role in men's health can be significant but is often uneasy; (2) challenges when talking to men about their health include health access, gender dynamics, and men's fear of health care; (3) women's understanding of research may be limited; (4) women use a range of strategies to address and overcome men's resistance to taking care of their health and participating in research.

CONCLUSIONS

The challenges women face when talking with men about their health affect their ability to effectively speak to men about research participation. However, EWC and similar telephone health services may be an effective means for recruiting low-income women to chemoprevention and other studies requiring healthy participants.

OBJECTIVE

This study assessed whether smoking in the movies was associated with smoking in young adults.

METHODS

A national web-enabled cross-sectional survey of 1528 young adults, aged 18-25, was performed between September and November 2005. Logistic regression and path analysis using probit regression were used to assess relationships between exposure to smoking in the movies and smoking behavior. Analysis was completed in December 2006.

RESULTS

Exposure to smoking in the movies predicted current smoking. The adjusted odds of current smoking increased by a factor of 1.21 for each quartile increase in exposure to smoking (p<0.01) in the movies, reaching 1.77 for the top exposure quartile. The unadjusted odds of established smoking (100+ cigarettes with current smoking) increased by 1.23 per quartile (p<0.001) of exposure, reaching 1.86 for the top quartile. This effect on established smoking was mediated by two factors related to smoking in the movies: positive expectations about smoking and exposure to friends and relatives who smoked, with positive expectations accounting for about two thirds of the effect.

CONCLUSIONS

The association between smoking in the movies and young adult smoking behavior exhibited a dose-response relationship; the more a young adult was exposed to smoking in the movies, the more likely he or she would have smoked in the past 30 days or have become an established smoker.

Cardiovascular disease (CVD) is the primary cause of death among women worldwide. In the United States, more women than men die of CVD every year. Research has shown that there are important sex differences in terms of prevention, diagnosis, treatment, and outcomes in patients with CVD. Although women are being included in clinical trials in increasing numbers, lack of knowledge about sex differences persists because sex-specific analysis and reporting of sex-specific results remains limited. This knowledge gap limits the ability of health care professionals to provide optimal care for both women and men. Ongoing support and encouragement is needed for both the inclusion of sufficient numbers of women in clinical trials and for the reporting of sex-specific results of CVD trials. This increased knowledge and awareness can then be used to optimize high quality care for men and women.

UNLABELLED

Acute biliary obstruction leads to periductal myofibroblasts and fibrosis, the origin of which is uncertain. Our study provides new information on this question in mice and humans. We show that bile duct obstruction induces a striking increase in cholangiocyte alphavbeta6 integrin and that expression of this integrin is directly linked to fibrogenesis through activation of transforming growth factor beta (TGF-beta). Administration of blocking antibody to alphavbeta6 significantly reduces the extent of acute fibrosis after bile duct ligation. Moreover, in beta6-null mice subjected to the injury, fibrosis is reduced by 50% relative to that seen in wild-type mice, whereas inflammation occurs to the same extent. The data indicate that alphavbeta6, rather than inflammation, is linked to fibrogenesis. It is known that alphavbeta6 binds latent TGF-beta and that binding results in release of active TGFbeta. Consistent with this, intracellular signaling from the TGFbeta receptor is increased after bile duct ligation in wild-type mice but not in beta6(-/-) mice, and a competitive inhibitor of the TGFbeta receptor type II blocks fibrosis to the same extent as antibody to alphavbeta6. In a survey of human liver disease, expression of alphavbeta6 is increased in acute, but not chronic, biliary injury and is localized to cholangiocyte-like cells.

CONCLUSION

Cholangiocytes respond to acute bile duct obstruction with markedly increased expression of alphavbeta6 integrin, which is closely linked to periductal fibrogenesis. The findings provide a rationale for the use of inhibitors of alphavbeta6 integrin or TGFbeta for down-regulating fibrosis in the setting of acute or ongoing biliary injury.

Since breaking onto the scene 26 years ago, HIV has proven an indefatigable foe. Over 60 million people have been infected with this retrovirus, and 25 million have already died of AIDS. HIV infection is hitting the hardest in the developing world 1. Tragically, 1600 babies continue to acquire HIV every day from their infected mothers. Over 12 million children have also been orphaned by AIDS, and this number will likely double by 2010. With these sobering statistics as a backdrop, this feature traces the history of the devastating HIV/AIDS pandemic and offers a view for what the future may hold.

OBJECTIVE

We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.

METHODS AND RESULTS

Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided P<0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in KIF6 (CHS HR=1.29; 90%CI 1.1 to 1.52), VAMP8 (HR=1.2; 90%CI 1.02 to 1.41), TAS2R50 (HR=1.13; 90%CI 1 to 1.27), and LPA (HR=1.62; 90%CI 1.09 to 2.42).

CONCLUSIONS

Although most of the SNPs investigated were not associated with MI in CHS, evidence from this investigation combined with previous studies suggests that 4 of these SNPs are likely associated with MI.

Visceral obesity is associated with insulin resistance, but the association of other regional adipose depots with insulin resistance is not understood. In HIV infection, buffalo hump (upper trunk fat) is associated, but the association of upper trunk fat with insulin resistance has not been examined in controls. To determine the independent association of adipose depots other than visceral with insulin resistance, we performed a cross-sectional analysis of controls and HIV-infected subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, who had measurements of glucose, insulin, and adipose tissue volumes by whole-body magnetic resonance imaging. We studied 926 HIV-positive persons from 16 academic medical center clinics and trials units with demographic characteristics representative of US patients with HIV infection and 258 FRAM controls from the population-based Coronary Artery Risk Development in Young Adults study. We measured visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume in the legs, arms, lower trunk (back and abdomen), and upper trunk (back and chest) and assessed their association with the homeostasis model of assessment (HOMA) and HOMA >4 by stepwise multivariable analysis. The prevalence of HOMA >4 as a marker of insulin resistance was 28% among controls compared with 37% among HIV-infected subjects (P = 0.005). Among controls, those in the highest tertile of upper trunk SAT volume had an odds ratio (OR) of 9.0 (95% confidence interval [CI]: 2.4 to 34; P = 0.001) for having HOMA >4 compared with the lowest tertile, whereas in HIV-positive subjects, the OR was lower (OR = 2.09, 95% CI: 1.36 to 3.19; P = 0.001). Among controls, the highest tertile of VAT volume had an OR of 12.1 (95% CI: 3.2 to 46; P = 0.0002) of having HOMA >4 compared with the lowest tertile, whereas in HIV-positive subjects, the OR was 3.12 (95% CI: 2.0 to 4.8; P < 0.0001). After adjusting for VAT and upper trunk SAT, the association of other SAT depots with HOMA >4 did not reach statistical significance. Thus, VAT and upper trunk SAT are independently associated with insulin resistance in controls and in HIV-infected persons.

The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and beta-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.

Squamous metaplasia (SM) is common in smokers and is associated with airway obstruction in chronic obstructive pulmonary disease (COPD). A major mechanism of airway obstruction in COPD is thickening of the small airway walls. We asked whether SM actively contributes to airway wall thickening through alteration of epithelial-mesenchymal interactions in COPD. Using immunohistochemical staining, airway morphometry, and fibroblast culture of lung samples from COPD patients; genome-wide analysis of an in vitro model of SM; and in vitro modeling of human airway epithelial-mesenchymal interactions, we provide evidence that SM, through the increased secretion of IL-1beta, induces a fibrotic response in adjacent airway fibroblasts. We identify a pivotal role for integrin-mediated TGF-beta activation in amplifying SM and driving IL-1beta-dependent profibrotic mesenchymal responses. Finally, we show that SM correlates with increased severity of COPD and that fibroblast expression of the integrin alpha(v)beta(8), which is the major mediator of airway fibroblast TGF-beta activation, correlated with disease severity and small airway wall thickening in COPD. Our findings have identified TGF-beta as a potential therapeutic target for COPD.