Planejamento e desenvolvimento de novos compostos com atividade frente a Leishmania spp: Síntese, avaliação da atividade e toxicidade de derivados 5-nitro-2-furfurilidênicos e estudos de relações estrutura-atividade / Design of new compounds against Leishmania spp: synthesis, biological evaluation and toxicity of 5-nitro-2-furfurylidene derivates and structure-activity relationship studies

A leishmaniose é uma zoonose de ampla distribuição mundial, causada pelos parasitas tripanossomatídeos do gênero Leishmania. Infelizmente, o arsenal terapêutico disponível é precário, mas vê-se crescente o interesse científico pela busca do potencial de derivados nitroheterocíclicos como alternativas terapêuticas. Nesse contexto, este trabalho analisou o potencial de derivados 5-nitro-2-furfurilidênicos contra diferentes cepas de Leishmania, assim como investigou um possível modo de ação para esta classe de nitrocompostos. Para tal, a quimioteca foi sintetizada de acordo com publicações prévias do grupo. O potencial de inibição de crescimento das culturas de promastigotas de L. (L.) infantum (Linf) e L. (L.) major (Lmaj) foi determinado, utilizando miltefosina (MILT) (Linf - IC50: 8,28±0,33 µM), anfotericina B (AMB) (Linf - IC50: 0,02±0,002 µM) e nifurtimox (NFX) (Lmaj - IC50: 3,5±0,09 µM) como referência. A maioria dos compostos apresentaram maior potencial que as referênias, destacando o composto 40 (Linf - IC50: 0,2±0,019 µM/ Lmaj - IC50: 0,087 ± 0,001 µM) como mais eficaz. Contra as formas amastigotas intracelulares, para Linf os compostos 40, 13 e 15 foram mais eficazes em reduzir a carga parasitária dos macrófagos infectados que fármacos de referência. Para Lmajor, o composto 40 (IC50: 0,006 ± 0,0003 µM) foi mais ativo que o NFX (IC50: 2,15 ± 0,01 µM). Também foi determinada a atividade da quimioteca frente a enzima nitrorredutase (NTR1), utilizando cepas de T. brucei superexpressantes de NTR1, e os compostos analisados foram até 18 vezes mais eficazes que à cepa wild-type. Ademais, a partir da análise exploratória de dados por análise de componentes principais (PCA) e de grupamentos hierárquicos (HCA), foi reconhecida a influência das propriedades relacionadas com o equilíbrio hidrófilo-lipófilo e da natureza estérica/geométrica das moléculas para atividade anti-Leishmania

Leishmaniasis is a worldwide zoonosis caused by trypanosomatid parasites of the genus Leishmania. Unfortunately, the available therapeutic arsenal is precarious, but there is growing scientific interest in searching the potential of nitroheterocyclic derivatives as therapeutic alternatives. In this context, this work analyzed the potential of 5-nitro-2-furfurylidene derivatives against different Leishmania strains, as well as investigated the potential mode of action for this nitro compounds class. To this end, the chemolibrary was synthesized according to our group's previous publications. The growth inhibitory potential potential for promastigote cultures of L. (L.) infantum (Linf) and L. (L.) major (Lmaj) was determined using miltefosine (MILT) (Linf - IC50: 8.28±0.33 µM), amphotericin B (AMB) (Linf - IC50: 0.02±0.002 µM) and nifurtimox (NFX) (Lmaj - IC50: 3.5±0.09 µM) as reference. Most of the compounds were more potent than the references, highlighting compound 40 (Linf - IC50: 0.2±0.019 µM/ Lmaj - IC50: 0.087 ± 0.001 µM) as the most effective. Against intracellular amastigote, for Linf, compounds 40, 13 and 15 were more effective in reducing the parasite load of infected macrophages than reference drugs. For Lmajor, compound 40 (IC50: 0.006 ± 0.0003 µM) was more active than NFX (IC50: 2.15 ± 0.01 µM). The activity against nitroreductase (NTR1) enzyme was determined using overexpressing NTR1 mutant T. brucei strains, and the analyzed compounds were up to 18 times more effective than wild-type. Furthermore, exploratory data analysis using principal component analysis (PCA) and hierarchical clustering (HCA) methods were used. The influence of properties related to the hydrophiliclipophilic balance and the steric/geometric nature of the molecules was associated with the anti-Leishmanial activity

O uso da análise de correspondências múltiplas (ACM) na pesquisa: o auxílio da tabela de proporções condicionais / The use of multiple correspondence analysis (MCA) in research: the aid of conditional proportions table

A análise de correspondências múltiplas (ACM) é uma técnica pertinente para a psicologia, pois permite estudar associações entre diversas variáveis categóricas tais como características individuais e respostas a questionários, produzindo um mapa que permite visualizá-las. No entanto, é frequentemente mal interpretada, pois trabalha com um nível alto de dimensões, o que torna difícil verificar os dados originais. O trabalho apresenta uma técnica auxiliar para a ACM, a tabela de proporções condicionais, que apresenta as proporções das variáveis incluídas isoladamente e em relações bivariadas, possibilitando a identificação de associações e sua magnitude de modo concreto. O trabalho inclui a aplicação empírica de análise de atribuições de tarefas domésticas a homens e mulheres, proveniente de pesquisa com 958 adultos que forneceram opiniões em levantamento de dados realizado no interior do Brasil. A principal contribuição da tabela de proporções condicionais está no esforço de tornar mais acessível e precisa a utilização da ACM para pesquisadores de psicologia.

Multiple correspondence analysis (MCA) is a relevant technique for psychology, since it allows the study of associations among various categorical variables such as individual characteristics or questionnaires responses, producing a map that makes it possible to visualize them. However, it is often misinterpreted as it deals with a high level of dimensions that makes it difficult to verify the original data. The paper presents an auxiliary technique for MCA, the conditional proportions table, which presents the proportions of the included variables in isolation and in bivariate relationships, enabling the identification of associations and their size in a concrete way. The paper includes an empirical application of the analysis of the attribution of domestic tasks to men and women, from a study with 958 adults who provided their opinions on a survey carried out in the Brazilian countryside. The main contribution of the conditional proportions table lies in the effort of making the use of MCA more accessible and precise for psychology researchers.

Analysis of diseases distribution in Medical Information Mart for Intensive Care Ⅲ database / 中华危重病急救医学

Objective To study the distribution of diseases in Medical Information Mart for Intensive Care Ⅲ(MIMIC-Ⅲ) database in order to provide reference for clinicians and engineers who use MIMIC-Ⅲ database to solve clinical research problems. Methods The exploratory data analysis technologies were used to explore the distribution characteristics of diseases and emergencies of patients (excluding newborns) in MIMIC-Ⅲ database were explored; then, neonatal gestational age, weight, length of hospital stay in intensive care unit (ICU) were analyzed with the same method. Results In the MIMIC-Ⅲ database, 46 428 patients were admitted for the first time, and 49 214 ICU records were recorded. There were 26 076 males and 20 352 females; the median age was 60.5 (38.6, 75.6) years, and most patients were between 60 and 80 years old. The first diagnosis in the disease spectrum analysis was firstly ranked by circulatory diseases (32%), followed by injury and poisoning (14%), digestive system disease (8%), tumor (7%), respiratory disease (6%) and so on. Patients with ischemic heart disease accounted for the largest proportion of circulatory disease (42%), the proportion of these patients gradually increased with age of 60-70 years old, then decreased. However, the proportion of patients with cerebrovascular disease declined first and then increased with age, which was the main cause of death of circulatory system disease (ICU mortality was 22.5%). Injury and poisoning patients showed a significant decrease with age. Digestive system diseases were younger than the general population (most people aged between 50 to 60 years), and non-infectious enteritis and colitis were the main causes of death (ICU mortality was 18.3%). Respiratory infections were predominant in infected patients (34%), but circulatory system infections were the main cause of death (ICU mortality was 25.6%). Secondly, in the neonatal care unit, premature infants accounted for the vast majority (82%). As the gestational age increased, the duration of ICU was decreased, and the mortality was decreased. Conclusions The diseases distribution of patients can be provided by MIMIC-Ⅲ database, which helps to grasp the overview of the volume and age distribution of the target patients in advance, and carry out the next step of research. Meanwhile, it points out the important role of exploratory data analysis in electronic health records analysis.

Introduction of Single Subject Designs as New Experimental Designs. (II). Analytical evaluation of experimental data / 全日本鍼灸学会雑誌

The present-paper offered the basic ideas and methods of analytical evaluation for the single subject data. Firstly, the reasons that emphasize clinical significance rather than statistical significance of independent variables were discussed, and the visual inspection method that is used most often for single subject data was introduced. Secondly, it was pointed out that the time-series analysis method is appropriate for single subject time-series data that have the possibility of the serial dependency, and C statistic was introduced as a useful analytical technique. Thirdly, the usefulness of nonparametric tests that don't require the normal distribution (distribution free) was discussed. Fourthly, it was suggested that the exploratory data analysis is fitted for the single subject designs and its use was recommended. Finally, the reasons were emphasized that while statistical tests for single subject data should be identified and developed from now on, it is important that the visual inspection method is adopted at the same time.

Spatial Exploratory Data Analysis of Birth Defect Risk Factors' Identification / 环境与健康杂志

Objective To acquire effective clues for identification of environmental risk factors to birth defects. Methods Spatial autocorrelation statistics Moran's I and spatial hotspots detect method Getis's G statistics was used to identify birth defect risk factor. Results The different kinds of birth defects have different spatial distribution. Neural tube birth defects have the properties of spatial autocorrelation and different clustering phenomena in different spatial scales. Two typical spatial patterns were discovered in spatial scales of about 6.84 kilometers and 22.8 kilometers. Conclusion Using spatial autocorrelation probing technique, we find that there may be some common environmental teratogenetic factors which affect birth defects occurring ratio in the study area. By hotspots analysis of the clustering phenomena, the risk factors leading to birth defect were further resolved.