Publications

Idiopathic pulmonary fibrosis (IPF) is a debilitating, fatal, chronic fibrosing lung disease with no known effective therapy. Endothelin-1 may underlie the pathogenesis of lung fibrosis, therefore it was hypothesized that the oral dual endothelin receptor antagonist bosentan may have efficacy for the treatment of IPF. The BUILD-1 study evaluated the efficacy, safety and tolerability of bosentan in patients with IPF. Bosentan was associated with a trend toward delayed time to disease progression or death and improvement in quality-of-life, both of which were more pronounced in patients with a biopsy-confirmed IPF diagnosis. These observations are being investigated in the ongoing BUILD-3 trial.

The skin serves the vital function of providing a barrier between the hostile external environment and the host. While the skin has many important barrier functions, the two that are absolutely essential for survival are the barrier to the movement of water and electrolytes (permeability barrier) and the barrier against invasive and toxic microorganisms (antimicrobial barrier). Lipids play an essential role in the formation and maintenance of both the permeability and antimicrobial barriers. A hydrophobic extracellular lipid matrix in the stratum corneum composed primarily of ceramides, cholesterol, and free fatty acids provides the barrier to the movement of water and electrolytes. A variety of lipids, such as fatty alcohols, monoglycerides, sphingolipids, phospholipids, and in particular free fatty acids, have antimicrobial activity and contribute to the antimicrobial barrier. In addition to these essential functions, we will also review the ability of skin surface cholesterol to reflect alterations in systemic lipid metabolism and the risk of atherosclerosis.

BACKGROUND

This study was conducted to determine the relationship between unintended pregnancy and maternal behaviors before, during and after pregnancy.

STUDY DESIGN

Data were analyzed from a stratified random sample of 9048 mothers who delivered live born infants between 2001 and 2006 and completed the Pregnancy Risk Assessment Monitoring System (PRAMS) survey 2 to 9 months after delivery. Binary and ordinal logistic regression methods with appropriate survey weights were used to control for socio-demographic factors.

RESULTS

Compared to women with intended pregnancies, mothers with unwanted pregnancies were more likely to consume less than the recommended amount of preconception folic acid [adjusted odds ratio (OR) 2.39, 95% confidence interval (CI) 1.7-3.2], smoke prenatally (OR 2.03, 95% CI 1.5-2.9), smoke postpartum (OR 1.86, 95% CI 1.35-2.55) and report postpartum depression (OR 1.98, 95% CI 1.48-2.64); they were less likely to initiate prenatal care during the first trimester (OR 0.34, 95% CI 0.3-0.5) and breastfeed for 8 or more weeks (OR 0.74, 95% CI 0.57-0.97). Compared to women with intended pregnancies, women with mistimed pregnancies were also more likely to consume inadequate folic acid, delay prenatal care and report postpartum depression.

CONCLUSION

Even after controlling for multiple socio-demographic factors, unwanted and mistimed pregnancies were associated with unhealthy perinatal behaviors.

Human immunodeficiency virus type 1 (HIV-1)-infected persons who maintain plasma viral loads of <50 copies RNA/ml without treatment have been termed elite controllers (EC). Factors contributing to durable control of HIV in EC are unknown, but an HLA-dependent mechanism is suggested by overrepresentation of "protective" class I alleles, such as B*27, B*51, and B*57. Here we investigated the relative replication capacity of viruses (VRC) obtained from EC (n = 54) compared to those from chronic progressors (CP; n = 41) by constructing chimeric viruses using patient-derived gag-protease sequences amplified from plasma HIV RNA and inserted into an NL4-3 backbone. The chimeric viruses generated from EC displayed lower VRC than did viruses from CP (P < 0.0001). HLA-B*57 was associated with lower VRC (P = 0.0002) than were other alleles in both EC and CP groups. Chimeric viruses from B*57(+) EC (n = 18) demonstrated lower VRC than did viruses from B*57(+) CP (n = 8, P = 0.0245). Differences in VRC between EC and CP were also observed for viruses obtained from individuals expressing no described "protective" alleles (P = 0.0065). Intriguingly, two common HLA alleles, A*02 and B*07, were associated with higher VRC (P = 0.0140 and 0.0097, respectively), and there was no difference in VRC between EC and CP sharing these common HLA alleles. These findings indicate that cytotoxic T-lymphocyte (CTL) selection pressure on gag-protease alters VRC, and HIV-specific CTLs inducing escape mutations with fitness costs in this region may be important for strict viremia control in EC of HIV.

BACKGROUND

Injection drug use is a growing public health crisis along the U.S.-Mexican border and rising rates of blood-borne infections highlight the pressing need for harm reduction interventions. We explored the acceptability and feasibility of such interventions in Tijuana, a city adjacent to San Diego, California.

METHODS

Using in-depth qualitative interviews conducted from August 2006-March 2007 with 40 key stakeholders - pharmacists, legal professionals, health officials, religious officials, drug treatment providers, and law enforcement personnel - we explored the acceptability and feasibility of interventions to reduce drug-related harm in Tijuana, Mexico. Interviews were taped with consent, transcribed verbatim, and translated. Content analysis was conducted to identify themes which included barriers, structural limitations, and suggestions for implementation.

RESULTS

Topics included acceptance and feasibility of needle exchange programmes (NEPs), syringe vending machines, and safer injection facilities (SIFs), structural barriers and suggestions for implementation. Of these interventions, NEPs were deemed the most acceptable (75%); however, only half believed these could be feasibly implemented, citing barriers involving religion, police, and lack of political will, public awareness, and funding.

CONCLUSIONS

Increasing HIV infection rates among injection drug users in Tijuana have prompted interest in public health responses. Our results may assist policy strategists in implementing social-structural interventions that will help create enabling environments that facilitate the scale-up and implementation of harm reduction in Tijuana.