Publications

Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is an intracellular pathogen of mononuclear phagocytes. Although M. tuberculosis has traditionally been thought to survive and replicate in macrophages, recent work in our laboratory and others has revealed that M. tuberculosis infects multiple subsets of mononuclear phagocytes in vivo and in vitro. In experimental animals, M. tuberculosis infects no fewer than five distinct cell subsets in the lungs, including resident alveolar macrophages and 4 types of cells that recruited to the lungs in response to inflammatory signals: neutrophils, monocytes, interstitial macrophages, and dendritic cells. A characteristic of the adaptive immune response in TB is that it is delayed for several weeks following infection, and we have determined that this delay is due to prolonged residence of the bacteria in lung phagocytes prior to acquisition of the bacteria by dendritic cells. Among the mechanisms used by M. tuberculosis to delay acquisition by dendritic cells is to inhibit apoptosis of alveolar macrophages and neutrophils, which sequester the bacteria and prevent their acquisition by dendritic cells in the early stages of infection. We hypothesize that each infected cell subset makes a distinct contribution to the overall biology of M. tuberculosis and allows the bacteria to evade elimination by T-cell responses and to avoid rapid killing by antimycobacterial drugs.

BACKGROUND

Low SES is associated with risk and protective factors for osteoporosis. However, there has been little examination of SES and osteoporosis in the U.S. Methods: We conducted a cross-sectional study of adults aged 50 or older in 2007–2008 NHANES, examining two predictors of SES: income and food insecurity. Our outcome was osteoporosis assessed from bone scans. Adjusted regression models (overall and gender-stratified) controlled for age, gender, race/ethnicity, education, BMI, smoking, alcohol consumption, physical activity, calcium and vitamin D, and medication use.

RESULTS

Of 2403 participants, 5% had osteoporosis. In adjusted models, there was a higher risk of osteoporosis in low-income (OR; 95% CI: 1.90;1.07–3.37) and food-insecure populations (3.48;1.43–8.48). There was a stronger association with food insecurity among women (4.91;2.40–10.0) than men (0.46;0.07–3.01).

CONCLUSIONS

Income and food insecurity may have significant implications not just for immediate nutritional outcomes, but also for conditions such as osteoporosis that develop over the lifespan.

Food insecurity has recently emerged as an important risk factor for HIV acquisition among women worldwide. No previous studies have used linked data that would permit investigation of the extent to which food insecurity may have differential associations with HIV transmission risk behaviors or symptoms of sexually transmitted infections (STIs) among men and women in the same households. We used nationally representative data on linked couples from the Nepal 2011 Demographic and Health Survey. The primary explanatory variable of interest was food insecurity, measured with a modified version of the Household Food Insecurity Access Scale. In multivariable logistic regression models, women in food insecure households were less likely to report recent condom use and more likely to report symptoms consistent with STIs. These patterns were absent among men. Interventions targeting food insecurity may have beneficial implications for both HIV prevention and gender equity in Nepal.

Antibiotic resistance is a global crisis driven by appropriate and inappropriate antibiotic use to treat human illness and promote animal growth. The antimicrobial resistance epidemic continues to spread due to the triple threat of unfettered access, minimal product regulation and oversight of antibiotic prescription, and lack of clinical diagnostic tools to support antibiotic de-escalation in low-resource settings. In high-resource settings, evidence-based strategies have improved the appropriateness of antibiotic use, limiting the spread of drug-resistant organisms and reducing hospital-associated infections, strategies which may also be effective to stop the spread of resistance in resource-poor countries. Current research and surveillance efforts on antimicrobial resistance and hospital-associated infections in low-resource settings are extremely limited and largely focused on intensive care units. Many challenges exist to improving antibiotic use and infection control in resource-limited settings, and turning the tide requires intensifying research and surveillance, antimicrobial stewardship, and developing new bedside diagnostic tools for bacterial infections and antimicrobial susceptibility.

BACKGROUND

Pacemakers and implantable cardioverter-defibrillators (ICDs) are increasingly implanted in adults with congenital heart disease (CHD), but little is known about implant-related complications and mortality.

OBJECTIVE

The purpose of this study was to compare pacemaker and ICD implantation complication rates between adults with and those without CHD using a comprehensive, statewide database.

METHODS

We used the Healthcare Cost and Utilization Project database to identify initial transvenous pacemaker and ICD implantations and implant-related complications in California hospitals from January 1, 2005, to December 31, 2011. We calculated relative risks of implant-related complications by comparing those with and those without CHD using Poisson regression with robust standard errors, adjusting for age and medical comorbidities.

RESULTS

We identified 105,852 patients undergoing pacemaker implantation, 1465 with noncomplex CHD and 66 with complex CHD. CHD was not associated with increased risk of pacemaker implant-related complications: adjusted risk ratio (aRR) 0.92, 95% confidence interval (CI) 0.74-1.14, P = .45. We identified 32,948 patients undergoing ICD implantation, 815 with noncomplex CHD and 87 with complex CHD. Patients with CHD had increased risk of ICD implant-related complications: aRR 1.36, 95% CI 1.05-1.76, P = .02. Patients with complex CHD had greater increased risk of ICD implant-related complications: aRR 2.14, 95% CI 1.16-3.95, P = .02. In patients receiving devices, CHD was associated with a trend toward lower 30-day in-hospital mortality after pacemaker (P = .07) and ICD (P = .19) implantation.

CONCLUSION

Among adult patients undergoing device implantation in California, CHD was associated with increased risk of ICD implant-related complications, but not pacemaker implant-related complications or higher 30-day in-hospital mortality.

BACKGROUND

Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study.

METHODS

We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors.

RESULTS

Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque.

CONCLUSIONS

sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.