Background:The discovery of small molecules to correct the trafficking defect of the mutant ⌬F508-CFTR protein has been challenging. Results: C4-ceramide rescues and stabilizes ⌬F508-CFTR. High basal secretion of interleukin-8 is also suppressed. Conclusion:Results identify a novel mechanism by which C4-ceramide activates the PDK1/SGK1 pathway, thereby rescuing ⌬F508-CFTR. Significance: C4-ceramide may be a novel candidate therapeutic for CF patients.

Background Vector-borne diseases are a major cause of disease burden in Guayaquil, Ecuador, especially arboviruses spread by Aedes aegypti mosquitoes. Understanding which household characteristics and risk factors lead to higher Ae. aegypti densities and consequent disease risk can help inform and optimize vector control programs. Methods Cross-sectional entomological surveys were conducted in Guayaquil between 2013 and 2016, covering household demographics, municipal services, potential breeding containers, presence of Ae. aegypti larvae and pupae, and history of using mosquito control methods. A zero-truncated negative binomial regression model was fitted to data for estimating the household pupal index. An additional model assessed the factors of the most productive breeding sites across all of the households. Results Of surveyed households, 610 satisfied inclusion criteria. The final household-level model found that collection of large solid items (e.g., furniture and tires) and rainfall the week of and 2 weeks before collection were negatively correlated with average pupae per container, while bed canopy use, unemployment, container water volume, and the interaction between large solid collection and rainfall 2 weeks before the sampling event were positively correlated. Selection of these variables across other top candidate models with ∆AICc < 1 was robust, with the strongest effects from large solid collection and bed canopy use. The final container-level model explaining the characteristics of breeding sites found that contaminated water is positively correlated with Ae. aegypti pupae counts while breeding sites composed of car parts, furniture, sewerage parts, vases, were all negatively correlated. Conclusions Having access to municipal services like bulky item pickup was effective at reducing mosquito proliferation in households. Association of bed canopy use with higher mosquito densities is unexpected, and may be a consequence of large local mosquito populations or due to limited use or effectiveness of other vector control methods. The impact of rainfall on mosquito density is multifaceted, as it may both create new habitat and “wash out” existing habitat. Providing services and social/technical interventions focused on monitoring and eliminating productive breeding sites is important for reducing aquatic-stage mosquito densities in households at risk for Ae. aegypti-transmitted diseases. Graphical Abstract

To test nest box utility in a Southeast Asian tropical forest, we set 30 wooden nest boxes on trees in the Cuc Phuong National Park, Vietnam for a year. During the rainy season, we checked each nest box each month in the daytime. We expected that arboreal rodents might be more likely to use the nest boxes as shelter from the heavy rain. During dry season, we additionally checked each nest box every two months. We expected that nest boxes would be used as a shelter from the rain by small arboreal mammals, such as rats and flying squirrels in the rainy season more than in the dry season. During the rainy season, we found ants, bees, and birds mainly nested the nest boxes for reproduction: bees in April; ants from May to August; and birds from April to June. From the late rainy season to the dry season, arboreal small mammals mainly used nest boxes: rats from August to February and flying squirrel in December. Nest resource competition between birds and rodents may be minimal since they use cavities in different seasons. Also, unlike our expectation, it was preliminary suggested that arboreal small rodents would use more frequently nest box in the dry season than in the rainy season.

The distribution and intensity of viral diseases transmitted by Aedes aegypti mosquitoes, including dengue, have rapidly increased over the last century. Ecuador is an interesting country to study drivers of dengue virus (DENV) transmission given it has multiple ecologically and demographically distinct regions. Here, we analyze province-level age-stratified dengue prevalence data from 2000-2019 using catalytic models to estimate the force of infection of DENV over eight decades and across provinces in Ecuador. We found that provinces established endemic DENV transmission at different time periods. Coastal provinces with the largest and most connected cities had the earliest and highest increase in DENV transmission, starting around 1980 and continuing to the present. In contrast, remote and rural areas with reduced access, like the northern coast and the Amazon regions, experienced a rise in DENV transmission and endemicity only in the last 10 to 20 years. The newly introduced chikungunya and Zika viruses have distinct age-specific prevalence distributions consistent with recent emergence across all provinces. We evaluated factors to the resolution of 1 hectare associated with geographic differences in vector suitability and arbovirus disease in the last 10 years by modeling 11,693 A aegypti presence points and 73,550 arbovirus cases. In total, 56% of the population of Ecuador lives in areas with high risk of Aedes aegypti. Most suitable provinces had hotspots for arbovirus disease risk, with population size, elevation, sewage connection, trash collection, and access to water as important determinants. Our investigation serves as a case study of the changes driving the expansion of DENV and other arboviruses globally and suggest that control efforts should be expanded to semi-urban and rural areas and to historically isolated regions to counteract increasing dengue outbreaks.

Mosquito-borne diseases are a global burden; however, current methods of evaluating human–mosquito contact rates are expensive and time consuming. Validated surveys of self-reported mosquito bites may be an inexpensive way to determine mosquito presence and bite exposure level in an area, but this remains untested. In this study, a survey of self-reported mosquito bites was validated against household mosquito abundance from six communities in Esmeraldas, Ecuador. From February 2021 to July 2022, households were interviewed monthly, and five questions were used to ask participants how often they were bitten by mosquitoes at different times during the day. At the same time, adult mosquitoes were collected using a Prokopack aspirator. Species were identified and counted. Survey responses were compared with the total number of mosquitoes found in the home using negative binomial regression. More frequent self-reported mosquito bites were significantly associated with higher numbers of collected adult mosquitoes. These associations were driven by the prevalence of the dominant genera, Culex. These results suggest that surveys of perceived mosquito bites relate to actual mosquito presence, making them a potentially useful tool for determining the impact of vector–control interventions on community perceptions of risk but less useful for assessing the risk of nondominant species such as Aedes aegypti. Further work is needed to examine the robustness of these results in other contexts.