Publications

OBJECTIVE

We examined associations between neighborhood socioeconomic disadvantage, perceived neighborhood safety and cardiometabolic risk factors, adjusting for health behaviors and socioeconomic status (SES) among African Americans.

METHODS

Study participants were non-diabetic African Americans (n = 3,909) in the baseline examination (2000-2004) of the Jackson Heart Study. We measured eight risk factors: the metabolic syndrome, its five components, insulin resistance and cardiovascular inflammation. We assessed neighborhood socioeconomic disadvantage with US Census 2000 data. We assessed perceived neighborhood safety, health behaviors and SES via survey. We used generalized estimating equations to estimate associations with a random intercept model for neighborhood effects.

RESULTS

After adjustment for health behaviors and SES, neighborhood socioeconomic disadvantage was associated with the metabolic syndrome in women (PR 1.13, 95% CI 1.01, 1.27). Lack of perceived safety was associated with elevated glucose (OR 1.36, 95% CI 1.03, 1.80) and waist circumference (PR 1.06, 95% CI 1.02, 1.11) among women, and with elevated glucose (PR 1.30, 95% CI 1.02, 1.66) and insulin resistance (PR 1.25, 95% CI 1.08, 1.46) among men.

CONCLUSIONS

Neighborhood socioeconomic disadvantage and perceived safety should be considered as targets for intervention to reduce cardiometabolic risks among African Americans.

Epidemic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is associated with more severe and acute forms of osteomyelitis than healthcare-associated (HA-) MRSA. Although S. aureus is now recognized as a facultative intracellular pathogen, the contribution of osteoblast invasion by CA-MRSA to the pathogenesis of osteomyelitis is unknown. Using an ex vivo model of intracellular infection of human osteoblasts, we demonstrated that CA-MRSA strains of diverse lineages share an enhanced ability to kill infected osteoblasts compared to HA-MRSA. Cytotoxicity comparisons of CA-MRSA isogenic deletion mutants revealed that phenol-soluble modulins (PSMs), a class of membrane-damaging exoproteins that are expressed at higher levels in CA-MRSA than in HA-MRSA, are involved in this osteoblast killing, whereas other major CA-MRSA virulence determinants, the Panton-Valentine leukocidin and alpha-toxin, are not involved. Similarly, functional agr and sarA regulators, which control the expression of PSMs and alpha-toxin, were required for the expression of the intracellular cytotoxic phenotype by CA-MRSA, whereas the saeRS regulator, which controls the expression of alpha-toxin but not PSMs, had no impact on cytotoxicity. Finally, PSM transcript levels determined by quantitative reverse-transcriptase PCR were significantly higher in CA-MRSA than in HA-MRSA strains and associated with cell damage in MRSA-infected osteoblasts. These findings provide new insights into the pathogenesis of severe CA-MRSA osteomyelitis and unravel a novel virulence strategy of CA-MRSA, based on the invasion and subsequent killing of osteoblasts by PSMs acting as intracellular toxins.

Treating drug-resistant tuberculosis (DR-TB) is particularly challenging in high human immunodeficiency virus (HIV) prevalence settings. Neither antiretroviral resistance testing nor viral load monitoring is widely available in sub-Saharan Africa, and antiretroviral resistance can complicate the clinical management for DR-TB/HIV coinfected patients. We describe six cases of antiretroviral resistance in DR-TB patients with HIV coinfection in Lesotho. Two patients died before or immediately after antiretroviral resistance was detected by genotyping; the remaining four patients were switched to effective antiretroviral therapy (ART) regimens. Favorable DR-TB treatment outcomes in coinfected patients require successful management of their HIV infection, including treatment with an effective ART regimen. Coinfected patients undergoing DR-TB treatment may require closer monitoring of their response to ART, including routine viral load testing, to ensure that they receive an effective ART regimen concurrent with DR-TB treatment.