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Abstract Background Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. Methods Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20–25 mosquitoes from each temperature regime (25–34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, β-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. Results Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. Conclusions This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate. Graphical Abstract

AbstractThere is close relationship between science & technology inputs and economic growth. Based on the data of science & technology input and economic growth, the paper makes the econometric models analysis on the economic growth and science & technology input of the three major coastal economic regions of China. The paper analyzes and compares the contribution rate of science & technology inputs to economic growth of the three major economic regions.

In biomedical scientific investigations, expositions of findings are conceptually simplest when they comprise comparisons of discrete groups of individuals or involve discrete features or characteristics of individuals. But the descriptive benefits of categorization become outweighed by their limitations in studies involving dose-response relationships, as in many teratogenic and environmental exposure studies. This article addresses a pair of categorization issues concerning the effects of prenatal alcohol exposure that have important public health consequences: the labeling of individuals as fetal alcohol syndrome (FAS) versus fetal alcohol effects (FAE) or alcohol-related neurodevelopmental disorder (ARND), and the categorization of prenatal exposure dose by thresholds. We present data showing that patients with FAS and others with FAE do not have meaningfully different behavioral performance, standardized scores of IQ, arithmetic and adaptive behavior, or secondary disabilities. Similarly overlapping distributions on measures of executive functioning offer a basis for identifying alcohol-affected individuals in a manner that does not simply reflect IQ deficits. At the other end of the teratological continuum, we turn to the reporting of threshold effects in dose-response relationships. Here we illustrate the importance of multivariate analyses using data from the Seattle, Washington, longitudinal prospective study on alcohol and pregnancy. Relationships between many neurobehavioral outcomes and measures of prenatal alcohol exposure are monotone without threshold down to the lowest nonzero levels of exposure, a finding consistent with reports from animal studies. In sum, alcohol effects on the developing human brain appear to be a continuum without threshold when dose and behavioral effects are quantified appropriately.

Forty-nine schools (N = 5,680 fifth and sixth grade students) were assigned to pre test/treatment, pretest/no treatment, no pretest/treatment, and no pretest/no treat ment conditions in the context of an alcohol misuse prevention study. At the first posttest, five months after the pretest and two months after the intervention, the effects of the pretest and of the intervention were examined. The analyses showed that failure to correct for the design effect due to clustering within schools resulted in the overestimation of the significance of treatment and pretest effects. After correction for the design effect, a significant treatment effect in the hypothesized direction was found with respect to students' awareness of the content of the curriculum. As hypo thesized, significant treatment effects on the alcohol use and misuse measures had not yet developed but are expected to occur at subsequent posttest occasions. Significant pretest effects were found for indices measuring trouble with peers resulting from students' alcohol use, students' internal health locus of control, and their perceptions of adults as a locus of control for their health. Two of the three pretest effects were in the direction that would be hypothesized if the pretest were providing the same impe tus as the intervention. Implications of these findings for school-based substance abuse prevention programs are discussed.

The interconversion of the ethanolate, hydrate and amorphous form of TMC114 ((3-[(4-amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl)-carbamic acid hexahydrofuro-[2,3-b]furan-3-yl ester) in open conditions was characterized. TMC114 hydrate and ethanolate form isostructural channel solvates. The crystal structure of TMC114 was obtained from single crystal X-ray diffraction, confirming that it is a channel solvate. Ethanol and water can exchange with one another. TMC114 ethanolate converts into TMC114 hydrate at moderate or high relative humidity (RH) at 25 degrees C, and it converts back into the ethanolate in ethanol atmosphere. The hydration level of the hydrate is determined by the environmental humidity. TMC114 hydrate collapses to the amorphous product when water is removed by drying at low RH or increasing temperature. TMC114 ethanolate becomes amorphous at elevated temperature in a dry environment below the desolvation temperature. Amorphous TMC114 obtained by dehydrating the hydrate during storage at room temperature/<5% RH, by increasing the temperature, or via desolvating the ethanolate by heating, converts into the hydrate at moderate or high RH at ambient conditions, and into TMC114 ethanolate in an ethanol atmosphere. Under ambient conditions, TMC114 ethanolate may convert into the hydrate, whereas the opposite will not occur under these conditions. The amorphous form, prepared by melting-quenching shows a limited water uptake. Whereas TMC114 ethanolate is stable in the commercialized drug product, special conditions can trigger its conversion.

Serum lipoproteins have received considerable notoriety as risk factors for atherosclerotic disease, yet the kinetic factors that determine serum concentrations are often unappreciated. Simple compartmental models for lipoprotein kinetics are herein presented which integrate key features of lipoprotein metabolism and allow prediction of very low-density lipoprotein and low-density lipoprotein levels in a wide variety of clinical circumstances. Possible changes in kinetic parameters responsible for hyperlipidemia in obesity, insulin resistance, diabetes, carbohydrate (sugar)-induced hypertriglyceridemia, alcoholic type V hyperlipemia, polyunsaturated fat diets, and several pharmacological interventions are discussed. Key features of lipoprotein metabolism are briefly reviewed.

Treatment of mice in vivo with 5% w/v ethanol given in a liquid diet causes marked changes in spleen, peripheral blood, and thymus lymphocytes. In both the thymus and spleen, there is an acute cellular depletion resulting in a significant decrease in gross tissue size and cell number. In spleen and peripheral blood, the percentage of T lymphocytes is increased relative to B lymphocytes, but the ratio of CD4+/CD8+ T cell sub‐populations remains unchanged. Splenic natural killer (NK) cell activity is increased in ethanol‐consuming mice, although the percentage of NK1.1+ cells is relatively unchanged.