Interventions for the control of Aedes aegypti in Latin America and the Caribbean: systematic review and meta-analysis

Objective: To determine the effectiveness and degree of implementation of interventions for the control of Aedes aegypti in Latin America and the Caribbean (LAC) as reported in scientific literature. Methods: We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, and LILACS, for experimental and observational studies, economic assessments and qualitative experiences carried out in LAC from 2000 to 2016. We assessed incidence and morbimortality of Aedes aegypti-related diseases and entomological indices: Breteau (containers), House, and Pupae per Person. We used GRADE methodology for assessing quality of evidence. Results: Of 1826 records retrieved, 75 were included and 9 cluster randomised clinical trials could be meta-analysed. We did not identify any intervention supported by a high certainty of evidence. In consistency with qualitative evidence, health education and community engagement probably reduces the entomological indices, as do the use of insecticide-treated materials, indoor residual spraying and the management of containers. There is low certainty of evidence supporting the use of ovitraps or larvitraps, and the integrated epidemiological surveillance strategy to improve indices and reduce the incidence of dengue. The reported degree of implementation of these vector control interventions was variable and most did not extend to whole cities and were not sustained beyond 2 years. Conclusions: We found a general lack of evidence on effectiveness of vector control in the region, despite a few interventions that showed moderate to low certainty of evidence. It is important to engage and educate the community, apart from achieving the implementation of integrated actions between the health and other sectors at national and regional level.Fil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: García Perdomo, Herney Andrés. Universidad del Valle; ColombiaFil: Alcaraz, Andrea. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Tapia López, Elena. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ruano Gandara, Ruth Amanda. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ruvinsky, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin

MicroRNA-20a Constrains p300-Driven Myocardial Angiogenic Transcription by Direct Targeting of p300

OBJECTIVE: To characterize downstream effectors of p300 acetyltransferase in the myocardium. BACKGROUND: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known. METHODS AND RESULTS: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17∼92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17∼92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3′UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts. CONCLUSION: p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a