METHODS: HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated.
RESULTS: There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure.
CONCLUSIONS: Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.
METHODOLOGY/PRINCIPAL FINDINGS: This yearlong field surveillance identified Ae. aegypti breeding in outdoor containers on an enormous scale. Through a sequence of experiments incorporating outdoors and indoors adapting as well as adapted populations, we observed that indoors provided better environment for the survival of Ae. aegypti and the observed death patterns could be explained on the basis of a difference in body size. The duration of gonotrophic period was much shorter in large-bodied females. Fecundity tended to be greater in indoor acclimated females. We also found increased tendency to multiple feeding in outdoors adapted females, which were smaller in size compared to their outdoors breeding counterparts.
CONCLUSION/SIGNIFICANCE: The data presented here suggest that acclimatization of Ae. aegypti to the outdoor environment may not decrease its lifespan or gonotrophic activity but rather increase breeding opportunities (increased number of discarded containers outdoors), the rate of larval development, but small body sizes at emergence. Size is likely to be correlated with disease transmission. In general, small size in Aedes females will favor increased blood-feeding frequency resulting in higher population sizes and disease occurrence.
MATERIALS AND METHODS: The Singapore Cardiovascular Cohort Study is a longitudinal follow-up study on a general population cohort of 5920 persons drawn from 3 previous cross-sectional surveys. Morbidity and mortality from IHD and stroke were ascertained by record linkage using a unique identification number with the death registry, Singapore Myocardial Infarct Registry and in-patient discharge databases.
RESULTS: There were 193 first IHD events and 97 first strokes during 52,806 person-years of observation. The overall incidence of IHD was 3.8/1000 person-years and that of stroke was 1.8/1000 person-years. In both males and females, Indians had the highest IHD incidence, followed by Malays and then Chinese. For males after adjusting for age, Indians were 2.78 times (95% CI 1.86, 4.17; P < 0.0001) and 2.28 times (95% CI 1.34, 3.88; P = 0.002) more likely to get IHD than Chinese and Malays respectively. For females after adjusting for age, Indians were 1.97 times (95% CI 1.07, 3.63; P = 0.03) and 1.37 times (95% CI 0.67, 2.80; P = 0.39) more likely to get IHD than Chinese and Malays respectively. For stroke, male Chinese and Indians had higher incidence than Malays (though not statistically significant). However, in females, Malays had the highest incidence of stroke, being 2.57 times (95% CI 1.31, 5.05; P = 0.008) more likely to get stroke than Chinese after adjustment for age.
CONCLUSIONS: This prospective study of both mortality and morbidity has confirmed the higher risk of IHD in Indians. It has also found that Malay females have a higher incidence of stroke, which deserves further study because of its potential public health importance.
MATERIALS AND METHODS: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models.
RESULTS: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments.
CONCLUSION: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway.