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      Control of neglected disease insect vectors: future prospects for the use of tools based on behavior manipulation-interference

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          Abstract

          The expression "neglected tropical diseases" (NTDs) represents a series of illnesses that affect the population of low-income countries, being vector insects responsible for the transmission of a large part of these diseases. Control tools are needed to impede contacts between humans and insects vectoring some of them. This control is currently attained by intensive insecticide use but resistance to such xenobiotics exists in the most relevant disease vector species. Therefore, alternative vector control methodologies are urgently needed to avoid most NTD transmission. The present review describes a series of molecules that could assist on developing vector control tools, which could be based on manipulating insect behaviors associated with them. Such relations include host odors used by arthropods to search for blood sources, as well as pheromones used by them to communicate in diverse contexts, e.g., reproduction. Additionally, avenues recently explored in the search of behavior modifying compounds by means of high throughput methodologies are discussed. Specifically, examples of how such methodologies mediate the search for new repellents and attractants are described.

          Translated abstract

          A expressão "doenças tropicais negligenciadas" (NTDs) representa uma série de doenças que afetam a população de países de baixa renda, sendo insetos vetores os responsáveis pela transmissão de grande parte dessas doenças. Ferramentas de controle são necessárias para impedir o contato entre humanos e insetos vetores destas doenças. Este controle é comumente realizado pelo uso intensivo de inseticidas, porém, resistência a estes xenobióticos ocorre nos casos mais relevantes de espécies de vetores de doenças. Portanto, metodologias alternativas para o controle de vetores são urgentemente necessárias para evitar a transmissão da maioria das NTDs. Nesta revisão, uma série de compostos químicos que podem auxiliar no desenvolvimento de ferramentas de controle desses vetores, as quais se baseiam na manipulação do comportamento dos insetos associado à estas moléculas, são descritas. Tais relações incluem os odores de hospedeiros usados por artrópodes na busca de fontes de sangue, assim como feromônios utilizados por estes em diversos contextos como, por exemplo, na reprodução. Adicionalmente, são apresentados caminhos recentemente explorados na busca de compostos capazes de modificar comportamentos através de metodologias de alto rendimento. Especificamente, são mostrados exemplos de como estas metodologias mediam a busca por novos repelentes e atrativos.

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          Preparation of Artificial Plasma Membrane Mimicking Vesicles with Lipid Asymmetry

          Lipid asymmetry, the difference in lipid distribution across the lipid bilayer, is one of the most important features of eukaryotic cellular membranes. However, commonly used model membrane vesicles cannot provide control of lipid distribution between inner and outer leaflets. We recently developed methods to prepare asymmetric model membrane vesicles, but facile incorporation of a highly controlled level of cholesterol was not possible. In this study, using hydroxypropyl-α-cyclodextrin based lipid exchange, a simple method was devised to prepare large unilamellar model membrane vesicles that closely resemble mammalian plasma membranes in terms of their lipid composition and asymmetry (sphingomyelin (SM) and/or phosphatidylcholine (PC) outside/phosphatidylethanolamine (PE) and phosphatidylserine (PS) inside), and in which cholesterol content can be readily varied between 0 and 50 mol%. We call these model membranes “artificial plasma membrane mimicking” (“PMm”) vesicles. Asymmetry was confirmed by both chemical labeling and measurement of the amount of externally-exposed anionic lipid. These vesicles should be superior and more realistic model membranes for studies of lipid-lipid and lipid-protein interaction in a lipid environment that resembles that of mammalian plasma membranes.
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            Long Term Outcomes Following Hospital Admission for Sepsis Using Relative Survival Analysis: A Prospective Cohort Study of 1,092 Patients with 5 Year Follow Up

            Background Sepsis is a leading cause of death in intensive care units and is increasing in incidence. Current trials of novel therapeutic approaches for sepsis focus on 28-day mortality as the primary outcome measure, but excess mortality may extend well beyond this time period. Methods We used relative survival analysis to examine excess mortality in a cohort of 1,028 patients admitted to a tertiary referral hospital with sepsis during 2007–2008, over the first 5 years of follow up. Expected survival was estimated using the Ederer II method, using Australian life tables as the reference population. Cumulative and interval specific relative survival were estimated by age group, sex, sepsis severity and Indigenous status. Results Patients were followed for a median of 4.5 years (range 0–5.2). Of the 1028 patients, the mean age was 46.9 years, 52% were male, 228 (22.2%) had severe sepsis and 218 (21%) died during the follow up period. Mortality based on cumulative relative survival exceeded that of the reference population for the first 2 years post admission in the whole cohort and for the first 3 years in the subgroup with severe sepsis. Independent predictors of mortality over the whole follow up period were male sex, Indigenous Australian ethnicity, older age, higher Charlson Comorbidity Index, and sepsis-related organ dysfunction at presentation. Conclusions The mortality rate of patients hospitalised with sepsis exceeds that of the general population until 2 years post admission. Efforts to improve outcomes from sepsis should examine longer term outcomes than the traditional primary endpoints of 28-day and 90-day mortality.
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              Outcomes in Patients with Acute and Stable Coronary Syndromes; Insights from the Prospective NOBORI-2 Study

              Background Contemporary data remains limited regarding mortality and major adverse cardiac events (MACE) outcomes in patients undergoing PCI for different manifestations of coronary artery disease. Objectives We evaluated mortality and MACE outcomes in patients treated with PCI for STEMI (ST-elevation myocardial infarction), NSTEMI (non ST-elevation myocardial infarction) and stable angina through analysis of data derived from the Nobori-2 study. Methods Clinical endpoints were cardiac mortality and MACE (a composite of cardiac death, myocardial infarction and target vessel revascularization). Results 1909 patients who underwent PCI were studied; 1332 with stable angina, 248 with STEMI and 329 with NSTEMI. Age-adjusted Charlson co-morbidity index was greatest in the NSTEMI cohort (3.78±1.91) and lowest in the stable angina cohort (3.00±1.69); P<0.0001. Following Cox multivariate analysis cardiac mortality was independently worse in the NSTEMI vs the stable angina cohort (HR 2.31 (1.10–4.87), p = 0.028) but not significantly different for STEMI vs stable angina cohort (HR 0.72 (0.16–3.19), p = 0.67). Similar observations were recorded for MACE (<180 days) (NSTEMI vs stable angina: HR 2.34 (1.21–4.55), p = 0.012; STEMI vs stable angina: HR 2.19 (0.97–4.98), p = 0.061. Conclusions The longer-term Cardiac mortality and MACE were significantly worse for patients following PCI for NSTEMI even after adjustment of clinical demographics and Charlson co-morbidity index whilst the longer-term prognosis of patients following PCI STEMI was favorable, with similar outcomes as those patients with stable angina following PCI.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                jbchs
                Journal of the Brazilian Chemical Society
                J. Braz. Chem. Soc.
                Sociedade Brasileira de Química (São Paulo )
                1678-4790
                October 2014
                : 25
                : 10
                : 1799-1809
                Affiliations
                [1 ] Fundação Oswaldo Cruz Brazil
                [2 ] Universidade Federal do Paraná Brazil
                Article
                S0103-50532014001000005
                10.5935/0103-5053.20140202

                http://creativecommons.org/licenses/by/4.0/

                Product
                Product Information: SciELO Brazil
                Categories
                CHEMISTRY, MULTIDISCIPLINARY

                General chemistry

                repellents, kairomones, pheromones, vector insects

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