Publications

In infected people, the HIV-1 envelope glycoprotein (Env) constantly evolves to escape the immune response while retaining the essential elements needed to mediate viral entry into target cells. The extensive genetic variation of Env is particularly striking in the V1/V2 hypervariable domains. In this study, we investigated the trade-off, in terms of fusion efficiency, for encoding V1/V2 domains of different lengths. We found that natural variations in V1/V2 length exert a profound impact on HIV-1 entry. Variants encoding compact V1/V2 domains mediated fusion with higher efficiencies than related Envs encoding longer V1/V2 domains. By exchanging the V1/V2 domains between Envs of the same infected person or between two persons linked by a transmission event, we further demonstrated that V1/V2 domains critically influence both Env incorporation into viral particles and fusion to primary CD4 T cells and monocyte-derived dendritic cells. Shortening the V1/V2 domains consistently increased Env incorporation and fusion, whereas lengthening the V1/V2 domains decreased Env incorporation and fusion. Given that in a new host transmitted founder viruses are distinguished by compact Envs with fewer glycosylation sites, our study points to fusion and possibly Env incorporation into virions as limiting steps for transmission of HIV-1 to a new host and suggests that the length and/or the N-glycosylation profile of the V1/V2 domain influences these early steps in the HIV life cycle.

BACKGROUND

In 2012, 6.6 million children under age five died worldwide, most from diseases with known means of prevention and treatment. A delivery gap persists between well-validated methods for child survival and equitable, timely access to those methods. We measured early child health care access, morbidity, and mortality over the course of a health system strengthening model intervention in Yirimadjo, Mali. The intervention included Community Health Worker active case finding, user fee removal, infrastructure development, community mobilization, and prevention programming.

METHODS AND FINDINGS

We conducted four household surveys using a cluster-based, population-weighted sampling methodology at baseline and at 12, 24, and 36 months. We defined our outcomes as the percentage of children initiating an effective antimalarial within 24 hours of symptom onset, the percentage of children reported to be febrile within the previous two weeks, and the under-five child mortality rate. We compared prevalence of febrile illness and treatment using chi-square statistics, and estimated and compared under-five mortality rates using Cox proportional hazard regression. There was a statistically significant difference in under-five mortality between the 2008 and 2011 surveys; in 2011, the hazard of under-five mortality in the intervention area was one tenth that of baseline (HR 0.10, p<0.0001). After three years of the intervention, the prevalence of febrile illness among children under five was significantly lower, from 38.2% at baseline to 23.3% in 2011 (PR = 0.61, p = 0.0009). The percentage of children starting an effective antimalarial within 24 hours of symptom onset was nearly twice that reported at baseline (PR = 1.89, p = 0.0195).

CONCLUSIONS

Community-based health systems strengthening may facilitate early access to prevention and care and may provide a means for improving child survival.

BACKGROUND

A posterior myocardial infarction (PMI) is associated with significant morbidity and delays in recognition may prevent the timely revascularization of these patients. The present study sought to evaluate the reperfusion times and in-hospital outcomes among patients with an isolated PMI.

METHODS

Clinical characteristics and reperfusion times were compared between those with an isolated PMI and those with all other ST-elevation myocardial infarctions (STEMI) in the NCDR ACTION-GWTG Registry from 2007 to 2012. Logistic generalized estimating equations were used to examine risk-adjusted mortality.

RESULTS

Among 117,739 subjects with a STEMI, 824 (0.7%) had evidence of an isolated PMI. The median time between patient arrival and initial electrocardiogram was similar between those with an isolated PMI and those with a non-PMI STEMI (6 vs. 6 minutes, P = .48). However, the median time from initial electrocardiogram to percutaneous coronary intervention was significantly longer among subjects with a PMI (69 vs 61 minutes, P < .01) and fewer patients achieved a door-to-balloon time less than 90 minutes (83% vs 89%, P < .01). After multivariable adjustment, in-hospital mortality was similar for PMI patients compared to those with a non-PMI STEMI (AOR: 1.11, 95% CI: 0.83-1.50).

CONCLUSION

The door-to-balloon times are significantly longer for those with an isolated PMI resulting in fewer patients receiving reperfusion within the guideline recommended time period. Ongoing educational initiatives to increase recognition of a PMI are needed to improve the reperfusion times and outcomes associated with this condition.